General physiology and biophysics最新文献

This study was aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of patients with clear-cell renal cell carcinoma (ccRCC). Based on the Surveillance, Epidemiology, and End Results (SEER) database, 24,477 patients diagnosed with ccRCC between 2010 and 2015 were collected. They were randomly divided into a training cohort (n = 17,133) and a validation cohort (n = 7,344). Univariate and multivariate Cox regression analyses were performed in the training cohort to identify independent prognostic factors for construction of nomogram. Then, the nomogram was used to predict the 3- and 5-year CSS. The performance of nomogram was evaluated by using concordance index (C-index), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA). Moreover, the nomogram and tumor node metastasis (TNM) staging system (AJCC 7th edition) were compared. Eleven variables were screened to develop the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) and the calibration plots indicated satisfactory ability of the nomogram. Compared with the AJCC 7th edition of TNM stage, C-index, NRI, and IDI showed that the nomogram had improved performance. Furthermore, the 3- and 5-year DCA curves of nomogram yielded more net benefits than the AJCC 7th edition of TNM stage in both the training and validation sets. We developed and validated a nomogram for predicting the CSS of patients with ccRCC, which was more precise than the AJCC 7th edition of TNM staging system.

Infection stones constitute a small but intractable group of diseases of urinary system. In this study, we explored the potential therapeutic effect of a small activation RNA, ds-320, encapsulated in chitosan (320-chitosan). Western blot analysis verified the downregulation of TRPV5 in patients and rat model of infection stones, as well as the stimulation of ds-320 on TRPV5 expression. MTT assay showed that chitosan-mediated delivery was less cytotoxic to ds-320 compared with liposome delivery. Further a modified invasion assay revealed an inhibitory effect of 320-chitosan on bacterial invasion into normal rat kidney epithelial NRK-52E cells. The establishment of infection stone model was performed by intravesical injection of 1×108 CFU of Proteus mirabilis. In animal experiments, no visible stones were obtained. The number of live bacteria and white blood cells in urine showed no difference among all infected rats at the time of sacrifice. However, we observed a decline in urine calcium and pH, suggesting the effect of acidification. Overall, our study provides evidence for the protective effect of 320-chitosan, for its ability to down-regulate urinary calcium, acidify urine, and inhibit bacteria from invading renal epithelial cells. Thus, it can be served as an important complementary therapy for infection stones.

This study aimed to investigate the effect of cerium oxide nanoparticles (CeO2-NPs) on non-alcoholic fatty liver disease in postmenopausal obesity and the underlying mechanisms.64 adult female rats were allocated into Sham, ovariectomized (OVX), high-fat high-fructose dietfed- OVX (HFHF-OVX), and HFHF-OVX-CeO2-NPs-treated (CeO2-HFHF-OVX) groups. OVX and HFHF-OVX rats presented a significant increase in overall and visceral obesity, dyslipidemia, liver enzymes, serum malondialdehyde, liver TNF-α, TGF-β1 and free fatty acids, liver X receptor (LXR) expression associated with decreased serum total antioxidant capacity and liver short heterodimer partner (SHP) expression vs. Sham group. Also, histomorphometric studies displayed a significant higher scores of liver steatosis, inflammation and fibrosis. All these parameters were significantly improved by CeO2-NPs treatment in CeO2-HFHF-OVX vs. HFHF-OVX rats. Thus, CeO2-NPs treatment ameliorates liver steatosis, steatohepatitis, and fibrosis in postmenopausal obese rats via alleviation of obesity, dyslipidemia, modulating liver genes involved in lipid metabolism (LXR and SHP), decreasing liver lipogenesis besides its antioxidant and anti-inflammatory effects.

Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.

Lung carcinoma is the "top killer" of all malignancies in the world. Early diagnosis of lung carcinoma significantly improves patient survival. Screening with biomarkers from peripheral blood could detect more patients at an early stage of the disease. MicroRNAs (miRNAs) could be a possible biomarker. These are 21-23 nucleotide long single-stranded RNA molecules playing an important role in the post-transcriptional regulation of gene activity. Individual miRNAs have the potential to regulate genes responsible for cell proliferation, differentiation, apoptosis, regulate cell cycle in cooperation with pro-oncogenes and tumor suppressor genes. In our study, we determined miRNA expression levels in individual samples of lung carcinoma patients and in a healthy control group. We used the reverse transcription method followed by qRT-PCR. The expression levels of the investigated miRNAs were evaluated in the QIAGEN GeneGlobe Data center software. We demonstrated the significance of miR-126 and let-7g as biomarkers of lung carcinoma in all clinical stages studied. We also observed significantly increased expression of miR-143 and miR-145 at the distant metastasis stage, and significantly decreased expression of miR-133a in the N2 disease group of lung carcinoma patients (N2 disease represents disease with metastases in the ipsilateral mediastinal and/or subcarinal lymph nodes or node). The investigated miRNAs showed no clear potential for detecting potentially resectable (N0-N1), locally advanced (N2) and distant organ metastatic (M1) lung carcinoma.

Hypoxia leads to hypoxic pulmonary hypertension (HPH), causing right ventricular hypertrophy (RVH). RVH becomes a significant and nonnegligible public health issue in the world. In our study, we successfully established the HPH rat model and found that RVH happened in HPH, and then we observed an increased inflammation response in the heart tissue of HPH-induced RVH rats. Moreover, increased N-deacetylase-N-sulfotransferase-1 (NDST1) and decreased nuclear localized protein 1 (NULP1) were found in the heart tissue of HPH-induced RVH rats. An in vitro cell experiment showed that inhibition of NDST1 expression enhanced cell viability, reduced cell apoptosis, alleviated cardiomyocyte hypertrophy, decreased inflammation and increased phosphorylated AKT level, however, over-expression of NDST1 had opposite effects on these aspects. NULP1 reversed the effects of NDST1 on these regulations. Finally, we found that up-regulated NDST1 reduced NULP1 expression and down-regulated NDST1 increased NULP1 expression. Our study confirmed that inhibition of the NDST1/NULP1 pathway might contribute to the attenuation of HPH-induced RVH, and the mechanism may be related to the reduction of inflammation, cardiomyocyte apoptosis, and AKT phosphorylation.

Study was focused on regulatory interactions between the circadian system and the renin-angiotensin system in control of microRNA (miRNA) biosynthesis. Responsiveness of the miRNA biosynthetic pathway, selected pre-miRNAs and clock genes to angiotensin II (AngII) infusion was analysed in the suprachiasmatic nuclei (SCN), liver, kidney and heart during a 24-h cycle. per2 exerted a rhythmic expression profile in all analysed tissues. clock expression showed a rhythmic pattern in the peripheral tissues with tissue-specific response to AngII. dgcr8 expression showed a tissue-specific rhythm only in peripheral tissues, which diminished in the heart and kidney after AngII delivery. Expression of pre-miR-30c was rhythmic in all studied peripheral tissues, pre-miR-34a expression exerted significant rhythm only in the liver. AngII delivery increased expression of pre-miR-30c and pre-miR-34a in the kidney. To conclude, peripheral oscillators are more likely to exhibit rhythmic miRNA biosynthesis responsive to AngII in a tissue-specific manner compared to SCN.

Favipiravir is a drug which shows antiviral activity by inhibiting RNA-dependent RNA polymerase. Favipiravir causes severe adverse effects at high doses. The aim of this study was to investigate the effects of low and high dose favipiravir on ovarian and reproductive function in female rats. The rats were divided into three groups: HG group (healthy rats), FAV-100 group (rats administered 100 mg/kg favipiravir), and FAV-400 group (rats administered 400 mg/kg favipiravir) with 12 rats in each group. Favipiravir was administered orally twice daily for 1 week. Six rats from each group were euthanized and their ovaries were removed. Oxidative and antioxidant parameters were measured in ovarian tissues and examined histopathologically. The remaining animals were kept to breed. Animals receiving favipiravir had increased oxidant content, decreased antioxidant activity, decreased histopathological damage, infertility, and gestational delay. Favipiravir treatment should be used with caution, especially in women of reproductive age.

Heart failure (HF) is the leading cause of death and public health problems in the global population. This study aimed to identify and validate ferroptosis-related biomarkers associated with HF in clinical medicine using bioinformatics and machine learning strategies. Weighted co-expression network analysis (WGCNA) was applied to screen the module genes and analyze their biological functions and pathways. Ferroptosis-associated genes (FAG) in HF were determined and then machine learning algorithms were used for screening. Next, multiple external independent microarrays were used to verify molecular biosignature. Simultaneously, CIBERSORT was applied to estimate the immune infiltration landscape. Combined with the results of the WGCNA, 25 FAGs were determined and 6 FAMBs were selected by machine learning strategies. In addition, Peroxiredoxin 6 (PRDX6) was finally selected as the key ferroptosis-associated molecular biological feature based on multiple verifications of independent data sets. From the results of the infiltration and enrichment analysis, we believed that PRDX6, as a protective biomarker related to ferroptosis in HF, may help provide new ideas in the immunotherapy of HF.