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Publisher: Elsevier   (Total: 3163 journals)

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Showing 1 - 200 of 3163 Journals sorted alphabetically
A Practical Logic of Cognitive Systems     Full-text available via subscription   (Followers: 9)
AASRI Procedia     Open Access   (Followers: 14)
Academic Pediatrics     Hybrid Journal   (Followers: 30, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 22, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 88, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 25, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 35, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 5)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 398, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 27, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 2)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 8, SJR: 0.18, CiteScore: 1)
Acta Haematologica Polonica     Free   (Followers: 1, SJR: 0.128, CiteScore: 0)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 244, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 10, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 27, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access  
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 6, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 6)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 16, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 8, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 9, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 22)
Advanced Cement Based Materials     Full-text available via subscription   (Followers: 3, SJR: 0.732, CiteScore: 3)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 136, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 11, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 16, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 8, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 12, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 28, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 10, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 10, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 22, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 14, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 29, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 7, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 3)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 12)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 27, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 28, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 19, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 11)
Advances in Digestive Medicine     Open Access   (Followers: 8)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 5)
Advances in Drug Research     Full-text available via subscription   (Followers: 23)
Advances in Ecological Research     Full-text available via subscription   (Followers: 42, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 27, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 7)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 43, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 53, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 15, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 8, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 6, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 21, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 22)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 2, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 37, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 8, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 9)
Advances in Marine Biology     Full-text available via subscription   (Followers: 14, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 11, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 6, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 5)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 4, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 3)
Advances in Oncobiology     Full-text available via subscription   (Followers: 1)
Advances in Organ Biology     Full-text available via subscription   (Followers: 1)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 16, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 6, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 24, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 10)
Advances in Pharmacology     Full-text available via subscription   (Followers: 16, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 8, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
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: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 18)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 19, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 59)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 5)
Advances in Space Research     Full-text available via subscription   (Followers: 386, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 10, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 30, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 17)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 13)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 46, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 337, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 10, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 437, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 15, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 43, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 1)
Agriculture and Natural Resources     Open Access   (Followers: 2)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 56, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 6, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 11, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 9)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 1, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 10, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 9, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 50, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 4, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 4, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 6)
American Heart J.     Hybrid Journal   (Followers: 50, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 51, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 44, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 10)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 32, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 26, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 34, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 43)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 201, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 61, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 27, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 27, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 37, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 6)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 63, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 15, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription  
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 39, SJR: 1.512, CiteScore: 5)
Analytical Biochemistry     Hybrid Journal   (Followers: 175, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 10, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 11)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 23, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)

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Journal Cover
Acta Pharmaceutica Sinica B
Journal Prestige (SJR): 1.793
Citation Impact (citeScore): 6
Number of Followers: 1  

  This is an Open Access Journal Open Access journal
ISSN (Print) 2211-3843 - ISSN (Online) 2211-3835
Published by Elsevier Homepage  [3163 journals]
  • Inhalation treatment of primary lung cancer using liposomal curcumin dry
           powder inhalers

    • Authors: Tongtong Zhang; Yanming Chen; Yuanyuan Ge; Yuzhen Hu; Miao Li; Yiguang Jin
      Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3
      Author(s): Tongtong Zhang, Yanming Chen, Yuanyuan Ge, Yuzhen Hu, Miao Li, Yiguang Jin
      Lung cancer is the leading cause of cancer-related deaths. Traditional chemotherapy causes serious toxicity due to the wide bodily distribution of these drugs. Curcumin is a potential anticancer agent but its low water solubility, poor bioavailability and rapid metabolism significantly limits clinical applications. Here we developed a liposomal curcumin dry powder inhaler (LCD) for inhalation treatment of primary lung cancer. LCDs were obtained from curcumin liposomes after freeze-drying. The LCDs had a mass mean aerodynamic diameter of 5.81 μm and a fine particle fraction of 46.71%, suitable for pulmonary delivery. The uptake of curcumin liposomes by human lung cancer A549 cells was markedly greater and faster than that of free curcumin. The high cytotoxicity on A549 cells and the low cytotoxicity of curcumin liposomes on normal human bronchial BEAS-2B epithelial cells yielded a high selection index partly due to increased cell apoptosis. Curcumin powders, LCDs and gemcitabine were directly sprayed into the lungs of rats with lung cancer through the trachea. LCDs showed higher anticancer effects than the other two medications with regard to pathology and the expression of many cancer-related markers including VEGF, malondialdehyde, TNF-α, caspase-3 and BCL-2. LCDs are a promising medication for inhalation treatment of lung cancer with high therapeutic efficiency.
      Graphical abstract image

      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.03.004
       
  • 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
      Pages: 137 - 146
      Abstract: Publication date: March 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 2
      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: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2017.09.003
       
  • 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
      Pages: 209 - 217
      Abstract: Publication date: March 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 2
      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: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2017.08.001
       
  • Correlation analysis between the chemical contents and bioactivity for the
           quality control of Alismatis Rhizoma

    • Authors: Xiaoxv Gao; Chengpeng Sun; Zhenglong Yu; Jian Cang; Xiangge Tian; Xiaokui Huo; Lei Feng; Xinguang Liu; Chao Wang; Baojing Zhang; Xiaochi Ma
      Pages: 242 - 251
      Abstract: Publication date: March 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 2
      Author(s): Xiaoxv Gao, Chengpeng Sun, Zhenglong 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: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2017.09.004
       
  • In situ monitoring of the structural change of microemulsions in simulated
           gastrointestinal conditions by SAXS and FRET

    • Authors: Xia Lv; Shuguang Zhang; Huipeng Ma; Peipei Dong; Xiaodong Ma; Ming Xu; Yan Tian; Zeyao Tang; Jinyong Peng; Haibo Chen; Jianbin Zhang
      Abstract: Publication date: Available online 23 May 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xia Lv, Shuguang Zhang, Huipeng Ma, Peipei Dong, Xiaodong Ma, Ming Xu, Yan Tian, Zeyao Tang, Jinyong Peng, Haibo Chen, Jianbin Zhang
      Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET spectra indicated micelles with smaller particle sizes were generated during lipolysis, which could be affected by CaCl2, bile salts and lecithin. Then, the effect of mucus on the structural change of lipolysed microemulsions was studied. The results of SAXS and FRET indicated that the liquid crystalline phases disappeared, and more micelles were generated. In summary, we studied the structural change of microemulsions in simulated gastrointestinal conditions by SAXS and FRET, and successfully monitored the appearance and disappearance of the liquid crystalline phases and micelles.
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      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.05.008
       
  • Targeting an oncogenic kinase/phosphatase signaling network for cancer
           therapy

    • Authors: Xiao-Mei Fang; Wang Matthew Mortensen Ryan Wertz Guan Chen
      Abstract: Publication date: Available online 22 May 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xiao-Mei Qi, Fang Wang, Matthew Mortensen, Ryan Wertz, Guan Chen
      Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention. p38γ is a unique MAPK family member that contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both PTPH1 dephosphorylation and inactivation of p38γ and for p38γ phosphorylation and activation of PTPH1. Moreover, the p38γ/PTPH1 complex can further regulate their substrates phosphorylation and dephosphorylation, which impacts Ras transformation, malignant growth and progression, and therapeutic response. This review will use the p38γ/PTPH1 signaling network as an example to discuss the potential of targeting the kinase/phosphatase signaling complex for development of novel targeted cancer therapy.
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      PubDate: 2018-06-01T11:07:00Z
       
  • Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and
           sensing purposes: Current strategies and future perspectives

    • Authors: Gantumur Battogtokh; Yeon Su Choi; Dong Seop Kang; Sang Jun Park; Min Suk Shim; Kang Moo Huh; Yong-Yeon Cho; Joo Young Lee; Hye Suk Lee; Han Chang Kang
      Abstract: Publication date: Available online 18 May 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Gantumur Battogtokh, Yeon Su Choi, Dong Seop Kang, Sang Jun Park, Min Suk Shim, Kang Moo Huh, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
      Mitochondrial targeting is a promising approach for solving current issues that occur in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that easily accumulates in the mitochondrial membrane and penetrates through the mitochondrial membrane due its high negative mitochondrial membrane potential. In addition, other moieties, including short peptides, dequalinium, guanidine, rhodamine, and F16, are known to be promising mitochondrial targeting agents. Direct conjugation of mitochondrial targeting moieties to anticancer drugs, antioxidants and sensors results in increased cytotoxicity, anti-oxidizing activity and sensing activity, respectively, compared with their non-targeting counterparts, especially in drug-resistant cells. Although many mitochondria-targeted anticancer drug conjugates have been investigated in vitro and in vivo, further clinical studies are needed in the near future. On the other hand, several mitochondria-targeting antioxidants have been analyzed in clinical phase I, II and III trials, and one conjugate has been approved for treating eye disease in Russia. Regarding mitochondria-targeted sensors, numerous studies are ongoing.
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      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.05.006
       
  • Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic
           and lipid-lowering efficacy

    • Authors: Yanbo Tang; Xiaolin Zhang; Zheng Chen; WenWen Yin; Guanglei Nan; Jinying Tian; Fei Ye; Zhiyan Xiao
      Abstract: Publication date: Available online 8 May 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yanbo Tang, Xiaolin Zhang, Zheng Chen, WenWen Yin, Guanglei Nan, Jinying Tian, Fei Ye, Zhiyan Xiao
      Based on a non-competitive and selective PTP1B inhibitor reported by us previously, thirty-nine benzamido derivatives were designed and synthesized as novel PTP1B inhibitors. Among them, twelve compounds exhibited IC50 values at micromolar level against human recombinant PTP1B, and most of them exhibited significant selectivity to PTP1B over TC-PTP and CD45. Further evaluation of the most potent compound 27 on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that 27 could modulate glucose metabolism and ameliorate dyslipidemia simultaneously.
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      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.05.001
       
  • Editor Profile: Guest Editor of Special Column on Molecular Imaging and
           Theranostics

    • Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3


      PubDate: 2018-06-01T11:07:00Z
       
  • Editorial for Molecular Imaging and Theranostics

    • Authors: Wei
      Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3
      Author(s): Wei Lu


      PubDate: 2018-06-01T11:07:00Z
       
  • 131I-Evans blue: evaluation of necrosis targeting property and preliminary
           assessment of the mechanism in animal models

    • Authors: Qiaomei Jin; Xin Shan Luo Dongjian Zhang Yuanyu Zhao Nan
      Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3
      Author(s): Qiaomei Jin, Xin Shan, Qi Luo, Dongjian 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.
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      PubDate: 2018-06-01T11:07:00Z
       
  • A novel nitroreductase-enhanced MRI contrast agent and its potential
           application in bacterial imaging

    • Authors: Yun Liu; Leilei Zhang Marc Nazare Qingqiang Yao Hai-Yu
      Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3
      Author(s): Yun Liu, Leilei Zhang, Marc Nazare, Qingqiang Yao, Hai-Yu Hu
      Nitroreductases (NTRs) are known to be able to metabolize nitro-substituted compounds in the presence of reduced nicotinamide adenine dinucleotide (NADH) as an electron donor. NTRs are present in a wide range of bacterial genera and, to a lesser extent, in eukaryotes hypoxic tumour cells and tumorous tissues, which makes it an appropriate biomarker for an imaging target to detect the hypoxic status of cancer cells and potential bacterial infections. To evaluate the specific activation level of NTR, great efforts have been devoted to the development of fluorescent probes to detect NTR activities using fluorogenic methods to probe its behaviour in a cellular context; however, NTR-responsive MRI contrast agents are still by far underexplored. In this study, para-nitrobenzyl substituted T 1-weighted magnetic resonance imaging (MRI) contrast agent Gd-DOTA-PNB (probe 1) has been designed and explored for the possible detection of NTR. Our experimental results show that probe 1 could serve as an MRI-enhanced contrast agent for monitoring NTR activity. The in vitro response and mechanism of the NTR catalysed reduction of probe 1 have been investigated through LC–MS and MRI. Para-nitrobenzyl substituted probe 1 was catalytically reduced by NTR to the intermediate para-aminobenzyl substituted probe which then underwent a rearrangement elimination reaction to Gd-DOTA, generating the enhanced T 1-weighted MR imaging. Further, LC–MS and MRI studies of living Escherichia coli have confirmed the NTR activity detection ability of probe 1 at a cellular level. This method may potentially be used for the diagnosis of bacterial infections.
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      PubDate: 2018-06-01T11:07:00Z
       
  • Biomonitoring for traditional herbal medicinal products using DNA
           metabarcoding and single molecule, real-time sequencing

    • Authors: Tianyi Xin; Zhichao Jing Jia Christine Leon Songnian Yulin Lin
      Abstract: Publication date: May 2018
      Source:Acta Pharmaceutica Sinica B, Volume 8, Issue 3
      Author(s): Tianyi Xin, Zhichao Xu, Jing Jia, Christine Leon, Songnian Hu, Yulin Lin, Subramanyam Ragupathy, Jingyuan Song, Steven G. Newmaster
      Global concerns have been paid to the potential hazard of traditional herbal medicinal products (THMPs). Substandard and counterfeit THMPs, including traditional Chinese patent medicine, health foods, dietary supplements, etc. are potential threats to public health. Recent marketplace studies using DNA barcoding have determined that the current quality control methods are not sufficient for ensuring the presence of authentic herbal ingredients and detection of contaminants/adulterants. An efficient biomonitoring method for THMPs is of great needed. Herein, metabarcoding and single-molecule, real-time (SMRT) sequencing were used to detect the multiple ingredients in Jiuwei Qianghuo Wan (JWQHW), a classical herbal prescription widely used in China for the last 800 years. Reference experimental mixtures and commercial JWQHW products from the marketplace were used to confirm the method. Successful SMRT sequencing results recovered 5416 and 4342 circular-consensus sequencing (CCS) reads belonging to the ITS2 and psbA-trnH regions. The results suggest that with the combination of metabarcoding and SMRT sequencing, it is repeatable, reliable, and sensitive enough to detect species in the THMPs, and the error in SMRT sequencing did not affect the ability to identify multiple prescribed species and several adulterants/contaminants. It has the potential for becoming a valuable tool for the biomonitoring of multi-ingredient THMPs.
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      PubDate: 2018-06-01T11:07:00Z
       
  • The enzymatic biosynthesis of acylated steroidal glycosides and their
           cytotoxic activity

    • Authors: Ming Liu; Jianqiang Kong
      Abstract: Publication date: Available online 1 May 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Ming Liu, Jianqiang Kong
      Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase (SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, a SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β- and 17β-hydroxyl steroids. Unexpectedly, in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded a SGA, specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides (AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides (AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides (SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 3′-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.
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      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.04.006
       
  • Taxane resistance in castration-resistant prostate cancer: mechanisms and
           therapeutic strategies

    • Authors: Brandon Bumbaca; Wei Li
      Abstract: Publication date: Available online 30 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Brandon Bumbaca, Wei Li
      Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters. These mechanisms contribute to reducing binding affinity and availability of taxanes. Second, taxane resistant tumors have increased stem cell like characteristics, indicating higher potential for further mutation in response to therapy. Third, the androgen receptor pathway is instrumental in the proliferation of CRPC and multiple hypotheses leading to this pathway reactivation have been reported. The connection of this pathway to the AKT pathway has received significant attention due to the upregulation of phosphorylated AKT in CRPC. This review highlights recent advances in elucidating taxane resistant mechanisms and summarizes potential therapeutic strategies for improved treatment of CRPC.

      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.04.007
       
  • Personalized medicine in non-small cell lung cancer: A review from a
           pharmacogenomics perspective

    • Authors: Wenxiao Jiang; Guiqing Cai; Peter C. Hu; Yue Wang
      Abstract: Publication date: Available online 30 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Wenxiao Jiang, Guiqing Cai, Peter C. Hu, Yue Wang
      Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase (TKI), anaplastic lymphoma kinase (ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s). Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.
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      PubDate: 2018-06-01T11:07:00Z
      DOI: 10.1016/j.apsb.2018.04.005
       
  • Drug metabolism in drug discovery and development

    • Authors: Zhoupeng Zhang; Wei Tang
      Abstract: Publication date: Available online 12 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhoupeng Zhang, Wei Tang
      Drug metabolism as a discipline plays an important role in drug discovery and development and the effects of drug metabolism on pharmacokinetics (PK), pharmacodynamics (PD), and safety should be carefully considered. This communication provides an overview of common strategies in the area of drug metabolism for improving PK/PD and safety profiles of drug candidates; these include, but are not limited to, collaboration with medicinal chemists on Structure‒activity relationships (SAR) to overcome high clearance, using deuterium replacement to further optimize a lead, prodrug approaches to circumvent formulation and delivery difficulties, and addressing issues such as species differences in metabolism, drug‒drug interactions (DDI) and formation of reactive metabolites.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.04.003
       
  • Genome-wide characterization and analysis of bHLH transcription factors in
           Panax ginseng

    • Authors: Chu Yang; Xiao Shuiming; Su He; Liao Baosheng; Zhang Jingjing; Xu Jiang; Chen Shilin
      Abstract: Publication date: Available online 12 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Chu Yang, Xiao Shuiming, Su He, Liao Baosheng, Zhang Jingjing, Xu Jiang, Chen Shilin
      Ginseng (Panax ginseng C.A. Meyer) is one of the best-selling herbal medicines, with ginsenosides as its main pharmacologically active constituents. Although extensive chemical and pharmaceutical studies of these compounds have been performed, genome-wide studies of the basic helix-loop-helix (bHLH) transcription factors of ginseng are still limited. The bHLH transcription factor family is one of the largest transcription factor families found in eukaryotic organisms, and these proteins are involved in a myriad of regulatory processes. In our study, 169 bHLH transcription factor genes were identified in the genome of P. ginseng, and phylogenetic analysis indicated that these PGbHLHs could be classified into 24 subfamilies. A total of 21 RNA-seq data sets, including two sequencing libraries for jasmonate (JA)-responsive and 19 reported libraries for organ-specific expression analyses were constructed. Through a combination of gene-specific expression patterns and chemical contents, 6 PGbHLH genes from 4 subfamilies were revealed to be potentially involved in the regulation of ginsenoside biosynthesis. These 6 PGbHLHs, which had distinct target genes, were further divided into two groups depending on the absence of MYC-N structure. Our results would provide a foundation for understanding the molecular basis and regulatory mechanisms of bHLH transcription factor action in P. ginseng.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.04.004
       
  • Bioactive thionic compounds and aromatic glycosides from Ligusticum
           chuanxiong

    • Authors: Xu Zhang; Bing Han; Ziming Feng; Jianshuang Jiang; Yanan Yang; Peicheng Zhang
      Abstract: Publication date: Available online 11 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Xu Zhang, Bing Han, Ziming Feng, Jianshuang Jiang, Yanan Yang, Peicheng Zhang
      Three new thionic compounds, (S)-2-(2-carboxyl-2-hydroxyethylthio)-ferulic acid (1), (E)-2-methoxy-4-(3-(methylsulfonyl)prop-1-en-1-yl)phenol (2), and thiosenkyunolide C (3), together with two new aromatic glycosides (4 and 5) were isolated from the rhizome of Ligusticum chuanxiong Hort. Two known compounds (6 and 7) were also obtained. Their structures were elucidated based on extensive spectroscopic data (UV, IR, 1D and 2D NMR, and HR-ESI-MS). Furthermore the absolute configurations were established by comparison of their calculated and experimental circular dichroism spectra and by a dimolybdenum tetraacetate [Mo2(AcO)4]-induced circular dichroism procedure. All compounds were evaluated against lipopolysaccharide (LPS)-induced NO production in BV2 cells, and compounds 4 and 5 showed strong inhibitory activities with IC50 values of 2.03 and 3.09 µmol/L, respectively (positive control curcumin, IC50 = 6.17 µmol/L). In addition, compound 1 showed weak proteintyrosine phosphatase-1B (PTP1B) inhibitory activity.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.04.002
       
  • Implantable sandwich PHBHHx film for burst-free controlled delivery of
           thymopentin peptide

    • Authors: Ke Peng; Chengyu Wu; Guoxu Wei; Jinghui Jiang; Zhirong Zhang; Xun Sun
      Abstract: Publication date: Available online 7 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Ke Peng, Chengyu Wu, Guoxu Wei, Jinghui Jiang, Zhirong Zhang, Xun Sun
      Sustained release and non-parental formulations of peptides and protein drugs are highly desirable because of enhanced therapeutic effects as well as improved patient compliance. This is especially true for small peptides such as thymopentin (TP5). To this end, implantable sandwich poly (hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) films were designed to prolong release time and to inhibit burst release phenomenon of TP5 by a simple volatilization method. In vitro release studies revealed that sandwich films had nearly no burst release. In vivo release time of sandwich films was prolonged to 42 days. Pharmacodynamic evaluation demonstrated that TP5 sandwich films significantly increased survival rates in a rat immunosuppressive model and normalized CD4+/CD8+ values. These results suggest that TP5 released from sandwich films can attenuate cyclophosphamide's immunosuppressive activity, and possibly achieve results comparable to daily TP5 injection therapy. Thus, sandwich PHBHHx films show excellent potential as a sustained, burst-free release system for small molecular weight, hydrophilic peptide drugs.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.003
       
  • The combined therapeutic effects of iodine 131-labeled multifunctional
           copper sulfide-loaded microspheres in treating breast cancer

    • Authors: Qiufang Liu; Yuyi Qian; Panli Li; Sihang Zhang; Zerong Wang; Jianjun Liu; Xiaoguang Sun; Michael Fulham; Dagan Feng; Shaoli Song; Wei Lu; Gang Huang
      Abstract: Publication date: Available online 7 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qiufang Liu, Yuyi Qian, Panli Li, Sihang Zhang, Zerong Wang, Jianjun Liu, Xiaoguang Sun, Michael Fulham, Dagan Feng, Shaoli Song, Wei Lu, Gang Huang
      Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres from 131I-labeled hollow copper sulfide nanoparticles loaded with paclitaxel (131I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. 18F-fluordeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P<0.05) following intra-tumoral (i.t.) injection with 131I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by 131I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results reveal that 131I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, 131I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.04.001
       
  • The application of CAR-T cell therapy in hematological malignancies:
           Advantages and challenges

    • Authors: Zijun Zhao; Yu Chen; Ngiambudulu M. Francisco; Yuanqing Zhang; Minhao Wu
      Abstract: Publication date: Available online 5 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zijun Zhao, Yu Chen, Ngiambudulu M. Francisco, Yuanqing Zhang, Minhao Wu
      Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.001
       
  • Helioscopianoids A–Q, bioactive jatrophane diterpenoid esters from
           Euphorbia helioscopia

    • Authors: Zhenpeng Mai; Gang Ni; Yanfei Liu; Zhao Zhang; Li Li; Naihong Chen; Dequan Yu
      Abstract: Publication date: Available online 1 April 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Zhenpeng Mai, Gang Ni, Yanfei Liu, Zhao Zhang, Li Li, Naihong Chen, Dequan Yu
      The EtOH extracts of the whole plants of Euphorbia helioscopia afforded 17 new jatrophane diterpenoid esters, helioscopianoids A–Q (1‒17), along with eight known compounds (18–25). Their structures were elucidated by extensive spectroscopic methods and Mo2(OAc)4-induced ECD analysis, and the structures of compounds 1, 2, and 7 were confirmed by X-ray crystallography. Compounds 1–17 were evaluated for inhibitory effects on P-glycoprotein (P-gp) in an adriamycin (ADM)-resistant human breast adenocarcinoma cell line (MCF-7/ADR) and neuroprotective effects against serum deprivation-induced and rotenone-induced PC12 cell damage. Compounds 8 and 16 increased the accumulation of ADM in MCF-7/ADR cells by approximately 3-fold at a concentration of 20 μmol/L. Compound 8 could attenuate rotenone-induced PC12 cell damage, and compounds 2, 8, and 12 showed neuroprotective activities against serum deprivation-induced PC12 cell damage.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.011
       
  • Recent developments in multimodality fluorescence imaging probes

    • Authors: Jianhong Zhao; Junwei Chen; Shengnan Ma; Qianqian Liu; Lixian Huang; Xiani Chen; Kaiyan Lou; Wei Wang
      Abstract: Publication date: Available online 30 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Jianhong Zhao, Junwei Chen, Shengnan Ma, Qianqian Liu, Lixian Huang, Xiani Chen, Kaiyan Lou, Wei Wang
      Multimodality optical imaging probes have emerged as powerful tools that improve detection sensitivity and accuracy, important in disease diagnosis and treatment. In this review, we focus on recent developments of optical fluorescence imaging (OFI) probe integration with other imaging modalities such as X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and photoacoustic imaging (PAI). The imaging technologies are briefly described in order to introduce the strengths and limitations of each techniques and the need for further multimodality optical imaging probe development. The emphasis of this account is placed on how design strategies are currently implemented to afford physicochemically and biologically compatible multimodality optical fluorescence imaging probes. We also present studies that overcame intrinsic disadvantages of each imaging technique by multimodality approach with improved detection sensitivity and accuracy.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.010
       
  • Radiopaque nano and polymeric materials for atherosclerosis imaging,
           embolization and other catheterization procedures

    • Authors: Li Tian; Linfeng Lu; James Feng; Marites P. Melancon
      Abstract: Publication date: Available online 27 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Li Tian, Linfeng Lu, James Feng, Marites P. Melancon
      A review of radiopaque nano and polymeric materials for atherosclerosis imaging and catheterization procedures is presented in this paper. Cardiovascular diseases (CVDs) are the leading cause of death in the US with atherosclerosis as a significant contributor for mortality and morbidity. In this review paper, we discussed the physics of radiopacity and X-ray/CT, clinically used contrast agents, and the recent progress in the development of radiopaque imaging agents and devices for the diagnosis and treatment of CVDs. We focused on radiopaque imaging agents for atherosclerosis, radiopaque embolic agents and drug eluting beads, and other radiopaque medical devices related to catheterization procedures to treat CVDs. Common strategies of introducing radiopacity in the polymers, together with examples of their applications in imaging and medical devices, are also presented.
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      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.002
       
  • Nanoparticles with high payloads of pipemidic acid, a poorly soluble
           crystalline drug: drug-initiated polymerization and self-assembly approach
           

    • Authors: Elisabetta Pancani; Mario Menendez-Miranda; Alexandra Pastor; François Brisset; Marie-Françoise Bernet-Camard; Didier Desmaële; Ruxandra Gref
      Abstract: Publication date: Available online 27 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Elisabetta Pancani, Mario Menendez-Miranda, Alexandra Pastor, François Brisset, Marie-Françoise Bernet-Camard, Didier Desmaële, Ruxandra Gref
      Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) remain the most common biomaterials to produce drug-loaded nanoparticles (NPs). Pipemidic acid (PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst. PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare self-assembled NPs with PIP contents as high as 27% (w/w). The NPs were characterized by microscopy, DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.008
       
  • C19-Diterpenoid alkaloid arabinosides from an aqueous extract of the
           lateral root of Aconitum carmichaelii and their analgesic activities

    • Authors: Qinglan Guo; Huan Xia; Xianhua Meng; Gaona Shi; Chengbo Xu; Chenggen Zhu; Tiantai Zhang; Jiangong Shi
      Abstract: Publication date: Available online 27 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Qinglan Guo, Huan Xia, Xianhua Meng, Gaona Shi, Chengbo Xu, Chenggen Zhu, Tiantai Zhang, Jiangong Shi
      Eight new C19-diterpenoid alkaloid arabinosides, named aconicarmichosides E−L (1−8), were isolated from an aqueous extract of the lateral roots of Aconitum carmichaelii (Fu Zi). Their structures were determined by spectroscopic and chemical methods including 2D NMR experiments and acid hydrolysis. Compounds 1−8, together with the previously reported four neoline 14-O-arabinosides from the same plant, represent the only examples of glycosidic diterpenoid alkaloids so far. At a dose of 1.0mg/kg (i.p.), as compared with the black control, compounds 1, 2, and 4‒6 exhibited analgesic effects with >65.6% inhibitions against acetic acid-induced writhing of mice. Structure‒activity relationship was also discussed.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.009
       
  • Surface-enhanced Raman nanoparticles for tumor theranostics applications

    • Authors: Yangyang Li; Qiaolin Wei; Fei Ma; Xin Li; Fengyong Liu; Min Zhou
      Abstract: Publication date: Available online 26 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Yangyang Li, Qiaolin Wei, Fei Ma, Xin Li, Fengyong Liu, Min Zhou
      Raman spectroscopy, amplified by surface-enhanced Raman scattering (SERS) nanoparticles, can provide an in vivo imaging modality due to its high molecular specificity, high sensitivity, and negligible autofluorescence. The basis, composition, and methodologies developed for SERS nanoparticles are herein described. The research hotspots that are the focus in this paper are tumor imaging-guided theranostics and biosensing. The next breakthrough may be the development of biocompatible SERS nanoparticles and spectroscopic devices for clinical applications.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.007
       
  • Fluorogen-activating proteins: beyond classical fluorescent proteins

    • Authors: Shengnan Xu; Hai-Yu Hu
      Abstract: Publication date: Available online 24 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Shengnan Xu, Hai-Yu Hu
      Fluorescence imaging is a powerful technique for the real-time noninvasive monitoring of protein dynamics. Recently, fluorogen activating proteins (FAPs)/fluorogen probes for protein imaging were developed. Unlike the traditional fluorescent proteins (FPs), FAPs do not fluoresce unless bound to their specific small-molecule fluorogens. When using FAPs/fluorogen probes, a washing step is not required for the removal of free probes from the cells, thus allowing rapid and specific detection of proteins in living cells with high signal-to-noise ratio. Furthermore, with different fluorogens, living cell multi-color proteins labeling system was developed. In this review, we describe about the discovery of FAPs, the design strategy of FAP fluorogens, the application of the FAP technology and the advances of FAP technology in protein labeling systems.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.02.001
       
  • Preparation and characterization of multimodal hybrid organic and
           inorganic nanocrystals of camptothecin and gold

    • Authors: Christin P. Hollis; Alan K. Dozier; Barbara L. Knutson; Tonglei Li
      Abstract: Publication date: Available online 22 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Christin P. Hollis, Alan K. Dozier, Barbara L. Knutson, Tonglei Li
      We demonstrate a novel inorganic-organic crystalline nanoconstruct, where gold atoms were imbedded in the crystal lattices as defects of camptothecin nanocrystals, suggesting its potential use as simultaneous agents for cancer therapy and bioimaging. The incorporation of gold, a potential computed tomography (CT) contrast agent, in the nanocrystals of camptothecin was detected by transmission electron microscope (TEM) and further quantified by energy dispersive X-ray spectrometry (EDS) and inductively coupled plasma-optical emission spectrometers (ICP-OES). Due to gold's high attenuation coefficient, only a relatively small amount needs to be present in order to create a good noise-to-contrast ratio in CT imaging. The imbedded gold atoms and clusters are expected to share the same biological fate as the camptothecin nanocrystals, reaching and accumulating in tumor site due to the enhanced permeation and retention (EPR) effect.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.005
       
  • 3D tissue engineering, an emerging technique for pharmaceutical research

    • Authors: Gregory Jensen; Christian Morrill; Yu Huang
      Abstract: Publication date: Available online 21 March 2018
      Source:Acta Pharmaceutica Sinica B
      Author(s): Gregory Jensen, Christian Morrill, Yu Huang
      Tissue engineering and the tissue engineering model have shown promise in improving methods of drug delivery, drug action, and drug discovery in pharmaceutical research for the attenuation of the central nervous system inflammatory response. Such inflammation contributes to the lack of regenerative ability of neural cells, as well as the temporary and permanent loss of function associated with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. This review is focused specifically on the recent advances in the tissue engineering model made by altering scaffold biophysical and biochemical properties for use in the treatment of neurodegenerative diseases. A portion of this article will also be spent on the review of recent progress made in extracellular matrix decellularization as a new and innovative scaffold for disease treatment.
      Graphical abstract image

      PubDate: 2018-04-15T22:17:31Z
      DOI: 10.1016/j.apsb.2018.03.006
       
  • Structure-based design, synthesis, and biological evaluation of novel
           pyrimidinone derivatives as PDE9 inhibitors

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

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

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

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

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

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

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

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

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

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

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

      PubDate: 2018-03-08T16:03:11Z
      DOI: 10.1016/j.apsb.2018.01.013
       
  • Mesoporous silica nanoparticles for drug and gene delivery

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

      PubDate: 2018-02-18T18:31:58Z
      DOI: 10.1016/j.apsb.2018.01.007
       
  • Activation of an unconventional meroterpenoid gene cluster in Neosartorya
           glabra leads to the production of new berkeleyacetals

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

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.005
       
  • Integrated metabolomic and transcriptomic analyses revealed the
           distribution of saponins in Panax notoginseng

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

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

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

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.004
       
  • Synergistic immunoreaction of acupuncture-like dissolving microneedles
           containing thymopentin at acupoints in immune-suppressed rats

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

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2017.12.006
       
  • 1,25-Dihydroxyvitamin D3 protects obese rats from metabolic syndrome via
           promoting regulatory T cell-mediated resolution of inflammation

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

      PubDate: 2018-02-07T16:43:24Z
      DOI: 10.1016/j.apsb.2018.01.001
       
  • A pilot study of the modulation of sirtuins on arylamine
           N-acetyltransferase 1 and 2 enzymatic activity

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

      PubDate: 2018-01-05T08:47:32Z
      DOI: 10.1016/j.apsb.2017.11.008
       
 
 
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