药学学报最新文献

This study was conducted to test the effects of schizandrin B (Sch B) on clozapine (CLZ) inducedchronic liver injury in mice and the mechanism of action, and this may provide a new approach for clinicalprevention of CLZ-induced side effects. The CLZ was given to mice for three weeks alone or co-administrationwith Sch B. The changes of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase(ALP) and antioxidation indexes superoxide dismutase (SOD), malonic dialdehyde (MDA), glutathione (GSH)and liver histological evaluation were determined. Expression of Nrf2 was assayed in hepatic cells by immunohistochemicalstaining and Western blotting. The changes of relative gene expression of NAD(P)H: quinoneoxidoreductase l (NQO1) and heme oxygenase 1 (HO-1) were assayed by real-time Q-PCR. The results showedthat pretreatment with a lower dosage of Sch B (25, 50 mg·kg−1) prevented CLZ-induced liver injury as indicatedby the reduced levels of ALT, AST and ALP, and the preserved activities of SOD, GSH and inhibiting MDA. Itwas shown that Sch B could up-regulate Nrf2 expression leading to nuclear accumulation of Nrf2 to induceoxidative response genes such as NQO1 and HO-1. These results suggest that Sch B could protect against liverinjury induced by CLZ via the activation of the Nrf2/ARE signal pathway in a dose-dependent manner.

Diabetic neuropathic pain (DNP) is the most common chronic complication of diabetes mellitus,significantly affecting people’s quality of life. Studies have indicated that ion channels play a very important rolein the occurrence of DNP. This review provides a summary in the role of ion channels in diabetic neuropathicpain and treatment strategies for diabetic neuropathy targeting ion channels.

In this study, water-dispersible magnetic iron oxide (Fe3O4) nanoparticles were synthesized withsolvothermal method. The nanoparticles were characterized with a transmission electron microscopy (TEM)and vibrating sample magnetometer (VSM). The in vitro magnetic resonance response and photothermalconversion characteristics of the nanoparticles were evaluated. In addition, the cellular uptake, cytotoxicityand biodistribution were studied. Finally, magnetic resonance/photothermal dual-modal imaging effect ofthe as-synthesized Fe3O4 nanoparticles was investigated in the tumor-bearing mice. The results showed thatthe obtained magnetic nanoparticles were uniform with a mean diameter of about 125 nm. Moreover, thesuperparamagnetic Fe3O4 nanoparticles showed remarkable magnetic resonance response and photothermalconversion properties. The results of cellular experiments showed that the cell viability was nearly 85% even theconcentration of the nanoparticles was up to 1 000 μg·mL−1, an indicator of good biocompatibility. In addition,the nanoparticles could be taken up by the tumor cells and then located in the cytoplasm. After intravenousinjection, the nanoparticles were tended to enrich in the tumor over time, which is helpful in achievingdual-modal magnetic resonance/photothermal imaging. In sum, the obtained Fe 3O4 nanoparticles showed greatpotential to be applied for multi-modal bio-imaging which may play an important role in the diagnosis of tumors.

Translating of scientific advances into clinical practice is a major challenge in the stroke researchfield in the past decades. There were many reasons involved: animal models might not accurately capture allaspects of clinical stroke in humans, the blind and randomized design principle was not closely followed, theinclusion and exclusion criteria was not previously established, sample size was inadequate, endpoint was notscientific nor blindly assessed, inadequate reporting of data and statistical flaws. To bridge the gap betweenexperimental and clinical research, international consortia have attempted to establish standardized guidelinesfor study design and data report, which include optimizing animal models as well as experimental design, usinginnovative approaches to assess endpoint, making raw data and negative results available, establishing priorregistration mechanism, conducting multicenter preclinical randomized controlled trials (pRCTs), systematicreviews and meta-analysis of preclinical studies, evolving the original focus on neuroprotection into a broaderconsideration of the role of neurovascular unit and ischemic cascade.

The biological potency assay and chemical fingerprint chromatogram were applied to qualityevaluation of rhubarb. Using the biological potency as indicators, we evaluated the differences in quality ofmultiple batches of rhubarbs and related products. Using the platelet aggregation analyzer, we determinedplatelet aggregation rate in the different rhubarbs preparations, and calculated the biological potency based on thesimplified probit principle. UPLC was adopted to establish the fingerprint spectra for rhubarbs. The spectralefficiency correlation analysis between chromatograms and biological potencies were conducted using the doublevariables of SPSS 22.0 software. We used three chemical composition to verify the potency. The biologicalpotency results suggest that Rheum palmatum has a more potent activity than Rheum tanguticum, andwine-treated rhubarb had a higher potentcy than charred. We identified 10 elements in the Fingerprint Spectrum.The relevant elements including rhein-8-O-β-D-glucoside, emodin-8-O-β-D-glucoside and rhein have thestrongest activity in the inhibition of platelet aggregation. In conclusion, this study provides a analyticalmethod for rhubarb biological potency based on determination of the maximum antagonism rate model. Therhein may be the effective substance. It may serve as a reference in the quality control of wine processedrhubarb products.

In recent years, owing to the abuse of antibiotics, the widespread of resistant bacterial strainsbecame a serious threat to public health. This status demands development of new antibacterial agents withnovel mechanisms of action. The reason for the limited new antibacterials is the small number of effectivetherapeutic targets, which cannot meet the current needs for the multiple drug-resistant treatment. Screening fornew targets is the key step in the development of novel antibacterial agents. Peptidoglycan is the main componentof the cell wall of bacteria, which is essential for survival of pathogenic bacteria. Within the biochemicalpathway for peptidoglycan biosynthes is the Murligases, described in this review as highly potential targets forthe development of new classes of antibacterial agents. This review provides an in-depth insight into the recentdevelopments in the field of inhibitors of the Mur enzymes (MurA-F). Moreover, the reasons for the lack ofcandidate inhibitors and the challenges to overcome the hurdles are also discussed.

Inhibition of apoptosis induced by oxidative stress is an effective way to reduce myocardial injury.In this study, we used H2O2-stimulated rat cardiac myoblast cell line (H9c2) as an oxidative damage model.Curcumin (Cur) was chosen as a model drug and mesoporous silica nanoparticles (MSNs) were chosen as thecarrier to construct a Cur-loaded delivery system (Cur@MSNs) and to examine its protective effects againstoxidative damage. The MSNs guaranteed efficient loading and controlled release of Cur. Besides, thehydrophilicsilanol groups on the surface of MSNs promoted the Cur solubility in water and increased itscellular uptake amount, which improved the bioavailability of Cur. The results suggest that the Cur@MSNswas pharmacologically active in the reduction of the oxidative damage of H9c2 cells. It was verified that agreat decrease of reactive oxygen species was inducted by Cur@MSNs, which led to the protective effectsagainst oxidative damage.

Bubali cornu (water buffalo horn) has been used as the substitute for Cornu rhinoceri asiatici(rhino horn) in clinical applications, and is the essential ingredient of Angong Niuhuang Wan. In recent years,there are a number of adulterants on the commercial herbal medicine markets. An efficient tool is requiredfor species identification. In this study, 155 Bubali cornu samples have been taken from original animals andcollected from commercial herbal medicine markets. 153 COI sequences have been successfully obtainedfrom 155 samples through DNA extraction, PCR amplification, bidirectional sequencing and assembly. 93COI sequences have been added to the DNA barcoding database of traditional Chinese animal medicine aftervalidation using DNA barcoding GAP and tree-based methods. The species identification of the 62 commercialBubali cornu medicines has been accomplished on the DNA barcoding system for identifying herbal medicineusing the updated animal medicine database (www.tcmbarcode.cn). Except two samples failed to obtain COIsequences, 54.8% of the commercial Bubali cornu medicines were water buffalo horns and 29% were yak horns.Our results showed that yak horn was the major adulterant of Bubali cornu and the DNA barcoding method mayaccurately discriminate Bubali cornu and their adulterants. Therefore, we recommend that supervision on theherbal medicine markets should be strengthened with this new method to warren the effectiveness of herbalmedicines.

Transglutaminase (TG) posttranslational modification of antibody permits more preciselyconjugating. Based on the amino acid sequence of an anti-CD24 antibody (cG7), this article is aimed togenerate a deglycosylated cG7 mutant (cG7Q). Firstly, we introduced additional glutamines at position 297(N297Q) by site-directed mutagenesis, and then transfected the recombinant plasmids into CHO-s cells viaelectroporation method and screened by Dot blot assay. Subsequently, cG7Q was expressed and purifiedthrough Protein A affinity chromatography, further identified by SDS-PAGE electrophoresis and Western blot.Its affinity was detected with surface plasmon resonance and flow cytometry assay, and ADCC effect wasdetermined by lactate dehydrogenase (LDH) release. Eventually, a cG7 mutant, cG7Q was successfullyexpressed with sequence-specific conjugation sites for further study.

This study was conducted to design and synthetize highly efficient, specific, non-resistantsmall MEK inhibitors. Based on active small molecules which have been reported, we studied the actionmode with MEK protein using Autodock 4.2, generated innovative and feasible design method, designednovel small MEK protein inhibitors with a reference to molecular modeling and docking. The anti-tumoractivities of four kinds of cells including MCF-7, PANC-1, SY5Y, A549 were tested with MTT methodin vitro. The structure of 10 new small molecules has been determined with 1H NMR and 13C NMR. Thecompounds 4, 6, 7, 8, 10 had high antitumor activities, the compounds 1, 3, 5 also showed good activity,and the compounds 2, 9 showed cell selectivity in killing tumor.