[Association between physical exercise and non-alcoholic fatty liver disease in people infected with hepatitis B virus].

Objective: To investigate the association between physical exercise and non-alcoholic fatty liver disease (NAFLD) in people infected with HBV. Methods: The information about the 3 813 participants infected with HBV, including the prevalence of NAFLD, prevalence of physical exercise and other covariates, were collected from the National Science and Technology Major Project of China during 2016-2020. The logistic regression model was used to evaluate the association between physical exercise and NAFLD in HBV infected patients, and subgroup analysis was performed to identify the effect modifiers. Results: A total of 2 259 HBV infected participants were included in the final analysis and 454 (20.10%) had NAFLD. After adjusting for covariates, we found that moderate physical exercise was a protective factor for NAFLD (OR=0.66, 95%CI: 0.46-0.94). Subgroup analysis suggested that the protective effect of moderate physical exercise on NAFLD might be stronger in women (OR=0.61, 95%CI: 0.36-1.01), those <45 years old (OR=0.24, 95%CI: 0.06-0.80), those who had low education level (OR=0.16, 95%CI: 0.04-0.49), those who had low annual income (OR=0.39, 95%CI: 0.16-0.89 for <30 000 yuan RMB; OR=0.64, 95%CI: 0.40-1.00 for 30 000-80 000 yuan RMB), those who had hypertension (OR=0.45, 95%CI: 0.21-0.88), those with BMI ≥24.0 kg/m2 (OR=0.66, 95%CI: 0.43-1.01), those who had more daily fruit or vegetable intake (OR=0.61, 95%CI: 0.38-0.97), those who had more daily meat intake (OR=0.49, 95%CI: 0.23-0.97), and those who had no smoking history (OR=0.66, 95%CI: 0.45-0.95) or passive smoking exposure (OR=0.61, 95%CI: 0.37-0.97). Conclusions: Among HBV infected patients, moderate physical exercise was negatively associated with the prevalence of NAFLD. Women, young people, those who had low education level, those who had low annual income, those with hypertension, those with high BMI, those who had more daily fruit or vegetable and meat intakes, and those who had no smoking history or passive smoking exposure might be more sensitive to the protective effect.

Manipulating the carrier concentration and phase transition via Nb content in SrTiO3.

SrTiO3 is a model of the perovskite-like compounds for structural transition which inducing the intriguing physical properties around the critical phase transition temperature TAFD (antiferrodistortive, abbrev. as AFD). Here we report that the electrical transport behavior is a new way to quantify Nb concentration for Nb-doped SrTiO3. The lattice parameter (c), phase transition temperature (TAFD), and the carrier concentration (n) of SrTiO3 may be manipulated by niobium doping. TAFD increases with increasing the niobium content in a rate of about 30 K per (wt%, i.e. niobium element's weight verses total weight) niobium and n in a rate of about 2.5 [Formula: see text] 1020/cm3 per (wt%) niobium.

Modulating the electronic and optical properties for SrTiO3/LaAlO3 bilayers treated as the 2D materials by biaxial strains.

The emerging two-dimensional (2D) materials such as graphene have opened the door to industrial applications. Here, we consider the oxide perovskite monolayer of SrTiO3 (STO), LaAlO3 (LAO) and their heterostructures as the 2D transitional metal system. Results show that a band-gap transition from indirect to direct occurs when the separated monolayer STO (indirect band gap of 3.210 eV), and LAO (indirect band gap of 4.024 eV), form the heterostructures (direct band gap of 2.976 eV). The obtained bandgap for the stable bilayers may effectively be modulated by biaxial strains from -12% to 8%. With 12% compressive biaxial strain, the band gap reduces to be 0.23 eV. The optical properties for the stable bilayers are also tuned by the biaxial strain. When the strain increases from compressive strain to tensile strain, the strongest peak of the imaginary part of dielectric function red shifts to lower energy. In comparing with the monolayer STO and LAO, the elastic property enhances obviously for the stable heterostructure, suggesting the heterostructure can be more stable freestanding or may be applied in device fabrications.

MiR-1294 acts as a tumor suppressor in clear cell renal cell carcinoma through targeting HOXA6.

OBJECTIVE: Renal cancer represents about 3% of all human cancers. Clear cell renal cell carcinoma (ccRCC) is the main type of renal cancer. MicroRNAs (miRNAs) have been reported to play crucial roles in the carcinogenesis of human cancers. This study was aimed to investigate the expression of miR-1294 and the mechanisms underlying miR-1294-mediated ccRCC progression. MATERIALS AND METHODS: The miR-1294 expression levels in ccRCC cell lines were analyzed by quantified real time-PCR (qRT-PCR). The effect of the miR-1294 expression on the overall survival of ccRCC patients was analyzed by the Kaplan-Meier Plotter. Cell proliferation, colony growth, and cell invasion were examined by cell counting kit-8 assay, colony formation assay, and transwell invasion assay, respectively. The luciferase activity reporter assay and Western blot assay were conducted to validate the connection between miR-1294 and homeobox A6 (HOXA6). RESULTS: MiR-1294 was downregulated in ccRCC cell lines and correlated with the poor overall survival of ccRCC patients. The overexpression of miR-1294 inhibits ccRCC cell proliferation, colony growth, and cell invasion. HOXA6 was validated as a target of miR-1294 and negatively regulated by miR-1294. The overexpression of HOXA6 attenuated the miR-1294-mediated effects on ccRCC cellular functions. CONCLUSIONS: Our results indicated that miR-1294 functions as a tumor suppressor in ccRCC. MiR-1294 suppressed cell proliferation, colony formation, and invasion in ccRCC partially via targeting HOXA6.

Therapeutic efficacy of atypical antipsychotic drugs by targeting multiple stress-related metabolic pathways.

Schizophrenia (SZ) is considered to be a multifactorial brain disorder with defects involving many biochemical pathways. Patients with SZ show variable responses to current pharmacological treatments of SZ because of the heterogeneity of this disorder. Stress has a significant role in the pathophysiological pathways and therapeutic responses of SZ. Atypical antipsychotic drugs (AAPDs) can modulate the stress response of the hypothalamic-pituitary-adrenal (HPA) axis and exert therapeutic effects on stress by targeting the prefrontal cortex (PFC) and hippocampus. To evaluate the effects of AAPDs (such as clozapine, risperidone and aripiprazole) on stress, we compared neurochemical profile variations in the PFC and hippocampus between rat models of chronic unpredictable mild stress (CUMS) for HPA axis activation and of long-term dexamethasone exposure (LTDE) for HPA axis inhibition, using an ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS)-based metabolomic approach and a multicriteria assessment. We identified a number of stress-induced biomarkers comprising creatine, choline, inosine, hypoxanthine, uric acid, allantoic acid, lysophosphatidylcholines (LysoPCs), phosphatidylethanolamines (PEs), corticosterone and progesterone. Specifically, pathway enrichment and correlation analyses suggested that stress induces oxidative damage by disturbing the creatine-phosphocreatine circuit and purine pathway, leading to excessive membrane breakdown. Moreover, our data suggested that the AAPDs tested partially restore stress-induced deficits by increasing the levels of creatine, progesterone and PEs. Thus, the present findings provide a theoretical basis for the hypothesis that a combined therapy using adenosine triphosphate fuel, antioxidants and omega-3 fatty acids as supplements may have synergistic effects on the therapeutic outcome following AAPD treatment.

[Methylation and demethylation of SOX2 gene promoter in BGC-823 gastric cancer cells].

OBJECTIVE: To study the significance and effect of methylation status of sex determining region Y-box 2 (SOX2) gene promoter, and to investigate the effect of demethylation on the cell proliferation and invasion in BGC-823 gastric cancer cells. METHODS: Methylation-specific PCR (MSP) was used to assess the role of 5-aza-2'-deoxycytidine (5-Aza-CdR) in the methylation of SOX2 promoter in the BGC-823 cell lines treated with different concentration of 5-Aza-CdR. We mapped the expression of SOX2 in the BGC-823 cell lines by the quantitative real-time PCR (qPCR) and Western blotting before and after treatment of 5-Aza-CdR. The survival of BGC-823 cells were detected by MTT assay. The invasion and migration of BGC-823 cells were investigated by transwell methods, and the migration of BGC-823 cells was also assessed by the scratch assay exposed to 5-Aza-CdR or vehicle control. Model of transplanted tumor on nude mouse were used to study the anticancer effect of 5-Aza-CdR in vivo by qPCR, Western blotting and immunohistochemistry. RESULTS: The methyltransferase inhibitor 5-Aza-CdR restored the loss of SOX2 expression in BGC-823 cell lines in a dose-dependent manner. The mRNA and protein expression of SOX2 had significant difference between the gastric cancer tissues and normal gastric mucosa (mRNA levels: 22.80±0.36 vs 20.36±0.45, P<0.05; protein levels: 0.49±0.01 vs 0.91±0.28, P<0.05). It also had significant difference among the BGC-823 cell lines treated with 5-Aza-CdR of the different concentrations (0, 1 and 10 µmol/L) (mRNA levels: 22.99±0.42 vs 21.78±0.41 vs 20.51±0.47, P<0.05; protein levels: 0.65±0.19 vs 0.73±0.13 vs 0.83±0.14, P<0.05). Compared with the control group (5-Aza-CdR concentration of 0 µmol/L), the survival rates of BGC-823 cell lines were significantly decreased in treatment groups (5-Aza-CdR concentrations of 1, 10 and 20 µmol/L, all P<0.05). Restored expression of SOX2 in the BGC-823 cell lines inhibited cell proliferation, colony formation and cell migration (P<0.05). Model of transplanted tumor on nude mouse in the 5-Aza-CdR group eventually had the smaller tumor size, the lighter tumor weight and the longer survival time than these in the PBS group [(286.6±37.5) vs (540.7±42.6)mm(3,) P<0.05; (325.2±32.2) vs (694.7±36.1)mg, P<0.05; (22.5±1.0) vs (18.7±1.6) d, P<0.05]. Meanwhile, the 5-Aza-CdR group increased the SOX2 protein expression levels and immunohistochemistry scores (0.96±0.25 vs 0.73±0.15, P<0.05; 6.23±0.45 vs 3.76±0.43, P<0.05). CONCLUSIONS: The SOX2 gene promotor is in the status of methylation in the BGC-823 cell. The recovery expression of SOX2 inhibits cell proliferation, invasion and the development of transplanted tumor in nude mice through DNA methyltransferase inhibition. It could suggest a new approach for the treatment of gastric cancer.

A potential mechanism underlying atypical antipsychotics-induced lipid disturbances.

Previous findings suggested that a four-protein complex, including sterol-regulatory element-binding protein (SREBP), SREBP-cleavage-activating protein (SCAP), insulin-induced gene (INSIG) and progesterone receptor membrane component 1 (PGRMC1), within the endoplasmic reticulum appears to be an important regulator responsible for atypical antipsychotic drug (AAPD)-induced lipid disturbances. In the present study, effects of typical antipsychotic drug and AAPDs as well as treatment outcome of steroid antagonist mifepristone (MIF) on the PGRMC1/INSIG/SCAP/SREBP pathway were investigated in rat liver using real-time quantitative polymerase chain reaction (qPCR) and western blot analysis. In addition, serum triacylglycerol, total cholesterol, free fatty acids and various hormones including progesterone, corticosterone and insulin were measured simultaneously. Following treatment with clozapine or risperidone, both lipogenesis and cholesterogenesis were enhanced via inhibition of PGRMC1/INSIG-2 and activation of SCAP/SREBP expressions. Such metabolic disturbances, however, were not demonstrated in rats treated with aripiprazole (ARI) or haloperidol (HAL). Moreover, the add-on treatment of MIF was effective in reversing the AAPD-induced lipid disturbances by upregulating the expression of PGRMC1/INSIG-2 and subsequent downregulation of SCAP/SREBP. Taken together, our findings suggest that disturbances in lipid metabolism can occur at an early stage of AAPD treatment before the presence of weight gain. Such metabolic defects can be modified by an add-on treatment of steroid antagonist MIF enhancing the PGRMC1 pathway. Thus, it is likely that PGRMC1/INSIG-2 signaling may be a therapeutic target for AAPD-induced weight gain.