Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD-, LRR- and pyrin domain-containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve- and synapse-related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase-1, the pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.     

Protective effect of Agrimonia pilosa polysaccharides on dexamethasone‐treated MC3T3‐E1 cells via Wnt/β‐Catenin pathway

A water‐soluble polysaccharide (APP‐AW) was isolated from Agrimonia pilosa and prepared to three sulphated derivatives (S1, S2 and S3). The results showed that pre‐treatment with APP‐AW, S1, S2 and S3 each at the concentration of 50 μg/mL for 48 hours was able to prevent cytotoxicity induced by 1 μmol/L dexamethasone (Dex) in MC3T3‐E1 cells via inhibition of apoptosis, which is in line with the findings in flow cytometry analysis. Meanwhile, the decreased ALP activity, collagen content, mineralization, BMP2, Runx2, OSX and OCN protein expression in DEX‐treated MC3T3‐E1 cells were reversed by the addition of APP‐AW, S1, S2 and S3. Moreover, APP‐AW, S1, S2 and S3 rescued DEX‐induced increase of Bax, cytochrome c and caspase‐3 and decrease of Bcl‐2, Wnt3, β‐catenin and c‐Myc protein expression in MC3T3‐E1 cells. Our findings suggest that pre‐treatment with APP‐AW, S1, S2 and S3 could significantly protect MC3T3‐E1 cells against Dex‐induced cell injury via inhibiting apoptosis and activating Wnt/β‐Catenin signalling pathway, thus application of these polysaccharides may be a promising alternative strategy for steroid‐induced avascular necrosis of the femoral head (SANFH) therapy.     

Association of suboptimal health status with intestinal microbiota in Chinese youths

Suboptimal health status (SHS), a physical state between health and disease, is a subclinical and reversible stage of chronic disease. Previous studies have shown alterations in the intestinal microbiota in patients with some chronic diseases. This study aimed to investigate the association between SHS and intestinal microbiota in a case‐control study with 50 SHS individuals and 50 matched healthy controls. Intestinal microbiota was analysed by MiSeq 250PE. Alpha diversity of intestinal microbiota in SHS individuals was higher compared with that of healthy controls (Simpson index, W = 2238, P = .048). Beta diversity was different between SHS and healthy controls (P = .018). At the phylum level, the relative abundance of Verrucomicrobia was higher in the SHS group than that in the controls (W = 2201, P = .049). Compared with that of the control group, nine genera were significantly higher and five genera were lower in abundance in the SHS group (all P < .05). The intestinal microbiota, analysed by a random forest model, was able to distinguish individuals with SHS from the controls, with an area under the curve of 0.79 (95% confidence interval: 0.77‐0.81). We demonstrated that the alteration of intestinal microbiota occurs with SHS, an early stage of disease, which might shed light on the importance of intestinal microbiota in the primary prevention of noncommunicable chronic diseases.     

Cardioprotective effect of isorhamnetin against myocardial ischemia reperfusion (I/R) injury in isolated rat heart through attenuation of apoptosis

In this study, we investigated the effects of isorhamnetin on myocardial ischaemia reperfusion (I/R) injury in Langendorff-perfused rat hearts. Isorhamnetin treatment (5, 10 and 20 μg/mL) significantly alleviated cardiac morphological injury, reduced myocardial infarct size, decreased the levels of marker enzymes (LDH and CK) and improved the haemodynamic parameters, reflected by the elevated levels of the left ventricular developed pressure (LVDP), coronary flow (CF) and the maximum up/down velocity of left ventricular pressure (+dp/dt_max). Moreover, isorhamnetin reperfusion inhibited apoptosis of cardiomyocytes in the rats subjected to cardiac I/R in a dose-dependent manner concomitant with decreased protein expression of Bax and cleaved-caspase-3, as well as increased protein expression of Bcl-2. In addition, I/R-induced oxidative stress was manifestly mitigated by isorhamnetin treatment, as showed by the decreased malondialdehyde (MDA) level and increased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). These results indicated that isorhamnetin exerts a protective effect against I/R-induced myocardial injury through the attenuation of apoptosis and oxidative stress.     

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX^promotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX^promotor‐AIM2 adenoviruses (Ad‐CAIX^promotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX^promotor, Ad‐CAIX^promotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX^promotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX^promotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX^promotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX^promotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.     

Direct Visualization of the Interfacial Degradation of Cathode Coatings in Solid State Batteries: A Combined Experimental and Computational Study

The interfacial instability between a thiophosphate solid electrolyte and oxide cathodes results in rapid capacity fade and has driven the need for cathode coatings. In this work, the stability, evolution, and performance of uncoated, Li₂ZrO₃‐coated, and Li₃B₁₁O₁₈‐coated LiNi_0.5Co_0.2Mn_0.3O₂ cathodes are compared using first‐principles computations and electron microscopy characterization. Li₃B₁₁O₁₈ is identified as a superior coating that exhibits excellent oxidation/chemical stability, leading to substantially improved performance over cells with Li₂ZrO₃‐coated or uncoated cathodes. The chemical and structural origin of the different performance is interpreted using different microscopy techniques which enable the direct observation of the phase decomposition of the Li₂ZrO₃ coating. It is observed that Li is already extracted from the Li₂ZrO₃ in the first charge, leading to the formation of ZrO₂ nanocrystallites with loss of protection of the cathode. After 50 cycles separated (Co, Ni)‐sulfides and Mn‐sulfides can be observed within the Li₂ZrO₃‐coated material. This work illustrates the severity of the interfacial reactions between a thiophosphate electrolyte and oxide cathode and shows the importance of using coating materials that are absolutely stable at high voltage.     

PVP Treatment Induced Gradient Oxygen Doping in In2S3 Nanosheet to Boost Solar Water Oxidation of WO3 Nanoarray Photoanode

The photoelectrochemical performance of the WO₃ photoanode is limited by the severe charge recombination in the bulk phase and at the WO₃/electrolyte interface. Herein, In₂S₃ nanosheets are integrated onto the surface of the WO₃ nanowall array photoanode, followed by a facile polyvinylpyrrolidone (PVP) solution treatment. The PVP treatment results in sulfur vacancies and a gradient oxygen doping into In₂S₃ from surface to interior, which induces the formation of a gradient energy band distribution. The gradient band structured In₂S₃ and type II band alignment at the WO₃/In₂S₃ interface simultaneously create a channel that favors photogenerated electrons to migrate from the surface to the conductive substrate, thereby suppressing bulk carrier recombination. Meanwhile, the sulfur vacancies and oxygen doping contribute to increased charge carrier concentration, prolonged carrier lifetime, more active sites, and small interfacial transfer impedance. As a consequence, the PVP treated WO₃/In₂S₃ heterostructure photoanode exhibits a significantly enhanced photocurrent of 1.61 mA cm^?2 at 1.23 V versus reversible hydrogen electrode (RHE) and negative onset potential of 0.02 V versus RHE.     

瑞芬太尼复合丙泊酚麻醉对结肠癌手术患者血流动力学、炎症反应及免疫球蛋白的影响

目的:探讨瑞芬太尼复合丙泊酚麻醉对结肠癌手术患者血流动力学、炎症反应及免疫球蛋白的影响。方法:选取2017年1月～2018年12月期间于新疆医科大学附属第一医院行腹腔镜下结肠癌根治术患者189例,根据随机数字表法将患者分成对照组(n=94,丙泊酚麻醉)和研究组(n=95,瑞芬太尼复合丙泊酚麻醉),比较两组患者围术期指标、血流动力学、炎症反应及免疫球蛋白水平,记录两组术中不良反应发生情况。结果:研究组患者苏醒时间、拔管时间、自主呼吸恢复时间、定向力恢复时间均短于对照组(P0.05)。对照组麻醉诱导10 min(T2)、术毕拔管后10 min(T3)时间点心率(HR)、平均动脉压(MAP)较T1时间点降低,T3时间点高于T2时间点(P0.05),研究组T2时间点HR、MAP较T1时间点降低(P0.05);研究组T2、T3时间点HR、MAP高于对照组同时间点(P0.05)。研究组术后1h(T4)、术后1d(T5)时间点白介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)低于对照组同时间点(P0.05)。研究组T4、T5时间点免疫球蛋白A(Ig A)、免疫球蛋白M(Ig M)、免疫球蛋白G(Ig G)高于对照组同时间点(P0.05)。两组不良反应发生率比较差异无统计学意义(P0.05)。结论:结肠癌手术中使用瑞芬太尼复合丙泊酚麻醉,可有效改善围术期各项指标,维持机体血流动力学稳定,减少机体炎症反应、免疫抑制,安全可靠。     

重庆地区人类免疫缺陷病毒携带者的微孢子虫感染情况调查

目前我国关于微孢子虫感染人的研究相对较少,更没有关于重庆地区人类免疫缺陷病毒(HIV)携带者感染微孢子虫的数据统计。对重庆市公共卫生医疗救治中心收治的22例HIV抗体阳性,但尚未接受抗病毒治疗的患者进行研究。将22例患者粪便样本分别提取总DNA,通过聚合酶链反应(PCR)法和DNA测序等技术对微孢子虫在患者中的感染情况进行检测,并对微孢子虫种类进行鉴定。同时对22例患者的免疫细胞亚群进行计数和分析。结果显示,微孢子虫的感染率为36.3%(8/22),主要由脑炎微孢子虫属(Encephalitozoon spp)的海伦脑炎微孢子虫(E. hellem)和肠脑炎微孢子虫(E. intestinalis)引起。22例患者的免疫细胞亚群分析显示,平均淋巴细胞数0.93±0.13×10⁹/L,CD4^＋T细胞数132±22 个/mL,CD8^＋T细胞数495±91 个/mL,CD4/CD8细胞比值0.37±0.1,表明患者免疫功能受到严重抑制。进一步将微孢子虫感染患者与未感染患者的免疫细胞亚群进行比较发现,感染患者淋巴细胞数为0.51±0.1×10⁹/L,未感染患者为1.17±0.17 ×10⁹/L,两者具有显著差异(P<0.05);感染患者CD4^＋T细胞数为71±27 个/mL,未感染患者为167±28 个/mL,两者具有显著差异(P<0.05);感染患者CD8^＋T细胞数为209±35 个/mL,未感染患者为658±123 个/mL,两者具有显著差异(P<0.05),以上表明微孢子虫感染组的免疫功能受损情况更严重。本研究结果提示微孢子虫的机会性感染与患者免疫功能受损情况密切相关,脑炎微孢子虫属在重庆地区有较高的感染率,这为进一步阐明微孢子虫与宿主相互作用关系奠定基础,也为公共卫生健康管理提供重要参考。