428 results match your criteria Acta Pharmaceutica Sinica B[Journal]


Theranostic nanoparticles with tumor-specific enzyme-triggered size reduction and drug release to perform photothermal therapy for breast cancer treatment.

Acta Pharm Sin B 2019 Mar 5;9(2):410-420. Epub 2018 Sep 5.

Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Although progress has been indeed made by nanomedicines, their efficacies for cancer treatment remain low, consequently leading to failures in translation to clinic. To improve the drug delivery efficiency, nanoparticles need to change size so as to fully utilize the enhanced permeability and retention (EPR) effect of solid tumor, which is the golden principle of nanoparticles used for cancer treatment. Herein, we employed cationic small-sized red emission bovine serum albumin (BSA) protected gold nanocluster (AuNC@CBSA, 21. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183043
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http://dx.doi.org/10.1016/j.apsb.2018.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438824PMC
March 2019
2 Reads

Glycyrrhetinic acid binds to the conserved P-loop region and interferes with the interaction of RAS-effector proteins.

Acta Pharm Sin B 2019 Mar 27;9(2):294-303. Epub 2018 Nov 27.

State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, China.

Members of the proto-oncogene superfamily are indispensable molecular switches that play critical roles in cell proliferation, differentiation, and cell survival. Recent studies have attempted to prevent the interaction of RAS/GTP with RAS guanine nucleotide exchange factors (GEFs), impair RAS-effector interactions, and suppress RAS localization to prevent oncogenic signalling. The present study aimed to investigate the effect of the natural triterpenoic acid inhibitor glycyrrhetinic acid, which is isolated from the roots of plant species, on RAS stability. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438844PMC

Small molecules for fat combustion: targeting obesity.

Acta Pharm Sin B 2019 Mar 19;9(2):220-236. Epub 2018 Sep 19.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa 999078, Macau, China.

Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches, either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue (BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438825PMC
March 2019
2 Reads

Biosynthesis of clinically used antibiotic fusidic acid and identification of two short-chain dehydrogenase/reductases with converse stereoselectivity.

Acta Pharm Sin B 2019 Mar 30;9(2):433-442. Epub 2018 Oct 30.

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437595PMC
March 2019
1 Read

Redox-sensitive prodrug nanoassemblies based on linoleic acid-modified docetaxel to resist breast cancers.

Acta Pharm Sin B 2019 Mar 31;9(2):421-432. Epub 2018 Aug 31.

Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Prodrug nanoassemblies, which can refrain from large excipients, achieve higher drug loading and control drug release, have been placed as the priority in drug delivery system. Reasoning that glutathione (GSH) and reactive oxygen species (ROS) are highly upgraded in tumor tissues which makes them attractive targets for drug delivery system, we designed and synthetized a novel prodrug which utilized mono thioether bond as a linker to bridge linoleic acid (LA) and docetaxel (DTX). This mono thioether-linked conjugates (DTX-S-LA) could self-assemble into nanoparticles without the aid of much excipients. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.08.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437471PMC

Transformative hyaluronic acid-based active targeting supramolecular nanoplatform improves long circulation and enhances cellular uptake in cancer therapy.

Acta Pharm Sin B 2019 Mar 29;9(2):397-409. Epub 2018 Nov 29.

Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China.

Hyaluronic acid (HA) is a natural ligand of tumor-targeted drug delivery systems (DDS) due to the relevant CD44 receptor overexpressed on tumor cell membranes. However, other HA receptors (HARE and LYVE-1) are also overexpressing in the reticuloendothelial system (RES). Therefore, polyethylene glycol (PEG) modification of HA-based DDS is necessary to reduce RES capture. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183068
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http://dx.doi.org/10.1016/j.apsb.2018.11.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437598PMC
March 2019
6 Reads

Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy.

Acta Pharm Sin B 2019 Mar 8;9(2):381-396. Epub 2018 Dec 8.

Department of Pharmaceutics, Shanghai General Hospital, Shanghai Jiao Tong University of Medicine, Shanghai 200080, China.

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437633PMC
March 2019
3 Reads

Cytotoxic and antibacterial polyketide-indole hybrids synthesized from indole-3-carbinol by .

Acta Pharm Sin B 2019 Mar 28;9(2):369-380. Epub 2018 Sep 28.

State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.

Two skeletally undescribed polyketide-indole hybrids (PIHs), named indolchromins A and B, were generated from indole-3-carbinol (I3C) in the fungal culture (). The indolchromin structures were elucidated mainly by their 1D and 2D NMR spectra with the former confirmed by the single-crystal X-ray crystallographic analysis. Each indolchromin alkaloid was chirally separated into four isomers, whose absolute configurations were assigned by comparing the recorded circular dichroism (CD) spectra with the electronic CD (ECD) curves computed for all optional stereoisomers. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437554PMC

Discovery of a series of dimethoxybenzene FGFR inhibitors with 5pyrrolo[2,3-]pyrazine scaffold: structure-activity relationship, crystal structural characterization and study.

Acta Pharm Sin B 2019 Mar 26;9(2):351-368. Epub 2018 Dec 26.

Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.12.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437634PMC

Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents.

Acta Pharm Sin B 2019 Mar 7;9(2):335-350. Epub 2019 Jan 7.

Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.

Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Read More

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http://dx.doi.org/10.1016/j.apsb.2019.01.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437665PMC
March 2019
2 Reads

LSD1 inhibition suppresses the growth of clear cell renal cell carcinoma upregulating P21 signaling.

Acta Pharm Sin B 2019 Mar 30;9(2):324-334. Epub 2018 Oct 30.

Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, China.

Histone lysine-specific demethylase 1 (LSD1) has been implicated in the disease progression of several types of solid tumors. This study provides the first evidence showing that LSD1 overexpression occurred in 62.6% (224/358) of clear cell renal cell carcinomas (ccRCC). Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437640PMC
March 2019
1 Read

The epigallocatechin gallate derivative Y reverses drug resistance mediated by the ABCB1 transporter both and .

Acta Pharm Sin B 2019 Mar 12;9(2):316-323. Epub 2018 Oct 12.

College of Pharmacy, Guangxi Medical University, Nanning 530021, China.

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183049
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http://dx.doi.org/10.1016/j.apsb.2018.10.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437594PMC
March 2019
4 Reads

SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade.

Acta Pharm Sin B 2019 Mar 5;9(2):304-315. Epub 2018 Sep 5.

State Key Laboratory of Pharmaceutical Biotechnology, Deparment of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, Nanjing 210023, China.

Tyrosine phosphatase SHP2 is a promising drug target in cancer immunotherapy due to its bidirectional role in both tumor growth promotion and T-cell inactivation. Its allosteric inhibitor SHP099 is known to inhibit cancer cell growth both and . However, whether SHP099-mediated SHP2 inhibition retards tumor growth anti-tumor immunity remains elusive. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183062
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http://dx.doi.org/10.1016/j.apsb.2018.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437555PMC
March 2019
2 Reads

Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway.

Acta Pharm Sin B 2019 Mar 15;9(2):279-293. Epub 2018 Dec 15.

Jiangsu Province Key Laboratory for Microbes and Functional Genomics, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). Read More

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http://dx.doi.org/10.1016/j.apsb.2018.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437636PMC

Recent progress and challenges in screening and characterization of UGT1A1 inhibitors.

Acta Pharm Sin B 2019 Mar 14;9(2):258-278. Epub 2018 Sep 14.

Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Uridine-diphosphate glucuronosyltransferase 1A1 (UGT1A1) is an important conjugative enzyme in mammals that is responsible for the conjugation and detoxification of both endogenous and xenobiotic compounds. Strong inhibition of UGT1A1 may trigger adverse drug/herb-drug interactions, or result in metabolic disorders of endobiotic metabolism. Therefore, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have recommended assaying the inhibitory potential of drugs under development on the human UGT1A1 prior to approval. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183043
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http://dx.doi.org/10.1016/j.apsb.2018.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437557PMC
March 2019
1 Read

Marine sponges of the genus as promising drug sources: chemical and biological aspects.

Acta Pharm Sin B 2019 Mar 16;9(2):237-257. Epub 2018 Oct 16.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.

Marine sponges of the genus are well known as rich sources of diverse and complex biologically relevant natural products, including alkaloids, terpenoids, peptides, lipids, and steroids. Some of these metabolites, with novel structures and promising biological activities, have attracted a lot of attention from chemists seeking to perform their total synthesis in parallel to intensive biological studies towards new drug leads. In this review, we summarized the distribution of the chemically investigated sponges, the isolation, synthesis and biological activities of their secondary metabolites, covering the literature from 1982 to early 2018. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437601PMC

Repurposing vitamin D for treatment of human malignancies targeting tumor microenvironment.

Acta Pharm Sin B 2019 Mar 6;9(2):203-219. Epub 2018 Sep 6.

Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.

Tumor cells along with a small proportion of cancer stem cells exist in a stromal microenvironment consisting of vasculature, cancer-associated fibroblasts, immune cells and extracellular components. Recent epidemiological and clinical studies strongly support that vitamin D supplementation is associated with reduced cancer risk and favorable prognosis. Experimental results suggest that vitamin D not only suppresses cancer cells, but also regulates tumor microenvironment to facilitate tumor repression. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437556PMC
March 2019
1 Read

Exploring the utility of the Chasing Principle: influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension.

Acta Pharm Sin B 2019 Jan 7;9(1):194-201. Epub 2018 Jul 7.

Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol (CAR), cinnarizine (CIN) or R3040 on drug solubilization in a two-compartment lipolysis model. Correlation of drug log or solubility in SNEDDS with drug solubilization during lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1 (1:1, /) and Kolliphor RH40, with ethanol at 10% (/) were used. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361727PMC
January 2019

Interaction between human serum albumin and cholesterol-grafted polyglutamate as the potential carriers of protein drugs.

Acta Pharm Sin B 2019 Jan 7;9(1):186-193. Epub 2018 Aug 7.

Key Laboratory of Advanced Materials (MOE), Department of Chemical Engineering, Tsinghua University, Beijing 100084, China.

Currently there is no successful platform technology for the sustained release of protein drugs. It seems inevitable to specifically develop new materials for such purpose, and hence the understanding of protein-material interactions is highly desirable. In this study, we synthesized cholesterol-grafted polyglutamate (PGA--Chol) as a hydrophobically-modified polypeptide, and thoroughly characterized its interaction with a model protein (human serum albumin) in the aqueous solution by using circular dichroism, fluorescence methods, and light scattering. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361731PMC
January 2019

Deep learning for prediction of pharmaceutical formulations.

Acta Pharm Sin B 2019 Jan 28;9(1):177-185. Epub 2018 Sep 28.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China.

Current pharmaceutical formulation development still strongly relies on the traditional trial-and-error methods of pharmaceutical scientists. This approach is laborious, time-consuming and costly. Recently, deep learning has been widely applied in many challenging domains because of its important capability of automatic feature extraction. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362259PMC
January 2019
1 Read

Efficient lung cancer-targeted drug delivery a nanoparticle/MSC system.

Acta Pharm Sin B 2019 Jan 3;9(1):167-176. Epub 2018 Sep 3.

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China.

Low targeting efficiency limits the applications of nanoparticles in cancer therapy. The fact that mesenchymal stem cells (MSC) trapped in the lung after systemic infusion is a disadvantage for cell therapy purposes. Here, we utilized MSC as lung cancer-targeted drug delivery vehicles by loading nanoparticles (NP) with anti-cancer drug. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362298PMC
January 2019
1 Read

Pharmacometabolomic prediction of individual differences of gastrointestinal toxicity complicating myelosuppression in rats induced by irinotecan.

Acta Pharm Sin B 2019 Jan 12;9(1):157-166. Epub 2018 Sep 12.

Key Laboratory of Drug Quality Control and Pharmacovigilance (Ministry of Education), State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China.

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362258PMC
January 2019
1 Read

Novel fluorescent probes of 10-hydroxyevodiamine: autophagy and apoptosis-inducing anticancer mechanisms.

Acta Pharm Sin B 2019 Jan 20;9(1):144-156. Epub 2018 Aug 20.

School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Natural product evodiamine and its derivatives represent a promising class of multi-target antitumor agents. However, the clinical development of these compounds has been hampered by a poor understanding of their antitumor mechanisms. To tackle this obstacle, herein, novel fluorescent probes were designed to elucidate the antitumor mode of action of 10-hydroxyevodiamine. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361730PMC
January 2019

Cordycepin promotes browning of white adipose tissue through an AMP-activated protein kinase (AMPK)-dependent pathway.

Acta Pharm Sin B 2019 Jan 17;9(1):135-143. Epub 2018 Oct 17.

Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China.

Obesity is a worldwide epidemic. Promoting browning of white adipose tissue (WAT) contributes to increased energy expenditure and hence counteracts obesity. Here we show that cordycepin (Cpn), a natural derivative of adenosine, increases energy expenditure, inhibits weight gain, improves metabolic profile and glucose tolerance, decreases WAT mass and adipocyte size, and enhances cold tolerance in normal and high-fat diet-fed mice. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361849PMC
January 2019

Preparation and characterization of multimodal hybrid organic and inorganic nanocrystals of camptothecin and gold.

Acta Pharm Sin B 2019 Jan 22;9(1):128-134. Epub 2018 Mar 22.

Department Industrial & Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.

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. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361724PMC
January 2019

Development of carrier-free nanocrystals of poorly water-soluble drugs by exploring metastable zone of nucleation.

Acta Pharm Sin B 2019 Jan 19;9(1):118-127. Epub 2018 Jun 19.

Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 201203, China.

There has been increasing interest in research and development of nanocrystals for the delivery of poorly water-soluble drugs that can be directly produced from solution. Compared with traditional carrier-based or encapsulation designs, drug nanocrystals circumvent possible side-effects due to carrier polymers and poor stability issues associated with encapsulation. The production of carrier-free nanocrystals requires careful control of nucleation and thus a thorough understanding of the relevant solution's metastable zone. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361733PMC
January 2019

Supersaturated polymeric micelles for oral silybin delivery: the role of the Soluplus-PVPVA complex.

Acta Pharm Sin B 2019 Jan 10;9(1):107-117. Epub 2018 Sep 10.

Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai 201203, China.

Increasing the degree of supersaturation of drugs and maintaining their proper stability are very important in improving the oral bioavailability of poorly soluble drugs by a supersaturated drug delivery system (SDDS). In this study, we reported a complex system of Soluplus-Copovidone (Soluplus-PVPVA) loaded with the model drug silybin (SLB) that could not only maintain the stability of a supersaturated solution but also effectively promote oral absorption. The antiprecipitation effect of the polymers on SLB was observed using the solvent-shift method. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361729PMC
January 2019
1 Read

Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of azilsartan.

Acta Pharm Sin B 2019 Jan 7;9(1):97-106. Epub 2018 Sep 7.

Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile -cyclodextrin (-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183037
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http://dx.doi.org/10.1016/j.apsb.2018.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361728PMC
January 2019
29 Reads

Intestinal uptake of barley protein-based nanoparticles for -carotene delivery.

Acta Pharm Sin B 2019 Jan 12;9(1):87-96. Epub 2018 Oct 12.

Department of Agricultural, Food and Nutritional Science, University of Alberta, Alberta T6G 2P5, Canada.

Our previous study introduced a barley protein microparticle for encapsulation of hydrophobic drug/nutraceutical, which could release nanoparticles upon gastric digestion and deliver encapsulated compound to a simulated intestinal environment intact. This work focused on evaluating the potential of liberated nanoparticles to improve the absorption of encapsulated compounds (., -carotene) using Caco-2 cell and small intestine models. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362262PMC
January 2019

Selenium-layered nanoparticles serving for oral delivery of phytomedicines with hypoglycemic activity to synergistically potentiate the antidiabetic effect.

Acta Pharm Sin B 2019 Jan 20;9(1):74-86. Epub 2018 Sep 20.

Department of Pharmaceutics, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Diabetes mellitus (DM) remains a great challenge in treatment due to pathological complexity. It has been proven that phytomedicines and natural medicines have prominent antidiabetic effects. This work aimed to develop selenium-layered nanoparticles (SeNPs) for oral delivery of mulberry leaf and extracts (MPE), a group of phytomedicines with significant hypoglycemic activities, to achieve a synergic antidiabetic effect. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361850PMC
January 2019
1 Read

The effects of pH, surfactant, ion concentration, coformer, and molecular arrangement on the solubility behavior of myricetin cocrystals.

Acta Pharm Sin B 2019 Jan 19;9(1):59-73. Epub 2018 Sep 19.

Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Pharmaceutical cocrystals are a promising technology that can be used to improve the solubility of poor aqueous compounds. The objective of this study was to systematically investigate the solubility of myricetin (MYR) cocrystals, including their kinetic solubility, thermodynamic solubility, and intrinsic dissolution rate (IDR). The effects of pH, surfactant, ion concentration, and coformers on the cocrystal solubility were evaluated. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.09.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361854PMC
January 2019
2 Reads

Emerging transporter-targeted nanoparticulate drug delivery systems.

Acta Pharm Sin B 2019 Jan 24;9(1):49-58. Epub 2018 Oct 24.

Department of Pharmacy, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.

Transporter-targeted nanoparticulate drug delivery systems (nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361857PMC
January 2019
1 Read

Adapting liposomes for oral drug delivery.

Acta Pharm Sin B 2019 Jan 20;9(1):36-48. Epub 2018 Jun 20.

Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835173073
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http://dx.doi.org/10.1016/j.apsb.2018.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362257PMC
January 2019
16 Reads

Advances in coamorphous drug delivery systems.

Acta Pharm Sin B 2019 Jan 16;9(1):19-35. Epub 2018 Aug 16.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

In recent years, the coamorphous drug delivery system has been established as a promising formulation approach for delivering poorly water-soluble drugs. The coamorphous solid is a single-phase system containing an active pharmaceutical ingredient (API) and other low molecular weight molecules that might be pharmacologically relevant APIs or excipients. These formulations exhibit considerable advantages over neat crystalline or amorphous material, including improved physical stability, dissolution profiles, and potentially enhanced therapeutic efficacy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183062
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http://dx.doi.org/10.1016/j.apsb.2018.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361732PMC
January 2019
14 Reads

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles.

Acta Pharm Sin B 2019 Jan 14;9(1):4-18. Epub 2018 Nov 14.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau, China.

Nanoparticles are considered to be a powerful approach for the delivery of poorly water-soluble drugs. One of the main challenges is developing an appropriate method for preparation of drug nanoparticles. As a simple, rapid and scalable method, the flash nanoprecipitation (FNP) has been widely used to fabricate these drug nanoparticles, including pure drug nanocrystals, polymeric micelles, polymeric nanoparticles, solid lipid nanoparticles, and polyelectrolyte complexes. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183061
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http://dx.doi.org/10.1016/j.apsb.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361851PMC
January 2019
5 Reads

Editorial: Persistent endeavors for the enhancement of dissolution and oral bioavailability.

Acta Pharm Sin B 2019 Jan 29;9(1):2-3. Epub 2019 Jan 29.

Key Laboratory of Smart Drug Delivery of MOE and PLA, School of Pharmacy, Fudan University, Shanghai 201203, China.

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http://dx.doi.org/10.1016/j.apsb.2019.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361848PMC
January 2019

The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity.

Acta Pharm Sin B 2018 Oct 1;8(6):981-994. Epub 2018 May 1.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase (SGT) from and a steroidal glycoside acyltransferase (SGA) from and their application in the biosynthesis of acylated steroidal glycosides (ASGs). Initially, an gene, designated as OsSGT1, was isolated from . OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251810PMC
October 2018
20 Reads

Accurate authentication of and its closely related species by comparative analysis of complete plastomes.

Acta Pharm Sin B 2018 Oct 1;8(6):969-980. Epub 2018 Jun 1.

College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

Owing to its great medicinal and ornamental values, is frequently adulterated with other species on the market. Unfortunately, the utilization of the common DNA markers ITS, ITS2, and + is unable to distinguish from 5 closely related species of it (, , , and ). Here, we compared 63 plastomes comprising 40 newly sequenced plastomes of the 6 species and 23 previously published plastomes. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.05.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251949PMC
October 2018
1 Read

Tat-functionalized Ag-FeO nano-composites as tissue-penetrating vehicles for tumor magnetic targeting and drug delivery.

Acta Pharm Sin B 2018 Oct 6;8(6):956-968. Epub 2018 Aug 6.

State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

In this paper, we prepared a dual functional system based on dextrin-coated silver nanoparticles which were further attached with iron oxide nanoparticles and cell penetrating peptide (Tat), producing Tat-modified Ag-FeO nanocomposites (Tat-FeAgNPs). To load drugs, an -SH containing linker, 3-mercaptopropanohydrazide, was designed and synthesized. It enabled the silver carriers to load and release doxorubicin (Dox) in a pH-sensitive pattern. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183017
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http://dx.doi.org/10.1016/j.apsb.2018.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251815PMC
October 2018
6 Reads

Cembrane-type diterpenoids from the South China Sea soft coral .

Acta Pharm Sin B 2018 Oct 19;8(6):944-955. Epub 2018 Jun 19.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

Eight cembrane-type diterpenoids, namely, (+)-(6)-6-hydroxyisosarcophytoxide (), (+)-(6)-6-acetoxyisosarcophytoxide (), (+)-17-hydroxyisosarcophytoxide (), sarcomililatins A-D (-), and sarcomililatol (), were isolated from the soft coral collected from Weizhou Island, Guangxi Autonomous Region, together with 2 known related analogues, (+)-isosarcophytoxide () and (+)-isosarcophine (). The structures of these compounds were elucidated by a combination of detailed spectroscopic analyses, chemical methods, and comparison with reported data. The absolute configuration of compound was established by the modified Mosher׳s method, while the absolute configurations of compounds and were assigned by electronic circular dichroism (ECD) spectroscopy and that of compound was established by time-dependent density functional theory electronic circular dichroism (TD-DFT ECD) calculation. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183021
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http://dx.doi.org/10.1016/j.apsb.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251813PMC
October 2018
17 Reads

Sulfur-enriched alkaloids from the root of .

Acta Pharm Sin B 2018 Oct 23;8(6):933-943. Epub 2018 Aug 23.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Five new sulfur-enriched alkaloids isatithioetherins A-E (-), and two pairs of scalemic enantiomers (+)- and (-)-isatithiopyrin B ( and ) and isoepigoitrin and isogoitrin and ), along with the known scalemic enantiomers epigoitrin and goitrin ( and ), were isolated and characterized from an aqueous extract of the roots. Their structures were determined by extensive spectroscopic data analysis, including 2D NMR and theoretical calculations of electronic circular dichroism (ECD) spectra based on the quantum-mechanical time-dependent density functional theory (TDDFT). Compounds - represent a novel group of sulfur-enriched alkaloids, biogenetically originating from stereoselective assemblies of epigoitrin-derived units. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183047
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http://dx.doi.org/10.1016/j.apsb.2018.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251858PMC
October 2018
15 Reads

Novel benzamido derivatives as PTP1B inhibitors with anti-hyperglycemic and lipid-lowering efficacy.

Acta Pharm Sin B 2018 Oct 8;8(6):919-932. Epub 2018 May 8.

Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

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 IC 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 on high-fat diet (HFD)-induced insulin-resistant (IR) obese mice indicated that could modulate glucose metabolism and ameliorate dyslipidemia simultaneously. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.05.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251817PMC
October 2018

Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells.

Acta Pharm Sin B 2018 Oct 26;8(6):909-918. Epub 2018 Jul 26.

Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China.

Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183016
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http://dx.doi.org/10.1016/j.apsb.2018.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251816PMC
October 2018
11 Reads

DNA recognition patterns of the multi-zinc-finger protein CTCF: a mutagenesis study.

Acta Pharm Sin B 2018 Oct 31;8(6):900-908. Epub 2018 Aug 31.

State Key Laboratory of Bioactive Substance and Function of Natural Medicine, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

CCCTC-binding factor (CTCF) is a zinc-finger protein, serving an important part in the genome architecture as well as some biochemical processes. Over 70,000 CTCF binding DNA sites have been detected genome-wide, and most anchors of chromatin loops are demarcated with the CTCF binding. Various protein or RNA molecules interact with DNA-bound CTCF to conduct different biological functions, and potentially the interfaces between CTCF and its cofactors can be targets for drug development. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183019
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http://dx.doi.org/10.1016/j.apsb.2018.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251859PMC
October 2018
13 Reads

High-throughput screening for small molecule inhibitors of the type-I interferon signaling pathway.

Acta Pharm Sin B 2018 Oct 10;8(6):889-899. Epub 2018 Jul 10.

The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai 201203, China.

Interferons (IFNs) are cytokines with fundamental roles in resistance to infections, cancer and other diseases. Type-I IFNs, interferon (IFN-) and interferon (IFN-), act through a shared receptor complex (IFNAR) comprised of IFNAR1 and IFNAR2 subunits. Binding of type-I IFN to IFNAR1 will robustly activate Janus activated kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Read More

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http://dx.doi.org/10.1016/j.apsb.2018.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251811PMC
October 2018
1 Read

Potassium 2-(1-hydroxypentyl)-benzoate improves depressive-like behaviors in rat model.

Acta Pharm Sin B 2018 Oct 20;8(6):881-888. Epub 2018 Aug 20.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

Potassium 2-(1-hydroxypentyl)-benzoate (PHPB) is a novel drug candidate for acute ischemic stroke. PHPB has been also shown to be beneficial for some neurodegenerative diseases. In this study, we demonstrated that PHPB improved depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183035
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http://dx.doi.org/10.1016/j.apsb.2018.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251814PMC
October 2018
7 Reads

Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives.

Acta Pharm Sin B 2018 Oct 18;8(6):862-880. Epub 2018 May 18.

Department of Pharmacy, Integrated Research Institute of Pharmaceutical Sciences, and BK21 PLUS Team for Creative Leader Program for Pharmacomics-based Future Pharmacy, College of Pharmacy, The Catholic University of Korea, Gyeonggi-do 14662, Republic of Korea.

Mitochondrial targeting is a promising approach for solving current issues 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 readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183005
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http://dx.doi.org/10.1016/j.apsb.2018.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251809PMC
October 2018
16 Reads

Recent developments in topoisomerase-targeted cancer chemotherapy.

Acta Pharm Sin B 2018 Oct 25;8(6):844-861. Epub 2018 Jul 25.

Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

The DNA topoisomerase enzymes are essential to cell function and are found ubiquitously in all domains of life. The various topoisomerase enzymes perform a wide range of functions related to the maintenance of DNA topology during DNA replication, and transcription are the targets of a wide range of antimicrobial and cancer chemotherapeutic agents. Natural product-derived agents, such as the camptothecin, anthracycline, and podophyllotoxin drugs, have seen broad use in the treatment of many types of cancer. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183014
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http://dx.doi.org/10.1016/j.apsb.2018.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251812PMC
October 2018
4 Reads

-Methyladenosine modification: a novel pharmacological target for anti-cancer drug development.

Acta Pharm Sin B 2018 Oct 6;8(6):833-843. Epub 2018 Jun 6.

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.

-Methyladenosine (mA) modification is the most pervasive modification of human mRNA molecules. It is reversible regulation of mA modification methyltransferase, demethylase and proteins that preferentially recognize mA modification as "writers", "erasers" and "readers", respectively. Altered expression levels of the mA modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835183024
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http://dx.doi.org/10.1016/j.apsb.2018.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251950PMC
October 2018
1 Read

3D tissue engineering, an emerging technique for pharmaceutical research.

Acta Pharm Sin B 2018 Sep 21;8(5):756-766. Epub 2018 Mar 21.

Department of Biological Engineering, Utah State University, Logan, UT, 84322, USA.

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. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22113835173054
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http://dx.doi.org/10.1016/j.apsb.2018.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148716PMC
September 2018
14 Reads