5-(4-Methyl­phen­yl)-1,3,4-oxadiazol-2-amine

In the crystal structure of the title compound, C9H9N3O, adjacent mol­ecules are linked through N—H⋯N hydrogen bonds into a three-dimensional network

Dexmedetomidine post-treatment attenuates cardiac ischaemia/reperfusion injury by inhibiting apoptosis through HIF-1α signalling.

Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post-treatment with dexmedetomidine (DEX) could protect against I/R-induced cardiac apoptosis in vivo and in vitro via regulating HIF-1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6-hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen-glucose deprivation for 6 hours followed by 3-hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R-induced myocardial injury or H/R-induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF-1α and modulated the expressions of apoptosis-related proteins including BCL-2, BAX, BNIP3, cleaved caspase-3 and cleaved PARP. Conversely, the HIF-1α prolyl hydroxylase-2 inhibitor IOX2 partly blocked DEX-mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down-regulated HIF-1α expression at the post-transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post-treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF-1α signalling

Effect of catch-up growth after food restriction on the entero-insular axis in rats

<p>Abstract</p> <p>Background</p> <p>Catch-up growth after food restriction (CUGFR) is characterized by a significant change in food intake which could theoretically lead to the change in glucagon-like peptide-1 (GLP-1) secretion that consequently results in altered functions of pancreatic islets.</p> <p>Methods</p> <p>Experimental rats were divided into two groups. Rats in CUGFR group were put on food-restriction for 4 weeks, and then allowed full access to food for 0, 2, 4 weeks respectively while rats in the control group were offered <it>ad libitum </it>access to food. Plasma glucose, insulin and GLP-1 level during OGTT were measured in all the rats. Moreover, morphology of intestinal mucosa, number of L cells, beta cell mass, incretin effect and the expression of GLP-1 receptor (GLP-1R) gene in the islets were also determined.</p> <p>Results</p> <p>The size of pancreatic islets, insulin concentration, plasma GLP-1 concentration, incretin effect, villus height-to-crypt depth ratio and L cells were all significantly decreased in CUGFR group at the end of a 4-week food-restriction period as compared with the controls. Insulin concentration and the villus height-to-crypt depth ratio were increased and finally exceeded the level of the control group over a 4-week catch-up period. Nevertheless, at the conclusion of the study, islet size, L cells number, plasma GLP-1 concentration and incretin effect increased but failed to reach the levels of the controls.</p> <p>Conclusion</p> <p>CUGFR decreases incretin effect and disturbs the entero-insular axis partially by decreasing GLP-1 concentration, which might be responsible for the increased risk of metabolic disorder during CUGFR.</p

catena-Poly[[copper(I)-bis[μ-bis(di­phenyl­phos­phino)methane-κ2 P:P′]-copper(I)-μ-2,2′-bipyridine-κ2 N:N′] bis(tetra­fluorido­borate) dichloromethane 2.5-solvate]

The title complex, {[Cu2(C10H8N2)(C25H22P2)2](BF4)2·2.5CH2Cl2}n, contains chains of CuI centres bridged alternately by two (diphenyl­phosphino)methane (dppm) and 4,4′-bipyridine (bpy) ligands. Each CuI atom is coordinated by one N atom of 4,4′-bipyridine (bpy) and two P atoms of two (diphenyl­phosphino)methane (dppm) ligand, and has a trigonal-planar coordination geometry. There is an inversion centre midway between each pair of adjacent Cu atoms. The distance of two CuI atoms separated by two (diphenyl­phosphino)methane bridging ligands is 3.732 (3) Å, and 4,4′-bipyridine 11.138 (5) Å

The protection of salidroside on oxidative stress induced in human lens epithelium cells

AIM: To explore the effect of different concentrations of salidroside on H2O2 induced oxidative stress damage in human lens epithelium cells(HLEC). METHODS: HLEC were cultured and divided into negative control group: cultured in normal cultivation; oxidative damage group: treated with 100μmol/L H2O2 for 12h; Salidroside low concentration group: 10μmol/L salidroside treated for 24h and H2O2 treated for 12h; Salidroside high concentration group: 100μmol/L salidroside treated for 24h and H2O2 treated for 12h. MTT method was applied to observe the effect of salidroside on HLEC survival rate. Morphological change of each group were observed and recorded under inverted microscope. DCFH-DA fluorescent probe was applied to detect intracellular ROS changes; content of malondialdehyde(MDA), superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in supernatants were detected by pectrophotometer. RESULTS: Salidroside obviously inhibited H2O2-induced HLEC vitality decline, inhibited ROS generation in cells, causing SOD, GSH-Px levels increased and MDA levels decreased. CONCLUSION: Salidroside inhibited H2O2 induced HLEC injury by decreasing the intracellular MDA content levels and increasing SOD, GSH-Px content levels, which conclude that salidroside may have a certain role in the treatment of HLEC damage

A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application

Invasive reperfusion after 12 hours of the symptom onset remains beneficial in patients with ST-segment elevation myocardial infarction: Evidence from a meta-analysis of published data

Background: Early myocardial reperfusion therapy (&lt; 12 h) in patients with acute myocardial infarc­tion (AMI) can significantly improve their prognosis. However, the effect of late reperfusion (&gt; 12 h) remains controversial. In this study, the effects of late reperfusion versus standard drug therapy on the outcomes of patients with AMI were evaluated by systematic review and meta-analysis. Methods: PubMed, Embase, Medline, Cochrane, Wanfang, and CNKI databases were searched for eligible studies for the present study. Meta-analysis was performed using RevMan 5.3.3 software. Rela­tive risk (RR) and the 95% confidence interval (CI) were used to compare the outcomes between the two groups. The main outcome measures were major adverse cardiac events (MACEs), all-cause mortality, recurrent myocardial infarction (MI), and heart failure. Results: Eighteen studies were identified including 14,677 patients, of whom 5157 received late reperfusion with percutaneous coronary intervention (PCI) and 9520 received medication therapy (MT). Compared to MT, late PCI was associated with decreased all-cause mortality (RR 0.60, 95% CI 0.44–0.83; p = 0.002), MACEs (RR 0.67; 95% CI 0.50–0.89; p &lt; 0.001), and heart failure (RR 0.76; 95% CI 0.60–0.97; p = 0.03), while there was also a trend toward decreased recurrent MI (RR 0.70; 95% CI 0.47–1.05; p = 0.08). However, subgroup analysis according to time to PCI showed that the clinical benefit was only from PCI after 12 h but not from 2 to 60 days of the onset of symptoms. Conclusions: The present meta-analysis suggested that PCI performed &gt; 12 h but not 2–60 days after AMI is associated with significant improvement in clinical outcomes. However, these results need further rigorously designed large sample size clinical trials to be validated

Predisposing factors for predicting the therapeutic response of adenomyosis after uterine artery embolization: serum CA125 levels and accompanying endometriosis

PURPOSE:We aimed to identify predisposing factors that could help predict the therapeutic response of adenomyosis after uterine artery embolization (UAE).METHODS:This was a retrospective, single-center study of patients admitted to the hospital for adenomyosis between 2013 and 2015. Sixty-eight patients with adenomyosis who underwent UAE with tris-acryl gelatin microspheres were divided into two groups based on their therapeutic response (complete or incomplete necrosis of lesions), and pre- and postprocedural pelvic magnetic resonance imaging (MRI) data. Patients were followed up for 12 months after UAE. Improvements in dysmenorrhea and menorrhagia were evaluated based on the symptom relief criteria. Improvement rates in both groups were analyzed and compared. Multivariate logistic regression analysis was used to identify the predisposing factors from retrospectively gathered baseline data that might affect the therapeutic response, including MRI features, clinical symptoms, biochemical index, and accompanying diseases of adenomyosis. Then, a prognostic model was established, and the receiver operating characteristic (ROC) curve of identified factors was drawn to determine their predictive value.RESULTS:Following UAE, 46 patients (67.6%) showed complete necrosis, while 22 patients (32.4%) showed incomplete necrosis. At 12-month follow-up, dysmenorrhea symptom improvement was seen in 94.7% of complete necrosis and 50% of incomplete necrosis group (P < 0.001); menorrhagia symptom improvement was seen in 96.2% of complete necrosis and 57.1% of incomplete necrosis groups (P = 0.004). Multivariate logistic regression analysis determined serum cancer antigen 125 (CA125) levels (odds ratio [OR], 1.006; 95% confidence interval [CI], 1.002–1.010; P = 0.005) and accompanying endometriosis (OR, 6.869; 95% CI, 1.881–25.016; P = 0.004) as predisposing factors. The areas under the ROC curve of CA125, endometriosis, and these two indicators combined were 0.785, 0.708, and 0.845, which corresponded to sensitivities of 95.5%, 66.7%, and 68.2% and specificities of 52.2%, 80.0%, and 87.0% at optimal cutoff values, respectively.CONCLUSION:Symptom relief of dysmenorrhea and menorrhagia for patients with complete necrosis was significantly better than that for patients with incomplete necrosis. Serum CA125 levels and accompanying endometriosis can effectively distinguish complete necrosis from incomplete necrosis