Subjects -> BIOLOGY (Total: 3174 journals)
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BIOLOGY (1491 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 401 - 600 of 1720 Journals sorted alphabetically
Cryoletters     Full-text available via subscription   (Followers: 4)
Cuadernos de Neuropsicología     Open Access   (Followers: 1)
Current Applied Science and Technology     Open Access  
Current Bioinformatics     Hybrid Journal   (Followers: 13)
Current Biology     Full-text available via subscription   (Followers: 236)
Current Genomics     Hybrid Journal   (Followers: 8)
Current Landscape Ecology Reports     Hybrid Journal   (Followers: 2)
Current Medical Science     Hybrid Journal   (Followers: 1)
Current Molecular Medicine     Hybrid Journal   (Followers: 2)
Current Opinion in Cell Biology     Hybrid Journal   (Followers: 51)
Current Opinion in Molecular Therapeutics     Full-text available via subscription   (Followers: 8)
Current Opinion in Neurobiology     Hybrid Journal   (Followers: 32)
Current Opinion in Structural Biology     Hybrid Journal   (Followers: 26)
Current Opinion in Systems Biology     Hybrid Journal   (Followers: 2)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Current Protein and Peptide Science     Hybrid Journal   (Followers: 8)
Current Proteomics     Hybrid Journal   (Followers: 4)
Current Protocols in Bioinformatics     Hybrid Journal   (Followers: 1)
Current Protocols in Cell Biology     Hybrid Journal  
Current Protocols in Molecular Biology     Hybrid Journal  
Current Protocols in Mouse Biology     Hybrid Journal  
Current Protocols in Neuroscience     Hybrid Journal  
Current Protocols in Plant Biology     Hybrid Journal   (Followers: 2)
Current Protocols in Protein Science     Hybrid Journal   (Followers: 1)
Current Protocols in Stem Cell Biology     Hybrid Journal  
Current Research in Bacteriology     Open Access   (Followers: 3)
Current Research in Biostatistics     Open Access   (Followers: 8)
Current Research in Chemical Biology     Open Access  
Current Research in Neurobiology     Open Access  
Current Research in Parasitology & Vector-Borne Diseases     Open Access  
Current Research in Structural Biology     Open Access   (Followers: 2)
Current Research in Translational Medicine     Full-text available via subscription   (Followers: 1)
Current Research in Virological Science     Open Access   (Followers: 2)
Current Science     Open Access   (Followers: 117)
Current Stem Cell Reports     Hybrid Journal   (Followers: 4)
Current Stem Cell Research & Therapy     Hybrid Journal   (Followers: 8)
Current Topics in Developmental Biology     Full-text available via subscription   (Followers: 3)
Current Topics in Membranes     Full-text available via subscription   (Followers: 1)
Cytotechnology     Hybrid Journal   (Followers: 10)
Database : The Journal of Biological Databases and Curation     Open Access   (Followers: 10)
Dendrochronologia     Hybrid Journal   (Followers: 1)
Developing World Bioethics     Hybrid Journal   (Followers: 6)
Developmental & Comparative Immunology     Hybrid Journal   (Followers: 5)
Developmental Biology     Hybrid Journal   (Followers: 26)
Developmental Cell     Full-text available via subscription   (Followers: 46)
Developmental Dynamics     Hybrid Journal   (Followers: 4)
Developmental Neurobiology     Hybrid Journal   (Followers: 6)
Dhaka University Journal of Biological Sciences     Open Access  
Diatom Research     Hybrid Journal   (Followers: 3)
Differentiation     Hybrid Journal  
Digital Biomarkers     Open Access   (Followers: 1)
Disease Models and Mechanisms     Open Access   (Followers: 1)
Diseases of Aquatic Organisms     Hybrid Journal  
DNA and Cell Biology     Hybrid Journal   (Followers: 9)
DNA Repair     Hybrid Journal   (Followers: 3)
DNA Research     Open Access   (Followers: 4)
Doklady Physics     Hybrid Journal   (Followers: 1)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
e-Jurnal Rekayasa dan Teknologi Budidaya Perairan     Open Access  
Ecocycles     Open Access   (Followers: 4)
Ecohydrology & Hydrobiology     Full-text available via subscription   (Followers: 4)
Ecología en Bolivia     Open Access  
Ecological Engineering     Hybrid Journal   (Followers: 4)
Ecological Questions     Open Access   (Followers: 5)
Ecological Solutions and Evidence     Open Access  
Ecology and Society     Open Access   (Followers: 51)
Ecology Letters     Hybrid Journal   (Followers: 256)
Economics & Human Biology     Hybrid Journal   (Followers: 1)
Ecoprint : An International Journal of Ecology     Open Access   (Followers: 4)
Ecoscience     Hybrid Journal   (Followers: 2)
Ecosystem Health and Sustainability     Open Access   (Followers: 1)
Ecosystems and People     Open Access   (Followers: 4)
Educational Technology Research and Development     Partially Free   (Followers: 45)
EDUSAINS     Open Access  
EFB Bioeconomy Journal     Open Access  
Egyptian Journal of Basic and Applied Sciences     Open Access  
Egyptian Journal of Biology     Open Access  
Egyptian Journal of Natural History     Open Access   (Followers: 1)
EJNMMI Research     Open Access  
Ekologia     Open Access  
el-Hayah     Open Access  
Electromagnetic Biology and Medicine     Hybrid Journal  
eLife     Open Access   (Followers: 97)
Embo Molecular Medicine     Open Access   (Followers: 9)
EMBO reports     Full-text available via subscription   (Followers: 23)
Emotion Review     Hybrid Journal   (Followers: 20)
Endangered Species Research     Open Access   (Followers: 6)
Endocrine Connections     Open Access   (Followers: 4)
Endothelium: Journal of Endothelial Cell Research     Full-text available via subscription   (Followers: 4)
Engineering & Technology     Hybrid Journal   (Followers: 23)
Engineering Economist, The     Hybrid Journal   (Followers: 4)
Engineering in Life Sciences     Hybrid Journal   (Followers: 3)
Engineering Optimization     Hybrid Journal   (Followers: 19)
Ensaios e Ciência : Ciências Biológicas, Agrárias e da Saúde     Open Access  
Environmental Biology of Fishes     Hybrid Journal   (Followers: 4)
Environmental DNA     Open Access   (Followers: 1)
Environmental Dynamics and Global Climate Change     Open Access   (Followers: 22)
Environmental Epigenetics     Open Access   (Followers: 2)
Environmental Microbiology     Hybrid Journal   (Followers: 27)
Environmental Microbiome     Open Access  
Environmental Science & Technology     Hybrid Journal   (Followers: 195)
Enzyme and Microbial Technology     Hybrid Journal   (Followers: 12)
Enzyme Research     Open Access   (Followers: 4)
Epidemiology & Infection     Open Access   (Followers: 23)
Epigenomes     Open Access  
EPMA Journal     Open Access  
Ethiopian Journal of Biological Sciences     Open Access   (Followers: 3)
Ethnobiology and Conservation     Open Access   (Followers: 3)
Ethnobiology Letters     Open Access  
Ethnobotany Research & Applications : a journal of plants, people and applied research     Open Access   (Followers: 2)
Ethnoscientia : Brazilian Journal of Ethnobiology and Ethnoecology     Open Access  
Ethology     Hybrid Journal   (Followers: 11)
Ethology Ecology & Evolution     Hybrid Journal   (Followers: 17)
EuPA Open Proteomics     Open Access   (Followers: 2)
EUREKA : Life Sciences     Open Access  
European Journal of Biological Research     Open Access   (Followers: 1)
European Journal of Biology     Open Access   (Followers: 1)
European Journal of Cell Biology     Hybrid Journal   (Followers: 6)
European Journal of Ecology     Open Access   (Followers: 1)
European Journal of Neuroscience     Hybrid Journal   (Followers: 36)
European Journal of Obstetrics & Gynecology and Reproductive Biology     Hybrid Journal   (Followers: 18)
European Journal of Obstetrics & Gynecology and Reproductive Biology : X     Open Access  
European Journal of Phycology     Hybrid Journal   (Followers: 4)
European Journal of Protistology     Hybrid Journal   (Followers: 5)
European Journal of Soil Biology     Hybrid Journal   (Followers: 3)
European Online Journal of Natural and Social Sciences     Open Access   (Followers: 4)
European Scientific Journal     Open Access   (Followers: 1)
Evidência - Ciência e Biotecnologia - Interdisciplinar     Open Access  
EvoDevo     Open Access   (Followers: 4)
Evolution     Partially Free   (Followers: 142)
Evolution and Human Behavior     Hybrid Journal   (Followers: 23)
Evolution Letters     Open Access   (Followers: 8)
Evolutionary Applications     Open Access   (Followers: 6)
Evolutionary Bioinformatics     Open Access   (Followers: 12)
Evolutionary Biology     Hybrid Journal   (Followers: 25)
Evolutionary Computation     Hybrid Journal   (Followers: 11)
Evolutionary Systematics     Open Access   (Followers: 2)
EXCLI Journal : Experimental and Clinical Sciences     Open Access  
Experimental & Molecular Medicine     Open Access  
Experimental and Applied Acarology     Hybrid Journal   (Followers: 1)
Experimental Parasitology     Hybrid Journal   (Followers: 1)
Expert Opinion on Biological Therapy     Hybrid Journal   (Followers: 4)
Expert Opinion on Environmental Biology     Hybrid Journal  
Expert Review of Proteomics     Hybrid Journal   (Followers: 4)
ExRNA     Open Access  
Extreme Life, Biospeology & Astrobiology - International Journal of the Bioflux Society     Full-text available via subscription   (Followers: 5)
Extremophiles     Hybrid Journal   (Followers: 1)
F&S Science : Official journal of the American Society for Reproductive Medicine     Open Access  
Facta Universitatis, Series : Medicine and Biology     Open Access  
Familial Cancer     Hybrid Journal   (Followers: 2)
FASEB BioAdvances     Open Access  
Fauna Norvegica     Open Access  
Fauna of New Zealand     Open Access  
Febs Journal     Hybrid Journal   (Followers: 26)
Feddes Repertorium     Hybrid Journal  
Fems Yeast Research     Hybrid Journal   (Followers: 11)
FIGEMPA : Investigación y Desarrollo     Open Access   (Followers: 1)
Fire Ecology     Open Access   (Followers: 2)
Fish & Shellfish Immunology     Hybrid Journal   (Followers: 10)
Fish and Shellfish Immunology Reports     Open Access   (Followers: 1)
Fishes     Open Access  
Fitoterapia     Hybrid Journal   (Followers: 4)
Florea : Jurnal Biologi dan Pembelajarannya     Open Access  
Fly     Full-text available via subscription  
Folia Biologica     Free   (Followers: 1)
Folia Histochemica et Cytobiologica     Open Access  
Folia Microbiologica     Hybrid Journal   (Followers: 2)
Folia Primatologica     Full-text available via subscription   (Followers: 4)
Food and Bioproducts Processing     Hybrid Journal   (Followers: 3)
Food and Ecological Systems Modelling Journal     Open Access  
Food and Waterborne Parasitology     Open Access  
Food Webs     Hybrid Journal   (Followers: 1)
Forensic Genomics     Full-text available via subscription   (Followers: 6)
Forest Pathology     Hybrid Journal   (Followers: 1)
Forschung     Hybrid Journal   (Followers: 1)
Foundations of Physics     Hybrid Journal   (Followers: 41)
Free Radical Biology and Medicine     Hybrid Journal   (Followers: 6)
Free Radical Research     Hybrid Journal   (Followers: 2)
Freshwater Science     Full-text available via subscription   (Followers: 14)
Frontiers in Ecology and Evolution     Open Access   (Followers: 45)
Frontiers in Evolutionary Neuroscience     Open Access   (Followers: 7)
Frontiers in Life Science     Hybrid Journal   (Followers: 1)
Frontiers in Marine Science     Open Access   (Followers: 14)
Frontiers in Network Physiology     Open Access   (Followers: 2)
Frontiers in Neurogenesis     Open Access   (Followers: 2)
Frontiers in Neuroprosthetics     Open Access   (Followers: 6)
Frontiers of Biogeography     Open Access   (Followers: 4)
Frontiers of Biology     Hybrid Journal   (Followers: 2)
Frontiers of Environmental Science & Engineering     Hybrid Journal   (Followers: 3)
Frontiers of Medical and Biological Engineering     Hybrid Journal  
Functional & Integrative Genomics     Hybrid Journal   (Followers: 7)
Fundamental and Applied Limnology / Archiv für Hydrobiologie     Full-text available via subscription   (Followers: 3)
Fundamental Research     Open Access  
Fungal Biology     Hybrid Journal   (Followers: 6)
Fungal Biology and Biotechnology     Open Access   (Followers: 2)
Fungal Biology Reviews     Full-text available via subscription   (Followers: 9)
Fungal Diversity     Hybrid Journal   (Followers: 2)
Fungal Ecology     Hybrid Journal   (Followers: 6)
Fungal Genetics Reports     Open Access  

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Similar Journals
Journal Cover
EXCLI Journal : Experimental and Clinical Sciences
Number of Followers: 0  

  This is an Open Access Journal Open Access journal
ISSN (Online) 1611-2156
Published by IfADo – Leibniz Research Centre for Working Environment and Human Factors Homepage  [1 journal]
  • Sex-specific differences in trimethylamine N-oxide (TMAO) concentrations
           before and after cardiac rehabilitation in acute myocardial infarction
           patients

    • Authors: Andreas Baranyi, Andreas Meinitzer, Dirk von Lewinski, Hans-Bernd Rothenhäusler, Omid Amouzadeh-Ghadikolai, Hanns Harpf, Leonhard Harpf, Heimo Traninger, Ronald Hödl, Birgit M. Harb, Barbara Obermayer-Pietsch, Melanie Schweinzer, Celine K. Braun, Dietmar Enko
      Pages: 1 - 10
      Abstract: Trimethylamine N-oxide (TMAO) is a biomarker of cardiovascular risk and may enhance the progression of atherosclerosis. The aim of the study was to determine whether there are sex-specific differences in TMAO concentrations before and after cardiac rehabilitation in acute myocardial infarction (AMI) patients. A total of 56 participants [45/56 (80.4 %) males, 11/56 (19.6 %) females] were drawn from AMI inpatients hospitalized at the Division of Cardiology, Medical University of Graz, Austria. For the assessment of TMAO, serum samples were collected within the first day after hospital admission due to AMI and at the start and end of cardiac rehabilitation. Shortly after hospital admission due to AMI, females had significantly higher TMAO blood concentrations than males. These initially high TMAO levels remained almost unchanged in the female AMI patients until the start of cardiac rehabilitation and only reached the lower TMAO concentrations observed in the male patients after rehabilitation [female patients: TMAO (acute myocardial infarction) = 5.93 μmol/L (SE = 1.835); TMAO (start of rehabilitation) = 5.68 μmol/L (SE = 1.217); TMAO (end of rehabilitation) = 3.89 μmol/L (SE = 0.554); male patients: TMAO (acute myocardial infarction) = 3.02 μmol/L (SE = 0.255), TMAO (start of rehabilitation) = 3.91 μmol/L (SE = 0.346), TMAO (end of rehabilitation) = 4.04 μmol/L (SE = 0.363)]. After AMI, women might be at higher cardiovascular risk due to persistently higher levels of TMAO. High TMAO levels in women might decrease after cardiac rehabilitation due to cardiac rehabilitation-associated lifestyle modifications. These lifestyle modifications after AMI might also prevent increases in TMAO concentrations in men.
      PubDate: 2022-01-03
      DOI: 10.17179/excli2021-4366
      Issue No: Vol. 21 (2022)
       
  • Large-scale comparative review and assessment of computational methods for
           phage virion proteins identification

    • Authors: Muhammad Kabir, Chanin Nantasenamat, Sakawrat Kanthawong, Phasit Charoenkwan, Watshara Shoombuatong
      Pages: 11 - 29
      Abstract: Phage virion proteins (PVPs) are effective at recognizing and binding to host cell receptors while having no deleterious effects on human or animal cells. Understanding their functional mechanisms is regarded as a critical goal that will aid in rational antibacterial drug discovery and development. Although high-throughput experimental methods for identifying PVPs are considered the gold standard for exploring crucial PVP features, these procedures are frequently time-consuming and labor-intensive. Thusfar, more than ten sequence-based predictors have been established for the in silico identification of PVPs in conjunction with traditional experimental approaches. As a result, a revised and more thorough assessment is extremely desirable. With this purpose in mind, we first conduct a thorough survey and evaluation of a vast array of 13 state-of-the-art PVP predictors. Among these PVP predictors, they can be classified into three groups according to the types of machine learning (ML) algorithms employed (i.e. traditional ML-based methods, ensemble-based methods and deep learning-based methods). Subsequently, we explored which factors are important for building more accurate and stable predictors and this included training/independent datasets, feature encoding algorithms, feature selection methods, core algorithms, performance evaluation metrics/strategies and web servers. Finally, we provide insights and future perspectives for the design and development of new and more effective computational approaches for the detection and characterization of PVPs.
      PubDate: 2022-01-03
      DOI: 10.17179/excli2021-4411
      Issue No: Vol. 21 (2022)
       
  • Risk factors, time to onset and recurrence of delirium in a mixed
           medical-surgical ICU population

    • Authors: Farshid Rahimibashar, Andrew C. Miller, Mahmood Salesi, Motahareh Bagheri, Amir Vahedian-Azimi, Sara Ashtari, Keivan Gohari Moghadam, Amirhossein Sahebkar
      Pages: 30 - 46
      Abstract: A retrospective secondary analysis of 4,200 patients was collected from two academic medical centers. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in all patients. Univariate and multivariate Cox models, logistic regression analysis, and Chi-square Automatic Interaction Detector (CHAID) decision tree modeling were used to explore delirium risk factors. Increased delirium risk was associated with exposed only to artificial light (AL) hazard ratio (HR) 1.84 (95 % CI: 1.66-2.044, P<0.001), physical restraint application 1.11 (95 % CI: 1.001-1.226, P=0.049), and high nursing care requirements (>8 hours per 8-hour shift) 1.18 (95 % CI: 1.048-1.338, P=0.007). Delirium incidence was inversely associated with greater family engagement 0.092 (95 % CI: 0.014-0.596, P=0.012), low staff burnout and anticipated turnover scores 0.093 (95 % CI: 0.014-0.600, P=0.013), non-ICU length-of-stay (LOS)<15 days 0.725 (95 % CI: 0.655-0.804, P<0.001), and ICU LOS ≤15 days 0.509 (95 % CI: 0.456-0.567, P<0.001). CHAID modeling indicated that AL exposure and age <65 years were associated with a high risk of delirium incidence, whereas SOFA score ≤11, APACHE IV score >15 and natural light (NL) exposure were associated with moderate risk, and female sex was associated with low risk. More rapid time to delirium onset correlated with baseline sleep disturbance (P=0.049), high nursing care requirements (P=0.019), and prolonged ICU and non-ICU hospital LOS (P<0.001). Delirium recurrence correlated with age >65 years (HR 2.198; 95 % CI: 1.101-4.388, P=0.026) and high nursing care requirements (HR 1.978, 95 % CI: 1.096-3.569), with CHAID modeling identifying AL exposure (P<0.001) and age >65 years (P=0.032) as predictive variables. Development of ICU delirium correlated with application of physical restraints, high nursing care requirements, prolonged ICU and non-ICU LOS, exposure exclusively to AL (rather than natural), less family engagement, and greater staff burnout and anticipated turnover scores. ICU delirium occurred more rapidly in patients with baseline sleep disturbance, and recurrence correlated with the presence of delirium on ICU admission, exclusive AL exposure, and high nursing care requirements.
      PubDate: 2022-01-04
      DOI: 10.17179/excli2021-4381
      Issue No: Vol. 21 (2022)
       
  • Potential dual inhibitors of PCSK-9 and HMG-R from natural sources in
           cardiovascular risk management

    • Authors: Mohd Waiz, Sahir Sultan Alvi, M. Salman Khan
      Pages: 47 - 76
      Abstract: Atherosclerotic cardiovascular disease (ASCVD) stands amongst the leading causes of mortality worldwide and has attracted the attention of world’s leading pharmaceutical companies in order to tackle such mortalities. The low-density lipoprotein-cholesterol (LDL-C) is considered the most prominent biomarker for the assessment of ASCVD risk. Distinct inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-R), the chief hepatic cholesterogenic enzyme, are being used since last seven decades to manage hypercholesterolemia. On the other hand, discovery and the association of proprotein convertase subtilisin/kexin type-9 (PCSK-9) with increased ASCVD risk have established PCSK-9 as a novel therapeutic target in cardiovascular medicine. PCSK-9 is well reckoned to facilitate the LDL-receptor (LDL-R) degradation and compromised LDL-C clearance leading to the arterial atherosclerotic plaque formation. The currently available HMG-R inhibitors (statins) and PCSK-9 inhibitors (siRNA, anti-sense oligonucleotides, and monoclonal antibodies) have shown great promises in achieving LDL-C lowering goals, however, their life long prescriptions have raised significant concerns. These deficits associated with the synthetic HMG-R and PCSK-9 inhibitors called for the discovery of alternative therapeutic candidates with potential dual HMG-R and PCSK-9 inhibitory activities from natural origins. Therefore, this report firstly describes the mechanistic insights into the cholesterol homeostasis through HMG-R, PCSK-9, and LDL-R functionality and then compiles the pharmacological effects of natural secondary metabolites with special emphasis on their dual HMG-R and PCSK-9 inhibitory action. In conclusion, various natural products exhibit atheroprotective effects via targeting HMG-R and PCSK-9 activities and lipoprotein metabolism, however, further clinical assessments are still warranted prior their approval for ASCVD risk management in hypercholesterolemic patients.
      PubDate: 2022-01-05
      DOI: 10.17179/excli2021-4453
      Issue No: Vol. 21 (2022)
       
  • Feeding to satiation induces mild oxidative/carbonyl stress in the brain
           of young mice

    • Authors: Oksana V. Kuzniak, Oksana M. Sorochynska, Maria M. Bayliak, Andrii Ya. Klonovskyi, Yulia V. Vasylyk, Halyna M. Semchyshyn, Kenneth B. Storey, Olga Garaschuk, Volodymyr I. Lushchak
      Pages: 77 - 92
      Abstract: Intermittent fasting as a dietary intervention can prevent overweight and obesity in adult organisms. Nevertheless, information regarding consequences of intermittent fasting for redox status and reactive metabolite-mediated processes that are crucial for the normal functioning of organisms is limited. Since the information on effects of intermittent fasting on parameters of oxidative/carbonyl stress in the brains of young mice was absent, the present study addressed these questions using an every-other-day fasting (EODF) protocol. The levels of carbonyl proteins were ~28 %, 22 % and 18 % lower in the cerebral cortex of EODF males and females and middle parts of the brain of EODF males, respectively, as compared to their ad libitum fed counterparts. Lipid peroxides and α-dicarbonyl compounds were lower only in the cortex and medulla part of EODF male brain. The EODF regimen resulted in higher total non-specific antioxidant capacity in different parts of male brain and a tendency to be higher this parameter in females. At the same time, EODF regimen had no effect on the activities of the defensive antioxidant enzymes, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, glyoxylase 1 and glucose-6-phosphate dehydrogenase in the cortex of both sexes, but even decreased activities of these enzymes in medulla and middle part of the brain. In general, the results suggest that in the brain of young mice ad libitum feeding induces mild oxidative/carbonyl stress which may be partially alleviated by the EODF regimen. The effect of EODF regimen is more pronounced in the medulla part than in the cortex.
      PubDate: 2022-01-05
      DOI: 10.17179/excli2021-4347
      Issue No: Vol. 21 (2022)
       
  • The COVID-19 vaccination acceptance/hesitancy rate and its determinants
           among healthcare workers of 91 Countries

    • Authors: Mehrdad Askarian, Aleksandr Semenov, Ferran Llopis, Francesca Rubulotta, Gorana Dragovac, Natalia Pshenichnaya, Ojan Assadian, Yvon Ruch, Zahra Shayan, Cristobal Padilla Fortunatti, Daniel Lucey, Abdullah Almohaizeie, Abu Hena Mostafa Kamal, Adenike Ogunshe, Aidos Konkayev, Asim Beg, Enzo Primerano, Fatma Amer, Hema Prakash Kumari Pilli, Ivan Hung, Folusakin Ayoade, Jean Yves Lefrant, Joanna Zajkowska, Jordi Rello, Momin Kazi, Mohammad Hossein Taghrir, Stijn Blot, Stephen Leib, Parisa Hosseinpour, Hamidreza Hosseinpour, Amirhossein Erfani, Roham Borazjani, Hossein Akbarialiabad, Masoud Najafi, Ardalan Askarian, Hakan Erdem
      Pages: 93 - 103
      Abstract: The aim of this study was to investigate the COVID-19 vaccination acceptance rate and its determinants among healthcare workers in a multicenter study. This was a cross-sectional multi-center survey conducted from February 5 to April 29, 2021. The questionnaire consisted of 26 items in 6 subscales. The English version of the questionnaire was translated into seven languages and distributed through Google Forms using snowball sampling; a colleague in each country was responsible for the forward and backward translation, and also the distribution of the questionnaire. A forward stepwise logistic regression was utilized to explore the variables and questionnaire factors tied to the intention to COVID-19 vaccination. 4630 participants from 91 countries completed the questionnaire. According to the United Nations Development Program 2020, 43.6 % of participants were from low Human Development Index (HDI) regions, 48.3 % high and very high, and 8.1 % from medium. The overall vaccination hesitancy rate was 37 %. Three out of six factors of the questionnaire were significantly related to intention to the vaccination. While ‘Perceived benefits of the COVID-19 vaccination’ (OR: 3.82, p-value<0.001) and ‘Prosocial norms’ (OR: 5.18, p-value<0.001) were associated with vaccination acceptance, ‘The vaccine safety/cost concerns’ with OR: 3.52, p-value<0.001 was tied to vaccination hesitancy. Medical doctors and pharmacists were more willing to take the vaccine in comparison to others. Importantly, HDI with OR: 12.28, 95 % CI: 6.10-24.72 was a strong positive determinant of COVID-19 vaccination acceptance. This study highlighted the vaccination hesitancy rate of 37 % in our sample among HCWs. Increasing awareness regarding vaccination benefits, confronting the misinformation, and strengthening the prosocial norms would be the primary domains for maximizing the vaccination coverage. The study also showed that the HDI is strongly associated with the vaccination acceptance/hesitancy, in a way that those living in low HDI contexts are more hesitant to receive the vaccine.
      PubDate: 2022-01-06
      DOI: 10.17179/excli2021-4439
      Issue No: Vol. 21 (2022)
       
  • Prevalence and predictors of adequate treatment of overt hypothyroidism
           – a population-based study

    • Authors: Julie Lindgård Nielsen, Jesper Karmisholt, Inge Bülow Pedersen, Allan Carlé
      Pages: 104 - 116
      Abstract: The aim of this study is to evaluate the adequacy of treatment, and to identify factors influencing treatment of hypothyroidism. Patients newly diagnosed with overt hypothyroidism (n=345) were identified via a register linked to a laboratory database. In selected periods with staff available, 165 patients were invited, and 113 (68.5 %) accepted participating in a comprehensive program including blood tests and completion of questionnaires. We performed a longitudinal follow-up on thyroid function tests 10 years after the diagnosis. Time to reach a serum TSH level of 0.2-10 mU/L (termed as clinically acceptable) and biochemical normalization (TSH: 0.2-5.0 mU/L), respectively, were analyzed using Kaplan Meier survival analysis. Predictors for longer duration to reach the normal TSH range were identified using cox proportional hazards regression. Only 67.7 % of the patients were in the euthyroid range on the long term after diagnosis of overt hypothyroidism (2 years: 59.4 %; 10 years: 67.7 %). Median time to the first normal TSH was 8.9 months (95 % CI: 7.6-10.2 months). The factors associated with longer duration until normalization of TSH after multivariate analysis were age (HR 0.79 per 10 years; 95 % CI: 0.66-0.94; P = <0.01), smoking (HR 0.47; 95 % CI: 0.26-0.83; P = <0.01), serum TSH at diagnosis (HR 0.96 per 10 mU/L; 95 % CI: 0.93-0.99; P = 0.02) and BMI (HR 0.96 per kg/m2; 95 % CI: 0.91-0.99; P = 0.03). A considerable number of hypothyroid patients remained inadequately treated. When treating hypothyroid patients, special attention should be addressed to those patients who never or lately obtain euthyroid status.
      PubDate: 2022-01-06
      DOI: 10.17179/excli2021-4291
      Issue No: Vol. 21 (2022)
       
  • Hypermethylation of RAD9A intron 2 in childhood cancer patients, leukemia
           and tumor cell lines suggest a role for oncogenic transformation

    • Authors: Danuta Galetzka, Julia Böck, Lukas Wagner, Marcus Dittrich, Olesja Sinizyn , Marco Ludwig, Heidi Rossmann, Claudia Spix, Markus Radsak, Peter Scholz-Kreisel, Johanna Mirsch, Matthias Linke, Walburgis Brenner, Manuela Marron, Alicia Poplawski, Thomas Haaf, Heinz Schmidberger, Dirk Prawitt
      Pages: 117 - 143
      Abstract: Most childhood cancers occur sporadically and cannot be explained by an inherited mutation or an unhealthy lifestyle. However, risk factors might trigger the oncogenic transformation of cells. Among other regulatory signals, hypermethylation of RAD9A intron 2 is responsible for the increased expression of RAD9A protein, which may play a role in oncogenic transformation. Here, we analyzed the RAD9A intron 2 methylation in primary fibroblasts of 20 patients with primary cancer in childhood and second primary cancer (2N) later in life, 20 matched patients with only one primary cancer in childhood (1N) and 20 matched cancer-free controls (0N), using bisulfite pyrosequencing and deep bisulfite sequencing (DBS). Four 1N patients and one 2N patient displayed elevated mean methylation levels (³10 %) of RAD9A. DBS revealed ³2 % hypermethylated alleles of RAD9A, indicative for constitutive mosaic epimutations. Bone marrow samples of NHL and AML tumor patients (n=74), EBV (Epstein Barr Virus) lymphoblasts (n=6), tumor cell lines (n=5) and FaDu subclones (n=13) were analyzed to substantiate our findings. We find a broad spectrum of tumor entities with an aberrant methylation of RAD9A. We detected a significant difference in mean methylation of RAD9A for NHL versus AML patients (p ≤0.025). Molecular karyotyping of AML samples during therapy with hypermethylated RAD9A showed an evolving duplication of 1.8 kb on Chr16p13.3 including the PKD1 gene. Radiation, colony formation assays, cell proliferation, PCR and molecular karyotyping SNP-array experiments using generated FaDu subclones suggest that hypermethylation of RAD9A intron 2 is associated with genomic imbalances in regions with tumor-relevant genes and survival of the cells. In conclusion, this is the very first study of RAD9A intron 2 methylation in childhood cancer and Leukemia. RAD9A epimutations may have an impact on leukemia and tumorigenesis and can potentially serve as a biomarker.
      PubDate: 2022-01-07
      DOI: 10.17179/excli2021-4482
      Issue No: Vol. 21 (2022)
       
  • Continous, non-invasive monitoring of oxygen consumption in a parallelized
           microfluidic in vitro system provides novel insight into the response to
           nutrients and drugs of primary human hepatocytes

    • Authors: Marius Busche, Dominik Rabl, Jan Fischer, Christian Schmees, Torsten Mayr, Rolf Gebhardt, Martin Stelzle
      Pages: 144 - 161
      Abstract: Oxygen plays a fundamental role in cellular energy metabolism, differentiation and cell biology in general. Consequently, in vitro oxygen sensing can be used to assess cell vitality and detect specific mechanisms of toxicity. In 2D in vitro models currently used, the oxygen supply provided by diffusion is generally too low, especially for cells having a high oxygen demand. In organ-on-chip systems, a more physiologic oxygen supply can be generated by establishing unidirectional perfusion. We established oxygen sensors in an easy-to-use and parallelized organ-on-chip system. We demonstrated the applicability of this system by analyzing the influence of fructose (40 mM, 80 mM), ammonium chloride (100 mM) and Na-diclofenac (50 µM, 150 µM, 450 µM, 1500 µM) on primary human hepatocytes (PHH). Fructose treatment for two hours showed an immediate drop of oxygen consumption (OC) with subsequent increase to nearly initial levels. Treatment with 80 mM glucose, 20 mM lactate or 20 mM glycerol did not result in any changes in OC which demonstrates a specific effect of fructose. Application of ammonium chloride for two hours did not show any immediate effects on OC, but qualitatively changed the cellular response to FCCP treatment. Na-diclofenac treatment for 24 hours led to a decrease of the maximal respiration and reserve capacity. We also demonstrated the stability of our system by repeatedly treating cells with 40 mM fructose, which led to similar cell responses on the same day as well as on subsequent days. In conclusion, our system enables in depth analysis of cellular respiration after substrate treatment in an unidirectional perfused organ-on-chip system. in an unidirectional perfused organ-on-chip system.
      PubDate: 2022-01-07
      DOI: 10.17179/excli2021-4351
      Issue No: Vol. 21 (2022)
       
  • Epidemiology and biology of early onset colorectal cancer

    • Authors: Anand Venugopal, John M. Carethers
      Pages: 162 - 182
      Abstract: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in men or women in the United States. Average-risk screening that begins at age 50 years has reduced incidence and mortality of CRC in those over 50 years of age, whereas CRC incidence in those under age 50 years (early onset colorectal cancer (eoCRC)) has recently and dramatically increased. In this review, we summarize the recent literature including risk factors for eoCRC, differences in clinicopathologic presentation and outcomes in eoCRC, and emerging evidence regarding the molecular pathways that are altered in eoCRC compared to later onset CRC (loCRC). Epidemiologic studies of eoCRC show predominance in distal colon and rectum, and association with several modifiable risk factors, including diabetes, obesity, diet, sedentary time, alcohol consumption and smoking. Data regarding potential risk factors of prior antibiotic exposure and microbiome alterations or direct carcinogen exposure are still emerging. Aggressive clinicopathologic features of eoCRC at presentation may be due to delay in diagnosis or more aggressive tumor biology. EoCRC outcomes are similar to loCRC when matched for stage, but overall mortality is greater due to higher frequency of advanced disease at a younger presentation, with more life-years lost. There are only few molecular evaluations of eoCRC to date, with findings of potential increase in TP53 and CTNNB1 somatic mutation and decrease in APC, KRAS and BRAF somatic mutation, compared to loCRC. Other findings include LINE-1 hypomethylation, absence of microsatellite instability (MSI-H), presence of chromosomal instability (CIN) or microsatellite and chromosomal stability (MACS). These studies are only now emerging and have not yet identified a specific molecular signature defining eoCRC. Further research evaluating genetic and molecular differences as well as environmental triggers for eoCRCs should provide a clearer understanding to inform targeted screening for pre-symptomatic at-risk younger individuals.
      PubDate: 2022-01-07
      DOI: 10.17179/excli2021-4456
      Issue No: Vol. 21 (2022)
       
  • The effects of low-toxic herbicide Roundup and glyphosate on mitochondria

    • Authors: Olha M. Strilbytska, Sviatoslav A. Tsiumpala, Ivanna I. Kozachyshyn, Tetiana Strutynska, Nadia Burdyliuk, Volodymyr Lushchak, Oleh Lushchak
      Pages: 183 - 196
      Abstract: The effects of pesticides on the health of non-target living organisms in agricultural areas are critically important aspects for their safe use. Their release into the environment is an inevitable aspect for predicting and evaluation of the risk of their application. Roundup, a glyphosate-based herbicide, has been designed as an effective pesticide against weeds and now is the most widely used agrochemicals around the world due to its highly specific action of the biosynthesis of certain amino acids in plants. Despite it is claimed to be low toxic for not-target organisms, due to its broad application Roundup and products of its degradation were detected in organisms of diverse animals and humans. In this review, we describe animal and human studies of general adverse effects of Roundup and its principal substance glyphosate with focus on endocrine disruption, oxidative stress and behavioral disorders. At mechanistic level, we focus on the potential toxicity of the herbicide Roundup and glyphosate as effectors of bioenergetic functions of mitochondria. Their effects on mitochondrial membrane potential and oxidative phosphorylation are among described to date critical components responsible for its toxicity. Finally, we discuss general molecular mechanisms potentially involved in the interaction between glyphosate and mitochondria which to some extent are associated with generation of reactive oxygen species.
      PubDate: 2022-01-10
      DOI: 10.17179/excli2021-4478
      Issue No: Vol. 21 (2022)
       
  • Cyclophosphamide and epirubicin induce high apoptosis in microglia cells
           while epirubicin provokes DNA damage and microglial activation at
           sub-lethal concentrations

    • Authors: Rafael de la Hoz-Camacho, Ana Luisa Rivera-Lazarin, Jose Manuel Vazquez-Guillen, Diana Caballero-Hernandez, Edgar Mendoza-Gamboa, Ana Carolina Martinez-Torres, Cristina Rodriguez-Padilla
      Pages: 197 - 212
      Abstract: Chemotherapy Related Cognitive Impairment (CRCI), also called chemobrain, diminishes cancer patient’s life quality. Breast cancer (BC) patients have been described to be importantly affected, however, the mechanism leading to CRCI has not been fully elucidated. Recent research proposes microglia as the main architect of CRCI, thus dysregulations in these cells could trigger CRCI. The aim of this research was to evaluate the effects of two drugs commonly used against breast cancer, cyclophosphamide (CTX) and epirubicin (EPI), on the microglia cell line SIM-A9, using the BC cell line, 4T1, as a control. Our results show that CTX and EPI decrease microglia-cell viability and increase cell death on a concentration-dependent manner, being 5 and 2 times more cytotoxic to microglia cell line than to breast cancer 4T1cells, respectively. Both chemotherapies induce cell cycle arrest and a significant increase in p53, p16 and γ-H2AX in breast cancer and microglia cells. Furthermore, mitochondrial membrane potential (ΔΨm) diminishes as cell death increases, and both chemotherapies induce reactive oxygen species (ROS) production on SIM-A9 and 4T1. Moreover, caspase activation increases with treatments and its pharmacological blockade inhibits CTX and EPI induced-cell death. Finally, low concentrations of CTX and EPI induce γ-H2AX, and EPI induces cytokine release, NO production and Iba-1 overexpression. These findings indicate that microglia cells are more sensitive to CTX and EPI than BC cells and undergo DNA damage and cell cycle arrest at very low concentrations, moreover EPI induces microglia activation and a pro-inflammatory profile.
      PubDate: 2022-01-10
      DOI: 10.17179/excli2021-4160
      Issue No: Vol. 21 (2022)
       
  • Preclinical safety profile of a liver-localized mitochondrial uncoupler

    • Authors: Yuki Inoue, Junichi Kino, Nobuya Ishiharada, Makoto Sato, Suguru Hatanaka, Hiroyuki Yokoi, Takahiro Shimada, Seiji Sato, Takashi Okamoto, Naohide Kanemoto
      Pages: 213 - 235
      Abstract: Mitochondrial uncouplers (mUncouplers) are known to exhibit a variety of toxic effects in animals. Here we report a safety profile of an mUncoupler, OPC-163493, recently synthesized at Otsuka Pharmaceutical Co, Ltd, and its development as a therapeutic agent for treating diabetes. To understand the acute and subchronic toxicity of OPC-163493, single and repeated oral dose studies in rats, dogs, and monkeys were performed. In the rat studies, rigor mortis and increased body temperatures were observed in the high dose group. Focal necrosis, fatty change, and granular eosinophilic cytoplasm of the hepatocytes were also observed in the high dose group. In the dog studies, gastrointestinal manifestations were observed with decreased body weight and decreased food consumption in the high dose group. Necrotizing arteritis was observed in multiple organs as well as meningitis with hemorrhage in the brain. In the monkey studies, vomiting, decreased food consumption, and decreased locomotor activity were observed in the high dose group. Degeneration of the proximal convoluted tubules and the straight tubular epithelium, regeneration of the proximal tubular epithelium, and degeneration of the collecting tubular epithelium were observed. The target organs of OPC-163493 were liver, blood vessels, and kidney in rats, dogs, and monkeys, respectively. In rats, dogs, and monkeys, safety ratios were 100:1, 13:1, and 20:1, respectively, in terms of total exposure (AUC24h). These safety ratios showed clear separation between exposure to OPC-163493 in animals at NOAEL and the exposure at the effective dose in ZDF rats. This information should contribute to the drug development of new and effective mUncoupler candidates.
      PubDate: 2022-01-11
      DOI: 10.17179/excli2021-4414
      Issue No: Vol. 21 (2022)
       
  • Enhancing the efficacy of albendazole for liver cancer treatment using
           mesoporous silica nanoparticles

    • Authors: Mohsen Ghaferi, Warda Zahra, Azim Akbarzadeh, Hasan Ebrahimi Shahmabadi, Seyed Ebrahim Alavi
      Pages: 236 - 249
      Abstract: The present study aimed to synthesize albendazole (ABZ)-loaded Mobil Composition of Matter No. 41 (MCM-41 NPs) to increase the efficacy of the drug against liver cancer. ABZ was loaded into MCM-41 NPs, and after in vitro characterization, such as size, size distribution, zeta potential, morphology, chemical composition, thermal profile, drug release, surface and pore volume, and pore size, their biological effects were evaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cell migration assays. The results demonstrated that monodispersed and spherical NPs with a size of 220 ± 11.5 and 293 ± 8.7 nm, for MCM-41 NPs and ABZ-loaded MCM-41 NPs, respectively, and drug loading efficiency of 30 % were synthesized. ABZ was loaded physically into MCM-41 NPs, leading to a decrease in surface volume, pore size, and pore volume. Also, MCM-41 NPs could increase the cytotoxicity effects of ABZ by 2.9-fold (IC50 = 23 and 7.9 µM for ABZ and ABZ-loaded MCM-41 NPs, respectively). In addition, both ABZ and ABZ-loaded MCM-41 NPs could restrain the cell migration by 12 %. Overall, the results of the present study suggest evaluating the potency of MCM-41 NPs, as a potent nanoplatform, for ABZ delivery in vivo environment.
      PubDate: 2022-01-11
      DOI: 10.17179/excli2021-4491
      Issue No: Vol. 21 (2022)
       
  • Prognostic significance and therapeutic potentials of immune checkpoints
           in osteosarcoma

    • Authors: Vafa Meftahpour, Ali Aghebati-Maleki, Ali Fotouhi, Elham Safarzadeh, Leili Aghebati-Maleki
      Pages: 250 - 268
      Abstract: Although there exist manifold strategies for cancer treatment, researchers are obliged to develop novel treatments based on the challenges that arise. One of these recent treatment approaches is cancer immunotherapy, which enjoys various types of strategies itself. However, one of the most significant methods, in this regard, is employing immune checkpoint proteins (ICPs). Bone sarcomas have several subtypes, with the most common ones being chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma. Although many aggressive treatment approaches, including radiotherapy, chemotherapy, and surgical resection, have been employed over the last decades, significantly improved outcomes have not been observed for Ewing sarcoma or osteosarcoma patients. Additionally, chordoma and chdrosarcoma resist against both radiation and chemotherapy. Accordingly, elucidating how recent therapies could affect bone sarcomas is necessary. Checkpoint inhibitors have attracted great attention for the treatment of several cancer types, including bone sarcoma. Herein, the recent advances of current immune checkpoint targets, such as anti-PD-1/PD-L1 and anti-CTLA-4 blockade, for the treatment of bone sarcoma have been reviewed.
      PubDate: 2022-01-12
      DOI: 10.17179/excli2021-4094
      Issue No: Vol. 21 (2022)
       
  • Seroprevalence of SARS-CoV-2 antibodies in radio and television workers

    • Authors: Paulo Ricardo Martins-Filho, Danilo Nobre da Silva, Danillo Menezes dos Santos, Márcia Santos Rezende, Jessica Paloma Rosa Silva, Josafá Bonifácio da Silva Neto, Dulce Marta Schimieguel, Lucindo José Quintans-Júnior, Jullyana de Souza Siqueira Quintans, Paula Santos Nunes, Adriano Antunes de Souza Araújo
      Pages: 269 - 272
      PubDate: 2022-01-12
      DOI: 10.17179/excli2021-4545
      Issue No: Vol. 21 (2022)
       
  • LOX-1: Implications in atherosclerosis and myocardial ischemia

    • Authors: Tanya Sharma, Francesco Romeo, Jawahar L. Mehta
      Pages: 273 - 278
      Abstract: Understanding the pathophysiology of atherosclerosis is fundamental to the practice of cardiovascular medicine. Atherosclerosis is a multi-step cascade of accumulation of lipids and downstream changes that lead to a fibro-fatty plaque formation in the arterial intima. Multiple biochemical stimuli, cellular receptors and intra-cellular signals are implicated in this complex mechanism. Lectin-type oxidized LDL receptor-1 or LOX-1 is a type II membrane glycoprotein receptor which has emerged as an important effector of atherosclerosis. Hence, LOX-1 modification and its clinical consequences are of much interest in recent times.
      PubDate: 2022-01-13
      DOI: 10.17179/excli2021-4532
      Issue No: Vol. 21 (2022)
       
  • “Nano-ghosts”: Risk assessment of submicron-sized particles in food
           biased towards fictional “nano”

    • Authors: Hanspeter Naegeli, Corina Gsell
      Pages: 279 - 299
      Abstract: Much confusion has been generated in the safety assessment of food-grade TiO2 (E171) by the comingling of studies conducted on submicron-sized particles with those examining the toxicity of more minuscule counterparts. As E171 displays a nano-sized tail in its particle distribution (up to 36 % of particles with a diameter < 100 nm), it was thought that potential hazards of this food additive can be extrapolated from studies on thoroughly nanoscale formulations. This simplistic procedure may, however, overestimate the effects of the nano-sized tail of E171 because TiO2 particles readily aggregate or agglomerate in aqueous suspensions and biological matrices. The resulting larger clusters display a reduced oral bioavailability in comparison to the same material in nano-sized dimensions. Also, even if taken up in trace amounts, the smaller particles likely remain appended to larger particles or clusters and these aggregates or conglomerates may nullify to a great extent their “nano” characteristics. The purpose of this review is, therefore, to reevaluate the literature on the toxicity of TiO2 particles focusing on studies that are directly relevant for the assessment of E171. The purpose is not to avert a ban on the use of E171 in food, which might well be justified in light of the uncertainties associated with this additive employed solely for its colorant properties. Instead, it will be important to avoid in the future this same bias towards a fictional “nano” hazard, especially when evaluating more innovative engineered particles that confer true benefits for example by enhancing nutritional properties, quality, freshness, traceability or sustainability of food.
      PubDate: 2022-01-13
      DOI: 10.17179/excli2022-4630
      Issue No: Vol. 21 (2022)
       
  • Inconsistent eating time is associated with obesity

    • Authors: Darbaz Adnan, Jonathan Trinh, Faraz Bishehsari
      Pages: 300 - 306
      Abstract: Obesity is characterized by an accumulation of redundant body fat linked to metabolic dysregulation and low-grade systemic inflammation. Lifestyle choices are imperative determining factors of obesity. The contemporary lifestyle is associated with behaviors that disrupt circadian rhythms, impacting metabolic homeostasis. Our animal and human studies suggest that circadian phenotypes could be related to the risk of metabolic dysregulation and obesity. The purpose of this study is to examine the role of inconsistent eating habits on body weight in adults. Individuals who presented for colon cancer screening were enrolled. Subjects received structured questionnaires to capture 7-day eating and sleeping times in a week prospectively. Bodyweight and height were extracted from medical records, and Body Mass Index (BMI) was calculated. Inconsistent eating times were defined as an average difference of >2 hours between the largest meal on weekdays and weekends. Forty-nine of the 61 (80.3 %) individuals enrolled in the study completed the questionnaires. The mean age and standard deviation (SD) were 60.8 (7.9), and 27 (55.1 %) were male. Subjects with inconsistent eating times had a significantly higher BMI (33.8 ± 3.6 SD, n = 9) than subjects who did not (27.5 ± 6.5 SD, n = 40; p = 0.001). The highest BMI was observed in subjects who ate inconsistently and late (35.8 ± 4.6 SD). In this cross-sectional study, time of eating habits was associated with BMI. Controlled cohort studies are needed to determine the potential link between eating time and the risk of obesity in the long term.
      PubDate: 2022-01-14
      DOI: 10.17179/excli2021-4324
      Issue No: Vol. 21 (2022)
       
  • Pupil size as an indicator of cognitive activity in mild Alzheimer’s
           disease

    • Authors: Mohamad El Haj, Guillaume Chapelet, Ahmed A. Moustafa, Claire Boutoleau-Bretonnière
      Pages: 307 - 316
      Abstract: It is well established that pupil activity indexes cognitive processing. For instance, research has consistently demonstrated that the pupil reacts to working memory span task performance. However, little is known about pupil reaction to cognitive processing in Alzheimer’s Disease (AD). We thus investigated whether span tasks can modulate pupil size in patients with AD. We invited 24 patients with AD and 24 healthy older adults to perform backward and forward spans, as well as to count aloud in a control condition, while their pupil activity was recorded with eye tracking glasses. In patients with AD, analysis demonstrated larger pupil size during backward spans (M = 2.12, SD = .39) than during forward spans (M = 1.98, SD = .36) [t(23) = 3.22, p = .004], larger pupil size during forward spans than during counting (M = 1.67, SD = .33) [t(23) = 4.75, p < .001], as well as larger pupil size during backward spans than during counting [t(23) = 10.60, p < .001]. In control participants, analysis demonstrated larger pupil size during backward spans (M = 3.36, SD = .49) than during forward spans (M = 2.85, SD = .68) [t(23) = 5.82, p < .001], larger pupil size during forward spans than during counting (M = 2.09, SD = .62) [t(23) = 5.42, < .001], as well as larger pupil size during backward spans than during counting [t(23) = 9.70, p < .001]. Results also demonstrated a significant interaction effect between groups and conditions [F(2,92) = 16.63, p < .001]; in other words, patients with AD have shown fewer variations on the pupil size across the conditions compared to the control participants. The larger pupil size during backward spans, compared with forward spans or counting, can be attributed to the high cognitive load of backward spans. The modulation of pupil size, as observed across backward/forward spans and counting, can possibly be attributed to sympathetic/adrenergic and parasympathetic/cholinergic activities. Our study demonstrates the value of pupillometry as a potential biomarker of cognitive processing in AD.
      PubDate: 2022-01-17
      DOI: 10.17179/excli2021-4568
      Issue No: Vol. 21 (2022)
       
  • Molecular mechanisms linking stress and insulin resistance

    • Authors: Habib Yaribeygi, Mina Maleki, Alexandra E. Butler, Tannaz Jamialahmadi, Amirhossein Sahebkar
      Pages: 317 - 334
      Abstract: To date, there is ample evidence to support the strong relationship between stress and insulin resistance. While diabetes mellitus acts as a potent stress inducer, stress may be an upstream event for insulin resistance as well. It is widely recognized that diabetes mellitus is more prevalent among people who have a stressful lifestyle; however, the underlying mechanisms are not well understood. In the current study, we surveyed the scientific literature for possible interactions between stress and insulin resistance and found that stress can impair glucose homeostasis, working through at least six molecular pathways.
      PubDate: 2022-01-24
      DOI: 10.17179/excli2021-4382
      Issue No: Vol. 21 (2022)
       
  • Ultrasound–guided posterior quadratus lumborum block for postoperative
           pain control after minimally invasive radical prostatectomy

    • Authors: Bartosz Horosz, Katarzyna Białowolska, Anna Kociuba, Jakub Dobruch, Małgorzata Malec-Milewska
      Pages: 335 - 343
      Abstract: A minimally invasive approach to radical prostatectomy offers improved ambulation and discharge times. Postoperative pain control is one of the key factors that facilitates rapid recovery. With the aim to assure adequate analgesia and minimize the use of opioids, application of truncal nerve blocks has been proposed in a number of endoscopic procedures. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of bilateral posterior quadratus lumborum block (pQLB) in alleviating pain and reducing postoperative opioid demand in patients following endoscopic extraperitoneal and laparoscopic prostatectomy. We enrolled 50 patients who were diagnosed with prostate cancer and scheduled for prostatectomy. They were randomized to receive preoperative, ultrasound-guided pQLB with the use of either 30 ml of 0.375 % ropivacaine (ropivacaine group) or 30 ml of 0.9 % NaCl (placebo group). Our primary endpoint was opioid consumption in the first 24 hours after surgery. Secondary endpoints were pain intensity at predefined timepoints and the incidence of nausea and vomiting and pruritus. No differences were detected between the ropivacaine and placebo groups in intravenous oxycodone consumption during the first 24 hours after surgery. Similarly, there were no differences in pain intensity at any of the timepoints assessed. The rate of nausea and vomiting was equal in both groups and pruritus was not observed. Application of bilateral pQLB does not reduce opioid consumption after minimally invasive prostatectomy.
      PubDate: 2022-01-27
      DOI: 10.17179/excli2021-4615
      Issue No: Vol. 21 (2022)
       
  • How to keep up with the analysis of classic and emerging neurotoxins:
           Age-resolved fitness tests in the animal model Caenorhabditis elegans

    • Authors: Indra Hering, Dang Tri Le, Anna von Mikecz
      Pages: 344 - 353
      Abstract: The global chemical inventory includes neurotoxins that are mostly interrogated concerning the biological response in developing organisms. Effects of pollutants on adults receive less attention, although vulnerabilities can be expected throughout the entire life span in young, middle-aged and old individuals. We use the animal model Caenorhabditis elegans to systematically quantify neurological outcomes by application of an age-resolved method. Adult hermaphrodite worms were exposed to pollutants or non-chemical stressors such as temperature in liquid culture on microtiter plates and locomotion fitness was analyzed in a whole-life approach. Cultivation at 15, 20 or 25 °C showed that worms held at 15 °C displayed an enhanced level of fitness concerning swimming movements until middle age (11-days-old) and then a decline. In contrast, C. elegans cultivated at ≥ 20 °C continually reduced their swimming movements with increasing age. Here, we provide a step-by-step protocol to investigate the health span of adult C. elegans that may serve as a platform for automation and data collection. Consistent with this, more neurotoxins can be investigated with respect to vulnerable age-groups as well as contributing non-chemical environmental factors such as temperature.
      PubDate: 2022-01-31
      DOI: 10.17179/excli2021-4626
      Issue No: Vol. 21 (2022)
       
  • Preventive role of Sapindus species in different neurological and
           metabolic disorders

    • Authors: Sarita Rawat, Gaurav Gupta, Anurag Mishra, Sachchidanand Pathak, Lakshmi Thangavelu, Sachin Kumar Singh, Niraj Kumar Jha, Deepak Kumar, Poonam Negi, Avvaru Praveen Kumar, Dinesh Kumar Chellappan, Kamal Dua
      Pages: 354 - 359
      PubDate: 2022-01-31
      DOI: 10.17179/excli2021-4625
      Issue No: Vol. 21 (2022)
       
  • Synthesis of acetamidosulfonamide derivatives with antioxidative and QSAR
           studies

    • Authors: Apilak Worachartcheewan, Somchai Pisutjaroenpong, Ratchanok Pingaew, Supaluk Prachayasittikul, Suphakit Siriwong, Somsak Ruchirawat, Virapong Prachayasittikul
      Pages: 360 - 379
      Abstract: A series of sixteen acetamidosulfonamide derivatives (1-16) have been synthesized and investigated for their antioxidant (radical scavenging and superoxide dismutase (SOD)) and antimicrobial activities. Most compounds exhibited antioxidant activities in which compound 15 displayed the most potent radical scavenging and SOD activities. Quantitative structure-activity relationship (QSAR) has been studied using multiple linear regression. The constructed QSAR models displayed high correlation coefficient (Q2/Loo-CV= 0.9708 and 0.8753 for RSA and SOD activities, respectively), but low root mean square error (RMSELOO-CV = 0.5105 and 1.3571 for RSA and SOD activities, respectively). The structure-activity relationship showed that an ethylene group connected to pyridine ring provided significant antioxidant activities. The QSAR models give insight into the rational designed of eighty new sulfonamides with various electron donating and withdrawing groups. The top five new designed sulfonamides with nitro group are potential antioxidants to be further developed for medicinal applications.
      PubDate: 2022-02-01
      DOI: 10.17179/excli2021-4590
      Issue No: Vol. 21 (2022)
       
  • Metabolic syndrome in childhood cancer survivors

    • Authors: Amena Firoz, Muhammad Haris
      Pages: 380 - 386
      PubDate: 2022-02-10
      DOI: 10.17179/excli2021-3916
      Issue No: Vol. 21 (2022)
       
  • Phlomis fruticosa L. exerts in vitro antineurodegenerative and antioxidant
           activities and induces prooxidant effect in glioblastoma cell line

    • Authors: Dejan Stojković, Danijela Drakulić, Maria Inês Dias, Gokhan Zengin, Lillian Barros, Marija Ivanov, Uroš Gašić, Nemanja Rajčević, Milena Stevanović, Isabel C. F. R. Ferreira, Marina Soković
      Pages: 387 - 399
      Abstract: Despite the significant advances in drug development we are witnessing the inability of health systems to combat both neurodegenerative diseases and cancers, especially glioblastoma. Hence, natural products are comprehensively studied in order to provide novel therapeutic options. This study aimed to explore anti-neurodegenerative and anti-glioblastoma potential of extract of Phlomis fruticosa L. using in vitro model systems. It was found that the methanol extract of P. fruticosa was able to efficiently reduce activities of enzymes linked to neurodegenerative disease including acetylcholinesterase, butyrylcholinesterase and tyrosinase. Furthermore, P. fruticosa extract has shown excellent antioxidant potential, as evidenced by six different methods. Analysis of cytotoxic effect of P. fruticosa extract on A172 glioblastoma cell line revealed that the concentration of the extract necessary for 50 % inhibition of A172 growth (IC50) was 710 μg/mL. The extract did not induce changes in proliferation and morphology of A172 glioblastoma cells. On the other side, production of ROS was increased in A172 cells treated with the extract. Observed cytotoxic effect of P. fruticosa extract might be based on increase in ROS generation upon treatment. Quantitative chemical analysis revealed the presence of twelve different polyphenols with the cis 3-O-caffeoylquinic acid being the most abundant. This study provided scientific evidence for further exploration of P. fruticosa as a promising natural anti-neurodegenerative therapeutic option.
      PubDate: 2022-02-14
      DOI: 10.17179/excli2021-4487
      Issue No: Vol. 21 (2022)
       
  • Molecular docking and mouse modeling suggest CMKLR1 and INSR as targets
           for improving PCOS phenotypes by minocycline

    • Authors: Mahdie Kian, Elham Hosseini, Tooba Abdizadeh, Taimour Langaee, Azadeh Khajouei, Sorayya Ghasemi
      Pages: 400 - 414
      Abstract: Polycystic ovary syndrome (PCOS) is the most common cause of women’s infertility. Some inflammatory pathways play a pivotal role in the pathogenesis of PCOS. This study aimed to investigate the possible beneficial effects of minocycline on chemokine-like receptor 1 (CMKLR1) and Insulin Receptor (INSR) in a PCOS model. A molecular docking study was implemented using Molecular Operating Environment (MOE) software. The PCOS was induced in NMRI mice (mean body weight 14.47±0.23) by 28 days estradiol valerate injection (2 mg/kg/day). The mice were then divided into six groups (n=8 per group, mean body weight 17.77± 0.26): control (received normal saline), PCOS model, control for minocycline, minocycline treated PCOS (50 mg/kg), letrozole treated PCOS (0.5 mg/kg), and metformin-treated PCOS (300 mg/kg). Serum FSH, LH, estradiol (E2), and testosterone were detected by ELISA. The ovarian tissues were stained by hematoxylin and eosin. The CMKLR1 and INSR expression levels were determined by Real-time-PCR. The molecular docking studies showed scores of -10.92 and -9.30 kcal/mol, respectively, for minocycline with CMKLR1 and INSR. Estradiol valerate treatment led to a significant increase in E2, graffian follicle, and decrease in corpus luteum (CL) numbers (P<0.05), while minocycline treatment improved these PCOS features. The minocycline treatment significantly decreased the CMKLR1 expression and increased the INSR expression (P<0.05) while the CMKLR1 expression was increased in PCOS model. Minocycline may improve ovulation in PCOS model by returning E2 to a normal level and increasing CL number (ovulation signs). These beneficial outcomes may be related to the changes in CMKLR1 and INSR gene expression involved in glucose metabolism and inflammation.
      PubDate: 2022-02-16
      DOI: 10.17179/excli2021-4534
      Issue No: Vol. 21 (2022)
       
  • Recent insights into the biological and pharmacological activity of
           lycopene

    • Authors: Jae Kwang Kim, Sang Un Park
      Pages: 415 - 425
      PubDate: 2022-02-16
      DOI: 10.17179/excli2022-4714
      Issue No: Vol. 21 (2022)
       
  • Helicobacter pylori infection and lactose intolerance increase expiratory
           hydrogen

    • Authors: Wolfgang J. Schnedl, Nathalie Meier-Allard, Michael Schenk, Sonja Lackner, Dietmar Enko, Harald Mangge, Sandra J. Holasek
      Pages: 426 - 435
      Abstract: Infection with Helicobacter pylori (H.pylori) may cause dyspepsia and/or unexplained functional nonspecific, gastrointestinal complaints of the irritable bowel syndrome (IBS) spectrum. Hitherto, in H. pylori infected patients with symptoms of the IBS spectrum the occurrence of additional food intolerance/malabsorption is not evaluated. We used a retrospective analysis of charts from 548 patients who presented with gastrointestinal complaints of the irritable bowel syndrome spectrum. An enzyme-linked IgA immunosorbent assay or histologic evaluation of gastric mucosa were used to detect H. pylori infection. A hydrogen breath (H2) test was performed to evaluate fructose malabsorption (FM) and lactose intolerance (LIT). Serum diamine oxidase value of <10 U/ml and a response to a histamine-reduced diet was used to identify histamine intolerance (HIT). We found 293 patients infected with H. pylori, within these were 58 H. pylori patients with LIT, 23 H. pylori LIT patients with FM and 46 H. pylori LIT patients with HIT. Additionally, 13 H. pylori, lactose- and histamine intolerance patients also had FM. The Kruskal Wallis test and pairwise comparison were used to analyze differences of the area under the curve of expiratory hydrogen. In lactose H2 breath tests compared with LIT-only patients, LIT with H. pylori, LIT and H. pylori with HIT, LIT and H. pylori with FM showed significantly higher exhaled H2 levels (p=0.022). Pairwise comparison demonstrated H. pylori infected patients with LIT exhaled more H2 compared to LIT-only (p=0.029). H. pylori with lactose- and histamine intolerance, and H. pylori with lactose-, histamine intolerance and FM compared to H. pylori-only patients indicated a significantly higher occurrence of stomach pain during lactose H2 breath tests (p=0.012 and p=0.005, respectively). We demonstrate that LIT patients with high expiratory H2 levels in lactose breath tests may have H. pylori infection and possibly additional food intolerance/malabsorption. Subsequently, besides H. pylori eradication, a dietician is necessary for an individually tailored reduction- or exclusion diet of symptom triggering food components.
      PubDate: 2022-02-17
      DOI: 10.17179/excli2021-4508
      Issue No: Vol. 21 (2022)
       
  • IKBKE-driven TPL2 and MEK1 phosphorylations sustain constitutive ERK1/2
           activation in tumor cells

    • Authors: Serkan Ismail Göktuna
      Pages: 436 - 453
      Abstract: IKBKE have been associated with numerous cancers. As a result, IKBKE have emerged as potential target for cancer therapy. Accumulating evidence support that IKBKE orchestrate tumor cell survival in cancers. Here we evaluated the possible link between IKBKE and ERK phosphorylation. The effects of IKBKE silencing on MAPK activation in tumor vs. normal cells were evaluated via WB and RT-PCR. Ectopically expressed IKBKE, TPL2 or MEK1 constructs were used to examine the possible interactions among them via co-IP. In vitro kinase assays were performed to understand nature of the observed interactions. In tumors, IKBKE regulates MEK/ERK constitutive activations in vitro and in vivo. IKBKE and TPL2 physically interact and this interaction leads to TPL2 phosphorylation. We describe here a novel regulatory link between IKBKE and constitutive ERK1/2 activation in tumor cells. This new circuitry may be relevant for tumor cell survival in various malignancies.
      PubDate: 2022-02-18
      DOI: 10.17179/excli2021-4578
      Issue No: Vol. 21 (2022)
       
  • Hypoxia-inducible factor (HIF)-3α2 serves as an endothelial cell fate
           executor during chronic hypoxia

    • Authors: Maciej Jaśkiewicz, Adrianna Moszyńska, Marcin Serocki, Jarosław Króliczewski, Sylwia Bartoszewska, James F. Collawn, Rafal Bartoszewski
      Pages: 454 - 469
      Abstract: The adaptive response to hypoxia involves the transcriptional induction of three transcription factors called hypoxia inducible factor alpha 1, 2 and 3 (HIF-1α, HIF-2α, and HIF-3α) which dimerize with constitutively expressed beta chains that together form the HIF-1, -2 and -3 transcription factors. During normoxic conditions, the alpha chain is expressed at low levels since its stability is regulated by prolyl-hydroxylation that promotes subsequent ubiquitination and degradation. During hypoxic conditions, however, the prolyl hydroxylases are less active, and the alpha chain accumulates through elevated protein stability and the elevated induction of expression. Two of the three HIFs isoforms present in mammals, HIF-1 and HIF-2, are well characterized and have overlapping functions that promote cell survival, whereas HIF-3’s role remains less clear. The HIF-3 response is complicated because the HIF3A gene can utilize different promotors and alternate splicing sites that result in a number of different HIF-3α isoforms. Here, using human umbilical vein endothelial cells (HUVECs), we demonstrate that one of the isoforms of HIF-3α, isoform 2 (HIF-3α2) accumulates at a late stage of hypoxia and induces the expression of DNA damage inducible transcript 3 (DDIT4), a gene known to promote apoptosis. We also demonstrate that caspase 3/7 activity is elevated, supporting that the role of the HIF-3α2 isoform is to promote apoptosis. Furthermore, we provide evidence that HIF-3α2 is also expressed in seven other primary endothelial cell types, suggesting that this may be a common feature of HIF-3α2 in endothelial cells.
      PubDate: 2022-02-21
      DOI: 10.17179/excli2021-4622
      Issue No: Vol. 21 (2022)
       
  • Quantitative aspects of nitric oxide production from nitrate and nitrite

    • Authors: Asghar Ghasemi
      Pages: 470 - 486
      Abstract: Nitric oxide (NO) is involved in many physiological and pathological processes in the human body. At least two major pathways produce NO: (1) the L-arginine-NO-oxidative pathway in which NO synthase (NOS) enzymes convert L-arginine to NO; (2) the nitrate-nitrite-NO reductive pathway in which NO is produced from the serial reduction of nitrate and nitrite. The deficiency of NO is involved in the pathophysiology of cardiometabolic disorders. Intervention with foods containing nitrate and nitrite can potentially prevent or treat some chronic diseases, including cardiovascular diseases and diabetes. A better understanding of the NO cycle would help develop effective strategies for preventing or treating the disorders in which NO homeostasis is disturbed. This review summarizes quantitative aspects of NO production, emphasizing the nitrate-nitrite-NO pathway. Available data indicates that total NO production by NOS-dependent L-arginine-NO pathway is about 1000 μmol.day-1. Of about 1700 μmol.day-1 ingested nitrate, ~25 % is extracted by the salivary glands and of which ~20 % is converted nitrite. It means that about 5 % of ingested nitrate is converted to nitrite in the oral cavity; assuming that all produced nitrite is reduced to NO in the stomach, it can be calculated that contribution of the nitrate-nitrite-NO pathway to the whole-body NO production is about 85 μmol.day-1 (1700 ×0.05=85) or approximately 100 μmol.day-1. The lower contribution of the nitrate-nitrite-NO pathway does not mean that this pathway has lower importance in the whole-body NO homeostasis. Even in the adequate L-arginine supply, NOS-dependent NO production is insufficient to meet all NO functions, and the nitrate-nitrite-NO pathway must provide the rest. In conclusion, the contribution of the nitrate-nitrite-NO pathway in the whole human body NO production is <10 %, and the nitrate-nitrite-NO pathway is complementary to the NOS-dependent NO production.
      PubDate: 2022-02-21
      DOI: 10.17179/excli2022-4727
      Issue No: Vol. 21 (2022)
       
  • Evaluating the adverse outcome of subtypes of heart failure with preserved
           ejection fraction defined by machine learning

    • Authors: Simon W. Rabkin
      Pages: 487 - 518
      Abstract: The ability to distinguish clinically meaningful subtypes of heart failure with preserved ejection fraction (HFpEF) has recently been examined by machine learning techniques but studies appear to have produced discordant results. The objective of this study is to synthesize the types of HFpEF by examining their features and relating them to phenotypes with adverse prognosis. A systematic search was conducted using the search terms “Diastolic Heart Failure” OR “heart failure with preserved ejection fraction” OR “heart failure with normal ejection fraction” OR “HFpEF” AND “machine learning” OR “artificial intelligence” OR ‘computational biology’. Ten studies were identified and they varied in their prevalence of ten clinical variables: age, sex, body mass index (BMI) or obesity, hypertension, diabetes mellitus, coronary artery disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease or symptom severity (NYHA class or BNP). The clinical findings associated with the different phenotypes in > 85 % of studies were age, hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity; an adverse outcome was in 65 % to 85 % of studies identified diabetes mellitus and female sex and in less than 65 % of studies was body mass index or obesity, and coronary artery disease. COPD was a relevant factor in only 33 % of studies. Adverse clinical outcome – death or admission to hospital (for heart failure) defined phenogroups with the worst outcome. Combining the 4 studies that calculated the MAGGIC score showed a significant (p<0.05) linear relationship between MAGGIC score and outcome, using the one-year event rate. A new score based on strength of the evidence of the HFpEF studies analyzed here, using 9 variables (eliminating COPD), showed a significant (p<0.009) linear relationship with one-year event rate. Three studies examined biomarkers in detail and the ones most prominently related to outcome or consistently found in the studies were GDF15, FABP4, FGF23, sST2, renin and TNF. The dominant factors that identified phenotypes of HFpEF with adverse outcome were hypertension, atrial fibrillation, chronic kidney disease and worse symptoms severity. A new simplified score, based on clinical factors, was proposed to assess prognosis in HFpEF. Several biomarkers were consistently elevated in phenogroups with adverse outcomes and may indicate the underlying mechanism or pathophysiology specific for phenotypes with an adverse prognosis.
      PubDate: 2022-02-22
      DOI: 10.17179/excli2021-4572
      Issue No: Vol. 21 (2022)
       
  • Toll-like receptors, innate immune system, and lung diseases

    • Authors: Vyoma K. Patel, Keshav R. Paudel, Shakti D. Shukla, Gang Liu, Brian G. Oliver, Philip M. Hansbro, Kamal Dua
      Pages: 519 - 523
      PubDate: 2022-02-25
      DOI: 10.17179/excli2022-4688
      Issue No: Vol. 21 (2022)
       
  • The effect of exercise interventions on Irisin level

    • Authors: Gholam Rasul Mohammad Rahimi, Keyvan Hejazi, Martin Hofmeister
      Pages: 524 - 539
      Abstract: Irisin is a hormone that is offered to be a hopeful remedial target in obesity and type 2 diabetes. It has received striking attention recently, whereas, the interactions between exercise training and irisin are still unclear. Therefore, this systematic review and meta-analysis investigated the impacts of exercise interventions on circulating irisin in adults. A systematic search was conducted in PubMed, CINAHL, MEDLINE, Cochrane, Google Scholar, and Scopus up to July 15, 2021. Twenty-four studies, which assessed a total of 921 participants were included and analyzed using a random-effects model to estimate weighted mean differences (MD) with 95 % confidence intervals (CI). Overall, data revealed that exercise training significantly increased circulating irisin (MD: 0.01, 95 % CI: 0.00, 0.01, p = 0.005), and declined insulin (MD: -2.09, 95 % CI: -2.81, -1.37, p < 0.00001), glucose (MD: -12.89, 95 % CI: -16.52, -9.26, p < 0.00001), and insulin resistance (MD: -0.89, 95 % CI: -1.15, -0.62, p < 0.00001). Subgroup analysis revealed that irisin raised significantly when resistance training (p = 0.04) and combined training (p = 0.002) were applied, and for the type 2 diabetes and prediabetes (p = 0.002 for both) groups. Moreover, subgroup analysis by the type of intervention demonstrated that insulin reduced when aerobic training (p < 0.00001) and combined training (p = 0.0003) were employed, but glucose and HOMA-IR reduced after all three types of exercise training. These findings demonstrate that exercise interventions may produce ameliorations in circulating irisin. Further long-term studies are required to confirm these findings.
      PubDate: 2022-02-25
      DOI: 10.17179/excli2022-4703
      Issue No: Vol. 21 (2022)
       
  • Use of intranasal esketamine in a girl with treatment-resistant depression
           and autism spectrum disorders

    • Authors: Miriam Olivola, Vincenzo Arienti, Nicola Bassetti, Serena Civardi, Natascia Brondino
      Pages: 540 - 543
      Abstract: Major depression is a common comorbidity in autism spectrum disorder (ASD), often difficult to identify and to treat. Autistic subjects are more at risk for suicidal thoughts and behaviors compared to typically developing peers. Unfortunately, ASD individuals are more frequently treatment-resistant and often show side-effects which reduce efficacy. Intranasal esketamine has been recently approved as an add-on medication for treatment-resistant depression (TRD), but it has never been used in ASD with comorbid major depression. Of note, a pilot study of intranasal ketamine has shown no effect on social withdrawal in ASD without depression. The present case report describes the first girl with ASD and comorbid TRD treated with intranasal esketamine.
      PubDate: 2022-02-28
      DOI: 10.17179/excli2022-4694
      Issue No: Vol. 21 (2022)
       
  • Oxidative stress and visual system

    • Authors: Samanta Taurone, Massimo Ralli, Marco Artico, Valentina Noemi Madia, Susanna Scarpa, Stefania Annarita Nottola, Antonio Maconi, Marta Betti, Pietro Familiari, Marcella Nebbioso, Roberta Costi, Alessandra Micera
      Pages: 544 - 553
      Abstract: Different types of tissues respond differently to the action of oxidative stress. The visual system is very sensitive to oxidative action due to continuous exposure to light. In consideration of the growing interest of scientific studies towards various compounds endowed with antioxidant and anti-inflammatory properties, we performed a review of the literature focusing on the use of some antioxidant molecules for the treatment of conditions affecting the visual system. In this study, we focused on the ability of two antioxidant agents, the small molecule α-lipoic acid (ALA) and the enzyme superoxide dismutase (SOD), to influence the neurodegenerative physiological processes related to aging and oxidative stress affecting the ocular segment. The literature data report that ALA and SOD can protect against neurodegenerative effects both the optic nerve and retina and, if administered together, they are able to lower the levels of oxidative stress, thus preventing neurodegeneration and reducing the apoptotic process.
      PubDate: 2022-03-01
      DOI: 10.17179/excli2022-4663
      Issue No: Vol. 21 (2022)
       
  • Empirical comparison and analysis of machine learning-based predictors for
           predicting and analyzing of thermophilic proteins

    • Authors: Phasit Charoenkwan, Nalini Schaduangrat, Md Mehedi Hasan, Mohammad Ali Moni, Pietro Lió, Watshara Shoombuatong
      Pages: 554 - 570
      Abstract: Thermophilic proteins (TPPs) are critical for basic research and in the food industry due to their ability to maintain a thermodynamically stable fold at extremely high temperatures. Thus, the expeditious identification of novel TPPs through computational models from protein sequences is very desirable. Over the last few decades, a number of computational methods, especially machine learning (ML)-based methods, for in silico prediction of TPPs have been developed. Therefore, it is desirable to revisit these methods and summarize their advantages and disadvantages in order to further develop new computational approaches to achieve more accurate and improved prediction of TPPs. With this goal in mind, we comprehensively investigate a large collection of fourteen state-of-the-art TPP predictors in terms of their dataset size, feature encoding schemes, feature selection strategies, ML algorithms, evaluation strategies and web server/software usability. To the best of our knowledge, this article represents the first comprehensive review on the development of ML-based methods for in silico prediction of TPPs. Among these TPP predictors, they can be classified into two groups according to the interpretability of ML algorithms employed (i.e., computational black-box methods and computational white-box methods). In order to perform the comparative analysis, we conducted a comparative study on several currently available TPP predictors based on two benchmark datasets. Finally, we provide future perspectives for the design and development of new computational models for TPP prediction. We hope that this comprehensive review will facilitate researchers in selecting an appropriate TPP predictor that is the most suitable one to deal with their purposes and provide useful perspectives for the development of more effective and accurate TPP predictors.
      PubDate: 2022-03-02
      DOI: 10.17179/excli2022-4723
      Issue No: Vol. 21 (2022)
       
  • Lithium in drinking water and suicide risk

    • Authors: Tomoyuki Kawada
      Pages: 571 - 572
      PubDate: 2022-03-03
      DOI: 10.17179/excli2022-4689
      Issue No: Vol. 21 (2022)
       
  • Current update on the protective effect of naringin in inflammatory lung
           diseases

    • Authors: Gaurav Gupta, Waleed Hassan Almalki, Imran Kazmi, Neeraj Kumar Fuloria, Shivkanya Fuloria, Vetriselvan Subramaniyan, Mahendran Sekar, Sachin Kumar Singh, Dinesh Kumar Chellappan, Kamal Dua
      Pages: 573 - 579
      PubDate: 2022-03-07
      DOI: 10.17179/excli2022-4752
      Issue No: Vol. 21 (2022)
       
  • Analysis of hematological parameters in rheumatoid arthritis patients
           receiving biological therapy

    • Authors: Jana Pereckova, Silvia Martiniakova, Juraj Payer, Martin Falk, Zdenko Killinger, Tomas Perecko
      Pages: 580 - 594
      Abstract: Administration of biological therapy (BT) in rheumatoid arthritis (RA) patients is often associated with hematological complications, which result in switching among therapies. Thus, there is an instant need for suitable screening parameters that will help to individualize the therapy and minimize the onset of adverse effects. We analyzed the hematological profile of 99 RA patients receiving TNFα (Adalimumab - ADA, Golimumab - GOL, Etanercept - ETA) or IL-6 receptor (Tocilizumab - TCZ) inhibitors in order to find possible indicators to improve personalization of RA therapy. BTs significantly affect the levels of observed hematological parameters. In contrast to TNF-α inhibitors, TCZ normalized almost all monitored hematological parameters to values of healthy donors. Only GOL from the TNF-α inhibitors studied, was able to normalize neutrophil counts, as well as platelet indicators. Importantly, effects on the blood parameters (e.g. lymphocytes or platelet count) differ even within the same therapeutic group (anti-TNFα). Variable effects of individual biological agents in RA treatment point to importance to evaluate the patient’s hematological profile to improve the selection of suitable BT. It will help to personalize the administration of BT and prevent unnecessary switching from an effective therapy just because of provocation of avoidable hematological complications.
      PubDate: 2022-03-08
      DOI: 10.17179/excli2022-4702
      Issue No: Vol. 21 (2022)
       
  • Low-toxic herbicides Roundup and Atrazine disturb free radical processes
           in Daphnia in environmentally relevant concentrations

    • Authors: Viktor Husak, Tetiana Strutynska, Nadia Burdyliuk, Anzhelika Pitukh, Volodymyr Bubalo, Halyna Falsfushynska, Olha Strilbytska, Oleh Lushchak
      Pages: 595 - 609
      Abstract: The use of glyphosate-based Roundup and triazine herbicide Atrazine has increased markedly in last decades. Thus, it is important to evaluate toxic effects of these herbicides to non-targeted organisms such as zooplankton to understand their safety toward aquatic ecosystems. In the current study, we performed Daphnia toxicity tests based on lethality to identify LC50 that provides acute aquatic toxicity classification criteria. LC50 for Roundup exposure for 24 hours was found to be 0.022 mg/L and 48 hours - 0.0008 mg/L. Atrazine showed LC50 at concentrations of 40 mg/L and 7 mg/L for 24 and 48 hours, respectively. We demonstrated that exposure to ecologically relevant concentrations of Roundup or Atrazine decreases lipid peroxidation and protein thiol levels, however caused increase in carbonyl protein and low-molecular-weight thiols content. Moreover, the herbicide treatments caused increase of superoxide dismutase activity. Our data suggest that at very low concentrations Roundup and Atrazine disturb free radical processes in D. magna.
      PubDate: 2022-03-09
      DOI: 10.17179/excli2022-4690
      Issue No: Vol. 21 (2022)
       
  • Analyzing the interaction of human ACE2 and RBD of spike protein of
           SARS-CoV-2 in perspective of Omicron variant

    • Authors: Arijit Samanta, Syed Sahajada Mahafujul Alam, Safdar Ali, Mehboob Hoque
      Pages: 610 - 620
      Abstract: The newly identified Omicron (B.1.1.529) variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has steered concerns across the world due to the possession of a large number of mutations leading to high infectivity and vaccine escape potential. The Omicron variant houses 32 mutations in spike (S) protein alone. The viral infectivity is determined mainly by the ability of S protein Receptor Binding Domain (RBD) to bind to the human Angiotensin I Converting Enzyme 2 (hACE2) receptor. In this paper, the interaction of the RBDs of SARS-CoV-2 variants with hACE2 was analyzed by using protein-protein docking and compared with the novel Omicron variant. Our findings reveal that the Omicron RBD interacts strongly with hACE2 receptor via unique amino acid residues as compared to the Wuhan and many other variants. However, the interacting residues of RBD are found to be the same in Lamda (C.37) variant. This unique binding of Omicron RBD with hACE2 suggests an increased potential of infectivity and vaccine evasion potential of the new variant. The evolutionary drive of the SARS-CoV-2 may not be exclusively driven by RBD variants but surely provides for the platform for emergence of new variants.
      PubDate: 2022-03-10
      DOI: 10.17179/excli2022-4721
      Issue No: Vol. 21 (2022)
       
  • Poorer and more densely populated regions have lower vaccination
           capability against COVID-19

    • Authors: Paulo Ricardo Martins-Filho, Ricardo Ruan Rocha Santana, Victor Santana Santos, Lorena G. Barberia
      Pages: 621 - 622
      PubDate: 2022-03-21
      DOI: 10.17179/excli2022-4798
      Issue No: Vol. 21 (2022)
       
  • Systems redox biology in health and disease

    • Authors: Martin Feelisch, Miriam M. Cortese-Krott, Jérôme Santolini, Stephen A. Wootton, Alan A. Jackson
      Pages: 623 - 646
      Abstract: Living organisms need to be able to cope with environmental challenges and other stressors and mount adequate responses that are as varied as the spectrum of those challenges. Understanding how the multi-layered biological stress responses become integrated across and between different levels of organization within an organism can provide a different perspective on the nature and inter-relationship of complex systems in health and disease. We here compare two concepts which have been very influential in stress research: Selye’s ‘General Adaptation Syndrome’ and Sies’s ‘Oxidative Stress’ paradigm. We show that both can be embraced within a more general framework of ‘change and response’. The ‘Reactive Species Interactome’ allows each of these to be considered as distinct but complementary aspects of the same system, representative of roles at different levels of organization within a functional hierarchy. The versatile chemistry of sulfur - exemplified by hydrogen sulfide, glutathione and proteinous cysteine thiols - enriched by its interactions with reactive oxygen, nitrogen and sulfur species, would seem to sit at the heart of the ‘Redox Code’ and underpin the ability of complex organisms to cope with stress.
      PubDate: 2022-03-21
      DOI: 10.17179/excli2022-4793
      Issue No: Vol. 21 (2022)
       
  • HDAC11: A novel inflammatory biomarker in Huntington’s disease

    • Authors: Vishal Kumar, Simranjit Kaur, Lakshay Kapil, Charan Singh, Arti Singh
      Pages: 647 - 650
      PubDate: 2022-03-24
      DOI: 10.17179/excli2022-4741
      Issue No: Vol. 21 (2022)
       
  • Clinical presentation vs endoscopy for an early diagnosis of eosinophilic
           esophagitis

    • Authors: Michele Di Stefano, Giacomo Grandi, Vera Bonaso, Elisabetta Pagani, Gino Roberto Corazza, Antonio Di Sabatino
      Pages: 651 - 655
      Abstract: Eosinophilic esophagitis (EoE) is a type-2 mediated, chronic inflammatory disease showing an increase of both incidence and prevalence. Early diagnosis is mandatory, to prevent fibrostenotic complication of the disease. Due to the low sensitivity of the classic endoscopic features of the disease, a strong clinical suspicion should drive the decision to collect mucosal biopsies of the esophagus. We describe the case of an atopic patient suffering from dysphagia with normal esophageal mucosa and frank histological hallmarks of the disease.
      PubDate: 2022-03-24
      DOI: 10.17179/excli2022-4838
      Issue No: Vol. 21 (2022)
       
  • The diaryl-imidazopyridazine anti-plasmodial compound, MMV652103, exhibits
           anti-breast cancer activity

    • Authors: Alexis Neumann-Mufweba, Serah Kimani, Saif Feroz Khan, Kelly Chibale, Sharon Prince
      Pages: 656 - 679
      Abstract: Breast cancer is the most common malignancy in women worldwide and it remains a global health burden, in part, due to poor response and tolerance to current therapeutics. Drug repurposing, which seeks to identify new indications for existing and investigational drugs, has become an exciting strategy to address these challenges. Here we describe the anti-breast cancer activity of a diaryl-imidazopyridazine compound, MMV652103, which was previously identified for its anti-plasmodial activity. We demonstrate that MMV652103 potently inhibits the oncogenic PI4KB and PIK3C2G lipid kinases, is selectively cytotoxic to MCF7 and T47D estrogen receptor positive breast cancer cells and inhibits their ability to survive and migrate. The underlying mechanisms involved included the induction of reactive oxygen species and activation of the DNA damage and p38 MAPK stress signaling pathways. This was associated with a G1 cell cycle arrest and an increase in levels of the cyclin-dependent kinase inhibitor p21 and activation of apoptotic and autophagic cell death pathways. Lastly, MMV652103 significantly reduced the weight and metastases of MCF7 induced tumors in an in vivo chick embryo model and displayed a favorable safety profile. These findings position MMV652103 as a promising chemotherapeutic in the treatment of oestrogen receptor positive breast cancers.
      PubDate: 2022-04-04
      DOI: 10.17179/excli2021-4323
      Issue No: Vol. 21 (2022)
       
  • Current update on anticancer effects of icariin

    • Authors: Mukta Gupta, Yachana Mishra, Vijay Mishra, Murtaza M. Tambuwala
      Pages: 680 - 686
      PubDate: 2022-04-06
      DOI: 10.17179/excli2022-4848
      Issue No: Vol. 21 (2022)
       
  • The “identikit” of subject with obesity and COVID-19 vaccine
           breakthrough

    • Authors: Giovanna Muscogiuri, Luigi Barrea, Ludovica Verde, Claudia Vetrani, Silvia Savastano, Annamaria Colao
      Pages: 687 - 694
      Abstract: The mRNA coronavirus disease 2019 (COVID-19) vaccines were highly effective in the prevention of symptomatic COVID-19, hospitalization, severe disease, and death. However, a minority of vaccinated individuals might become infected and experience significant morbidity. Risk factors of COVID-19 vaccine breakthrough in obesity have not been elucidated. Thus, we aimed to portray the subjects with obesity developing COVID-19 vaccine breakthrough despite vaccination. Coronavirus 2019 (COVID-19) mRNA vaccines have been highly effective in preventing symptomatic COVID-19, hospitalization, severe illness and death. However, a minority of vaccinated individuals may become infected and experience considerable morbidity. The risk factors for COVID-19 vaccine breakthrough in obesity have not been elucidated. Therefore, we aimed to depict individuals with obesity who develop COVID-19 vaccine breakthrough despite vaccination. An online questionnaire was distributed to respondents via a snowball sampling method among subjects with obesity belonging to Italian Associations for people living with obesity aged 18 years and above. Two hundred and thirty-five respondents (44.5±14 years; BMI: 33.3±7.2 kg/m2) were included in the study. COVID-19 vaccine breakthrough was noted in 34 % of respondents. A higher prevalence of grade III obesity was detected in subjects with COVID-19 vaccine breakthrough compared to subjects that did not (27.5 % vs 13.5 %; p=0.014). In addition, a significant lower prevalence of respondents that completed third dose were found in respondents with COVID-19 vaccine breakthrough compared with respondents that did not develop it (33.8 % vs 72.9 %; p<0.001). After stratifying respondents with COVID-19 vaccine breakthrough according to the completed doses of vaccine, we found that, although no differences were detected in terms of clinical manifestations of COVID-19, there was a significant higher prevalence of type 2 diabetes and hypertension in respondents that completed third doses compared to respondents that completed first and second doses. In conclusion, COVID-19 vaccine breakthrough was more common in subjects with grade III obesity. The presence of type 2 diabetes and hypertension could counteract the immune potentiating effects of vaccine booster against COVID-19.
      PubDate: 2022-04-08
      DOI: 10.17179/excli2022-4864
      Issue No: Vol. 21 (2022)
       
  • Medical history, medication use and physical activity in adults in their
           eighth and ninth decade of life in the Hertfordshire Cohort Study

    • Authors: Gregorio Bevilacqua, Jean Zhang, Camille Parsons, Faidra Laskou, Nicholas Fuggle, Cyrus Cooper, Elaine Dennison
      Pages: 695 - 703
      Abstract: While there are many known health benefits to maintained physical activity levels in late adulthood, there have been very few studies that have considered relationships between morbidity profile and physical activity in the eighth decade of life. We studied 1097 participants, 555 men and 542 women from the Hertfordshire Cohort Study, a UK community based sample. Validated questionnaire based data were used to relate self-reported physical activity (PA) levels to medical history, and medication use. Regression analyses were adjusted for age, BMI, smoker status, alcohol consumption. The mean (SD) age of participants in the study was 80.2 (2.7) years for men and 80.2 (2.6) for women. A higher proportion of men (33.7 %) than women (24 %) were in the high activity score group. 20.8 % of female participants and 22.6 % male participants reported having no comorbid disease; 10.5 % men and 8.4 % women were taking no medication. Higher number of chronic conditions was associated with lower levels of PA [men (OR 0.73, 95 % CI 0.63-0.84, p<0.001); women (OR 0.74, 95 % CI 0.64-0.86, p<0.001)] as was being prescribed a higher number of medications [men (OR 0.88, 95 % CI 0.84-0.93, p<0.001); women (OR 0.86, 95 % CI 0.82-0.91, p<0.001)]. All these associations remained robust following adjustments. Strong relationships were seen in both sexes between PA and taking medication for disorders of the central nervous system and gastrointestinal system, with relationships generally stronger in men. We have observed relationships between comorbid medical history and medication use with physical activity in a cohort of community dwelling older adults. These highlight the need to consider medical history when considering how best to optimize PA in older adults.
      PubDate: 2022-04-19
      DOI: 10.17179/excli2022-4874
      Issue No: Vol. 21 (2022)
       
  • Transplantation of SDF-1α-loaded liver extracellular matrix repopulated
           with autologous cells attenuated liver fibrosis in a rat model

    • Authors: Mostafa Najar-Asl, Hossein Bahadoran, Mohammad-Hossein Asadi, Mona Saheli, Mohammad-Hassan Asghari, Niloofar Sodeifi, Mohammad Kazemi Ashtiani, Massoud Vosough, Hossein Baharvand, Abbas Piryaei
      Pages: 704 - 721
      Abstract: Cell-based therapy and tissue engineering are promising substitutes for liver transplantation to cure end-stage liver disorders. However, the limited sources for healthy and functional cells and poor engraftment rate are main challenges to the cell-based therapy approach. On the other hand, feasibility of production and size of bioengineered tissues are primary bottlenecks in tissue engineering. Here, we induce regeneration in a rat fibrotic liver model by transplanting a natural bioengineered scaffold with a native microenvironment repopulated with autologous stem/progenitor cells. In the main experimental group, a 1 mm3 stromal derived factor-1α (SDF-1α; S) loaded scaffold from decellularized liver extracellular matrix (LEM) was transplanted (Tx) into a fibrotic liver and the endogenous stem/progenitor cells were mobilized via granulocyte colony stimulating factor (G-CSF; G) therapy. Four weeks after transplantation, changes in liver fibrosis and necrosis, efficacy of cell engraftment and differentiation, vasculogenesis, and liver function recovery were assessed in this (LEM-TxSG) group and compared to the other groups. We found significant reduction in liver fibrosis stage in the LEM-TxSG, LEM-TxS and LEM-TxG groups compared to the control (fibrotic) group. Liver necrosis grade, and alanine transaminase (ALT) and aspartate transaminase (AST) levels dramatically reduced in all experimental groups compared to the control group. However, the number of engrafted cells into the transplanted scaffold and ratio of albumin (Alb) positive cells per total incorporated cells were considerably higher in the LEM-TxSG group compared to the LEM-Tx, LEM-TxS and LEM-TxG groups. Serum Alb levels increased in the LEM-Tx, LEM-TxS, and LEM-TxG groups, and was highest in the LEM-TxSG group, which was significantly more than the fibrotic group. Small vessel formation in the LEM-TxSG group was significantly higher than the LEM-Tx and LEM-TxS groups. Totally, these findings support application of the in vivo tissue engineering approach as a possible novel therapeutic strategy for liver fibrosis.
      PubDate: 2022-04-22
      DOI: 10.17179/excli2022-4761
      Issue No: Vol. 21 (2022)
       
  • Cytotoxic capability and the associated proteomic profile of cell-free
           coelomic fluid extracts from the edible sea cucumber Holothuria tubulosa
           on HepG2 liver cancer cells

    • Authors: Claudio Luparello, Rossella Branni, Giulia Abruscato, Valentina Lazzara, Laszlo Drahos, Vincenzo Arizza, Manuela Mauro, Vita Di Stefano, Mirella Vazzana
      Pages: 722 - 743
      Abstract: Hepatocellular carcinoma (HCC) is an aggressive cancer histotype and one of the most common types of cancer worldwide. The identification of compounds that might intervene to restrain neoplastic cell growth appears imperative due to its elevated overall mortality. The marine environment represents a reservoir rich in bioactive compounds in terms of primary and secondary metabolites produced by aquatic animals, mainly invertebrates. In the present study, we determined whether the water-soluble cell-free extract of the coelomic fluid (CFE) of the edible sea cucumber Holothuria tubulosa could play an anti-HCC role in vitro by analyzing the viability and locomotory behavior, cell cycle distribution, apoptosis and autophagy modulation, mitochondrial function and cell redox state of HepG2 HCC cells. We showed that CFE causes an early block in the cell cycle at the G2/M phase, which is coupled to oxidative stress promotion, autophagosome depletion and mitochondrial dysfunction ultimately leading to apoptotic death. We also performed a proteomic analysis of CFE identifying a number of proteins that are seemingly responsible for anti-cancer effects. In conclusion, H. tubulosa’s CFE merits further investigation to develop novel promising anti-HCC prevention and/or treatment agents and also beneficial supplements for formulation of functional foods and food packaging material.
      PubDate: 2022-04-25
      DOI: 10.17179/excli2022-4825
      Issue No: Vol. 21 (2022)
       
  • Ergonomic assessment of postal workers’ pain symptoms and
           musculoskeletal risks related to parcel processing activity for delivery

    • Authors: Lincoln Silva, Nélson Costa, Carolina Schutz Rosa, Irandir Izaquiel Paulo, Natália Mattos da Silva, Cesar Giracca, Sabrina da Silveira Simões, Adriana do Nascimento Aquini, Giselle Merino, Eugenio Andrés Díaz Merino
      Pages: 744 - 756
      Abstract: The parcel delivery activity is carried out all over the world and workers in this sector have suffered from musculoskeletal disorders (MSDs) due to the strong demand for work generated by the recent increase in e-commerce. This study aimed to evaluate postal workers' pain symptoms, movements and identify MSDs risks related to the parcel processing activity for delivery, proposing preventive measures. A sample of thirty-two workers was evaluated with the application of sociodemographic and Nordic questionnaires and electrical bioimpedance. The motion capture sensors were used to evaluate right/left shoulder joints, segment C7-T1 (Cervical) and segment L5-S1 (Lumbar) of three postal workers (percentiles of anthropometric data: 5, 50, and 95) during four real work activities that are part of the parcel processing. The analyzed workers presented musculoskeletal complaints in practically all body regions, with a greater prevalence in shoulders, hands, lower back, and knees. According to the Body Mass Index (BMI), they were on average overweight (27.8 ± 3.7 kg/m2). In the movement analysis, we identified risks related to cervical protrusion, anterior trunk flexion, and shoulder flexion, in addition to repetitive movements. In some activities, the higher stature showed an increase in lumbar and cervical anterior flexion. The set of evaluations showed that the activity of processing orders for delivery offers musculoskeletal risks. We identify that ergonomic adaptations are necessary to adapt the heights of the work environment to the statures of the postal workers. Relevance to industry: The activity of processing orders for delivery is carried out practically all over the world generating jobs and income for its employees. Nonetheless, there are still situations of ergonomic disadvantage that can generate musculoskeletal risks. The findings elucidate ergonomic risks and provide useful information for future ergonomic interventions in the postal/delivery workplace environment.
      PubDate: 2022-04-27
      DOI: 10.17179/excli2022-4857
      Issue No: Vol. 21 (2022)
       
  • Recent development of machine learning-based methods for the prediction of
           defensin family and subfamily

    • Authors: Phasit Charoenkwan, Nalini Schaduangrat, S. M. Hasan Mahmud, Orawit Thinnukool, Watshara Shoombuatong
      Pages: 757 - 771
      Abstract: Nearly all living species comprise of host defense peptides called defensins, that are crucial for innate immunity. These peptides work by activating the immune system which kills the microbes directly or indirectly, thus providing protection to the host. Thus far, numerous preclinical and clinical trials for peptide-based drugs are currently being evaluated. Although, experimental methods can help to precisely identify the defensin peptide family and subfamily, these approaches are often time-consuming and cost-ineffective. On the other hand, machine learning (ML) methods are able to effectively employ protein sequence information without the knowledge of a protein’s three-dimensional structure, thus highlighting their predictive ability for the large-scale identification. To date, several ML methods have been developed for the in silico identification of the defensin peptide family and subfamily. Therefore, summarizing the advantages and disadvantages of the existing methods is urgently needed in order to provide useful suggestions for the development and improvement of new computational models for the identification of the defensin peptide family and subfamily. With this goal in mind, we first provide a comprehensive survey on a collection of six state-of-the-art computational approaches for predicting the defensin peptide family and subfamily. Herein, we cover different important aspects, including the dataset quality, feature encoding methods, feature selection schemes, ML algorithms, cross-validation methods and web server availability/usability. Moreover, we provide our thoughts on the limitations of existing methods and future perspectives for improving the prediction performance and model interpretability. The insights and suggestions gained from this review are anticipated to serve as a valuable guidance for researchers for the development of more robust and useful predictors.
      PubDate: 2022-05-05
      DOI: 10.17179/excli2022-4913
      Issue No: Vol. 21 (2022)
       
  • Plasma lncRNA profiling identified BC200 and NEAT1 lncRNAs as potential
           blood-based biomarkers for late-onset Alzheimer’s disease

    • Authors: Majid Khodayi, Mohammad Khalaj-Kondori, Mohammad Ali Hoseinpour Feizi, Mortaza Jabarpour Bonyadi, Mahnaz Talebi
      Pages: 772 - 785
      Abstract: Long non-coding RNAs (lncRNA) play critical roles in pathogenesis of neurodegenerative diseases. Human plasma carries lncRNAs that are stable in the blood, and their disease-specific profile have made them valuable biomarkers for some diseases. This study reports screening of the plasma levels of 90 lncRNAs in patients with Alzheimer disease (AD) to find out plasma-based AD biomarkers. Total RNA was isolated from plasma samples of 50 AD and 50 matched healthy controls. The plasma samples of 10 advanced AD patients and 10 matched healthy controls were screened for expression levels of 90 lncRNAs using Human LncRNA Profiler qPCR Array Kit (SBI). Based on the profiling results, lncRNAs BC200, NDM29, NEAT1, FAS-AS1 and GAS5-AS1 were selected for further analysis in all samples and their biomarker potency was evaluated by ROC curve analysis. We further surveyed RNAseq data by in silico analysis. We found that the NEAT1 and BC200 levels in the plasma of the AD patients were significantly higher compared with the control group (P=0.0021, p= 0.02, respectively). ROC curve analysis showed that the plasma level of NEAT1 and BC200 discriminated AD patients from healthy controls with sensitivity of 72 % and 60 %, and specificity of 84 % and 91 % respectively. Moreover, NEAT1 discriminated MCI (60 % sensitivity and 91 % specificity) and advanced-AD patients from healthy controls (73 % sensitivity and 71 % specificity). Besides, plasma level of BC200 discriminated the pre-clinical subjects from healthy controls with 83 % sensitivity and 66 % specificity. A positive correlation was also observed between plasma levels of BC200 with the age patients (r = 0.34, p=0.02). In silico RNAseq data analysis showed that a total of 33 lncRNAs were up-regulated but 13 lncRNAs were down-regulated significantly in AD patients compared with the healthy controls. In conclusion, this study elucidated that the plasma levels of lncRNAs NEAT1 and BC200 might be considered as potential blood-based biomarkers for AD development and progression.
      PubDate: 2022-05-09
      DOI: 10.17179/excli2022-4764
      Issue No: Vol. 21 (2022)
       
  • What are risk factors for COVID-19 vaccine breakthrough infections in
           patients with previous history of bariatric surgery'

    • Authors: Gerardo Sarno, Pietro Calabrese, Luigi Schiavo, Francesco Izzo, Vincenzo Pilone
      Pages: 786 - 790
      PubDate: 2022-05-12
      DOI: 10.17179/excli2022-4873
      Issue No: Vol. 21 (2022)
       
  • A revolution in health: Opportunities and challenges of the Metaverse

    • Authors: Milad Ahmadi Marzaleh, Mahmoudreza Peyravi, Fatemeh Shaygani
      Pages: 791 - 792
      PubDate: 2022-05-31
      DOI: 10.17179/excli2022-5017
      Issue No: Vol. 21 (2022)
       
  • Immunomodulatory components of Trichinella spiralis excretory-secretory
           products with lactose-binding specificity

    • Authors: Natasa Ilic, Zanka Bojic-Trbojevic, Britta Lundström-Stadelmann, Danica Cujic, Ivana Mitic, Alisa Gruden-Movsesijan
      Pages: 793 - 813
      Abstract: The immunomodulatory potential of Trichinella spiralis muscle larvae excretory-secretory products (ES L1) has been well documented in vitro on dendritic cells (DCs) and in animal models of autoimmune diseases. ES L1 products possess the potential to induce tolerogenic DCs and consequently trigger regulatory mechanisms that maintain immune homeostasis. The use of ES L1 as a potential treatment for various inflammatory disorders proved to be beneficial in animal models, although the precise immunomodulatory factors have not yet been identified. This study aimed at the isolation and characterization of ES L1 components that possess galectin family member properties. Galectin-1-like proteins (TsGal-1-like) were isolated from ES L1 based on the assumption of the existence of a lactose-specific carbohydrate-recognition domain and were recognized by anti-galectin-1 antibodies in Western blot. This TsGal-1-like isolate, similar to galectin-1, induced DCs with tolerogenic properties and hence, the capacity to polarize T cell response towards a regulatory type. This was reflected by a significantly increased percentage of CD4+CD25+Foxp3+ regulatory T cells and significantly increased expression of IL-10 and TGF-β within this cell population. Proteomic analysis of TsGal-1-like isolate by mass spectrometry identified nineteen proteins, seven with annotated function after blast analysis against a database for T. spiralis and the UniProt database. To our surprise, none of the identified proteins possesses homology with known galectin family members. Nevertheless, the isolated components of ES L1 possess certain galectin-1 properties, such as specific lactose binding and the potential to elicit a regulatory immune response, so it would be worth further investigating the structure of sugar binding within isolated proteins and its biological significance.
      PubDate: 2022-06-03
      DOI: 10.17179/excli2022-4954
      Issue No: Vol. 21 (2022)
       
  • Introducing a new index for selecting genetic polymorphisms for
           association studies

    • Authors: Nafiseh Omidpanah, Mostafa Saadat
      Pages: 814 - 817
      PubDate: 2022-06-10
      DOI: 10.17179/excli2022-5004
      Issue No: Vol. 21 (2022)
       
  • The association of ACE1, ACE2, TMPRSS2, IFITM3 and VDR polymorphisms with
           COVID-19 severity

    • Authors: Zorana Dobrijević, Dragana Robajac, Nikola Gligorijević, Miloš Šunderić, Ana Penezić, Goran Miljuš, Olgica Nedić
      Pages: 818 - 839
      Abstract: Genes involved in the regulation of viral recognition and its entry into a host cell have been identified as candidates for genetic association studies on COVID-19 severity. Published findings on the effects of polymorphisms within ACE1, ACE2, TMPRSS2, IFITM3 and VDR genes remained inconclusive, so we conducted a systematic review and meta-analysis in order to elucidate their potential involvement in the genetic basis underlying the severity of COVID-19 and/or an outcome of SARS-CoV-2 infection. Identification of potentially eligible studies was based on PubMed, Scopus and Web of Science database search. Relevant studies (n=29) with a total number of 8247 SARS-CoV-2-positive participants were included in qualitative synthesis, while results of 21 studies involving 5939 were pooled in meta-analysis. Minor allele I of rs1799752 located within ACE1 was identified as a protective variant against severe COVID-19, while its effect on mortality rate was opposite. Similarly, minor allele A of ACE2 polymorphism, rs2285666, was found to associate with a decreased risk of severe COVID-19 (P = 0.003, OR = 0.512, 95 % CI = 0.331-0.793). Statistical significance was also seen for the association between COVID-19 severity and rs12329760 located within TMPRSS2. Our results did not support the supposed association of rs12252 in IFITM3 and polymorphisms within VDR with disease severity. We conclude that genetic variants within ACE1, ACE2 and TMPRSS2 may be potential biomarkers of COVID-19 severity, which needs to be further confirmed in a larger set of studies.
      PubDate: 2022-06-20
      DOI: 10.17179/excli2022-4976
      Issue No: Vol. 21 (2022)
       
  • Effects of curcumin on low-density lipoprotein oxidation

    • Authors: Fatemeh Baratzadeh, Alexandra E. Butler, Prashant Kesharwani, Seyed Adel Moallem, Amirhossein Sahebkar
      Pages: 840 - 851
      Abstract: Atherosclerosis is the most frequent cause of death globally. Oxidized low-density lipoprotein (ox-LDL) has an essential role in the formation of atherosclerotic plaques and foamy macrophages. Ox-LDL increases the uptake of cholesterol by macrophages and is the major cause of blood flow disruption. Ox-LDL is produced during oxidative stress and treatment with antioxidants could inhibit the production and function of ox-LDL. Curcumin is a potent antioxidant and has a strong track record in the treatment of numerous diseases. Recent studies indicate that Curcumin exerts a lipid-lowering effect, and can modulate the formation of atherosclerotic plaque. The current review focuses upon the role of Curcumin in oxidation of LDL and foam cell formation in atherosclerotic lesions.
      PubDate: 2022-06-22
      DOI: 10.17179/excli2022-4878
      Issue No: Vol. 21 (2022)
       
  • Integrated bioinformatics analysis reveals that EZH2-rich domains promote
           transcriptional repression in cervical cancer

    • Authors: Eric Genaro Salmerón-Bárcenas, Ana Elvira Zacapala-Gómez, Julio Ortiz-Ortiz, Francisco Israel Torres-Rojas, Pedro Antonio Avila-Lopez
      Pages: 852 - 868
      Abstract: Cervical cancer is the third female cancer most common worldwide. The carcinogenic process involves an alteration of the mechanisms associated with transcription. Several studies have reported an oncogenic role of the polycomb complex subunit, EZH2. However, the role of EZH2 in cervical cancer is unknown. Hence, the objective of this study was to determine the role of EZH2 in transcriptional regulation in cervical cancer. The EZH2 expression and the methylation status of its promoter were analyzed in The Cancer Genome Atlas. The EZH2 enrichment profile was analyzed using chromatin immunoprecipitation with massively parallel DNA sequencing data provided by ENCODE project. The chromatin compartments were identified in the 4D Nucleome Data Portal. The functional annotation was examined in Enrichr. We report that EZH2 expression is increased in cervical cancer which is associated with hypomethylation of its promoter. EZH2 is enriched at promoter and distal intergenic regions. We identified that EZH2 defines chromatin domains enriched with H3K27me3 within repressive compartments in the HeLa-S3 cell line. Additionally, high EZH2 expression is associated with the repression of the senescent phenotype in cervical cancer patients. Our results suggest the participation of EZH2 in the generation of domains with a silencer function in cervical cancer, which regulate the expression of genes associated with cellular senescence.
      PubDate: 2022-06-23
      DOI: 10.17179/excli2022-5029
      Issue No: Vol. 21 (2022)
       
  • Transient receptor potential channel involvement in antinociceptive effect
           of citral in orofacial acute and chronic pain models

    • Authors: Sacha Aubrey Alves Rodrigues Santos, Marina de Barros Mamede Vidal Damasceno, Francisco Ernani Alves Magalhães, Barry John Sessle, Breytiner Amaro de Oliveira, Francisco Lucas Alves Batista, Antônio Eufrásio Vieira-Neto, Adriana Rolim Campos
      Pages: 869 - 887
      Abstract: This study aimed to test for the possible antinociceptive effect of the naturally occurring terpene citral in rodent models of acute and chronic orofacial pain and to test for the possible involvement of transient receptor potential (TRP) channels in this effect. Acute nociceptive behavior was induced in one series of experiments by administering formalin, cinnamaldehyde, menthol or capsaicin to the upper lip. Nociceptive behavior was assessed by orofacial rubbing, and the effects of pre-treatment with citral (0.1, 0.3 or 1.0 mg/Kg) or vehicle (control) were tested on the behavior. Nociceptive behavior was also induced by formalin injected into the temporomandibular joint or mustard oil injected into the masseter muscle, preceded by citral or vehicle (control) treatment. The chronic pain model involved infraorbital nerve transection (IONX) that induced mechanical hypersensitivity which was assessed by von Frey hair stimulation of the upper lip. Motor activity was also evaluated. Docking experiments were performed using TRPV1 and TRPM8 channels. Citral but not vehicle produced significant (p<0.01, ANOVA) antinociception on all the acute nociceptive behaviors, and these effects were attenuated by TRPV1 antagonist capsazepine, TRPM3 antagonist mefenamic acid and by TRPM8 desensitization, but not by ruthenium red and TRPA1 antagonist HC-030031. The IONX animals developed facial mechanical hypersensitivity that was significantly reduced by citral but not by vehicle. The docking experiments revealed that citral may interact with TRPV1 and TRPM8 channels. These results indicate the potential use of citral as an inhibitor of orofacial nociception in both acute and chronic pain states through TRPV1, TRPM3 and TRPM8 channels.
      PubDate: 2022-06-24
      DOI: 10.17179/excli2022-5042
      Issue No: Vol. 21 (2022)
       
  • Tryptophan recovery index as a new biomarker for fitness

    • Authors: Alexander Pichler, Andreas Meinitzer, Dietmar Enko, Peter Schober, Georg Singer, Christoph Castellani, Markus Herrmann, Sandra J. Holasek, Holger Till, Jana Maria Windhaber
      Pages: 888 - 896
      Abstract: The maximal oxygen uptake (VO2max) and maximal power output (Pmax) are commonly used parameters to evaluate the endurance fitness status. A connection between exercise and the kynurenine pathway (KP), which describes the metabolism of unused tryptophan, has already been reported. However, a potential association of the KP with endurance fitness levels remains unknown. In this study, adolescent competitive athletes performed an exhaustive incremental exercise test. Blood samples were taken before, directly after, and 30 minutes after the end of exercise. Tryptophan (Trp), kynurenine (Kyn) and kynurenic acid (KA) serum levels were determined by high-performance liquid chromatography (HPLC). Forty-four male and 27 female athletes (median age: 16 years) were recruited. During exhaustive exercise tests, Trp initially declined and then increased 30 minutes after discontinuing exercise. Similar findings were observed for Kyn, whereas KA levels behaved inversely. After incremental exhaustive exercise the relative increase of Trp concentrations, termed the tryptophan-recovery-index (TRI), showed a highly significant positive correlation with VO2max and Pmax (r=0.468 and 0.491, p-values <0.001). There was a significant gender-difference with higher levels of all metabolites at all measured time points in male participants. In the present study, a highly significant correlation was found between the TRI and the maximal oxygen uptake in well-trained athletes. The implementation of TRI can therefore be suggested as a biomarker for physical fitness.
      PubDate: 2022-06-24
      DOI: 10.17179/excli2022-4889
      Issue No: Vol. 21 (2022)
       
  • Current update on the protective effect of epicatechin in
           neurodegenerative diseases

    • Authors: Riya Thapa, Gaurav Gupta, Piyush Dave, Santosh Kumar Singh, Abhay Raizaday, Waleed Hassan Almalki, Govind Vyas, Sachin Kumar Singh, Kamal Dua, Yogendra Singh
      Pages: 897 - 903
      PubDate: 2022-06-24
      DOI: 10.17179/excli2022-5034
      Issue No: Vol. 21 (2022)
       
  • Need to focus on inhibitory activity of benzimidazole analogues against
           indolamine 2,3-dioxygenase-1 (IDO-1)

    • Authors: Akshansh Sharma, Rajiv Tonk, Ravi Shekhar, Sushil Dohare, Deepak Kumar
      Pages: 904 - 905
      PubDate: 2022-06-28
      DOI: 10.17179/excli2022-4988
      Issue No: Vol. 21 (2022)
       
  • Elevated risk of thrombotic manifestations of SARS-CoV-2 infection in
           cancer patients

    • Authors: Annunziata Stefanile, Maria Cellerino, Tatiana Koudriavtseva
      Pages: 906 - 920
      Abstract: Coronavirus disease 2019 (COVID-19) results in higher risks of hospitalization or death in older patients and those with multiple comorbidities, including malignancies. Patients with cancer have greater risks of COVID-19 onset and worse prognosis. This excess is mainly explained by thrombotic complications. Indeed, an imbalance in the equilibrium between clot formation and bleeding, increased activation of coagulation, and endothelial dysfunction characterize both COVID-19 patients and those with cancer. With this review, we provide a summary of the pathological mechanisms of coagulation and thrombotic manifestations in these patients and discuss the possible therapeutic implications of these phenomena.
      PubDate: 2022-06-30
      DOI: 10.17179/excli2022-5073
      Issue No: Vol. 21 (2022)
       
  • Insights into the mechanisms of non-coding RNAs’ implication in the
           pathogenesis of Alzheimer’s disease

    • Authors: Majid Khodayi-Shahrak, Mohammad Khalaj-Kondori, Mohammad Ali Hosseinpour Feizi, Mahnaz Talebi
      Pages: 921 - 940
      Abstract: Non-coding RNAs including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in the regulation of gene expression at transcriptional, posttranscriptional, and epigenetic levels. Several studies in cell lines, animal models, and humans, have revealed that non-coding RNAs play crucial roles in the pathogenesis of Alzheimer's disease (AD). Detailed knowledge on their mechanism of implication in the AD pathogenesis can help to develop novel therapeutic and disease management strategies. The two main pathological hallmarks of AD are amyloid plaques resulting from the β-amyloid accumulation, and neurofibrillary tangles (NFT) due to the phosphorylated tau accumulation. Several lncRNAs and miRNAs play crucial roles in both these hallmarks of the AD pathogenesis and other AD-related pathological procedures such as neuronal and synaptic plasticity, neuroinflammation, neuronal differentiation and neuronal apoptosis. In this review, we outlined the non-coding RNAs and further discussed how they are implicated in these AD-related pathological procedures.
      PubDate: 2022-06-30
      DOI: 10.17179/excli2022-5006
      Issue No: Vol. 21 (2022)
       
  • Interventions on soy isoflavone molecules to improve their therapeutic
           potential for prostate cancer treatment

    • Authors: Vladimir Ajdžanović, Branka Šošić-Jurjević, Vesna Vodnik, Branko Filipović
      Pages: 941 - 947
      PubDate: 2022-07-01
      DOI: 10.17179/excli2022-5130
      Issue No: Vol. 21 (2022)
       
 
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