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Publisher: Elsevier   (Total: 3175 journals)

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Showing 1 - 200 of 3175 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 28, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 90, SJR: 1.109, h-index: 94)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.612, h-index: 27)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 33, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 6, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 375, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 236, SJR: 3.683, h-index: 202)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.615, h-index: 21)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.442, h-index: 21)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.915, h-index: 53)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.311, h-index: 16)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1)
Acta Poética     Open Access   (Followers: 4)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.365, h-index: 73)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.059, h-index: 77)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 14)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.967, h-index: 57)
Addictive Behaviors     Hybrid Journal   (Followers: 15, SJR: 1.514, h-index: 92)
Addictive Behaviors Reports     Open Access   (Followers: 7)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 131, SJR: 5.2, h-index: 222)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.265, h-index: 53)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 27, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 0.801, h-index: 26)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 1.286, h-index: 49)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 3.31, h-index: 42)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.277, h-index: 43)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 28, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 0.9, h-index: 30)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 2.139, h-index: 42)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.183, h-index: 23)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.665, h-index: 29)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 10)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 21)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 6)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 42, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 7)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 54, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 15)
Advances in Genetics     Full-text available via subscription   (Followers: 14, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 7)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 2.325, h-index: 20)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.906, h-index: 24)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.497, h-index: 31)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 23)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 1, SJR: 0.396, h-index: 27)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.152, h-index: 85)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 1.645, h-index: 45)
Advances in Mathematics     Full-text available via subscription   (Followers: 10, SJR: 3.261, h-index: 65)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.489, h-index: 25)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.44, h-index: 51)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 15, SJR: 2.885, h-index: 45)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 2.37, h-index: 73)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.4, h-index: 28)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 15, SJR: 1.718, h-index: 58)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.384, h-index: 26)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.248, h-index: 11)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 7)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 18, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.1, h-index: 2)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 374, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 9, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 29, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 1.878, h-index: 68)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 335, SJR: 0.816, h-index: 49)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.318, h-index: 36)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 9, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 429, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.879, h-index: 120)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.434, h-index: 14)
Air Medical J.     Hybrid Journal   (Followers: 5, SJR: 0.234, h-index: 18)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.285, h-index: 3)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 0.922, h-index: 66)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.436, h-index: 12)
Alexandria J. of Medicine     Open Access   (Followers: 1)
Algal Research     Partially Free   (Followers: 9, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 5, SJR: 0.776, h-index: 35)
Alpha Omegan     Full-text available via subscription   (SJR: 0.121, h-index: 9)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.158, h-index: 9)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 48, SJR: 4.289, h-index: 64)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 50, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 42, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10, SJR: 1.091, h-index: 45)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.653, h-index: 93)
American J. of Human Genetics     Hybrid Journal   (Followers: 31, SJR: 8.769, h-index: 256)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.259, h-index: 81)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 32, SJR: 2.313, h-index: 172)
American J. of Medicine     Hybrid Journal   (Followers: 42, SJR: 2.023, h-index: 189)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 190, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 62, SJR: 2.803, h-index: 148)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 6)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.249, h-index: 88)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, h-index: 45)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.653, h-index: 228)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.286, h-index: 125)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.653, h-index: 70)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.066, h-index: 51)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 61, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 14)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 2, SJR: 0.209, h-index: 27)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription   (SJR: 0.104, h-index: 3)
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 4, SJR: 2.577, h-index: 7)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 164, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 1)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 22, SJR: 0.421, h-index: 40)
Angiología     Full-text available via subscription   (SJR: 0.124, h-index: 9)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1)

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Journal Cover Acta Pharmaceutica Sinica B
  [1 followers]  Follow
    
  This is an Open Access Journal Open Access journal
   ISSN (Print) 2211-3843 - ISSN (Online) 2211-3835
   Published by Elsevier Homepage  [3175 journals]
  • Editorial for biomimetic nanoparticles for drug delivery

    • Authors: Jianxin Wang
      Pages: 2 - 3
      Abstract: Publication date: January 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 1
      Author(s): Jianxin Wang


      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2018.01.003
       
  • Structure-based design, synthesis, and biological evaluation of novel
           pyrimidinone derivatives as PDE9 inhibitors

    • Authors: Xu-Nian Wu; Ya-Dan Huang; Jin-Xuan Li; Yan-Fa Yu; Zhou Qian; Chen Zhang; Yinuo Wu; Hai-Bin Luo
      Abstract: Publication date: Available online 12 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xu-Nian Wu, Ya-Dan Huang, Jin-Xuan Li, Yan-Fa Yu, Zhou Qian, Chen Zhang, Yinuo Wu, Hai-Bin Luo
      The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPARγ agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC50 values <5nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Compound 11a, the most effective one, gave the IC50 of 1.1nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structureactivity relationships and provide evidence for further structural modifications.
      Graphical abstract image

      PubDate: 2018-03-20T08:37:48Z
      DOI: 10.1016/j.apsb.2017.12.007
       
  • Separation and simultaneous quantitation of PGF2α and its epimer
           8-iso-PGF2α using modifier-assisted differential mobility spectrometry
           tandem mass spectrometry

    • Authors: Chunsu Liang; Hui Sun; Xiangjun Meng; Lei Yin; J. Paul Fawcett; Huaidong Yu; Ting Liu; Jingkai Gu
      Abstract: Publication date: Available online 10 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chunsu Liang, Hui Sun, Xiangjun Meng, Lei Yin, J. Paul Fawcett, Huaidong Yu, Ting Liu, Jingkai Gu
      Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS–MS/MS method to separate and simultaneously quantify epimers, taking PGF2α and its 8-epimer, 8-iso-PGF2α, as an example. Good accuracy and precision were achieved in the range of 10–500 ng/mL with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.
      Graphical abstract image

      PubDate: 2018-03-20T08:37:48Z
      DOI: 10.1016/j.apsb.2018.01.011
       
  • Anti-retroviral drugs: Current state and development in the next decade

    • Authors: Xingquan Zhang
      Abstract: Publication date: Available online 7 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xingquan Zhang
      The pace of discovery of new antiretroviral (ARV) drugs has slowed, although the efficacy and safety of once-daily fixed dose combinations have been extensively investigated. Several traditional ARV drugs remain in phase III clinical trials. This review summarizes current information on ARV drugs in phase III clinical trials and focuses on the development of ARV drugs in the next decade.
      Graphical abstract image

      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.012
       
  • Design of SERS nanoprobes for Raman imaging: materials, critical factors
           and architectures

    • Authors: Mingwang Li; Yuanyuan Qiu; Chenchen Fan; Kai Cui; Yongming Zhang; Zeyu Xiao
      Abstract: Publication date: Available online 5 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mingwang Li, Yuanyuan Qiu, Chenchen Fan, Kai Cui, Yongming Zhang, Zeyu Xiao
      Raman imaging yields high specificity and sensitivity when compared to other imaging modalities, mainly due to its fingerprint signature. However, intrinsic Raman signals are weak, thus limiting medical applications of Raman imaging. By adsorbing Raman molecules onto specific nanostructures such as noble metals, Raman signals can be significantly enhanced, termed surface-enhanced Raman scattering (SERS). Recent years have witnessed great interest in the development of SERS nanoprobes for Raman imaging. Rationally designed SERS nanoprobes have greatly enhanced Raman signals by several orders of magnitude, thus showing great potential for biomedical applications. In this review we elaborate on recent progress in design strategies with emphasis on material properties, modifying factors, and structural parameters.
      Graphical abstract image

      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.010
       
  • Biocatalytic access to diverse prenylflavonoids by combining a
           

    • Authors: Jianhua Li; Ridao Chen; Ruishan Wang; Xiao Liu; Kebo Xie; Dawei Chen; Jungui Dai
      Abstract: Publication date: Available online 5 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jianhua Li, Ridao Chen, Ruishan Wang, Xiao Liu, Kebo Xie, Dawei Chen, Jungui Dai
      Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific chalcone prenyltransferase, and GuCHI, a stereospecific chalcone isomerase that has promiscuous activity for both chalcones and prenylchalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylchalcones and optical prenylflavanones with chalcone origins.
      Graphical abstract image

      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.009
       
  • Designing the new generation of intelligent biocompatible carriers for
           protein and peptide delivery

    • Authors: Angela M. Wagner; Margaret P. Gran; Nicholas A. Peppas
      Abstract: Publication date: Available online 2 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Angela M. Wagner, Margaret P. Gran, Nicholas A. Peppas
      Therapeutic proteins and peptides have revolutionized treatment for a number of diseases, and the expected increase in macromolecule-based therapies brings a new set of challenges for the pharmaceutics field. Due to their poor stability, large molecular weight, and poor transport properties, therapeutic proteins and peptides are predominantly limited to parenteral administration. The short serum half-lives typically require frequent injections to maintain an effective dose, and patient compliance is a growing issue as therapeutic protein treatments become more widely available. A number of studies have underscored the relationship of subcutaneous injections with patient non-adherence, estimating that over half of insulin-dependent adults intentionally skip injections. The development of oral formulations has the potential to address some issues associated with non-adherence including the interference with daily activities, embarrassment, and injection pain. Oral delivery can also help to eliminate the adverse effects and scar tissue buildup associated with repeated injections. However, there are several major challenges associated with oral delivery of proteins and peptides, such as the instability in the gastrointestinal (GI) tract, low permeability, and a narrow absorption window in the intestine. This review provides a detailed overview of the oral delivery route and associated challenges. Recent advances in formulation and drug delivery technologies to enhance bioavailability are discussed, including the co-administration of compounds to alter conditions in the GI tract, the modification of the macromolecule physicochemical properties, and the use of improved targeted and controlled release carriers.
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      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.013
       
  • Liposomes and lipid disks traverse the BBB and BBTB as intact forms as
           revealed by two-step Förster resonance energy transfer imaging

    • Authors: Tongcheng Dai; Kuan Jiang; Weiyue Lu
      Abstract: Publication date: Available online 26 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Tongcheng Dai, Kuan Jiang, Weiyue Lu
      The blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB) prevent drug and nano-drug delivery systems from entering the brain. However, ligand-mediated nano-drug delivery systems have significantly enhanced the therapeutic treatment of glioma. In this study we investigated the mechanism especially the integrity of liposomes and lipid disks while traversing the BBB and BBTB both in vitro and in vivo. Fluorophores (DiO, DiI and DiD) were loaded into liposomes and lipid disks to form Förster resonance energy transfer (FRET) nano-drug delivery systems. Using brain capillary endothelial cells as a BBB model, we show that liposomes and disks are present in the cytoplasm as their intact forms and traverse the BBB with a ratio of 0.68‰ and 1.67‰, respectively. Using human umbilical vein endothelial cells as BBTB model, liposomes and disks remained intact and traversed the BBTB with a ratio of 2.31‰ and 8.32‰ at 3 h. Ex vivo imaging and immunohistochemical results revealed that liposomes and disks could traverse the BBB and BBTB in vivo as intact forms. In conclusion, these observations explain in part the mechanism by which nano-drug delivery systems increase the therapeutic treatment of glioma.
      Graphical abstract image

      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.004
       
  • Synthesis and biological evaluation of novel tricyclic matrinic
           derivatives as potential anti-filovirus agents

    • Authors: Xin Zhang; Qiang Liu; Qianqian Li; Yinghong Li; Zhandong Liu; Hongbin Deng; Sheng Tang; Yanxiang Wang; Youchun Wang; Danqing Song
      Abstract: Publication date: Available online 21 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xin Zhang, Qiang Liu, Qianqian Li, Yinghong Li, Zhandong Liu, Hongbin Deng, Sheng Tang, Yanxiang Wang, Youchun Wang, Danqing Song
      Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structureactivity relationship analysis indicated: (i) 12N-dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC50 value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.
      Graphical abstract image

      PubDate: 2018-02-26T13:38:15Z
      DOI: 10.1016/j.apsb.2018.01.006
       
  • Authentic compound-free strategy for simultaneous determination of primary
           coumarins in Peucedani Radix using offline high performance liquid
           chromatography–nuclear magnetic resonance spectroscopy–tandem mass
           spectrometry

    • Authors: Yao Liu; Qingqing Song; Wenjing Liu; Peng Li; Jun Li; Yunfang Zhao; Liang Zhang; Pengfei Tu; Yitao Wang; Yuelin Song
      Abstract: Publication date: Available online 21 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yao Liu, Qingqing Song, Wenjing Liu, Peng Li, Jun Li, Yunfang Zhao, Liang Zhang, Pengfei Tu, Yitao Wang, Yuelin Song
      Herein, a strategy is proposed for the simultaneous determination of primary coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of three consecutive steps: 1) Semi-preparative LC in combination with a home-made automated fraction collection module to fragment the universal metabolome standard into ten fractions (Frs. I–X); 2) LC–accurate MS/MS and quantitative 1H NMR spectroscopy conducted in parallel to acquire the qualitative and quantitative data of each fraction; 3) Robust identification and quantification of components by use of LC coupled to multiple reaction monitoring. In this final step, the most significant fractions (Frs. III–X) were pooled to serve as the pseudo-mixed standard solution. Meticulous online parameter optimization was performed to obtain the optimal parameters, including ion transitions and collision energies. Concerns were particularly paid onto pursuing the parameters being capable of monitoring regio-specific isomers, notably praeruptorin E vs. 3′-isovaleryl-4′-angeloylkhellactone. The quantitative performance of the method was validated according to diverse assays. Eleven primary coumarins (1–11) were unambiguously identified and absolutely quantified, even though no external reference compound was used. Above all, the integrated strategy not only provides a feasible pipeline for the quality assessment of Peucedani Radix, but more importantly, shows the potential for authentic compound-free quantitative evaluation of traditional Chinese medicines.
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      PubDate: 2018-02-26T13:38:15Z
      DOI: 10.1016/j.apsb.2018.01.005
       
  • Epigenetic modification in histone deacetylase deletion strain of
           Calcarisporium arbuscula leads to diverse diterpenoids

    • Authors: Jian Bai; Rong Mu; Man Dou; Daojiang Yan; Bingyu Liu; Qian Wei; Jun Wan; Yi Tang; Youcai Hu
      Abstract: Publication date: Available online 21 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jian Bai, Rong Mu, Man Dou, Daojiang Yan, Bingyu Liu, Qian Wei, Jun Wan, Yi Tang, Youcai Hu
      Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula ΔhdaA strain resulted in the isolation of twelve new diterpenoids including three cassanes (1−3), one cleistanthane (4), six pimaranes (5−10), and two isopimaranes (11 and 12) along with two know cleistanthane analogues. Their structures were elucidated by extensive NMR spectroscopic data analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer (MCF-7) cells.
      Graphical abstract image

      PubDate: 2018-02-26T13:38:15Z
      DOI: 10.1016/j.apsb.2017.12.012
       
  • Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy

    • Authors: Feifei Liu; Xiaotong Yang; Meiyu Geng; Min Huang
      Abstract: Publication date: Available online 16 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Feifei Liu, Xiaotong Yang, Meiyu Geng, Min Huang
      The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors. However, the clinical benefits of these inhibitors are compromised by the frequently occurring acquired resistance due to cancer heterogeneity and genomic instability. This review briefly introduces the key protein kinases involved in this pathway as well as their activation mechanisms. We also generalize the correlations between mutations of MAPK members and human cancers, followed by a summarization of progress made on the development of small molecule MAPK kinases inhibitors. In particular, this review highlights the potential advantages of ERK inhibitors in overcoming resistance to upstream targets and proposes that targeting ERK kinase may hold a promising prospect for cancer therapy.
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      PubDate: 2018-02-18T18:31:58Z
      DOI: 10.1016/j.apsb.2018.01.008
       
  • Rhizospheric microbial communities are driven by Panax ginseng at
           different growth stages and biocontrol bacteria alleviates replanting
           mortality

    • Authors: Linlin Dong; Jiang Xu; Lianjuan Zhang; Ruiyang Cheng; Guangfei Wei; He Su; Juan Yang; Jun Qian; Ran Xu; Shilin Chen
      Abstract: Publication date: Available online 13 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Linlin Dong, Jiang Xu, Lianjuan Zhang, Ruiyang Cheng, Guangfei Wei, He Su, Juan Yang, Jun Qian, Ran Xu, Shilin Chen
      The cultivation of Panax plants is hindered by replanting problems, which may be caused by plant-driven changes in the soil microbial community. Inoculation with microbial antagonists may efficiently alleviate replanting issues. Through high-throughput sequencing, this study revealed that bacterial diversity decreased, whereas fungal diversity increased, in the rhizosphere soils of adult ginseng plants at the root growth stage under different ages. Few microbial community, such as Luteolibacter, Cytophagaceae, Luteibacter, Sphingomonas, Sphingomonadaceae, and Zygomycota, were observed; the relative abundance of microorganisms, namely, Brevundimonas, Enterobacteriaceae, Pandoraea, Cantharellales, Dendryphion, Fusarium, and Chytridiomycota, increased in the soils of adult ginseng plants compared with those in the soils of 2-year-old seedlings. Bacillus subtilis 50-1, a microbial antagonist against the pathogenic Fusarium oxysporum, was isolated through a dual culture technique. These bacteria acted with a biocontrol efficacy of 67.8%. The ginseng death rate and Fusarium abundance decreased by 63.3% and 46.1%, respectively, after inoculation with B. subtilis 50-1. Data revealed that microecological degradation could result from ginseng-driven changes in rhizospheric microbial communities; these changes are associated with the different ages and developmental stages of ginseng plants. Biocontrol using microbial antagonists alleviated the replanting problem.
      Graphical abstract image

      PubDate: 2018-02-18T18:31:58Z
      DOI: 10.1016/j.apsb.2017.12.011
       
  • Mesoporous silica nanoparticles for drug and gene delivery

    • Authors: Yixian Zhou; Guilan Quan; Qiaoli Wu; Xiaoxu Zhang; Boyi Niu; Biyuan Wu; Ying Huang; Xin Pan; Chuanbin Wu
      Abstract: Publication date: Available online 12 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yixian Zhou, Guilan Quan, Qiaoli Wu, Xiaoxu Zhang, Boyi Niu, Biyuan Wu, Ying Huang, Xin Pan, Chuanbin Wu
      Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
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      PubDate: 2018-02-18T18:31:58Z
      DOI: 10.1016/j.apsb.2018.01.007
       
  • Activation of an unconventional meroterpenoid gene cluster in Neosartorya
           glabra leads to the production of new berkeleyacetals

    • Authors: Tao Zhang; Jun Wan; Zhajun Zhan; Jian Bai; Bingyu Liu; Youcai Hu
      Abstract: Publication date: Available online 3 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Tao Zhang, Jun Wan, Zhajun Zhan, Jian Bai, Bingyu Liu, Youcai Hu
      Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis, yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of Neosartorya glabra. The cryptic or down-regulated pathway was activated by constitutive expression of pathway-specific regulator gene berA encoded within ber biosynthetic gene cluster. Chemical analysis of mutant Ng-OE: berA extracts enabled the isolation of four berkeleyacetal congeners, in which two of them are new. On the basis of careful bioinformatic analysis of the coding enzymes in the ber gene cluster, the biosynthetic pathway of berkeleyacetals was proposed. These results indicate that this approach would be valuable for discovery of novel natural products and will accelerate the exploitation of prodigious natural products in filamentous fungi.
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      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.005
       
  • Integrated metabolomic and transcriptomic analyses revealed the
           distribution of saponins in Panax notoginseng

    • Authors: Guangfei Wei; Linlin Dong; Juan Yang; Lianjuan Zhang; Jiang Xu; Feng Yang; Ruiyang Cheng; Ran Xu; Shilin Chen
      Abstract: Publication date: Available online 3 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Guangfei Wei, Linlin Dong, Juan Yang, Lianjuan Zhang, Jiang Xu, Feng Yang, Ruiyang Cheng, Ran Xu, Shilin Chen
      Panax notoginseng is famous for its important therapeutic effects. Saponins are bioactive compounds found in different parts and developmental stages of P. notoginseng plants. Thus, it is urgently to study saponins distribution in different parts and growth ages of P. notoginseng plants. In this study, potential biomarkers were found, and their chemical characteristic differences were revealed through metabolomic analysis. High-performance liquid chromatography data indicated the higher content of saponins (i.e., Rg1, Re, Rd, and Rb1) in the underground parts than that in the aerial parts. 20(S)-Protopanaxadiol saponins were mainly distributed in the aerial parts. Additionally, the total saponin content in the 3-year-old P. notoginseng plant (188.0mg/g) was 1.4-fold higher than that in 2-year-old plant (130.5mg/g). The transcriptomic analysis indicated the tissue-specific transcription expression of genes, namely, PnFPS, PnSS, PnSE1, PnSE2, and PnDS, which encoded critical synthases in saponin biosyntheses. These genes showed similar expression patterns among the parts of P. notoginseng plants. The expression levels of these genes in the flowers and leaves were 5.2fold higher than that in the roots and fibrils. These results suggested that saponins might be actively synthesized in the aerial parts and transformed to the underground parts. This study provides insights into the chemical and genetic characteristics of P. notoginseng to facilitate the synthesis of its secondary metabolites and a scientific basis for appropriate collection and rational use of this plant.
      Graphical abstract image

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.010
       
  • Plastome-wide comparison reveals new SNV resources for the authentication
           of Dendrobium huoshanense and its corresponding medicinal slice (Huoshan
           Fengdou)

    • Authors: Zhitao Niu; Jiajia Pan; Qingyun Xue; Shuying Zhu; Wei Liu; Xiaoyu Ding
      Abstract: Publication date: Available online 1 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhitao Niu, Jiajia Pan, Qingyun Xue, Shuying Zhu, Wei Liu, Xiaoyu Ding
      Dendrobium species and their corresponding medicinal slices have been extensively used as traditional Chinese medicine (TCM) in many Asian countries. However, it is extremely difficult to identify Dendrobium species based on their morphological and chemical features. In this study, the plastomes of D. huoshanense were used as a model system to investigate the hypothesis that plastomic mutational hotspot regions could provide a useful single nucleotide variants (SNVs) resource for authentication studies. We surveyed the plastomes of 17 Dendrobium species, including the newly sequenced plastome of D. huoshanense. A total of 19 SNVs that could be used for the authentication of D. huoshanense were detected. On the basis of this comprehensive comparison, we identified the four most informative hotspot regions in the Dendrobium plastome that encompass ccsA to ndhF, matK to 3′trnG, rpoB to psbD, and trnT to rbcL. Furthermore, to established a simple and accurate method for the authentication of D. huoshanense and its medicinal slices, a total of 127 samples from 20 Dendrobium species including their corresponding medicinal slices (Fengdous) were used in this study. Our results suggest that D. huoshanense and its medicinal slices can be rapidly and unequivocally identified using this method that combines real-time PCR with the amplification refractory mutation system (ARMS).
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      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.004
       
  • Synergistic immunoreaction of acupuncture-like dissolving microneedles
           containing thymopentin at acupoints in immune-suppressed rats

    • Authors: Qian Zhang; Chuncao Xu; Shiqi Lin; Huanbin Zhou; Gangtao Yao; Hu Liu; Lili Wang; Xin Pan; Guilan Quan; Chuanbin Wu
      Abstract: Publication date: Available online 1 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qian Zhang, Chuncao Xu, Shiqi Lin, Huanbin Zhou, Gangtao Yao, Hu Liu, Lili Wang, Xin Pan, Guilan Quan, Chuanbin Wu
      Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.
      Graphical abstract image

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.006
       
  • Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic
           activity

    • Authors: Jian Chen; Xiaona Fan; Jianhua Zhu; Liyan Song; Zhiwei Li; Fei Lin; Rongmin Yu; Hanhong Xu; Jiachen Zi
      Abstract: Publication date: Available online 1 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jian Chen, Xiaona Fan, Jianhua Zhu, Liyan Song, Zhiwei Li, Fei Lin, Rongmin Yu, Hanhong Xu, Jiachen Zi
      Four new limonoid-type nortriterpenoids, 1-detigloyl-1-O-methacryloylsalannin (1), 28-deoxo-2,3-dihydronimbolide (2), 12-acetoxy-3-O-acetyl-7-O-tigloylvilasinin (3) and 12-acetoxy-3-O-acetyl-7-O-methacryloylvilasinin (4), along with five known ones, were isolated from seeds of Azadirachta indica A. Juss. Their structures were elucidated by various spectroscopic methods, including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation, as well as by comparison of their spectroscopic data with those reported. In the in vitro cytotoxic assay, 2 showed inhibitory activity against human breast cancer MDA-MB-231 cell line with IC50 value of 7.68±1.74μmol/L, and 5 inhibited growth of human cervical cancer Hela cell line, melanoma A375 cell line and promyelocytic leukemia HL-60 cell line, with IC50 12.00±2.0817.44±2.1113.95±5.74μmol/L, respectively.
      Graphical abstract image

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.009
       
  • 1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via
           promoting regulatory T cell-mediated resolution of inflammation

    • Authors: Wen Jin; Bing Cui; Pingping Li; Fang Hua; Xiaoxi Lv; Jichao Zhou; Zhuowei Hu; Xiaowei Zhang
      Abstract: Publication date: Available online 1 February 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wen Jin, Bing Cui, Pingping Li, Fang Hua, Xiaoxi Lv, Jichao Zhou, Zhuowei Hu, Xiaowei Zhang
      Vitamin D3 has been found to produce therapeutic effects on obesity-associated insulin resistance and dyslipidemia through its potent anti-inflammatory activity, but the precise immunomodulatory mechanism remains poorly understood. In the present study we found that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the biologically active form of vitamin D3, significantly attenuated monosodium glutamate (MSG)-induced obesity and insulin resistance as indicated by body weight reduction, oral glucose tolerance improvement, and a glucose infusion rate increase as detected with hyperinsulinemic-euglycemic clamp. Moreover, 1,25(OH)2D3 not only restored pancreatic islet functions but also improved lipid metabolism in insulin-targeted tissues. The protective effects of 1,25(OH)2D3 on glycolipid metabolism were attributed to its ability to inhibit an obesity-activated inflammatory response in insulin secretory and targeted tissues, as indicated by reduced infiltration of macrophages in pancreas islets and adipose tissue while enhancing the expression of Tgf-β1 in liver tissue, which was accompanied by increased infiltration of Treg cells in immune organs such as spleen and lymph node as well as in insulin-targeted tissues such as liver, adipose, and muscle. Together, our findings suggest that 1,25(OH)2D3 serves as a beneficial immunomodulator for the prevention and treatment of obesity or metabolic syndrome through its anti-inflammatory effects.

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2018.01.001
       
  • Editor Profile: Guest Editor of Special Issue on Biomimetic Nanoparticles
           for Drug Delivery

    • Abstract: Publication date: January 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 1


      PubDate: 2018-02-07T16:43:24Z
       
  • Letter to the editor: Comment on the Regulatios of the Simplified
           Registration and Approval Management for Compound Recipe of Classical
           Prescription of Traditional Chinese Medicine

    • Authors: Shilin Chen; Aihua Liang; Boli Zhang
      Abstract: Publication date: Available online 19 January 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Shilin Chen, Aihua Liang, Boli Zhang


      PubDate: 2018-01-27T14:16:08Z
      DOI: 10.1016/j.apsb.2017.12.003
       
  • Leukocyte-derived biomimetic nanoparticulate drug delivery systems for
           cancer therapy

    • Authors: Yukun Huang; Xiaoling Gao; Jun Chen
      Abstract: Publication date: Available online 10 January 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yukun Huang, Xiaoling Gao, Jun Chen
      Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes (including monocytes/macrophages, neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers, leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.
      Graphical abstract image

      PubDate: 2018-01-10T09:01:22Z
      DOI: 10.1016/j.apsb.2017.12.001
       
  • Enhanced glioma-targeting and stability of LGICP peptide coupled with
           stabilized peptide DA7R

    • Authors: Mingfei Zhang; Weiyue Lu
      Abstract: Publication date: Available online 3 January 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mingfei Zhang, Weiyue Lu
      Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide DA7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability. By linking DA7R and GICP, a multi-receptor targeting molecule was obtained. The stability of these three peptides was evaluated and their targeting efficiency on tumor-related cells and models was compared. The ability of these peptides to cross the blood--tumor barrier (BTB) was also determined. The results indicate that the coupled Y-shaped peptide DA7R–GICP exhibited improved tumor and neovasculature targeting ability and had higher efficiency in crossing the BTB than either individual peptide.
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      PubDate: 2018-01-05T08:47:32Z
      DOI: 10.1016/j.apsb.2017.11.004
       
  • A pilot study of the modulation of sirtuins on arylamine
           N-acetyltransferase 1 and 2 enzymatic activity

    • Authors: Turiján-Espinoza Eneida; Salazar-González Raul Alejandro; Uresti-Rivera Edith Elena; Ortega-Juarez Montserrat; Hernandez-Hernandez Estela; Milán-Segovia Rosa del Carmen; Portales-Pérez Diana Patricia
      Abstract: Publication date: Available online 30 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Turiján-Espinoza Eneida, Salazar-González Raul Alejandro, Uresti-Rivera Edith Elena, Ortega-Juarez Montserrat, Hernandez-Hernandez Estela, Milán-Segovia Rosa del Carmen, Portales-Pérez Diana Patricia
      Arylamine N-acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot. The in situ activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist (resveratrol) and inhibitor (nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1+ cells compared to SIRT6 in lymphocytes. In situ NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence of resveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.
      Graphical abstract image

      PubDate: 2018-01-05T08:47:32Z
      DOI: 10.1016/j.apsb.2017.11.008
       
  • Surface modification of PGP for a neutrophil–nanoparticle co-vehicle to
           enhance the anti-depressant effect of baicalein

    • Authors: Baoyu Chen; Man Luo; Jianming Liang; Chun Zhang; Caifang Gao; Jue Wang; Jianxin Wang; Yongji Li; Desheng Xu; Lina Liu; Ning Zhang; Huijun Chen; Jing Qin
      Abstract: Publication date: Available online 29 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Baoyu Chen, Man Luo, Jianming Liang, Chun Zhang, Caifang Gao, Jue Wang, Jianxin Wang, Yongji Li, Desheng Xu, Lina Liu, Ning Zhang, Huijun Chen, Jing Qin
      Exploiting cells as vehicles for nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. N-Acetyl Pro–Gly–Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils in vivo. Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed in vitro and in vivo. The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell–nanoparticle delivery system for depression therapy.
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      PubDate: 2018-01-05T08:47:32Z
      DOI: 10.1016/j.apsb.2017.11.012
       
  • The current agonists and positive allosteric modulators of α7 nAChR for
           CNS indications in clinical trials

    • Authors: Taoyi Yang; Ting Xiao; Qi Sun; Kewei Wang
      Pages: 611 - 622
      Abstract: Publication date: November 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 6
      Author(s): Taoyi Yang, Ting Xiao, Qi Sun, Kewei Wang
      The alpha-7 nicotinic acetylcholine receptor (α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.09.001
       
  • 8,4′-Oxyneolignane glucosides from an aqueous extract of “ban lan
           gen” (Isatis indigotica root) and their absolute configurations

    • Authors: Lingjie Meng; Qinglan Guo; Yufeng Liu; Jiangong Shi
      Pages: 638 - 646
      Abstract: Publication date: November 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 6
      Author(s): Lingjie Meng, Qinglan Guo, Yufeng Liu, Jiangong Shi
      Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A−F (1–6), were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis and enzyme hydrolysis. The validity of Δδ C8-C7 values to distinguish threo and erythro aryl glycerol units and Cotton effects at 235±5nm to determine absolute configurations at C-8 in 1–6 and their aglycones (1a–6a) are discussed.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.09.006
       
  • Highlights for the 6th International Ion Channel Conference: ion channel
           structure, function, disease and therapeutics

    • Authors: Limei Wang; Kewei Wang
      Pages: 665 - 669
      Abstract: Publication date: November 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 6
      Author(s): Limei Wang, Kewei Wang
      To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6th International Ion Channel Conference (IICC-2017) was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on (1) Ion channel structure and function; (2) Ion channel physiology and human diseases; (3) Ion channels as targets for drug discovery; (4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC (No mechanoreceptor potential C), a member of the transient receptor potential (TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1 (TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.09.007
       
  • Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for
           drug delivery

    • Authors: Xinyi Ma; Qingxiang Song; Xiaoling Gao
      Abstract: Publication date: Available online 24 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xinyi Ma, Qingxiang Song, Xiaoling Gao
      High-density lipoproteins (HDL) are naturally-occurring nanoparticles that are biocompatible, non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and microRNA from donor cells to recipient cells. Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins (rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative, promising avenue for efficient targeting transport of nanomedicine.
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      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.11.006
       
  • Biomimetic nanoparticles for inflammation targeting

    • Authors: Kai Jin; Zimiao Luo; Bo Zhang; Zhiqing Pang
      Abstract: Publication date: Available online 24 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Kai Jin, Zimiao Luo, Bo Zhang, Zhiqing Pang
      There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
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      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.12.002
       
  • Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral
           delivery of insulin

    • Authors: Haisheng He; Yi Lu; Jianping Qi; Weili Zhao; Xiaochun Dong; Wei Wu
      Abstract: Publication date: Available online 23 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Haisheng He, Yi Lu, Jianping Qi, Weili Zhao, Xiaochun Dong, Wei Wu
      Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption via vitamin ligand–receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125–150nm and an insulin entrapment efficiency of approximately 30%–36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.
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      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.11.007
       
  • Cell membrane-based nanoparticles: a new biomimetic platform for tumor
           diagnosis and treatment

    • Authors: Ruixiang Li; Yuwei He; Shuya Zhang; Jing Qin; Jianxin Wang
      Abstract: Publication date: Available online 23 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Ruixiang Li, Yuwei He, Shuya Zhang, Jing Qin, Jianxin Wang
      Taking inspiration from nature, the biomimetic concept has been integrated into drug delivery systems in cancer therapy. Disguised with cell membranes, the nanoparticles can acquire various functions of natural cells. The cell membrane-coating technology has pushed the limits of common nano-systems (fast elimination in circulation) to more effectively navigate within the body. Moreover, because of the various functional molecules on the surface, cell membrane-based nanoparticles (CMBNPs) are capable of interacting with the complex biological microenvironment of the tumor. Various sources of cell membranes have been explored to camouflage CMBNPs and different tumor-targeting strategies have been developed to enhance the anti-tumor drug delivery therapy. In this review article we highlight the most recent advances in CMBNP-based cancer targeting systems and address the challenges and opportunities in this field.
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      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.11.009
       
  • Improved method for synthesis of low molecular weight
           protamine–siRNA conjugate

    • Authors: Zhili Yu; Junxiao Ye; Xing Pei; Lu Sun; Ergang Liu; Jianxin Wang; Yongzhuo Huang; Seung Jin Lee; Huining He
      Abstract: Publication date: Available online 19 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhili Yu, Junxiao Ye, Xing Pei, Lu Sun, Ergang Liu, Jianxin Wang, Yongzhuo Huang, Seung Jin Lee, Huining He
      RNAi technology has aroused wide public interest due to its high efficiency and specificity to treat multiple types of diseases. However, the effective delivery of siRNA remains a challenge due to its large molecular weight and strong anionic charge. Considering their remarkable functions in vivo and features that are often desired in drug delivery carriers, biomimetic systems for siRNA delivery become an effective and promising strategy. Based on this, covalent attachment of synthetic cell penetrating peptides (CPP) to siRNA has become of great interest. We developed a monomeric covalent conjugate of low molecular weight protamine (LMWP, a well-established CPP) and siRNA via a cytosol-cleavable disulfide linkage using PEG as a crosslinker. Results showed that the conjugates didn't generate coagulation, and exhibited much better RNAi potency and intracellular delivery compared with the conventional charge-complexed CPP/siRNA aggregates. Three different synthetic and purification methods were compared in order to optimize synthesis efficiency and product yield. The methodology using hetero-bifunctional NHS–PEG–OPSS as a crosslinker to synthesize LMWP–siRNA simplified the synthesis and purification process and produced the highest yield. These results pave the way towards siRNA biomimetic delivery and future clinical translation.

      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.11.011
       
  • Rapid and sensitive liquid chromatography–tandem mass spectrometric
           method for the quantitative determination of potentially harmful substance
           5,5′-oxydimethylenebis (2-furfural) in traditional Chinese medicine
           injections

    • Authors: Qingce Zang; Yang Gao; Luojiao Huang; Jiuming He; Sheng Lin; Hongtao Jin; Ruiping Zhang; Zeper Abliz
      Abstract: Publication date: Available online 18 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qingce Zang, Yang Gao, Luojiao Huang, Jiuming He, Sheng Lin, Hongtao Jin, Ruiping Zhang, Zeper Abliz
      With the rapid development and wide application of traditional Chinese medicine injection (TCMI), a number of adverse events of some TCMIs have incessantly been reported and have drawn broad attention in recent years. Establishing effective and practical analytical methods for safety evaluation and quality control of TCMI can help to improve the safety of TCMIs in clinical applications. In this study, a sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method has been developed and validated for the quantitative determination of potentially harmful substance 5,5′-oxydimethylenebis (2-furfural, OMBF) in TCMI samples. Chromatographic separation was performed on a C18 reversed-phase column (150mm×2.1mm, 5µm) by gradient elution, using methanol–water containing 0.1% formic acid as mobile phase at the flow rate of 0.3mL/min. MS/MS detection was performed on a triple quadrupole mass spectrometer with positive electrospray ionization in the multiple reaction-monitoring mode. The method was sensitive with a limit of quantification of 0.3ng/mL and linear over the range of 0.3–30ng/mL (r=0.9998). Intra- and inter-day precision for analyte was <9.52% RSD with recoveries in the range 88.0–109.67% at three concentration levels. The validated method was successfully applied to quantitatively determine the compound OMBF in TCMIs and glucose injections. Our study indicates that this method is simple, sensitive, practicable and reliable, and could be applied for safety evaluation and quality control of TCMIs and glucose injections.
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      PubDate: 2017-12-27T06:25:11Z
      DOI: 10.1016/j.apsb.2017.11.002
       
  • Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast
           cancer

    • Authors: Pallabita Chowdhury; Prashanth K.B. Nagesh Sheema Khan Bilal Hafeez Subhash
      Abstract: Publication date: Available online 10 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Pallabita Chowdhury, Prashanth K.B. Nagesh, Sheema Khan, Bilal B. Hafeez, Subhash C. Chauhan, Meena Jaggi, Murali M. Yallapu
      The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81nm as detected by transmission electron microscopy (TEM). FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation (MTS) and clonogenic (colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein (Bcl-xL), upregulation of apoptosis-associated proteins (Bid, Bax, cleaved caspase 7, and cleaved PARP) and β-tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.
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      PubDate: 2017-12-18T03:37:25Z
       
  • Biomacromolecules as carriers in drug delivery and tissue engineering

    • Authors: Yujie Zhang; Tao Sun; Chen Jiang
      Abstract: Publication date: Available online 9 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yujie Zhang, Tao Sun, Chen Jiang
      Natural biomacromolecules have attracted increased attention as carriers in biomedicine in recent years because of their inherent biochemical and biophysical properties including renewability, nontoxicity, biocompatibility, biodegradability, long blood circulation time and targeting ability. Recent advances in our understanding of the biological functions of natural-origin biomacromolecules and the progress in the study of biological drug carriers indicate that such carriers may have advantages over synthetic material-based carriers in terms of half-life, stability, safety and ease of manufacture. In this review, we give a brief introduction to the biochemical properties of the widely used biomacromolecule-based carriers such as albumin, lipoproteins and polysaccharides. Then examples from the clinic and in recent laboratory development are summarized. Finally the current challenges and future prospects of present biological carriers are discussed.
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      PubDate: 2017-12-18T03:37:25Z
      DOI: 10.1016/j.apsb.2017.11.005
       
  • Beneficial effects of Houttuynia cordata polysaccharides on “two-hit”
           acute lung injury and endotoxic fever in rats associated with
           anti-complementary activities

    • Authors: Yan Lu; Yun Jiang; Lijun Ling; Yunyi Zhang; Hong Li; Daofeng Chen
      Abstract: Publication date: Available online 8 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yan Lu, Yun Jiang, Lijun Ling, Yunyi Zhang, Hong Li, Daofeng Chen
      Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins, and has also been used for the treatment of severe acute respiratory syndrome (SARS). In vitro, the crude H. cordata polysaccharides (CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury (ALI) induced by hemorrhagic shock plus lipopolysaccharide (LPS) instillation (two-hit) and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the “two-hit” ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid (BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidant-antioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heat-clearing function of H. cordata.
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      PubDate: 2017-12-18T03:37:25Z
      DOI: 10.1016/j.apsb.2017.11.003
       
  • A novel nitroreductase-enhanced MRI contrast agent and its potential
           application in bacterial imaging

    • Authors: Yun Liu; Leilei Zhang; Marc Nazare; Qingqiang Yao; Hai-Yu Hu
      Abstract: Publication date: Available online 6 December 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yun Liu, Leilei Zhang, Marc Nazare, Qingqiang Yao, Hai-Yu Hu
      Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T 1-weighted magnetic resonance imaging (MRI) contrast agent Gd-DOTA-PNB (probe 1) has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T 1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.
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      PubDate: 2017-12-18T03:37:25Z
      DOI: 10.1016/j.apsb.2017.11.001
       
  • Garlic-derived compound S-allylmercaptocysteine inhibits
           hepatocarcinogenesis through targeting LRP6/Wnt pathway

    • Authors: Jia Xiao; Feiyue Xing; Yingxia Liu; Yi Lv; Xiaogang Wang; Ming-Tat Ling; Hao Gao; Songying Ouyang; Min Yang; Jiang Zhu; Yu Xia; Kwok-Fai So; George L. Tipoe
      Abstract: Publication date: Available online 10 November 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jia Xiao, Feiyue Xing, Yingxia Liu, Yi Lv, Xiaogang Wang, Ming-Tat Ling, Hao Gao, Songying Ouyang, Min Yang, Jiang Zhu, Yu Xia, Kwok-Fai So, George L. Tipoe
      Whether and how garlic-derived S-allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes. SAMC directly interacted with Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over-expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and its over-expression only correlated with the over-expression of β-catenin, but not with age, gender, tumor size, stage and metastasis. Deficiency or over-expression of LRP6 in hepatoma cells could partly mimic or counteract the anti-tumor properties of SAMC, respectively. In vivo administration of SAMC significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor without causing undesirable side effects. In addition, stable down-regulation of LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.10.003
       
  • Biomonitoring for traditional herbal medicinal products using DNA
           metabarcoding and single molecule, real-time sequencing

    • Authors: Tianyi Xin; Zhichao Xu; Jing Jia; Christine Leon; Songnian Hu; Yulin Lin; Subramanyam Ragupathy; Jingyuan Song; Steven G. Newmaster
      Abstract: Publication date: Available online 6 November 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Tianyi Xin, Zhichao Xu, Jing Jia, Christine Leon, Songnian Hu, Yulin Lin, Subramanyam Ragupathy, Jingyuan Song, Steven G. Newmaster
      Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and psbA-trnH regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.10.001
       
  • Substance P-modified human serum albumin nanoparticles loaded with
           paclitaxel for targeted therapy of glioma

    • Authors: Chunhui Ruan; Lisha Liu; Yifei Lu; Yu Zhang; Xi He; Xinli Chen; Yujie Zhang; Qinjun Chen; Qin Guo; Tao Sun; Chen Jiang
      Abstract: Publication date: Available online 6 November 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chunhui Ruan, Lisha Liu, Yifei Lu, Yu Zhang, Xi He, Xinli Chen, Yujie Zhang, Qinjun Chen, Qin Guo, Tao Sun, Chen Jiang
      The blood–brain barrier (BBB) and the poor ability of many drugs to cross that barrier greatly limits the efficacy of chemotherapies for glioblastoma multiforme (GBM). The present study exploits albumin as drug delivery vehicle to promote the chemotherapeutic efficacy of paclitaxel (PTX) by improving the stability and targeting efficiency of PTX/albumin nanoparticles (NPs). Here we characterize PTX-loaded human serum albumin (HSA) NPs stabilized with intramolecular disulfide bonds and modified with substance P (SP) peptide as the targeting ligand. The fabricated SP-HSA-PTX NPs exhibited satisfactory drug-loading content (7.89%) and entrapment efficiency (85.7%) with a spherical structure (about 150nm) and zeta potential of −12.0mV. The in vitro drug release from SP-HSA-PTX NPs occurred in a redox-responsive manner. Due to the targeting effect of the SP peptide, cellular uptake of SP-HSA-PTX NPs into brain capillary endothelial cells (BCECs) and U87 cells was greatly improved. The low IC50, prolonged survival period and the obvious pro-apoptotic effect shown by TUNEL analysis all demonstrated that the fabricated SP-HSA-PTX NPs showed a satisfactory anti-tumor effect and could serve as a novel strategy for GBM treatment.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.09.008
       
  • Comparative untargeted proteomic analysis of ADME proteins and tumor
           antigens for tumor cell lines

    • Authors: Xiaomei Gu; Qing Xiao; Qian Ruan; Yuezhong Shu; Ashok Dongre; Ramaswamy Iyer; W. Griffith Humphreys; Yurong Lai
      Abstract: Publication date: Available online 4 November 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiaomei Gu, Qing Xiao, Qian Ruan, Yuezhong Shu, Ashok Dongre, Ramaswamy Iyer, W. Griffith Humphreys, Yurong Lai
      In the present study, total membrane proteins from tumor cell lines including HepG2, Hep3B2, H226, Ovcar3 and N87 were extracted and digested with γLysC and trypsin. The resulting peptide lysate were pre-fractionated and subjected to untargeted quantitative proteomics analysis using a high resolution mass spectrometer. The mass spectra were processed by the MaxQuant and the protein abundances were estimated using total peak area (TPA) method. A total of 6037 proteins were identified, and the analysis resulted in the identification of 2647 membrane proteins. Of those, tumor antigens and absorption, metabolism, disposition and elimination (ADME) proteins including UDP-glucuronosyltransferase, cytochrome P450, solute carriers and ATP-binding cassette transporters were detected and disclosed significant variations among the cell lines. The principal component analysis was performed for the cluster of cell lines. The results demonstrated that H226 is closely related with N87, while Hep3B2 aligned with HepG2. The protein cluster of Ovcar3 was apart from that of other cell lines investigated. By providing for the first time quantitative untargeted proteomics analysis, the results delineated the expression profiles of membrane proteins. These findings provided a useful resource for selecting targets of choice for anticancer therapy through advancing data obtained from preclinical tumor cell line models to clinical outcomes.
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      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.10.002
       
  • Biomimetic albumin-modified gold nanorods for photothermo-chemotherapy and
           macrophage polarization modulation

    • Authors: Dongdong Meng; Zhang Fan Yingzhi Chen Binfan Chen Chang Huihai
      Abstract: Publication date: Available online 10 October 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Dongdong Li, Meng Zhang, Fan Xu, Yingzhi Chen, Binfan Chen, Ya Chang, Huihai Zhong, Hongyue Jin, Yongzhuo Huang
      Nanotechnology-based photothermal therapy has attracted great attention in the past decade. Nevertheless, photothermal therapy has some inherent drawbacks, such as the uneven heat production and limited laser penetration, often leading to insufficient treatment outcomes. Here, we developed a combination strategy to improve cancer therapy. The biomimetic albumin-modified gold nanorods (AuNRs) were prepared with incorporation of paclitaxel (PTX). This therapeutic system was characterized by several features. First, the albumin modification enhanced the biocompatibility and colloidal stability. Second, the surface-coated albumin promoted cellular uptake via the albumin-binding protein pathway. Third, PTX was incorporated via hydrophobic interaction between PTX and the albumin lipophilic domain. Fourth, the system can be used for combined photothermo-chemotherapy for yielding synergistic effects. The antitumor activity of the system was evaluated both in vitro and in vivo using the HCT116 colon cancer cell and tumor model. The combination therapy was found with an enhanced treatment efficiency and no obvious side effect. Most importantly, the thermal effect was also discovered with the ability to modulate the tumor microenvironments and suppress the macrophages polarization towards the M2 pro-tumor phenotype. It could be a mechanism for photothermal immunotherapy. The combination strategy and the system provide a potential method for cancer therapy.
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      PubDate: 2017-10-10T21:45:19Z
       
  • Comparison of the inhibition potentials of icotinib and erlotinib against
           human UDP-glucuronosyltransferase 1A1

    • Authors: Xuewei Cheng; Xia Lv; Hengyan Qu; Dandan Li; Mengmeng Hu; Wenzhi Guo; Guangbo Ge; Ruihua Dong
      Abstract: Publication date: Available online 1 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xuewei Cheng, Xia Lv, Hengyan Qu, Dandan Li, Mengmeng Hu, Wenzhi Guo, Guangbo Ge, Ruihua Dong
      UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a key role in detoxification of many potentially harmful compounds and drugs. UGT1A1 inhibition may bring risks of drug–drug interactions (DDIs), hyperbilirubinemia and drug-induced liver injury. This study aimed to investigate and compare the inhibitory effects of icotinib and erlotinib against UGT1A1, as well as to evaluate their potential DDI risks via UGT1A1 inhibition. The results demonstrated that both icotinib and erlotinib are UGT1A1 inhibitors, but the inhibitory effect of icotinib on UGT1A1 is weaker than that of erlotinib. The IC50 values of icotinib and erlotinib against UGT1A1-mediated NCHN-O-glucuronidation in human liver microsomes (HLMs) were 5.15 and 0.68 μmol/L, respectively. Inhibition kinetic analyses demonstrated that both icotinib and erlotinib were non-competitive inhibitors against UGT1A1-mediated glucuronidation of NCHN in HLMs, with the K i values of 8.55 and 1.23 μmol/L, respectively. Furthermore, their potential DDI risks via UGT1A1 inhibition were quantitatively predicted by the ratio of the areas under the concentration–time curve (AUC) of NCHN. These findings are helpful for the medicinal chemists to design and develop next generation tyrosine kinase inhibitors with improved safety, as well as to guide reasonable applications of icotinib and erlotinib in clinic, especially for avoiding their potential DDI risks via UGT1A1 inhibition.
      Graphical abstract image

      PubDate: 2017-09-06T16:55:12Z
      DOI: 10.1016/j.apsb.2017.07.004
       
  • Application of 1H NMR-based metabolomics for discrimination of different
           parts and development of a new processing workflow for Cistanche deserti

    • Authors: Pingping Zou; Yuelin Song; Wei Lei; Jun Li; Pengfei Tu; Yong Jiang
      Abstract: Publication date: Available online 26 August 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Pingping Zou, Yuelin Song, Wei Lei, Jun Li, Pengfei Tu, Yong Jiang
      Cistanche deserticola (CD) is one of the two authoritative source plants of Cistanches Herba, a well-known medicinal plant. Herein, 1H NMR spectroscopy was employed to characterize the chemical profile and to distinguish the different parts, as well as to propose a new processing workflow for CD. Signal assignment was achieved by multiple one and two dimensional NMR spectroscopic techniques in combination with available databases and authentic compounds. The upper parts of the plant were distinguished from the lower parts by combining 1H NMR spectroscopic dataset with multivariate statistical analysis. A new processing method that hyphenated steaming with freeze-drying, was demonstrated to be superior to either steaming coupled with oven-drying or direct freeze-drying via holistic 1H NMR-based metabolomic characterization. Phenylethanoid glycosides, mainly echinacoside and acteoside, were screened out and confirmed as the chemical markers responsible for exhibiting the superiority of the new processing workflow, whereas serial primary metabolites, especially carbohydrates and tricarboxylic acid cycle metabolites, were found as the primary molecules governing the discrimination between the upper and lower parts of the plant. Collectively, 1H NMR spectroscopy was demonstrated as a versatile analytical tool to characterize the chemical profile and to guide the in-depth exploitation of CD by providing comprehensive qualitative and quantitative information.
      Graphical abstract image

      PubDate: 2017-08-31T16:17:57Z
      DOI: 10.1016/j.apsb.2017.07.003
       
  • Chinese herbal medicine compound Yi-Zhi-Hao pellet inhibits replication of
           influenza virus infection through activation of heme oxygenase-1

    • Authors: Jinqiu Yin; Linlin Ma; Huiqiang Wang; Haiyan Yan; Jin Hu; Wen Jiang; Yuhuan Li
      Abstract: Publication date: Available online 20 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jinqiu Yin, Linlin Ma, Huiqiang Wang, Haiyan Yan, Jin Hu, Wen Jiang, Yuhuan Li
      As a leading cause of respiratory disease, influenza A virus (IAV) presents a pandemic threat in annual seasonal outbreaks. Given the limitation of existing anti-influenza therapies, there remains to be a requirement for new drugs. Compound Yi-Zhi-Hao pellet (CYZH) is a famous traditional Chinese medicine (TCM) used in the clinic, whose formula has been recorded in Complication of National Standard for Traditional Chinese Medicine to treat common cold. In this study, we found that CYZH exhibited a broad-spectrum anti-influenza activity and inhibited the expression of viral RNA and proteins in vitro. Mechanistically, CYZH had no inhibitory activities against viral protein hemagglutinin and IAV RNA-dependent RNA polymerase. Instead, it induced activation of erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB), which subsequently upregulated heme oxygenase-1 (HO-1) expression. Also, CYZH protected cells from oxidative damage induced by reactive oxygen series. In conclusions, CYZH inhibits IAV replication in vitro, at least partly by activating expression of the Nrf2/HO-1 pathway.
      Graphical abstract image

      PubDate: 2017-06-22T16:57:59Z
      DOI: 10.1016/j.apsb.2017.05.006
       
  • Mitochondrial uncoupler triclosan induces vasorelaxation of rat arteries

    • Authors: Xiyue Zhang; Xinzi Zhang; Yanqiu Zhang; Mingyu Liu; Jing Jin; Jie Yan; Xin Shen; Nan Hu; Deli Dong
      Abstract: Publication date: Available online 16 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiyue Zhang, Xinzi Zhang, Yanqiu Zhang, Mingyu Liu, Jing Jin, Jie Yan, Xin Shen, Nan Hu, Deli Dong
      Our previous studies found that mitochondrial uncouplers induced vasodilation. Triclosan, the broad spectrum antibacterial agent, is the active ingredient in soaps and toothpastes. It was reported that triclosan induced mitochondrial uncoupling, so we aim to investigate the effects of triclosan on vascular function of rat mesenteric arteries and aorta. The isometric tension of rat mesenteric artery and thoracic aorta was recorded by multi-wire myograph system. The cytosolic [Ca2+]i, mitochondrial reactive oxygen species (mitoROS), and mitochondrial membrane potential of smooth muscle cells (A10 cells) were measured using laser scanning confocal microscopy. Triclosan treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with triclosan inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, triclosan also relaxed PE- and KPSS-induced constriction. Triclosan induces vasorelaxation without involving KATP channel activation in smooth muscle cells of arteries. Triclosan treatment increased cytosolic [Ca2+]i, mitochondrial ROS production and depolarized mitochondrial membrane potential in A10 cells. In conclusion, triclosan induces mitochondrial uncoupling in vascular smooth muscle cells and relaxes the constricted rat mesenteric arteries and aorta of rats. The present results suggest that triclosan would indicate vasodilation effect if absorbed excessively in vivo.
      Graphical abstract image

      PubDate: 2017-06-17T16:32:29Z
      DOI: 10.1016/j.apsb.2017.06.001
       
 
 
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