OBJECTIVES: To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. METHODS: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. RESULTS: The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. CONCLUSIONS rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.
Animals ; Mice ; Sepsis/drug therapy* ; Male ; Schistosoma japonicum/chemistry* ; Mice, Inbred C57BL ; Cystatins/therapeutic use* ; Interleukin-10/metabolism* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Disease Models, Animal ; Transforming Growth Factor beta/metabolism*

Arachidonic acid can be transformed into a variety of metabolites that trigger an inflammatory response through cyclooxygenase, lipoxygenase, cytochrome P450 enzymes, and other metabolic pathways. Moreover, it plays a key role in the occurrence and development of inflammatory diseases. In recent years, multi-target drugs based on the arachidonic acid metabolic pathway have become an important direction of anti-inflammatory drug research. This article summarizes the opportunities and challenges of arachidonic acid metabolic pathways as well as their interference in the development of anti-inflammatory drugs, reviews the research progress of multi-target drug design, synthesis, and anti-inflammatory activity based on the arachidonic acid metabolic pathway, and discusses the difficulties and prospects of multi-target drugs based on metabolic pathways in anti-inflammatory drug development, aiming to provide some reference and inspiration for the study of multi-target anti-inflammatory drugs based on the arachidonic acid metabolic pathway.

Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.

3-iodothyronamine（T1AM）is an endog enous derivative of thyroid hormone. It can also be used as exogenous drug. It can play pharmacological effects such as reducing cardiac output and coronary flow ，slowing heart rate ，promoting lipolysis ， reducing basic metabolism and improving learning and memory ability. Its regulatory effect on metabolism is similar to that of thyroxine，but regulatory effect on heart and thermogenic function is opposite to that of thyroxine. As a new chemical messenger ， T1AM can exert different pharmacological effects through a variety of receptors and signal pathways. This review summarizes the research progress of various pharmacological effects and mechanisms of exogenous T 1AM，in order to provide new therapeutic drugs of cardiovascular ，metabolic diseases and nervous system diseases.

Objective : To explore the material basis and mechanism of Yindan Xinnaotong soft capsule( YD) in treating myocardial ischemia⁃reperfusion injury (MIRI) based on network pharmacology , so as to provide theoreti⁃ cal reference for the treatment of MIRI. Methods : The main active components and action targets of YD were searched by TCMSP , SwissTargetPrediction and China knowledge Network . The disease targets of MIRI were screened by GeneCards database. The“ drug⁃component⁃disease⁃target ”network relationship was constructed by fication was carried out between the top three main active components and the top six targets in PPI network. Human myocardial AC⁃16 cells were constructed hypoxia/reoxygenation (H/R) model to initially verify the core target. Using CCK⁃8 assay was usedto detect cell viability and explore the optimal drugconcentration. The influence of YD on cell morphology was observed by using optical microscope. LDH content was detected to assess the integrity of cell membrane ; Western blot was used to detect the expression of STAT3 , p ⁃STAT3 , PI3K , AKT1 and p ⁃AKT1 . Results : A total of 105 active components , 382 drug targets , 1223 MIRI disease targets and 160 drug⁃disease common targets of YD were obtained. The key targets involved AKT1 , STAT3 , VEGFA , TNF , MAPK8 , PIK3CA and so on. GO analysis mainly involved apoptosis , lipolysis , muscle cell proliferation , cytokine⁃mediated inflammation , oxidative stress and so on. The results of molecular docking showed that VEGFA , APP and PIK3CA could bind to quercetin , luteolin and kaempferol. Our results showed that 200 mg/L YD could significantly promote the proliferation of AC⁃16 cells and reduce LDH leakage. Western blot results showed that YD could activate STAT3 and PI3K⁃AKT1 signaling pathways and protect myocardium. Conclusion YD can protect MIRI through multi⁃components , multi⁃targets and multi⁃pathways.

0.05). But the incidence of rehospitalization in combination group because of adverse cardiovascular events wasn’t more two times than that of non-combination group (OR=2.07; 95% confidence interval ranged from 1.87 to 2.20). CONCLUSION: The results of study are similar to other studies of foreign countries. PPI can influent the anti-platelet effect of clopidogrel so as to increase the incidence of rehospitalization risk resulted from adverse cardiovascular events. Physicians should apply PPI with cautions.

2,3,5,4'-tetra-hydroxystilbene-2-O-glucoside (THSG), the water-soluble active components extracted from dried tuber root of Polygonum multiflorum (Polygonaceae), can promote the release of nitric oxide (NO) from vascular endothelial cells and has strong antioxidation. The postconditioning's protection of THSG on cardiac ischemia-reperfusion injury and the mechanism were investigated. After reperfusion for 3 h following occlusion of rat left anterior descending coronary artery (LAD) for 30 min, SαT recovery speed, arrhythmia and cardiac infarct size were observed.The ischemic size and infarct size was identified by using Evans blue and TTC staining methods respectively. The results showed that the infarct size in THSG 7. 5 mg/kg postconditioning group was significantly decreased from 43.6 %±9.1 % in mode group to 16.5 %±6.5 % (P＜0.01).SαT recovery was quicker and the incidence of arrhythmia (55.6 % vs 100 %, P＜0.05) was significantly lower than in control group. The infarct size in THSG+glybenclamide group was greater than in THSG group, but equivalent to that in control group (46.8 %±9.8 % vs 43.6 %±9. 1 %, P ＞0. 05), SαT recovery speed slower and the incidence of arrhythmia also lower (33. 3 % vs 100 %, P＜0. 01), suggesting that glybenclamide could abolish the effects of THSG postconditioning reducing the cardiac infart size. It was concluded that THSG administration before reperfusion could effectively alleviate the cardiac reperfusion injury and possessed the postconditioning effects of reducing cardiac infarct size, which might be related with the KATP channel opening.

Most of the CHD patients reveal string pulse, mainly due to damage of heart function, lowering of arterial compliance and increase of total peripheral resistance. The common pulse in patients of blood diseases reveal frequent, tiny, string and slippery characteristic, mostly due to the increase of compensatory pumping action of the heart, shortening of ejection time of the left heart, with better vessel compliance and hemorheology, low total peripheral resistance.