Celastrol inhibits cancer metastasis by suppressing M2-like polarization of macrophages.

In recent years, a large amount of clinical and experimental data has shown that M2-like polarized tumor-associated macrophages (TAMs) play an important role in cancer metastasis. Therefore, TAMs, especially M2-like TAMs is a promising target for anti-tumor metastasis therapy. Here, we found that celastrol dose-dependently suppressed IL-13 induced CD206 expression both in RAW264.7 and in primary macrophages. Consistently, celastrol also inhibited the expression of M2-like specific genes, including MRC1, Arg1, Fizz1, Mgl2 and CD11c. Further, by the employment of 4T1 breast cancer model, we found that celastrol significantly prevented cancer metastasis in vivo. Mechanistically, celastrol completely ameliorated STAT6 phosphorylation, which is the key signal molecule responsible for M2 polarization. Our research puts forward a new application of celastrol in anti-cancer metastasis, by intervening M2-like polarization through inhibiting STAT6.

Application of artificial neural network model in bioequivalence study of candesartan cilexetil tablets / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C

Bioequivalence of norfloxacin tablets in Chinese Healthy volunteers under Fasting and Fed Condition / 中国临床药理学与治疗学

AIM: To compare the bioavailability of norfloxacin tablets produced by Zhejiang Pharmaceutical Co., Ltd with the original product BACCIDAL, and to evaluate bioequivalence of two formulations, a randomized, open, two-cycle, self-crossing trial in healthy Chinese population was designed. METHODS: Under fasting and fed conditions, healthy volunteers were given a single dose of norfloxacin test or reference tablets for 100 mg. Liquid chromatography-mass spectrometry (LC-MS/MS) method were used to determine drug concentration in the plasma taken at different time points before and after dosing. Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software. RESULTS: A total of 28 healthy volunteers were enrolled and completed the fasting test. The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: C

Role of hydrogen sulfide mediated autophagy related genes in intestinal function injury of sepsis / 中华危重病急救医学

Sepsis is an organ dysfunction that endangers a patient's life caused by an imbalanced infection response, and is a clinically critical illness. Despite a deep understanding of the pathogenesis of sepsis, there has been no significant improvement in sepsis mortality during clinical treatment at home and abroad. In recent years, the role of autophagy in the pathogenesis of sepsis has become a new research point in the field of medical research. Autophagy may protect the body by removing pathogenic microorganisms, neutralizing microbial toxins, and regulating cytokine release in sepsis. Studies have shown that autophagy plays a role in heart and lung organ dysfunction and inflammatory immune response in sepsis. Studies have also shown that hydrogen sulphide (H 2S) can activate autophagy through multiple signaling pathways, such as adenylate-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR), phosphoinositide 3 kinase/Akt/mTOR (PI3K/Akt/mTOR), liver kinase B1/STE20 related adapter protein/mouse protein 25 (LKB1/STRAD/MO25) and microRNA-30c (miR-30c), etc. signaling pathways. This article reviewed the effects of H 2S on autophagy-related genes Beclin-1 and microtubule-associated protein light 3 chain (LC3) on intestinal function of sepsis in order to explore the H 2S-mediated autophagy gene expression in pus. The protective role of autophagy gene for intestinal dysfunction provides a new strategy for the treatment of sepsis in the future.

Protective effect of total flavones from Elsholtzia blanda (TFEB) on myocardial ischemia induced by coronary occlusion in canines.

This study was undertaken to determine the effect of total flavones from Elsholtzia blanda (Benth.) Benth. (TFEB), a traditional Chinese medicine, on myocardial ischemia induced by coronary occlusion in Beagle dogs. Infarct size of left ventricle, serum activity of creatine kinase-MB (CK-MB) and malondialdehyde (MDA), hemorrheologic variables and homodynamic parameters including mean arterial pressure (MAP), coronary blood flow (CBF), coronary vascular resistance (CVR), end-diastolic pressure of left ventricle (LVEDP), rate of rise and decline of left ventricular pressure (+/-dp/dtmax) were measured in this study. Administration with TFEB produced a dose-dependent reduction in infarct size. TFEB 100 mg/kg exerted notable inhibition in the elevation of serum CK-MB and MDA activity. TFEB significantly reduced MAP and CVR. The decrease in CBF also tended to be smaller in treated dogs. TFEB improved the recovery of myocardial function by depressing the degree of reduction in +/-dp/dtmax and LVEDP. TFEB also showed a capacity to resist ischemic damage through lowering blood viscosity. The results indicated that TFEB kept heart from ischemic damage due to coronary occlusion in Beagle dogs.