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- Harnessing Nutritional Powerhouse: Millets and Probiotics in Anticancer
Therapy-
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Abstract: Purpose of Review This review highlights the importance and effects of millet and probiotics for the prevention of cancer. Recent Findings Millets are renowned as yesterday’s coarse grains and today’s nutri-cereals, which have a rich source of vitamins, minerals, dietary fibers, and bioactive compounds, containing anti-inflammatory, anti-cancer, and antioxidant properties. India is ranking first in millet production which have been cultivated globally. Probiotics are microorganisms that have health benefits when consumed or applied to the body by improving or restoring the gut microbiota. Probiotics are found in yogurt, fermented foods, and dietary supplements. Bioactive compounds of millet and probiotics have the potential to treat several health problems, including colon cancer, breast cancer, and cervical cancer. Millet is also used in the food industry to produce millet food products because of its high nutritional value. Millets and probiotics can be used as effective anticancer therapies. Therefore, in this study, we have highlighted the significance and effects of millet and probiotics on health and disease prevention, particularly for cancer management. Summary The use of probiotics and millet may open the door to novel dietary supplements and therapeutic interventions for the prevention and treatment of cancer, thereby enhancing the overall health of individuals.
PubDate: 2024-07-22
- Systematic Review on Flow Cytometry as a Versatile Tool for Disease
Diagnosis-
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Abstract: Purpose of Review Quantification and identification of cell fate remain to be the most important step within research and diagnostic laboratories.With advances in diagnostics and precision-medicine, there is a huge demand for cost effective, precise and specific cell counting methodologies. Cell counting techniques have evolved over the past 150 years commencing from manual countingusing a microscope and hemocytometer to automated cell counters followed by flow cytometric techniques. In this review, we have discussed on the applications of Flow Cytometry in diagnosing various diseases and its role as a multifaceted tool. Recent Findings Flow cytometry is an instrument with a sophisticated technology to analyze various parameters of individual cells flowing in a suspended form through a liquid medium. Physical characteristics such as size, granularity and other parameters can be determined by the property of scattering of light by individual cells under investigation. Its use has also been expanded to various fields in basic and applied research, biotechnology and clinical diagnostics. Furthermore, immunophenotyping of peripheral blood cells and various neoplasms, diagnosis of various diseases by analyzing cytokine detection, protein analysis, cell cycle and DNA analysis and finally, viral and bacterial cell population counts can also be performed using flow cytometry. Summary The amazing way in which this technique can provide minuscule details of single cells with a great degree of specificity and accuracy from a complex population of cells within a very short span, has made flow cytometry, an ingenuous tool for disease investigation.
PubDate: 2024-07-03
- Effect of millets and probiotics on cancer prevention:exploring its
nutritional composition and health benefits-
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Abstract: Purpose of Review This article explores the potential of millets and probiotics for the prevention of cancer, highlighting their contributions to the prevention and treatment of cancer. Recent Findings Cancer is a major global health concern, necessitating intensive research on preventative strategies and treatment options. Millets, a type of small-seeded grass, have gained popularity because of their high nutritional content, which includes fiber, vitamins, minerals, and phytochemicals. These nutritional elements have anti-inflammatory and antioxidant properties that are crucial for preventing cancer and tumor growth. Additionally, millets have a low glycemic index, which aids in blood sugar regulation and may reduce the risk of insulin-related cancer. Furthermore, probiotics or beneficial bacteria found in fermented meals are important for gut health and immune system modulation. Probiotics have the capability to prohibit the multiple facets of cancer development, such as suppressing tumor growth, improving the effectiveness of chemotherapy, and reducing the adverse effects of treatment. Furthermore, probiotics enhance the production of short-chain fatty acid, which have anticancer properties through a variety of pathways, comprising the stimulation of apoptosis and inhibition of tumor cell growth. Millets provide a wide range of nutrients that can supplement the metabolic requirements of probiotics and potentially enhance their beneficial impact on host health. Therefore, millet and probiotics may have powerful impacts on the management and prevention of cancer. Summary In conclusion, this review discusses the incorporation of probiotics and millet in dietary supplements, which holds immense potential in both avoiding and reducing cancer risk in people.
PubDate: 2024-06-18
- Mental Health and the Microbiome: A Review of Psychological Impacts of Gut
Microflora-
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Abstract: Purpose of Review Starting from scratch to understand what a microbiome is and its significance in our daily lives has become a crucial subject of study. This review aims to delve into the impact of diet on the gut microbiota and how alterations in the gut microflora can contribute to dysbiosis, anxiety, depression, and other neurological disorders. Recent Findings Over the past one decade, extensive research has been conducted to explore the role of the gut microbiome in mental health and its potential involvement in causing mental illnesses. Some studies have made hypotheses about how gut microbes can influence both psychological and neurological aspects. One primary area of investigation has been the impact of diet on shaping the composition of the gut microbiota and whether it can affect brain function or even play a role in the prevention or management of mental disorders such as depression, anxiety, schizophrenia, and Alzheimer's disease. These conditions and neurological diseases have garnered significant attention from the scientific community due to their growing burden on the field of medical science. Summary While many studies on the gut-brain axis (GBA) have traditionally focused on aspects like satiety and digestive processes, it is important to recognize that the gut microbiota constitutes a complex and dynamic ecosystem that plays a vital role in the overall functioning of the human body. Consequently, it exerts a profound influence on an individual's health and their susceptibility to various illnesses.
PubDate: 2024-06-01
DOI: 10.1007/s40495-024-00357-z
- Mitochondria Modulating Therapeutic Approaches in the Management of
Huntington’s Disease-
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Abstract: Purpose of Review Mitochondrial dysfunctions are considered epistatic to cellular malfunctions during advancement of neurodegenerative disorders, including Huntington's disease (HD). Recent Findings In HD, such compromised mitochondrial functioning contributes to perturb neuronal functioning via unwarranted free radicals generation, reduced ATP production, altered mitochondrial permeability transition and enhanced mitochondrial DNA lesions with concomitant failure in mitochondrial dynamics. Available pharmacological interventions in controlling HD progression are focused mainly in managing symptoms observed in HD, with limited ability to ameliorate behavioral and cognitive dysfunctions. Mitochondria targeted pharmacological molecules are now being considered as potent therapeutic interventions to efficiently ameliorate mitochondrial dysfunctions observed in HD, though this approach is still at its inception. Therefore, it is necessary to screen potent drug molecule/s which could be supplemented alone or in combination, and assist in managing HD. Summary This review highlights the therapeutic potential of mitochondrial drug targeting and limitations of currently available mitochondria-targeted drugs (synthetic and natural antioxidants) under investigation in treating HD, encouraging the demand for designing perspective therapeutic strategies targeting mitochondria in efficient management of HD.
PubDate: 2024-05-17
DOI: 10.1007/s40495-024-00356-0
- Current Insights into Signature MicroRNA Networks and Signal Transduction
in Osteosarcoma-
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Abstract: Purpose of Review Osteosarcoma is one of the most common types of primary bone tumors that mainly occurs in children and adolescents. It is characterized by the development of immature bones or osteoid tissue by the tumor cells. Osteosarcoma is also often caused by metastatic tumors, and has a high global incidence. Treatment strategies are limited by the intractable nature of the disease and the likelihood for metastasis. Recent Findings MicroRNAs (miRNAs) are a class of noncoding RNAs composed of 18–24 nucleotides that are major components for various biological processes like cell differentiation, cell growth, and cell death. Dysregulation of miRNAs in cells leads to altered gene expression leading to several phenotypic and genotypic changes in cells which initiate and promote carcinogenesis. Several miRNAs are involved in the pathogenesis of osteosarcoma thereby affecting the prognosis for the patient. These miRNAs, when altered, have the ability to function either as oncogenes or as tumor suppressor genes. We discuss osteosarcoma in the light of dysregulated miRNA signature networks and their biomarker targets and the delineation of miRNA-target interactions in osteosarcoma. We also elucidate key signal transduction pathways that are modulated by miRNAs in osteosarcoma. Further, we summarize dysregulated osteosarcoma miRNAs that play key role(s) in other pediatric tumors. Summary Taken together, we present an overview of the architecture of signature miRNA networks in osteosarcoma and provide a mechanistic basis to augment our understanding of miRNA regulation in osteosarcoma.
PubDate: 2024-05-13
DOI: 10.1007/s40495-024-00355-1
- Redoxification (of the Organism) Through Diet and Supplementation with a
Focus on Natural Polymeric Redox Modulators-
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Abstract: Purpose of Review Oxidative stress, characterized by an imbalance between reactive oxygen species production and the body’s antioxidant defence mechanisms, has been implicated in the pathogenesis of numerous diseases. This review highlights the possible mechanisms of influence of natural polymeric redox modulators in human organism as well as an importance of supplementation with these metabolites as a promising tool to counteract oxidative stress. Resent Findings The first part provides an overview of oxidative stress and its role in the development of various pathological conditions. The second part of the manuscript focuses on natural redox modulators, highlighting their unique properties and diverse sources, including plant-based bioactive polymers. The third section explores the potential therapeutic applications of natural polymeric redox modulators in oxidative stress–related diseases. Furthermore, the potential synergistic effects of natural redox modulators with conventional therapies have also been discussed, suggesting their value in combination treatments. The review article also addresses the challenges and opportunities in the field of natural polymeric redox modulator supplementation, including enhanced bioavailability, stability and safety considerations. Future directions and emerging research areas, such as personalized supplementation, are also explored, underscoring the need for further investigation and optimization of these compounds. Summary Supplementation with natural polymeric redox modulators represents a promising strategy to combat oxidative stress–related diseases. Their unique properties, diverse sources and potential synergistic effects open avenues for novel therapeutic interventions and improved patient outcomes. According to the current-stage investigation, further research and clinical trials are warranted to harness the full potential of these natural compounds.
PubDate: 2024-03-26
DOI: 10.1007/s40495-024-00353-3
- Assessing the Clinical Correlation between Alzheimer's disease and Type-2
Diabetes Mellitus: Current Strategies and Emerging Perspectives-
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Abstract: Purpose of Review This article aims to provide a brief overview of novel therapeutic approaches for combating type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). Recent Findings The most prevalent disorders in elderly patients are type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD), raising worldwide concern. Recent research indicates that insulin resistance develops in patients with AD, owing to insufficient glucose absorption by the human body. Amyloid precursor protein (APP), present on the cellular membrane of neurons, helps develop and repair damaged brain neurons. Insulin resistance, hyperinsulinemia and elevated blood sugar levels (hyperglycemia) are the three primary clinical features of T2DM. The first is insulin resistance, which appears because of diminished or poor insulin sensitivity in the liver, muscles and fat cells. The linkable pathophysiology of AD and DM starts from the abnormal formation of ⍺ cells and β cells in the pancreas, which leads to an increase in the action of glycogen synthase kinase (GSK), glucose, insulin and TNF⍺ in the cell tissue in the skeletal muscle, which leads to insulin resistance in the liver and ultimately mitochondrial dysfunction, which promotes the formation amyloid β plaques which hinder the neuronal signalling. Along with these factors, glucagon-like peptide-1(GLP-1) receptor signalling also plays an essential role in reducing the pathogenicity of the disease. Summary APP significantly affects insulin gene expressions and glucose-dependent insulin release through the pancreas and is also helpful in suppressing neurodegenerative cascades that help improve both diabetes and neurodegenerative illness. This article also explores recent research studies demonstrating various therapy approaches that help in the amelioration of AD and T2DM.
PubDate: 2024-03-18
DOI: 10.1007/s40495-024-00354-2
- Stem Cells and Regenerative Strategies for Wound Healing: Therapeutic and
Clinical Implications-
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Abstract: Abstract The skin is the largest organ of the body and performs various functions. Various stem cells are responsible for repairing damaged tissues and restoration of tissue proportion, which results in wound repair. If the wound healing process is not completed or impaired, it results in non-healing or delayed healing of wounds and known as chronic wounds. Sometimes, rupture of stem cells causes chronic wound by molecular and cellular actions in which the reason is not known. In the present review, we describe different types of stem cells for therapeutic application including adult mesenchymal stem cells, bone marrow stem cells, embryonic stem cells, umbilical cord stem cells, and induced pluripotent stem cells. Here, we enlighten on recent advances surrounding stem cell therapies for wound healing and their clinical acceptance criteria. We summarize an overview of the original function and therapeutic applications of the most promising stem cell populations for wound healing. Better therapeutic research on chronic wound healing is ongoing as current therapies have limited efficacy for this; adult stem cells can become good options for several skin pathologies. Keratinocytes are produced by epidermal stem cells. Due to the skin barrier properties of the keratinized layer through terminal differentiation caused by keratinocytes, it supports to the skin epidermis for regeneration. As stem cells can regenerate and distinguish the biomolecular location, it is gaining appreciation from three decades for the treatment of ulcers (venous) and diabetic chronic disease. This review also described various therapeutic approaches for the treatment of non-healing wounds and discussed about epidermal stem cell strategy, along with skin tissue engineering and follicle repair approach.
PubDate: 2024-02-08
DOI: 10.1007/s40495-024-00352-4
- Pharmacological Profile of FDA-Approved Orphan Drugs in the Year 2022
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Abstract: Purpose of Review This manuscript aimed to provide a scientific report of recently FDA-approved orphan drugs for helping patients, researchers, clinicians, and academicians engaged in rare diseases. Recent Findings The development of an orphan drug is really challenging (due to the small number of potential patients and the poor business potential despite substantial financial investment and the use of other resources) but vital (as it creates new hope for patients and families affected by rare diseases) process. FDA approved about 54% (20 out of 37) novel orphan drug therapies for varying rare diseases such as refractory follicular lymphoma, acid sphingomyelinase deficiency, amyotrophic lateral sclerosis, and generalized pustular psoriasis. It has been reported that 50% of these orphan drugs (e.g., adagrasib, futibatinib, pacritinib, olutasidenib, and tebentafusp-tebn) are recommended for uncommon or care cancers such as KRAS G12C mutated form of non-small cell lung cancer, locally advanced or metastatic intrahepatic cholangiocarcinoma (cancer of the intrahepatic part of the bile duct), intermediate or high-risk primary or secondary myelofibrosis, relapsed or refractory acute myeloid leukemia with susceptible IDH1 mutation, unresectable or metastatic uveal melanoma. This manuscript, describing the pharmacological aspects such as therapeutic applications, mechanisms of action, pharmacokinetics, adverse effects, doses, and special cases particularly in pediatrics, geriatrics, pregnant women, and lactating mothers, summarized twenty orphan drugs approved by the FDA in the year 2022 and price (for determining the cost of therapy), shall serve as a helpful document for concerned patients and clinicians. Summary This manuscript, the pharmacological report of recently FDA-approved twenty orphan drugs depicting the pharmacological profile, serves as an essential handy document for health professionals as well as patients concerned with rare diseases. Graphical 
PubDate: 2024-01-30
DOI: 10.1007/s40495-024-00351-5
- Efficacy and Safety of Topical Sirolimus for the Treatment of
Angiofibromas in Tuberous Sclerosis: a Systematic Review and Meta-analysis
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Abstract: Background/Purpose Facial angiofibromas (FAs) are common skin manifestations of tuberous sclerosis complex (TSC) that occur in up to 80% of patients. Sirolimus seems to be effective in decreasing FAs. The aim of our study was to investigate the efficacy and safety of topically applied sirolimus in TSC patients with FAs. Methods The methods and the results were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. PubMed/MEDLINE, SCOPUS, and Cochrane database were systematically searched until April 21, 2022, using the PICO tool (Patient, Interventions, Comparisons, Outcome). Studies regarding efficacy and/or safety of topical sirolimus for the treatment of FAs in TSC with a published full-text in English were included. Safety was assessed based on adverse effects and sirolimus’ blood levels, and efficacy was documented by clinical improvement and reduction of Facial Angiofibroma Severity Index (FASI). For Meta-analysis, Review Manager (RevMan) 5.4.1 software was used, using random-effects model and standardized mean difference (SMD) with 95% confidence interval (CI). Results Twenty-one final studies were included. Regarding safety, in the included studies, the observed adverse effects were mainly local, while the blood levels of sirolimus were within safe limits, decreasing the likelihood of systemic immunosuppression. The meta-analysis revealed a statistically significant decrease in post-treatment FASI (SMD: − 1.31, 95% CI: [− 1.85, − 0.77], p-value < 0.00001). Subgroup and sensitivity analyses indicated similar findings. No publication bias was found to this association. Conclusion The application of topical sirolimus to FAs can safely decrease their severity in patients with TSC.
PubDate: 2023-12-13
DOI: 10.1007/s40495-023-00350-y
- A Comprehensive Review on the Effect of Natural Products on Colorectal
Cancer-
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Abstract: Purpose of Review This article provides insight and information on selected natural products against colorectal cancer and its mechanism of action. Recent Findings Colorectal cancer (CRC) is the fourth primary occurring cancer, rectal cancer is eighth throughout the world, and both are the third most commonly occurring and deadliest cancer types around the globe. The overall CRC occurrence and mortality rates are rapidly increasing in developing countries, and the rates are decreasing or stabilizing in developed countries due to high-fat and low-fiber diets. On the other hand, natural products are versatile molecules that possess benefits, including antioxidant, anticancer, anti-inflammatory, anti-diabetic, cardioprotective, hepatoprotective, and neuroprotective. Various signal transduction pathways contribute to the pathogenesis of CRC. Summary Hence, in this review, we documented the natural products against colorectal cancer and their mechanism of action that augments the signal transduction pathways that are highly dysregulated in colorectal cancer.
PubDate: 2023-12-13
DOI: 10.1007/s40495-023-00349-5
- Biological Activities of Carrageenan from Red Algae: a Mini Review
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Abstract: Purpose of Review Marine sources play a major role in producing structurally distinct environmental products, and one such potential marine source is algae. Among various algae, there is a growing interest noticed in red algae because of its productive properties in cosmetics, pharmaceuticals, and especially food products. Recent Findings Carrageenan is such compound isolated from red seaweed which is a water-soluble polysaccharide obtained from the internal algae matrix and cell walls of the Rhodophyceae family. This polysaccharide is used in both commercial and nutraceutical products. Carrageenan has recently received a lot of attention due to its multifunctional qualities such as antioxidant, anti-hypocholesterolemic, antibacterial activity, anti-viral, anticancer, anticoagulant, and immunomodulating properties. Furthermore, they have been applied in drug delivery and tissue engineering Summary This review has discussed the various types of carrageenan-based biomedical products and their application.
PubDate: 2023-12-06
DOI: 10.1007/s40495-023-00348-6
- Analgesic and Anti-inflammatory Potential of Ricinus communis Linn.:
Evidence from Pharmacology to Clinical Studies-
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Abstract: Purpose of Review Ricinus communis Linn. is a rapidly growing perennial herb (aka Eranda or castor plant) that has long been used to cure a range of ailments in traditional medicine. An extensive search on its ethnomedicinal, phytochemistry, and pharmacotherapeutic potential is completed by meticulously examining information retrieved from Web of Science, PubMed, SciFinder, Google Scholar, Embase, and Infrastructure databases. Recent Findings The plant has yielded beneficial chemical compounds such as alkaloids, flavonoids, coumarins, terpenoids, sterols, and fatty acids. Several reports are available on the anti-inflammatory, antinociceptive, antiasthmatic, antifertility, antihistaminic, hepatoprotective, antimicrobial, free radical scavenging activities, antioxidant, and various other biological roles of the crude herb and its metabolites. This review comprehensively discusses the biopotential of R. communis in pain and inflammation, as evident from in vitro, in vivo, and clinical data, as well as safety and toxicity concerns, various market formulations, and drug-drug interactions. R. communis shows potent anti-inflammatory and analgesic activity possibly by NF-kB, Nrf2, RAF/ERK, Fas receptor, and caspase-mediate apoptosis and Wnt signalling pathways. Summary R. communis is widely distributed globally and is rich in bioactive phytoconstituents with multifaceted therapeutic roles. It modulates numerous inflammatory and biochemical markers and highlights its potential in the management of nociception and inflammation. These findings could pave the way for the identification and developing more effective strategies to combat nociception and inflammatory disorders. Graphical 
PubDate: 2023-12-02
DOI: 10.1007/s40495-023-00347-7
- Do Marine Polysaccharides Carrageenans Modulate Non-apoptotic Regulated
Cell Deaths ' (a Review)-
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Abstract: Purpose of Review A growing number of studies indicate that a network of regulated cell death (RCD) pathways plays a vital role in tumorigenesis suggesting its targeting to be a promising therapeutic avenue for cancer treatment. In this review, we firstly systematically summarize the current knowledge on the impact of carrageenans on different non-conventional non-apoptotic RCDs and explore a therapeutic potential of carrageenans as RCDs-modulating agents. Furthermore, we cover the knowledge gaps and controversies in our understanding of cell death-related carrageenan-mediated effects and highlight the directions of further research aiming at studying the pharmacological potential of carrageenans. Recent Findings A compelling body of evidence indicates that non-apoptotic RCDs, including necroptosis, ferroptosis, pyroptosis, and autophagy-related cell death, are involved in modulating tumorigenesis and immune response in cancer. Recent advances in our understanding of the role of distinct non-apoptotic RCDs suggest that pharmacological modulation of diverse RCDs is a tempting anti-cancer therapeutic strategy. In particular, carrageenans, which are a group of heterogenous anionic hydrocolloids of polysaccharide nature widely used as food additives (E407 and E407a), have been shown to have anti-viral, anti-cancer, and immunomodulatory activity. The anti-cancer activity of carrageenans is attributed to a certain extent to activation of apoptosis, but the effects of carrageenan on other RCD modes, which can be targeted in oncopathology, are poorly summarized. Summary Anti-cancer, immunomodulatory, and anti-viral properties of marine polysaccharides carrageenans are at least partly explained by their modulation of RCD modalities, primarily pyroptosis. Thus, carrageenans can be considered promising RCD-regulating agents, which can be therapeutically exploitable. Furthermore, we emphasize the need to consider induction of non-conventional RCDs as one of the possible molecular mechanisms of carrageenan toxicity. Graphical 
PubDate: 2023-12-01
DOI: 10.1007/s40495-023-00339-7
- Current Scenario and Strategies to Tackle Cardiovascular Disease Risk in
HIV Geriatrics-
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Abstract: Abstract Owing to the advent of antiretroviral (ART) drugs, human immunodeficiency virus (HIV) has become a controllable infection, but pernicious health outcomes due to the infection are inevitable. Older people living with HIV (PLHIV) may face more problems than younger PLHIV, such as financial constraints, physical strength, and adaptability. Cardiovascular diseases (CVDs) are a major group of age-related disorders. A plethora of studies have reported the contribution of HIV to the development of various CVDs. Furthermore, the risk of CVD in the geriatric HIV population is higher than in the younger population. CVDs can be attributed to several risk factors, including immune dysfunction, damage to the endothelial cells lining blood vessels, abnormal lipid levels, high blood pressure, obesity, diabetes, smoking, excessive alcohol consumption, sleep disorders, persistent inflammation, compromised immune function, and the use of ART in PLHIV. Despite the availability of data on CVD risk in the general population, the knowledge gap regarding the risk of CVD in geriatric PLHIV requires further exploration. Furthermore, the key strategies to overcome the risk of CVD in geriatrics are lifestyle changes and dietary management, followed by the selection of appropriate antiretroviral drugs and statins for the treatment of elderly PLHIV. This narrative review briefly discusses the epidemiology, risk factors, mechanisms, and CVD risk in older PLHIV, and strategies to overcome them.
PubDate: 2023-12-01
DOI: 10.1007/s40495-023-00332-0
- Time-Dependent Pharmacokinetics of Immune Checkpoint Inhibitors and their
Implications and Considerations for Exposure–Response Analysis-
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Abstract: Purpose The purpose of this review is to provide a comprehensive summary of recent studies characterizing the pharmacokinetics of newly approved immune checkpoint inhibitors (ICIs) monoclonal antibodies and highlight the latest finding and advancements in understanding time-dependent PK, wherein their clearance changes with time. Additionally, the article will discuss key considerations and implications when conducting exposure–response analysis. Recent Findings The majority of papers documenting time-varying PK are fairly recent as ICIs as a class of drugs have emerged as successful anti-cancer agents in the last 10 years or so. The review paper is split in two, somewhat connected, parts. The first one is focused on the association of time-varying PK and disease state. In order to provide a comprehensive context, the review paper starts with the cases of nivolumab and pembrolizumab, and then look at publications documenting that phenomenon for other therapies, such as cemiplimab, retifanlimab, atezolizumab, avelumab, durvalumab, ipilimumab, tremelimumab, and relatlimab. The second part discusses the implication of varying PK for the exposure response of efficacy. Building upon the strong correlation between drug clearance over time and the overall survival highlighted above, this part of the paper studies how the potential for this interaction between treatment response and PK leads to biased E-R (exposure–response) relationships, especially for efficacy. Special emphasis is placed on a recent white paper with authors from industry, academia, and government (Ruiz-Garcia et al. JPKPD 50:147-172, 2023) that highlights the various challenges and some possible solutions for conducting and interpreting ER-efficacy analyses in oncology. Summary Recognizing and accounting for the dynamic PK characteristics are crucial for optimizing dosing strategies, predicting drug exposure, and understanding the association between drug exposure and clinical outcomes in patients undergoing checkpoint inhibitor therapy. This paper provides a succinct summary of relevant publications and some practical considerations.
PubDate: 2023-11-03
DOI: 10.1007/s40495-023-00346-8
- Exploration of the Growing Therapeutic Potentials of Quercetin in Ovarian
Cancer Management-
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Abstract: Purpose of Review This review aims to offer a comprehensive insight and a recent update into the etiology and pathophysiology of ovarian cancer, a recent update on the usage of quercetin for ovarian cancer management. Recent Findings Over the last few decades, an alarming increase in global rates of ovarian cancer has been observed, resulting in increased pressure on the healthcare system. In order to effectively address the situation, there is a need to explore alternatives to currently dominant treatment regimes. The usage of phytoconstituents, such as polyphenols as anti-cancer agents, has emerged as a promising alternative. Quercetin, a widely distributed dietary flavonol, possesses potent antioxidant, anti-inflammatory, and cytoprotective properties, and has been used in the amelioration of a variety of metabolic disorders. In addition to effectively managing various types of cancer, it has been seen to pose lowered side effects and improve the overall quality of life of patients. Summary Literature search of quercetin showed remarkable properties like antioxidant, anti-cancer, anti-apoptotic, anti-inflammatory, and bioavailability-enhancing abilities that fit its appropriate use in pathological conditions. However, being a product of natural origin, bioavailability and optimal delivery may prove to be challenging to achieving the desired therapeutic efficacy. This review, in turn, furthers our understanding of the applications of quercetin in cancer management and the identification of challenges and future perspectives, to enable the maximization of therapeutic efficacy.
PubDate: 2023-10-13
DOI: 10.1007/s40495-023-00343-x
- Guillain Barre Syndrome as a Complication of Infections Including
COVID-19: a Review-
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Abstract: Purpose of Review The purpose was to analyze scientific findings on Guillain Barre Syndrome (GBS) related to COVID-19 and emphasize its relationship with GBS. In this article, besides COVID-19, we explained various causative agents associated with GBS, their mechanism of action, diagnosis, and treatment. Recent Findings GBS is an acute inflammatory immune-mediated polyradiculoneuropathy. Patients with infections linked to GBS frequently produce antibodies against the gangliosides of the human peripheral nerves. This results in the entry of viruses or bacteria, like COVID-19 and Zika, into the body, generating antibodies against viruses or bacteria. Due to molecular mimicry, these antibodies target various lipo-oligosaccharides in microbes and structurally similar gangliosides in the brain. Target on gangliosides by the antibodies leads to demyelination of neurons, leading to loss of neurons that leads to GBS. Even though the relationship between GBS and COVID-19 has recently been the subject of numerous case reports, the degree of this relationship and the characteristics of GBS in this instance remain largely unknown. Guillain–Barre syndrome connected with COVID-19 has shown more severe symptoms. Summary We establish a significant correlation between the two diseases (COVID-19 and GBS) and the mechanism of action of other causative agents responsible for GBS, its diagnosis, and treatment. We explained the different types of GBS and the differences in how the disease appears. Graphical 
PubDate: 2023-09-22
DOI: 10.1007/s40495-023-00334-y
- Cross Talk on P2X4 Purinergic Receptors and Neuropathic Pain
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Abstract: Purpose of Review Considerable interest has been paid to purinergic receptors, a group of cell surface receptors that react to extracellular purines like adenosine and ATP, as possible biomarkers in a variety of physiological and pathological states. The P2X purinoreceptor 4 protein, which is encoded by the P2X4 gene, controls the microglial immune response and is linked to various aspects of brain illness. In the past ten years, P2X4 receptors have become known as possible therapeutic targets for CNS diseases. Recent Findings Purines can be synthesized with the salvage or de novo pathways and are crucial for cellular metabolism. For synaptic plasticity and signal transmission, the P2X4 receptor must be expressed at low levels in the central nervous system. Exocytosis, which secretes ATP-rich synaptic vesicles, causes an accumulation of ATP in the neuronal terminal, which activates P2X2 and P2X2/3 on the pre-synaptic side and P2X2, P2X4, and P2X6 on the post-synaptic side. When triggered with ATP, P2X4-mediated neuropathic pain is increased and produces brain-derived neurotrophic factor (BDNF). In vitro research on the P2X4 receptor is scant; however, it has been linked to neuropathic pain, inflammation, and alcohol use disease (AUD). Research from mouse models have suggested that an increase of P2X4 surface receptor in the hippocampus results in synaptic deficits and altered long-term potentiation (LTP) and long-term depression (LTD) recognized as a plasticity indicator. Interaction of both P2X4R and ATP also causes a massive release of brain-derived neurotrophic factor (BDNF), and in macrophages, it has a link with prostaglandin E2 (PGE2) release. Summary Ionotropic P2XR and metabotropic P2YR interact with each other to form complex signaling. In different cases of pathogenesis and in different tissues, ATP is found to be the key player, whose stimulation is found to activate the downstream signaling and transmission, and P2X4R is responsible for early inflammatory response. P2X receptors of different subunits are considered as promising targets for neuropathic pain because of their widespread availability/ expression in different tissues.
PubDate: 2023-09-19
DOI: 10.1007/s40495-023-00341-z
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