Explore the effect of LLY‐283 on the ototoxicity of auditory cells caused by cisplatin: A bioinformatic analysis based on RNA‐seq

BackgroundCisplatin is a commonly used chemotherapeutic drug in clinics, and long‐term application will lead to hearing impairment. LLY‐283, an inhibitor of PRMT5, has not been reported in deafness. Our study aimed to explore the mechanism of LLY‐283 in hearing impairment.Materials and MethodsFirst, we performed RNA‐seq (cisplatin in the experimental group and DMSO in the control group) to obtain the biological processes mainly involved in differentially expressed genes (DEGs). CCK‐8 and LDH experiments were used to observe the effect of LLY‐283 on cisplatin‐induced auditory cell injury. ROS experiment was used to monitor the impact of LLY‐283 on oxidative damage of auditory cells. Effect of LLY‐283 on apoptosis of auditory cells detected by TUNEL experiment. PCR and Western blotting were used to detect the expression of genes and proteins related to auditory cell apoptosis in LLY‐283 cells. Meanwhile, we explored the effect of LLY‐283 on the expression of PRMT5 in cisplatin‐induced hearing impaired cells at RNA and protein levels.ResultsBiological process analysis showed that DEGs were mainly enriched in the apoptotic process involved in morphogenesis (‐Log₁₀ P = 3.71). CCK‐8 and LDH experiments confirmed that LLY‐283 could save cisplatin‐induced auditory cell injury. ROS experiments confirmed that LLY‐283 could rescue cisplatin‐induced oxidative damage to auditory cells. TUNEL experiments confirmed that LLY‐283 could protect cisplatin‐induced apoptosis of auditory cells. Meanwhile, LLY‐283 could inhibit the expression of PRMT5 in auditory cells induced by cisplatin.ConclusionLLY‐283 can rescue cisplatin‐induced auditory cell apoptosis injury. LLY‐283 can inhibit the increase in PRMT5 expression induced by cisplatin.     

CrkⅡ表达水平对喉癌细胞Hep-2增殖、迁移及侵袭的影响

目的探讨CrkⅡ表达水平对喉癌细胞Hep-2增殖、迁移及侵袭的影响。方法采用免疫组化法检测CrkⅡ在108例喉癌患者喉癌组织及癌旁正常组织中的表达情况,分析不同临床特征喉癌患者喉癌组织中CrkⅡ蛋白的阳性表达情况。构建并验证CrkⅡRNA干扰质粒,将培养后的Hep-2细胞分为空白对照组(未转染质粒)、阴性对照组(转染阴性对照质粒)和实验组(转染CrkⅡ干扰质粒),细胞转染后行实时聚合酶链反应(PCR)扩增。采用蛋白质印迹法(Western blot)检测转染后Hep-2细胞中CrkⅡ的表达水平,噻唑蓝(MTT)法检测细胞的增殖情况,Transwell实验检测细胞的侵袭和迁移能力,细胞划痕实验检测细胞的迁移情况。结果喉癌组织中CrkⅡ蛋白的阳性表达率明显高于癌旁正常组织(P﹤0.01)。临床分期为Ⅲ~Ⅳ期、组织分化程度为中低分化、有淋巴结转移喉癌患者喉癌组织中CrkⅡ蛋白的阳性表达率均高于临床分期为Ⅰ~Ⅱ期、组织分化程度为高分化、无淋巴结转移的喉癌患者(P﹤0.05)。实验组喉癌细胞Hep-2中CrkⅡmRNA和蛋白的相对表达量均低于阴性对照组、空白对照组(P﹤0.05)。实验组穿过基质膜至下室的细胞数目低于阴性对照组和空白对照组(P﹤0.05)。转染48 h时,实验组细胞的迁移率低于阴性对照组、空白对照组(P﹤0.05)。细胞培养24、48、72 h时,实验组Hep-2细胞的光密度(OD)值均低于空白对照组和阴性对照组(P﹤0.05)。结论喉癌细胞Hep-2中CrkⅡ的表达下调可降低细胞的增殖、迁移和侵袭能力,CrkⅡ有可能成为喉癌临床治疗的新靶点。     

Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues

Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.     

Parallel group ICA+ICA: Joint estimation of linked functional network variability and structural covariation with application to schizophrenia

There is growing evidence that rather than using a single brain imaging modality to study its association with physiological or symptomatic features, the field is paying more attention to fusion of multimodal information. However, most current multimodal fusion approaches that incorporate functional magnetic resonance imaging (fMRI) are restricted to second‐level 3D features, rather than the original 4D fMRI data. This trade‐off is that the valuable temporal information is not utilized during the fusion step. Here we are motivated to propose a novel approach called “parallel group ICA+ICA” that incorporates temporal fMRI information from group independent component analysis (GICA) into a parallel independent component analysis (ICA) framework, aiming to enable direct fusion of first‐level fMRI features with other modalities (e.g., structural MRI), which thus can detect linked functional network variability and structural covariations. Simulation results show that the proposed method yields accurate intermodality linkage detection regardless of whether it is strong or weak. When applied to real data, we identified one pair of significantly associated fMRI‐sMRI components that show group difference between schizophrenia and controls in both modalities, and this linkage can be replicated in an independent cohort. Finally, multiple cognitive domain scores can be predicted by the features identified in the linked component pair by our proposed method. We also show these multimodal brain features can predict multiple cognitive scores in an independent cohort. Overall, results demonstrate the ability of parallel GICA+ICA to estimate joint information from 4D and 3D data without discarding much of the available information up front, and the potential for using this approach to identify imaging biomarkers to study brain disorders.     

Short-term effects of splenectomy on serum fibrosis indexes in liver cirrhosis patients

Objective: To determine the changing patterns of 4 liver fibrosis markers pre and post splenectomy (combined with pericardial devascularization [PCDV]) and to examine the short-term effects of splenectomy on liver fibrosis. Methods: Four liver fibrosis markers of 39 liver cirrhosis patients were examined pre, immediately post, 2 days post, and 1 week post (15 cases) splenectomy (combined with PCDV). Results: The laminin (LN) level decreased immediately post surgery compared with the preoperative LN level (P < 0.05). The type IV collagen level decreased immediately post surgery compared with that pre surgery (P < 0.05), it significantly increased (P < 0.05) 2 days post surgery and significantly decreased 1 week post surgery (P < 0.05). Hyaluronic acid and the procollagen III N-terminal peptide levels increased significantly 2 days post surgery compared with that pre and immediately post surgery, they significantly decreased 1 week post surgery compared to 2 days post surgery (P < 0.05). Conclusions: In the short-term, the 4 liver fibrosis markers and the FibroScans post splenectomy showed characteristic changes, splenectomy may transiently initiate the degradation process of liver fibrosis.     

The Performance Evaluation of Asphalt Mortar and Asphalt Mixture Containing Municipal Solid Waste Incineration Fly Ash

The aim of the research is to quantify the property of asphalt mortar and asphalt mixture containing municipal solid waste incineration (MSWI) fly ash. The potential of partially replacing mineral fillers with MSWI fly ash in asphalt mixture production was investigated. Five different MSWI fly ash replacement ratios, which include 0%, 25%, 50%, 75%, and 100%, were adopted to assess the influence of fly ash dosage, and the optimum fly ash replacement ratio was proposed. The rheological characteristics of asphalt mortar with MSWI fly ash were assessed with the dynamic shear rheometer (DSR) and bending beam rheometer (BBR). The high temperature properties of the mixture with MSWI fly ash were assessed with the Marshall stability test and the rutting test. The low temperature cracking property was determined with the indirect tensile strength test at low temperatures. The moisture stability property was identified with the immersed Marshall test and the freeze-thaw cycles conditioned indirect tensile strength test. Based on the test results, the addition of fly ash and mineral filler remarkably increased the ǀG*ǀ of the asphalt mortar. The δ of asphalt decreased as the dosage of fly ash and mineral filler increased. The addition of fly ash and mineral filler degraded the low temperature characteristics of the mortar. Fly ash improved the high temperature characteristics of the asphalt mixture. The asphalt mixture with MSWI fly ash was more susceptible to thermal cracking than the control sample. The addition of fly ash weakened the moisture stability of the asphalt mixture. In order to guarantee the low temperature characteristics and the moisture susceptibility of the asphalt mixture, the fly ash replacement ratio was recommended to be set around 25%. With proper mixture design and fly ash dosage, the asphalt mixture would have adequate performance, as well as reduced environmental impact.     

Chemoembolization for Hepatocellular Carcinoma in Patients with Extrahepatic Spread: Prognostic Determinants and Appropriate Candidates

Purpose

To investigate treatment outcome, prognostic factors for overall survival, and appropriate candidates for transarterial chemoembolization among patients with hepatocellular carcinoma (HCC) and extrahepatic spread (EHS).

Acupuncture anaesthesia in inguinal hernia repair

Background: The present study was undertaken to evaluate the efficacy of acupuncture anaesthesia in inguinal hernia repair. Methods: Twelve patients with non‐recurrent inguinal hernia had Lichtenstein mesh repair under acupuncture anaesthesia. Selected acupuncture loci were stimulated with fine needles connected to low frequency current. Supplementary local anaesthetic was given when required. Results: Four (33%) patients reported satisfactory analgesic effect throughout the operation without need for additional medication, eight (67%) patients experienced mild discomfort during the operation requiring 1?4 mL of 1% lignocaine injection. Blood pressure and heart rate were stable during the procedure. All patients were able to sit up and resume their diet immediately post­operatively. All but one patient were discharged on day one after the procedure, with no early or late complications reported. Most patients were satisfied with the analgesic effect of acupuncture anaesthesia. Conclusions: Acupuncture anaesthesia is a feasible anaesthetic option. It reduces the amount of local anaesthetic required, and thus the associated potential complications. It is effective in pain relief and inhibiting gastrointestinal upset. Postoperative recovery was rapid and complication free.