for Journals by Title or ISSN
for Articles by Keywords

Publisher: Elsevier   (Total: 3049 journals)

 A  B  C  D  E  F  G  H  I  J  K  L  M  N  O  P  Q  R  S  T  U  V  W  X  Y  Z  

        1 2 3 4 5 6 7 8 | Last   [Sort by number of followers]   [Restore default list]

Showing 1 - 200 of 3049 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 7)
AASRI Procedia     Open Access   (Followers: 15)
Academic Pediatrics     Hybrid Journal   (Followers: 25, SJR: 1.402, h-index: 51)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.008, h-index: 75)
Accident Analysis & Prevention     Partially Free   (Followers: 86, 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: 30, SJR: 2.515, h-index: 90)
Achievements in the Life Sciences     Open Access   (Followers: 4)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 5, SJR: 0.338, h-index: 19)
Acta Astronautica     Hybrid Journal   (Followers: 364, SJR: 0.726, h-index: 43)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 3)
Acta Biomaterialia     Hybrid Journal   (Followers: 25, SJR: 2.02, h-index: 104)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 1)
Acta de Investigación Psicológica     Open Access   (Followers: 2)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.172, h-index: 29)
Acta Haematologica Polonica     Free   (SJR: 0.123, h-index: 8)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.604, h-index: 38)
Acta Materialia     Hybrid Journal   (Followers: 229, 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   (Followers: 1)
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 3, 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: 24, 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: 4)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 3)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 4, SJR: 0.383, h-index: 19)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 2)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 5, SJR: 0.141, h-index: 3)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 4, SJR: 0.112, h-index: 2)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 4)
Acute Pain     Full-text available via subscription   (Followers: 13)
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: 6)
Additive Manufacturing     Hybrid Journal   (Followers: 7, SJR: 1.039, h-index: 5)
Additives for Polymers     Full-text available via subscription   (Followers: 21)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 133, 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: 17, SJR: 0.739, h-index: 33)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.299, h-index: 15)
Advances in Agronomy     Full-text available via subscription   (Followers: 15, SJR: 2.071, h-index: 82)
Advances in Anesthesia     Full-text available via subscription   (Followers: 26, SJR: 0.169, h-index: 4)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 3)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 6, SJR: 1.054, h-index: 35)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, 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: 16, 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: 3, SJR: 0.619, h-index: 48)
Advances in Cancer Research     Full-text available via subscription   (Followers: 25, SJR: 2.215, h-index: 78)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, 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: 4)
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: 9, SJR: 1.268, h-index: 45)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 29, SJR: 0.938, h-index: 33)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 18, SJR: 2.314, h-index: 130)
Advances in Computers     Full-text available via subscription   (Followers: 16, SJR: 0.223, h-index: 22)
Advances in Dermatology     Full-text available via subscription   (Followers: 12)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 7)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 22)
Advances in Ecological Research     Full-text available via subscription   (Followers: 45, SJR: 3.25, h-index: 43)
Advances in Engineering Software     Hybrid Journal   (Followers: 26, SJR: 0.486, h-index: 10)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.465, h-index: 64)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 3)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 8)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 51, SJR: 0.674, h-index: 38)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 16)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 2.558, h-index: 54)
Advances in Genome Biology     Full-text available via subscription   (Followers: 12)
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: 22, 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: 26)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, 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: 9, SJR: 1.132, h-index: 42)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 3, SJR: 1.274, h-index: 27)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 4)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.764, h-index: 15)
Advances in Lipobiology     Full-text available via subscription   (Followers: 2)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 16, 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: 22)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 10)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 8, SJR: 0.324, h-index: 8)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 4)
Advances in Oncobiology     Full-text available via subscription   (Followers: 3)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
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: 7, SJR: 0.148, h-index: 11)
Advances in Parasitology     Full-text available via subscription   (Followers: 7, 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: 13)
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: 8)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 5)
Advances in Porous Media     Full-text available via subscription   (Followers: 4)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 17)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 1.5, h-index: 62)
Advances in Psychology     Full-text available via subscription   (Followers: 62)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 5, SJR: 0.478, h-index: 32)
Advances in Radiation Oncology     Open Access  
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 2, 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: 360, SJR: 0.606, h-index: 65)
Advances in Structural Biology     Full-text available via subscription   (Followers: 8)
Advances in Surgery     Full-text available via subscription   (Followers: 7, SJR: 0.823, h-index: 27)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 1.321, h-index: 56)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 16)
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: 44, SJR: 2.408, h-index: 94)
Aeolian Research     Hybrid Journal   (Followers: 5, SJR: 0.973, h-index: 22)
Aerospace Science and Technology     Hybrid Journal   (Followers: 333, 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: 5, SJR: 0.344, h-index: 6)
Ageing Research Reviews     Hybrid Journal   (Followers: 8, SJR: 3.289, h-index: 78)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 416, SJR: 1.385, h-index: 72)
Agri Gene     Hybrid Journal  
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 16, SJR: 2.18, h-index: 116)
Agricultural Systems     Hybrid Journal   (Followers: 30, SJR: 1.275, h-index: 74)
Agricultural Water Management     Hybrid Journal   (Followers: 40, SJR: 1.546, h-index: 79)
Agriculture and Agricultural Science Procedia     Open Access  
Agriculture and Natural Resources     Open Access   (Followers: 1)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 55, 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: 8)
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: 8, SJR: 2.05, h-index: 20)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 3)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.46, h-index: 29)
Allergology Intl.     Open Access   (Followers: 4, 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: 46, 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: 5)
American Heart J.     Hybrid Journal   (Followers: 49, SJR: 3.157, h-index: 153)
American J. of Cardiology     Hybrid Journal   (Followers: 48, SJR: 2.063, h-index: 186)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 40, SJR: 0.574, h-index: 65)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 9, 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: 32, 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: 46, 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: 198, SJR: 2.255, h-index: 171)
American J. of Ophthalmology     Hybrid Journal   (Followers: 59, 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: 25, SJR: 2.764, h-index: 154)
American J. of Surgery     Hybrid Journal   (Followers: 35, 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: 58, SJR: 0.124, h-index: 9)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 12)
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: 37, SJR: 1.548, h-index: 152)
Analytical Biochemistry     Hybrid Journal   (Followers: 168, SJR: 0.725, h-index: 154)
Analytical Chemistry Research     Open Access   (Followers: 8, SJR: 0.18, h-index: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 12)
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  
Animal Behaviour     Hybrid Journal   (Followers: 173, SJR: 1.907, h-index: 126)

        1 2 3 4 5 6 7 8 | Last   [Sort by number of followers]   [Restore default list]

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  [3049 journals]
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.09.007
  • Understanding peroral absorption: regulatory aspects and contemporary
           approaches to tackling solubility and permeability hurdles

    • Authors: Prachi B. Shekhawat; Varsha B. Pokharkar
      Pages: 260 - 280
      Abstract: Publication date: May 2017
      Source:Acta Pharmaceutica Sinica B, Volume 7, Issue 3
      Author(s): Prachi B. Shekhawat, Varsha B. Pokharkar
      Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2016.09.005
  • 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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      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.
      Graphical abstract image

      PubDate: 2017-11-25T06:39:40Z
      DOI: 10.1016/j.apsb.2017.10.002
  • Establishment of pseudovirus infection mouse models for in vivo
           pharmacodynamics evaluation of filovirus entry inhibitors

    • Authors: Qing Chen; Ke Tang; Xiaoyu Zhang; Panpan Chen; Ying Guo
      Abstract: Publication date: Available online 22 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qing Chen, Ke Tang, Xiaoyu Zhang, Panpan Chen, Ying Guo
      Filoviruses cause severe and fatal viral hemorrhagic fever in humans. Filovirus research has been extensive since the 2014 Ebola outbreak. Due to their high pathogenicity and mortality, live filoviruses require Biosafety Level-4 (BSL-4) facilities, which have restricted the development of anti-filovirus vaccines and drugs. An HIV-based pseudovirus cell infection assay is widely used for viral entry studies in BSL-2 conditions. Here, we successfully constructed nine in vitro pseudo-filovirus models covering all filovirus genera and three in vivo pseudo-filovirus-infection mouse models using Ebola virus, Marburg virus, and Lloviu virus as representative viruses. The pseudo-filovirus-infected mice showed visualizing bioluminescence in a dose-dependent manner. A bioluminescence peak in mice was reached on day 5 post-infection for Ebola virus and Marburg virus and on day 4 post-infection for Lloviu virus. Two known filovirus entry inhibitors, clomiphene and toremiphene, were used to validate the model. Collectively, our study shows that all genera of filoviruses can be well-pseudotyped and are infectious in vitro. The pseudo-filovirus-infection mouse models can be used for in vivo activity evaluation of anti-filovirus drugs. This sequential in vitro and in vivo evaluation system of filovirus entry inhibitors provides a secure and efficient platform for screening and assessing anti-filovirus agents in BSL-2 facilities.
      Graphical abstract image

      PubDate: 2017-10-13T22:00:53Z
      DOI: 10.1016/j.apsb.2017.08.003
  • 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.
      Graphical abstract image

      PubDate: 2017-10-10T21:45:19Z
  • Correlation analysis between the chemical contents and bioactivity for the
           quality control of Alismatis Rhizoma

    • Authors: Xiaoxv Gao; Chengpeng Sun; Zhenlong Yu; Jian Cang; Xiangge Tian; Xiaokui Huo; Lei Feng; Xinguang Liu; Chao Wang; Baojing Zhang; Xiaochi Ma
      Abstract: Publication date: Available online 30 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiaoxv Gao, Chengpeng Sun, Zhenlong Yu, Jian Cang, Xiangge Tian, Xiaokui Huo, Lei Feng, Xinguang Liu, Chao Wang, Baojing Zhang, Xiaochi Ma
      In order to clarify regions of production and to discriminate processing methods, quantitative and qualitative analyses for saccharides and terpenes in 35 batches of Alismatis Rhizoma were performed. Methodologies included HPLCPDA, HPLCVWD and UHPLCMS n , combined with principal component analysis (PCA) and partial least squares regression techniques (PLSR). The inhibitory effects of triterpenes and Alismatis Rhizoma extracts on lipase activity were evaluated in vitro. PLSR analysis revealed significant positive correlations (R 2 = 0.5795) between the contents of triterpenes 10, 14, 15, 18 and 22 and the inhibitory effects of Alismatis Rhizoma. The present study establishes an effective method for simultaneous determination of multiple components, and identifies key bioactive triterpenes. These results can be used for systematic and novel analytical strategies for the quality control of Alismatis Rhizoma production.
      Graphical abstract image

      PubDate: 2017-10-01T20:57:38Z
      DOI: 10.1016/j.apsb.2017.09.004
  • An updated overview on the development of new photosensitizers for
           anticancer photodynamic therapy

    • Authors: Juan Zhang; Chengshi Jiang; João Paulo Figueiró Longo; Ricardo Bentes Azevedo; Hua Zhang; Luis Alexandre Muehlmann
      Abstract: Publication date: Available online 22 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Juan Zhang, Chengshi Jiang, João Paulo Figueiró Longo, Ricardo Bentes Azevedo, Hua Zhang, Luis Alexandre Muehlmann
      Photodynamic therapy (PDT), based on the photoactivation of photosensitizers (PSs), has become a well-studied therapy for cancer. Photofrin®, belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology.
      Graphical abstract image

      PubDate: 2017-09-24T20:15:49Z
      DOI: 10.1016/j.apsb.2017.09.003
  • 131I-Evans blue: evaluation of necrosis targeting property and preliminary
           assessment of the mechanism in animal models

    • Authors: Qiaomei Jin; Xin Shan; Qi Luo; Dong Jian Zhang; Yuanyu Zhao; Nan Yao; Fei Peng; Dejian Huang; Zhiqi Yin; Wei Liu; Jian Zhang
      Abstract: Publication date: Available online 19 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qiaomei Jin, Xin Shan, Qi Luo, Dong Jian Zhang, Yuanyu Zhao, Nan Yao, Fei Peng, Dejian Huang, Zhiqi Yin, Wei Liu, Jian Zhang
      Necrosis is a form of cell death, which is related to various serious diseases such as cardiovascular disease, cancer, and neurodegeneration. Necrosis-avid agents (NAAs) selectively accumulated in the necrotic tissues can be used for imaging and/or therapy of related diseases. The aim of this study was to preliminarily investigate necrosis avidity of 131I-evans blue (131I-EB) and its mechanism. The biodistribution of 131I-EB at 24h after intravenous administration showed that the radioactivity ratio of necrotic to viable tissue was 3.41 in the liver and 11.82 in the muscle as determined by γ counting in model rats. Autoradiography and histological staining displayed preferential uptake of 131I-EB in necrotic tissues. In vitro nuclear extracts from necrotic cells exhibited 82.3% of the uptake in nuclei at 15min, as well as 79.2% of the uptake at 2h after 131I-EB incubation. The DNA binding study demonstrated that evans blue (EB) has strong binding affinity with calf-thymus DNA (CT-DNA) (K sv=5.08×105 L/(mol/L)). Furthermore, the accumulation of 131I-EB in necrotic muscle was efficiently blocked by an excess amount of unlabeled EB. In conclusion, 131I-EB can not only detect necrosis by binding the DNA released from necrotic cells, but also image necrotic tissues generated from the disease clinically.
      Graphical abstract image

      PubDate: 2017-09-24T20:15:49Z
      DOI: 10.1016/j.apsb.2017.08.002
  • A novel quantified bitterness evaluation model for traditional Chinese
           herbs based on an animal ethology principle

    • Authors: Xue Han; Hong Jiang; Li Han; Xi Xiong; Yanan He; Chaomei Fu; Runchun Xu; Dingkun Zhang; Junzhi Lin; Ming Yang
      Abstract: Publication date: Available online 13 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xue Han, Hong Jiang, Li Han, Xi Xiong, Yanan He, Chaomei Fu, Runchun Xu, Dingkun Zhang, Junzhi Lin, Ming Yang
      Traditional Chinese herbs (TCH) are currently gaining attention in disease prevention and health care plans. However, their general bitter taste hinders their use. Despite the development of a variety of taste evaluation methods, it is still a major challenge to establish a quantitative detection technique that is objective, authentic and sensitive. Based on the two-bottle preference test (TBP), we proposed a novel quantitative strategy using a standardized animal test and a unified quantitative benchmark. To reduce the difference of results, the methodology of TBP was optimized. The relationship between the concentration of quinine and animal preference index (PI) was obtained. Then the PI of TCH was measured through TBP, and bitterness results were converted into a unified numerical system using the relationship of concentration and PI. To verify the authenticity and sensitivity of quantified results, human sensory testing and electronic tongue testing were applied. The quantified results showed a good discrimination ability. For example, the bitterness of Coptidis Rhizoma was equal to 0.0579mg/mL quinine, and Nelumbinis Folium was equal to 0.0001mg/mL. The validation results proved that the new assessment method for TCH was objective and reliable. In conclusion, this study provides an option for the quantification of bitterness and the evaluation of taste masking effects.
      Graphical abstract image

      PubDate: 2017-09-18T19:40:01Z
      DOI: 10.1016/j.apsb.2017.08.001
  • Remodeling the blood–brain barrier microenvironment by natural products
           for brain tumor therapy

    • Authors: Xiao Zhao; Rujing Chen; Mei Liu; Jianfang Feng; Jun Chen; Kaili Hu
      Abstract: Publication date: Available online 1 September 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiao Zhao, Rujing Chen, Mei Liu, Jianfang Feng, Jun Chen, Kaili Hu
      Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%–30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system (CNS) damage which endangers the patients' lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved. At present, chemotherapy is the treatment of choice for many cancers, but the special structure of the blood–brain barrier (BBB) limits most chemotherapeutic agents from passing through the BBB and penetrating into tumors in the brain. The BBB microenvironment contains numerous cell types, including endothelial cells, astrocytes, peripheral cells and microglia, and extracellular matrix (ECM). Many chemical components of natural products are reported to regulate the BBB microenvironment near brain tumors and assist in their treatment. This review focuses on the composition and function of the BBB microenvironment under both physiological and pathological conditions, and the current research progress in regulating the BBB microenvironment by natural products to promote the treatment of brain tumors.
      Graphical abstract image

      PubDate: 2017-09-06T16:55:12Z
      DOI: 10.1016/j.apsb.2017.07.002
  • 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
  • Molecular cloning and functional identification of sterol
           C24-methyltransferase gene from Tripterygium wilfordii

    • Authors: Hongyu Guan; Yujun Zhao; Ping Su; Yuru Tong; Yujia Liu; Tianyuan Hu; Yifeng Zhang; Xianan Zhang; Jia Li; Xiaoyi Wu; Luqi Huang; Wei Gao
      Abstract: Publication date: Available online 14 August 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Hongyu Guan, Yujun Zhao, Ping Su, Yuru Tong, Yujia Liu, Tianyuan Hu, Yifeng Zhang, Xianan Zhang, Jia Li, Xiaoyi Wu, Luqi Huang, Wei Gao
      Sterol C24-methyltransferase (SMT) plays multiple important roles in plant growth and development. SMT1, which belongs to the family of transferases and transforms cycloartenol into 24-methylene cycloartenol, is involved in the biosynthesis of 24-methyl sterols. Here, we report the cloning and characterization of a cDNA encoding a sterol C24-methyltransferase from Tripterygium wilfordii (TwSMT1). TwSMT1 (GenBank access number KU885950) is a 1530bp cDNA with a 1041bp open reading frame predicted to encode a 346-amino acid, 38.62kDa protein. The polypeptide encoded by the SMT1 cDNA was expressed and purified as a recombinant protein from Escherichia coli (E. coli) and showed SMT activity. The expression of TwSMT1 was highly up-regulated in T. wilfordii cell suspension cultures treated with methyl jasmonate (MeJA). Tissue expression pattern analysis showed higher expression in the phellem layer compared to the other four organs (leaf, stem, xylem and phloem), which is about ten times that of the lowest expression in leaf. The results are meaningful for the study of sterol biosynthesis of T. wilfordii and will further lay the foundations for the research in regulating both the content of other main compounds and growth and development of T. wilfordii.
      Graphical abstract image

      PubDate: 2017-08-21T14:46:23Z
      DOI: 10.1016/j.apsb.2017.07.001
  • Biosynthesis of antibiotic chuangxinmycin from Actinoplanes tsinanensis

    • Authors: Yuanyuan Shi; Zhibo Jiang; Xingxing Li; Lijie Zuo; Xuan Lei; Liyan Yu; Linzhuan Wu; Jiandong Jiang; Bin Hong
      Abstract: Publication date: Available online 12 August 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yuanyuan Shi, Zhibo Jiang, Xingxing Li, Lijie Zuo, Xuan Lei, Liyan Yu, Linzhuan Wu, Jiandong Jiang, Bin Hong
      Chuangxinmycin is an antibiotic isolated from Actinoplanes tsinanensis CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed in vitro antibacterial activity and in vivo efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of A. tsinanensis CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cxn cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in Streptomyces coelicolor M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in S. coelicolor M1146 harboring the cxn gene cluster with an inactivated cxnD. Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.
      Graphical abstract image

      PubDate: 2017-08-21T14:46:23Z
      DOI: 10.1016/j.apsb.2017.07.005
  • Antihyperuricemic effect of mangiferin aglycon derivative J99745 by
           inhibiting xanthine oxidase activity and urate transporter 1 expression in

    • Authors: Zhizhen Qin; Shoubao Wang; Yihuang Lin; Ying Zhao; Shengqian Yang; Junke Song; Tao Xie; Jinlong Tian; Song Wu; Guanhua Du
      Abstract: Publication date: Available online 16 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhizhen Qin, Shoubao Wang, Yihuang Lin, Ying Zhao, Shengqian Yang, Junke Song, Tao Xie, Jinlong Tian, Song Wu, Guanhua Du
      A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600mg/kg xanthine once daily for 7 days and intraperitoneally injected 250mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30mg/kg), allopurinol (20mg/kg) or benzbromarone (20mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent.
      Graphical abstract image

      PubDate: 2017-07-31T12:39:30Z
      DOI: 10.1016/j.apsb.2017.05.004
  • Potassium 2-(1-hydroxypentyl)-benzoate attenuates neuronal apoptosis in
           neuron–astrocyte co-culture system through neurotrophy and
           neuroinflammation pathway

    • Authors: Dongmei Liu; Man Zhang; Xianfang Rong; Jiang Li; Xiaoliang Wang
      Abstract: Publication date: Available online 15 July 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Dongmei Liu, Man Zhang, Xianfang Rong, Jiang Li, Xiaoliang Wang
      Potassium 2-(1-hydroxypentyl)-benzoate (d,l-PHPB), a new drug candidate for ischemic stroke at the phase II clinic trial, has been shown to protect neurons by inhibiting oxidative injury and reducing neuron apoptosis in previous studies. But the mechanisms of d,l-PHPB remain to be studied. In this study, a neuron–astrocytes co-culture system was used to elucidate the roles of astrocytes in neuroprotection of d,l-PHPB under oxygen-glucose deprivation/reoxygenation (OGD/R) condition. Our data showed that d,l-PHPB reduced neuronal apoptosis in mono-culture system and this effect was enhanced in neuron–astrocyte co-culture system under the OGD/R condition. Meanwhile, d,l-PHPB obviously increased the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), which were mainly secreted from astrocytes, in the co-culture system after OGD/R. The PI3K/AKT and ERK signaling pathways as well as the p-TRKA/B receptors were involved in the process. In addition, the levels of TNF-α and IL-1β secreted from astrocytes after OGD/R were markedly reduced after d,l-PHPB treatment, which was mainly due to the suppression of phosphorylated p38. In conclusion, the present study demonstrates that the neuroprotective effects of d,l-PHPB were improved by astrocytes, mainly mediated by increasing the release of BDNF/NGF and attenuating inflammatory cytokines.
      Graphical abstract image

      PubDate: 2017-07-23T18:27:18Z
      DOI: 10.1016/j.apsb.2017.06.006
  • The reaction of cinnamaldehyde and cinnam(o)yl derivatives with thiols

    • Authors: Alessandro Autelitano; Alberto Minassi; Alberto Pagani; Orazio Taglialatela-Scafati; Giovanni Appendino
      Abstract: Publication date: Available online 8 July 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Alessandro Autelitano, Alberto Minassi, Alberto Pagani, Orazio Taglialatela-Scafati, Giovanni Appendino
      Spurred by the alleged relevance of the thia-Michael reaction in the bioactivity of various classes of cinnam(o)yl natural products and by the development of a quick NMR assay to study this reaction, we have carried out a systematic study of the “native” reactivity of these compounds with dodecanethiol and cysteamine as models, respectively, of simple thiols and reactive protein thiols that can benefit from iminium ion catalysis in Michael reactions. Cinnamoyl esters and amides, as well as cinnamyl ketones and oximes, did not show any reactivity with the two probe thiols, while cinnamaldehyde (1a) reacted with cysteamine to afford a mixture of a thiazoline derivative and compounds of multiple addition, and with aliphatic thiols to give a single bis-dithioacetal (6). Chalchones and their vinylogous C5-curcuminoid derivatives were the only cinnamoyl derivatives that gave a thia-Michael reaction. From a mechanistic standpoint, loss of conjugation in the adduct might underlie the lack of a native Michael reactivity. This property is restored by the presence of another conjugating group on the carbonyl, as in chalcones and C5-curcuminoids. A critical mechanistic revision of the chemical and biomedical literature on cinnamaldehyde and related compounds seems therefore required.
      Graphical abstract image

      PubDate: 2017-07-13T16:19:05Z
      DOI: 10.1016/j.apsb.2017.06.005
  • Regulation of immune-related diseases by multiple factors a meeting report
           of 2017 International Workshop of the Chinese Academy of Medical Sciences
           Initiative for Innovative Medicine on Tumor Immunology

    • Abstract: Publication date: Available online 6 July 2017
      Source:Acta Pharmaceutica Sinica B

      PubDate: 2017-07-13T16:19:05Z
  • Biased activity of soluble guanylyl cyclase: the Janus face of

    • Authors: Charlotte Detremmerie; Paul M. Vanhoutte; Susan Leung
      Abstract: Publication date: Available online 3 July 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Charlotte Detremmerie, Paul M. Vanhoutte, Susan Leung
      The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3ʹ,5ʹ-cyclic monophosphate (cyclic IMP) rather than guanosine 3ʹ,5ʹ-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.
      Graphical abstract image

      PubDate: 2017-07-13T16:19:05Z
      DOI: 10.1016/j.apsb.2017.06.003
  • Phytochemical study of Illicium angustisepalum and its biological

    • Authors: Karina M. Szymulanska-Ramamurthy; Ming Zhao; Chun-Tao Che
      Abstract: Publication date: Available online 24 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Karina M. Szymulanska-Ramamurthy, Ming Zhao, Chun-Tao Che
      Sixteen compounds, including two new natural products (1 and 2), were obtained from the twigs of Illicium angustisepalum. The structures were elucidated based on NMR, MS, IR data and optical rotation values. Compounds 4, 5, 6 and 8 displayed moderate antibacterial activities against clinical isolates; compounds 4, 5, 8, 9 and 15 protected neural cells against oxidative stress; and compounds 10 and 14 exhibited anti-acetylcholinesterase activity.
      Graphical abstract image

      PubDate: 2017-07-03T15:28:26Z
      DOI: 10.1016/j.apsb.2017.06.002
  • Isocartormin, a novel quinochalcone C-glycoside from Carthamus tinctorius

    • Authors: Feng Li; Zhisheng He; Yang Ye
      Abstract: Publication date: Available online 21 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Feng Li, Zhisheng He, Yang Ye
      A new semi-quinonechalcone C-glycoside isocartormin along with cartormin and safflomin C were isolated from the water extract of Carthamus tinctorius L. The structure of isocartormin was determined by extensive analysis of HR-MS, 1D- and 2D NMR data, and by comparison with those of cartormin reported previously by our group. Isocartormin was identified as a diastereoisomer of cartormin with a reverse configuration at C-18.
      Graphical abstract image

      PubDate: 2017-06-22T16:57:59Z
      DOI: 10.1016/j.apsb.2017.04.005
  • 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
  • The potential of natural products for targeting PPARα

    • Authors: Daniela Rigano; Carmina Sirignano; Orazio Taglialatela-Scafati
      Abstract: Publication date: Available online 16 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Daniela Rigano, Carmina Sirignano, Orazio Taglialatela-Scafati
      Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e.g. rosiglitazone and pioglitazone) are ligands for the various PPAR isoforms. More precisely, antidiabetic thiazolidinediones act on PPARγ, while PPARα is the main molecular target of antidyslipidemic fibrates. Over the past few years, our understanding of the mechanism underlying the PPAR modulation of gene expression has greatly increased. This review presents a survey on terrestrial and marine natural products modulating the PPARα system with the objective of highlighting how the incredible chemodiversity of natural products can provide innovative leads for this “hot” target.
      Graphical abstract image

      PubDate: 2017-06-17T16:32:29Z
      DOI: 10.1016/j.apsb.2017.05.005
  • 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
  • Arylamine N-acetyltransferase 2 genotype-dependent N-acetylation of
           isoniazid in cryopreserved human hepatocytes

    • Authors: Mark A. Doll; Raúl A. Salazar-González; Srineil Bodduluri; David W. Hein
      Abstract: Publication date: Available online 7 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Mark A. Doll, Raúl A. Salazar-González, Srineil Bodduluri, David W. Hein
      Cryopreserved human hepatocytes were used to investigate the role of arylamine N-acetyltransferase 2 (NAT2; EC polymorphism on the N-acetylation of isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination assay and INH N-acetylation was measured by high performance liquid chromatography. INH N-acetylation rates in vitro exhibited a robust and highly significant (P 0.005) NAT2 phenotype-dependent metabolism. N-acetylation rates in situ were INH concentration- and time-dependent. Following incubation for 24h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly (P = 0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association between NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.
      Graphical abstract image

      PubDate: 2017-06-12T15:43:53Z
      DOI: 10.1016/j.apsb.2017.05.003
  • Identification and characterization of loop7 motif and its role in
           regulating biological function of human APOBEC3G through molecular
           modeling and biological assay

    • Authors: Congjie Zhai; Ling Ma; Zhixin Zhang; Jiwei Ding; Jing Wang; Yongxin Zhang; Xiaoyu Li; Fei Guo; Liyan Yu; Jinming Zhou; Shan Cen
      Abstract: Publication date: Available online 2 June 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Congjie Zhai, Ling Ma, Zhixin Zhang, Jiwei Ding, Jing Wang, Yongxin Zhang, Xiaoyu Li, Fei Guo, Liyan Yu, Jinming Zhou, Shan Cen
      Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G–Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G–Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.
      Graphical abstract image

      PubDate: 2017-06-03T04:02:25Z
      DOI: 10.1016/j.apsb.2017.05.002
  • Insects: an underrepresented resource for the discovery of biologically
           active natural products

    • Authors: Lauren Seabrooks; Longqin Hu
      Abstract: Publication date: Available online 30 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Lauren Seabrooks, Longqin Hu
      Nature has been the source of life-changing and -saving medications for centuries. Aspirin, penicillin and morphine are prime examples of Nature׳s gifts to medicine. These discoveries catalyzed the field of natural product drug discovery which has mostly focused on plants. However, insects have more than twice the number of species and entomotherapy has been in practice for as long as and often in conjunction with medicinal plants and is an important alternative to modern medicine in many parts of the world. Herein, an overview of current traditional medicinal applications of insects and characterization of isolated biologically active molecules starting from approximately 2010 is presented. Insect natural products reviewed were isolated from ants, bees, wasps, beetles, cockroaches, termites, flies, true bugs, moths and more. Biological activities of these natural products from insects include antimicrobial, antifungal, antiviral, anticancer, antioxidant, anti-inflammatory and immunomodulatory effects.
      Graphical abstract image

      PubDate: 2017-06-03T04:02:25Z
      DOI: 10.1016/j.apsb.2017.05.001
  • Approaches to establish Q-markers for the quality standards of traditional
           Chinese medicines

    • Authors: Wenzhi Yang; Yibei Zhang; Wanying Wu; Luqi Huang; Dean Guo; Changxiao Liu
      Abstract: Publication date: Available online 23 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wenzhi Yang, Yibei Zhang, Wanying Wu, Luqi Huang, Dean Guo, Changxiao Liu
      Traditional Chinese medicine (TCM) has played a pivotal role in maintaining the health of Chinese people and is now gaining increasing acceptance around the global scope. However, TCM is confronting more and more concerns with respect to its quality. The intrinsic “multicomponent and multitarget” feature of TCM necessitates the establishment of a unique quality and bioactivity evaluation system, which is different from that of the Western medicine. However, TCM is investigated essentially as “herbal medicine” or “natural product”, and the pharmacopoeia quality monographs are actually chemical-markers-based, which can ensure the consistency only in the assigned chemical markers, but, to some extent, have deviated from the basic TCM theory. A concept of “quality marker” (Q-marker), following the “property-effect-component” theory, is proposed. The establishment of Q-marker integrates multidisciplinary technologies like natural products chemistry, analytical chemistry, bionics, chemometrics, pharmacology, systems biology, and pharmacodynamics, etc. Q-marker-based fingerprint and multicomponent determination conduce to the construction of more scientific quality control system of TCM. This review delineates the background, definition, and properties of Q-marker, and the associated technologies applied for its establishment. Strategies and approaches for establishing Q-marker-based TCM quality control system are presented and highlighted with a few TCM examples.
      Graphical abstract image

      PubDate: 2017-05-29T02:35:50Z
      DOI: 10.1016/j.apsb.2017.04.012
  • Crystal structures, absolute configurations and molecular docking studies
           of naftopidil enantiomers as α1D-adrenoceptor antagonists

    • Authors: Wei Xu; Junjun Huang; Renwang Jiang; Mu Yuan
      Abstract: Publication date: Available online 16 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wei Xu, Junjun Huang, Renwang Jiang, Mu Yuan
      Chiral drug naftopidil (NAF), a specific α 1D-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the α 1D-AR, but the binding mechanism of these two stereochemical NAF isomers to the α 1D receptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data of R and S enantiomers matched satisfactorily the pharmacophore model for α 1D-selective antagonists. Based on the constructed α 1D homology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to α 1D-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.
      Graphical abstract image

      PubDate: 2017-05-18T16:23:15Z
      DOI: 10.1016/j.apsb.2017.04.011
  • Anti-diabetic effects and mechanisms of action of a Chinese herbal
           medicine preparation JQ-R in vitro and in diabetic KKAy mice

    • Authors: Quan Liu; Shuainan Liu; Lihui Gao; Sujuan Sun; Yi Huan; Caina Li; Yue Wang; Nan Guo; Zhufang Shen
      Abstract: Publication date: Available online 16 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Quan Liu, Shuainan Liu, Lihui Gao, Sujuan Sun, Yi Huan, Caina Li, Yue Wang, Nan Guo, Zhufang Shen
      Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAy mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKAy mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-κB p65), inhibitor of NF-κB (IκB α), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKAy mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus.
      Graphical abstract image

      PubDate: 2017-05-18T16:23:15Z
      DOI: 10.1016/j.apsb.2017.04.010
  • Schisandra sphenanthera extract (Wuzhi Tablet) protects against
           chronic-binge and acute alcohol-induced liver injury by regulating the
           NRF2-ARE pathway in mice

    • Authors: Xuezhen Zeng; Xi Li; Chenshu Xu; Fulin Jiang; Yufei Mo; Xiaomei Fan; Yaoting Li; Yiming Jiang; Dongshun Li; Min Huang; Huichang Bi
      Abstract: Publication date: Available online 11 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xuezhen Zeng, Xi Li, Chenshu Xu, Fulin Jiang, Yufei Mo, Xiaomei Fan, Yaoting Li, Yiming Jiang, Dongshun Li, Min Huang, Huichang Bi
      Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract from Schisandra sphenanthera that is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.002
  • Potassium 2-(l-hydroxypentyl)-benzoate attenuates neuroinflammatory
           responses and upregulates heme oxygenase-1 in systemic
           lipopolysaccharide-induced inflammation in mice

    • Authors: Chunyang Zhao; Weizhen Hou; Hui Lei; Longjian Huang; Shan Wang; Dandan Cui; Changhong Xing; Xiaoliang Wang; Ying Peng
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chunyang Zhao, Weizhen Hou, Hui Lei, Longjian Huang, Shan Wang, Dandan Cui, Changhong Xing, Xiaoliang Wang, Ying Peng
      A neuroinflammatory response is commonly involved in the progression of many neurodegenerative diseases. Potassium 2-(1-hydroxypentyl)-benzoate (PHPB), a novel neuroprotective compound, has shown promising effects in the treatment of ischemic stroke and Alzheimer׳s disease (AD). In the present study, the anti-inflammatory effects of PHPB were investigated in the plasma and brain of C57BL/6 mice administered a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS). Levels of iNOS and the cytokines TNFα, IL-1β and IL-10 were elevated in plasma, cerebral cortex and hippocampus after LPS injection and the number of microglia and astrocytes in cortex and hippocampus were increased. LPS also upregulated the expression of heme oxygenase-1 (HO-1) in the cortex and hippocampus. PHPB reduced the levels of iNOS and cytokines in the plasma and brain, decreased the number of microglia and astrocytes and further enhanced the upregulation of HO-1. In addition, PHPB inhibited the LPS-induced phosphorylation of ERK, P38 and JNK. These results suggest that PHPB is a potential candidate in the treatment of neurodegenerative diseases through inhibiting neuroinflammation.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.007
  • In vivo retention of poloxamer-based in situ hydrogels for vaginal
           application in mouse and rat models

    • Authors: Yu Liu; Fujin Yang; Linglin Feng; Long Yang; Lingyun Chen; Gang Wei; Weiyue Lu
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yu Liu, Fujin Yang, Linglin Feng, Long Yang, Lingyun Chen, Gang Wei, Weiyue Lu
      The purpose of this study is to evaluate the in vivo retention capabilities of poloxamer-based in situ hydrogels for vaginal application with nonoxinol-9 as the model drug. Two in situ hydrogel formulations, which contained 18% poloxamer 407 plus 1% poloxamer 188 (GEL1, relative hydrophobic) or 6% poloxamer 188 (GEL2, relative hydrophilic), were compared with respect to the rheological properties, in vitro hydrogel erosion and drug release. The vaginal retention capabilities of these hydrogel formulations were further determined in two small animal models, including drug quantitation of vaginal rinsing fluid in mice and isotope tracing with 99mTc in rats. The two formulations exhibited similar phase transition temperatures ranging from 27 to 32°C. Increasing the content of poloxamer 188 resulted in higher rheological moduli under body temperature, but slightly accelerated hydrogel erosion and drug release. When compared in vivo, GEL1 was eliminated significantly slower in rat vagina than GEL2, while the vaginal retention of these two hydrogel formulations behaved similarly in mice. In conclusion, increases in the hydrophilic content of formulations led to faster hydrogel erosion, drug release and intravaginal elimination. Rats appear to be a better animal model than mice to evaluate the in situ hydrogel for vaginal application.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.03.003
  • Syringaresinol-4-O-β-D-glucoside alters lipid and glucose metabolism in
           HepG2 cells and C2C12 myotubes

    • Authors: Shuai Wang; Chongming Wu; Xin Li; Yue Zhou; Quanyang Zhang; Fuchao Ma; Jianhe Wei; Xiaopo Zhang; Peng Guo
      Abstract: Publication date: Available online 9 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Shuai Wang, Chongming Wu, Xin Li, Yue Zhou, Quanyang Zhang, Fuchao Ma, Jianhe Wei, Xiaopo Zhang, Peng Guo
      Syringaresinol-4-O-β-D-glucoside (SSG), a furofuran-type lignan, was found to modulate lipid and glucose metabolism through an activity screen of lipid accumulation and glucose consumption, and was therefore considered as a promising candidate for the prevention and treatment of metabolic disorder, especially in lipid and glucose metabolic homeostasis. In this study, the effects of SSG on lipogenesis and glucose consumption in HepG2 cells and C2C12 myotubes were further investigated. Treatment with SSG significantly inhibited lipid accumulation by oil red O staining and reduced the intracellular contents of total lipid, cholesterol and triglyceride in HepG2 cells. No effect was observed on cell viability in the MTT assay at concentrations of 0.1–10 μmol/L. SSG also increased glucose consumption by HepG2 cells and glucose uptake by C2C12 myotubes. Furthermore, real-time quantitative PCR revealed that the beneficial effects were associated with the down-regulation of sterol regulatory element-binding proteins-1c, -2 (SREBP-1c, -2), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC) and hydroxyl methylglutaryl CoA reductase (HMGR), and up-regulation of peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ). SSG also significantly elevated transcription activity of PPARγ tested by luciferase assay. These results suggest that SSG is an effective regulator of lipogenesis and glucose consumption and might be a candidate for further research in the prevention and treatment of lipid and glucose metabolic diseases.
      Graphical abstract image

      PubDate: 2017-05-13T15:45:44Z
      DOI: 10.1016/j.apsb.2017.04.008
  • 3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

    • Authors: Hasnah Osman; Nor Hashima Idris; Ezatul Ezleen Kamarulzaman; Habibah A. Wahab; Mohd. Zaheen Hassan
      Abstract: Publication date: Available online 4 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Hasnah Osman, Nor Hashima Idris, Ezatul Ezleen Kamarulzaman, Habibah A. Wahab, Mohd. Zaheen Hassan
      Dengue is a severe mosquito-borne viral infection causing half a million deaths annually. Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a 4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones (4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and 16.23µmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28µmol/L.
      Graphical abstract image

      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.04.009
  • Steroids hydroxylation catalyzed by the monooxygenase mutant 139-3 from
           Bacillus megaterium BM3

    • Authors: Xing Liu; Jian-Qiang Kong
      Abstract: Publication date: Available online 4 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xing Liu, Jian-Qiang Kong
      The search of new substrates with pharmaceutical and industrial potential for biocatalysts including cytochrome P450 enzymes is always challenging. Cytochrome P450 BM3 mutant 139-3, a versatile biocatalyst, exhibited hydroxylation activities towards fatty acids and alkanes. However, there were limited reports about its hydroxylation activity towards steroids. Herein, an Escherichia coli–based whole-cell extract containing the recombinant 139-3 protein was used as the biocatalyst to screen 13 steroids. Results revealed that 139-3 was able to specifically hydroxylate androstenedione (1) at 1α-position, generating a hydroxylated steroid 1α-OH-androstenedione (1a). To investigate whether C-1α hydroxylation catalyzed by BM3 mutant 139-3 could be industrially used, an optimization of catalyzing conditions was performed. Accordingly, the BM3 mutant 139-3 enzyme was observed to display maximum activity at 37°C, under pH 7.0 for 4h, with 37% transformation rate. Moreover, four 139-3 variants were generated by random mutagenesis with the aim of improving its activity and expanding substrate scope. Surprisingly, these mutants, sharing a common mutated site R379S, lost their activities towards androstenedione (1). These data clearly indicated that arginine residue located at site 379 played key role in the hydroxylation activities of 139-3. Overall, these new findings broadened the substrate scope of 139-3 enzyme, thereby expanding its potential applications as a biocatalyst on steroids hydroxylation in pharmaceutical industry.
      Graphical abstract image

      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.04.006
  • Amino-functionalized poloxamer 407 with both mucoadhesive and
           thermosensitive properties: preparation, characterization and application
           in a vaginal drug delivery system

    • Authors: Liqian Ci; Zhigang Huang; Yu Liu; Zhepeng Liu; Gang Wei; Weiyue Lu
      Abstract: Publication date: Available online 3 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Liqian Ci, Zhigang Huang, Yu Liu, Zhepeng Liu, Gang Wei, Weiyue Lu
      Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.
      Graphical abstract image

      PubDate: 2017-05-08T14:43:45Z
      DOI: 10.1016/j.apsb.2017.03.002
  • Nine compounds from the root bark of Lycium chinense and their
           anti-inflammatory activitieslammatory activitiesretain-->

    • Authors: Yanan Yang; Yawen An; Wei Wang; Ning Du; Jinghua Zhang; Ziming Feng; Jianshuang Jiang; Peicheng Zhang
      Abstract: Publication date: Available online 3 May 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yanan Yang, Yawen An, Wei Wang, Ning Du, Jinghua Zhang, Ziming Feng, Jianshuang Jiang, Peicheng Zhang
      Two new compounds, named lyciumlignan D (1) and lyciumphenyl propanoid A (2), along with seven known compounds, were isolated from the root bark of Lycium chinense. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds 3 9 were isolated from this genus for the first time. In the in vitro assay, compounds 3, 6, and 7 exhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10μmol/L.
      Graphical abstract image

      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.04.004
  • Establishment and characterization of arsenic trioxide resistant KB/ATO

    • Authors: Yun-Kai Zhang; Chunling Dai; Chun-gang Yuan; Hsiang-Chun Wu; Zhijie Xiao; Zi-Ning Lei; Dong-Hua Yang; X. Chris Le; Liwu Fu; Zhe-Sheng Chen
      Abstract: Publication date: Available online 28 April 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yun-Kai Zhang, Chunling Dai, Chun-gang Yuan, Hsiang-Chun Wu, Zhijie Xiao, Zi-Ning Lei, Dong-Hua Yang, X. Chris Le, Liwu Fu, Zhe-Sheng Chen
      Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.
      Graphical abstract image

      PubDate: 2017-05-03T14:06:15Z
      DOI: 10.1016/j.apsb.2017.04.001
  • Advances in ultrasound-targeted microbubble–mediated gene therapy
           for liver fibrosis

    • Authors: Cuiyuan Huang; Hong Zhang; Ruidan Bai
      Abstract: Publication date: Available online 15 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Cuiyuan Huang, Hong Zhang, Ruidan Bai
      Hepatic fibrosis develops as a wound-healing scar in response to acute and chronic liver inflammation and can lead to cirrhosis in patients with chronic hepatitis B and C. The condition arises due to increased synthesis and reduced degradation of extracellular matrix (ECM) and is a common pathological sequela of chronic liver disease. Excessive deposition of ECM in the liver causes liver dysfunction, ascites, and eventually upper gastrointestinal bleeding as well as a series of complications. However, fibrosis can be reversed before developing into cirrhosis and has thus been the subject of extensive researches particularly at the gene level. Currently, therapeutic genes are imported into the damaged liver to delay or prevent the development of liver fibrosis by regulating the expression of exogenous genes. One technique of gene delivery uses ultrasound targeting of microbubbles combined with therapeutic genes where the time and intensity of the ultrasound can control the release process. Ultrasound irradiation of microbubbles in the vicinity of cells changes the permeability of the cell membrane by its cavitation effect and enhances gene transfection. In this paper, recent progress in the field is reviewed with emphasis on the following aspects: the types of ultrasound microbubbles, the construction of an ultrasound-mediated gene delivery system, the mechanism of ultrasound microbubble–mediated gene transfer and the application of ultrasound microbubbles in the treatment of liver fibrosis.
      Graphical abstract image

      PubDate: 2017-03-17T16:42:06Z
      DOI: 10.1016/j.apsb.2017.02.004
  • Dissecting the role of AMP-activated protein kinase in human diseases

    • Authors: Jin Li; Liping Zhong; Fengzhong Wang; Haibo Zhu
      Abstract: Publication date: Available online 3 March 2017
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jin Li, Liping Zhong, Fengzhong Wang, Haibo Zhu
      AMP-activated protein kinase (AMPK), known as a sensor and a master of cellular energy balance, integrates various regulatory signals including anabolic and catabolic metabolic processes. Accompanying the application of genetic methods and a plethora of AMPK agonists, rapid progress has identified AMPK as an attractive therapeutic target for several human diseases, such as cancer, type 2 diabetes, atherosclerosis, myocardial ischemia/reperfusion injury and neurodegenerative disease. The role of AMPK in metabolic and energetic modulation both at the intracellular and whole body levels has been reviewed elsewhere. In the present review, we summarize and update the paradoxical role of AMPK implicated in the diseases mentioned above and put forward the challenge encountered. Thus it will be expected to provide important clues for exploring rational methods of intervention in human diseases.
      Graphical abstract image

      PubDate: 2017-03-04T13:41:31Z
      DOI: 10.1016/j.apsb.2016.12.003
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
Home (Search)
Subjects A-Z
Publishers A-Z
Your IP address:
About JournalTOCs
News (blog, publications)
JournalTOCs on Twitter   JournalTOCs on Facebook

JournalTOCs © 2009-2016