Prenatal exposure to low-dose bisphenol A disrupts hippocampal DNA methylation and demethylation in male rat offspring.

Earlier research has demonstrated that developmental exposure to bisphenol A (BPA) has persistent impacts on both adult brain growth and actions. It has been suggested that BPA might obstruct the methylation coding of the genes in the brain. In this study, the methylation changes in the hippocampus tissue of male rat pups were examined following prenatal BPA exposure. Pregnant Sprague-Dawley rats were treated with either vehicle (tocopherol-stripped corn oil) or BPA (4, 40, or 400 µg/kg·body weight/day) throughout the entire duration of gestation and lactation. At 3 weeks of age, the male rat offspring were euthanized, and the hippocampus were dissected out for analysis. The expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and DNA demethylases (TET1, Gadd45a, Gadd45b, and Apobec1) were analyzed in the hippocampus by means of quantitative real-time polymerase chain reaction and Western blotting, respectively. The results showed that prenatal exposure to BPA upregulated the expression of enzymes associated with DNA methylation and demethylation processes in the hippocampus of male rat offspring. These findings suggest that prenatal exposure to a low dose of BPA could potentially disrupt the balance of methylation and demethylation in the hippocampus, thereby perturbing epigenetic modifications. This may represent a neurotoxicity mechanism of BPA.

Association of vitamin D deficiency and subclinical diabetic peripheral neuropathy in type 2 diabetes patients.

Background: Diabetic peripheral neuropathy (DPN) contributes to disability and imposes heavy burdens, while subclinical DPN is lack of attention so far. We aimed to investigate the relationship between vitamin D and distinct subtypes of subclinical DPN in type 2 diabetes (T2DM) patients. Methods: This cross-sectional study included 3629 T2DM inpatients who undertook nerve conduction study to detect subclinical DPN in Zhongshan Hospital between March 2012 and December 2019. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25(OH)D) level < 50 nmol/L. Results: 1620 (44.6%) patients had subclinical DPN and they were further divided into subgroups: distal symmetric polyneuropathy (DSPN) (n=685), mononeuropathy (n=679) and radiculopathy (n=256). Compared with non-DPN, DPN group had significantly lower level of 25(OH)D (P < 0.05). In DPN subtypes, only DSPN patients had significantly lower levels of 25(OH)D (36.18 ± 19.47 vs. 41.03 ± 18.47 nmol/L, P < 0.001) and higher proportion of vitamin D deficiency (78.54% vs. 72.18%, P < 0.001) than non-DPN. Vitamin D deficiency was associated with the increased prevalence of subclinical DPN [odds ratio (OR) 1.276, 95% confidence interval (CI) 1.086-1.501, P = 0.003] and DSPN [OR 1. 646, 95% CI 1.31-2.078, P < 0.001], independent of sex, age, weight, blood pressure, glycosylated hemoglobin, T2DM duration, calcium, phosphorus, parathyroid hormone, lipids and renal function. The association between vitamin D deficiency and mononeuropathy or radiculopathy was not statistically significant. A negative linear association was observed between 25(OH)D and subclinical DSPN. Vitamin D deficiency maintained its significant association with subclinical DSPN in all age groups. Conclusions: Vitamin D deficiency was independently associated with subclinical DSPN, rather than other DPN subtypes.

Icariin ameliorates osteoporosis by activating autophagy in ovariectomized rats.

BACKGROUND: Osteoporosis (OP) is a major problem that increases the mortality and disability rate worldwide. With an increase in the aging population, OP has become a major public threat to human health. Searching for effective and suitable targets for drug treatment in OP has become an urgent need. OBJECTIVES: Osteoporosis is a metabolic bone disease characterized by reduced bone mass and density as well as micro-architectural deterioration. Icariin is a flavonoid extracted from plants of the genus Epimedium and has been shown to exert potential anti-OP activity. The present study was designed to observe the effect of icariin on OP and to clarify the underlying mechanisms in ovariectomized (OVX) rats. MATERIAL AND METHODS: Hematoxylin and eosin (H&E) staining, von Kossa staining and micro-computed tomography (micro-CT) confirmed significant bone loss in the OVX group. Protein expression level was detected with western blot analysis. RESULTS: Icariin reversed a trend of increased bone turnover by reducing serum alkaline phosphatase (ALP), procollagen type I N-terminal propeptide (PINP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and C-telopeptide of type I collagen (CTX-I). Furthermore, icariin decreased sequestosome 1 (p62) and increased microtubule-associated protein 1 light chain 3II/microtubule-associated protein 1 light chain 3I (LC3II/LC3I), autophagy-related protein 7 (Atg7), and Beclin 1 in the femur of OVX rats, improving the indicators of impaired autophagy in OP. CONCLUSIONS: Icariin reversed the significant upregulation of the serine/threonine protein kinase (Akt), mammalian target of rapamycin (mTOR) and unc-51-like autophagy activating kinase 1 (ULK1) at Ser757, and the downregulation of p-AMP-activated protein kinase (p-AMPK) and ULK1 phosphorylated at Ser555 in the OVX rats, suggesting that the mechanism of icariin action in OP treatment involves the activation and suppression of the AMPK/ULK1 and AKT/mTOR/ULK1 autophagy pathways, respectively.

Perinatal exposure to bisphenol A impairs cognitive function via the gamma-aminobutyric acid signaling pathway in male rat offspring.

Bisphenol A (BPA) is a common synthetic endocrine disruptor that can be utilized in the fabrication of materials such as polycarbonates and epoxy resins. Numerous studies have linked BPA to learning and memory problems, although the precise mechanism remains unknown. Gamma-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the vertebrate central nervous system, and it is intimately related to learning and memory. This study aims to evaluate whether altered cognitive behavior involves the GABA signaling pathway in male offspring of rats exposed to BPA during the prenatal and early postnatal periods. Pregnant rats were orally given BPA (0, 0.04, 0.4, and 4 mg/kg body weight (BW)/day) from the first day of pregnancy to the 21st day of breastfeeding. Three-week-old male rat offspring were selected for an open-field experiment and a new object recognition experiment to evaluate the effect of BPA exposure on cognitive behavior. Furthermore, the role of GABA signaling markers in the cognition affected by BPA was investigated at the molecular level using western blotting and real-time polymerase chain reaction (RT-PCR). The research demonstrated that BPA exposure impacted the behavior and memory of male rat offspring and elevated the expression of glutamic acid decarboxylase 67 (GAD67), GABA type A receptors subunit (GABAARα1), and GABA vesicle transporter (VGAT) in the hippocampus while decreasing the expression levels of GABA transaminase (GABA-T) and GABA transporter 1 (GAT-1). These findings indicate that the alteration in the expression of GABA signaling molecules may be one of the molecular mechanisms by which perinatal exposure to BPA leads to decreased learning and memory in male rat offspring.

Rapid neck elongation in Sauropterygia (Reptilia: Diapsida) revealed by a new basal pachypleurosaur from the Lower Triassic of China.

Neck elongation has appeared independently in several tetrapod groups, including giraffes and sauropod dinosaurs on land, birds and pterosaurs in the air, and sauropterygians (plesiosaurs and relatives) in the oceans. Long necks arose in Early Triassic sauropterygians, but the nature and rate of that elongation has not been documented. Here, we report a new species of pachypleurosaurid sauropterygian, Chusaurus xiangensis gen. et sp. nov., based on two new specimens from the Early Triassic Nanzhang-Yuan'an Fauna in the South China Block. The new species shows key features of its Middle Triassic relatives, but has a relatively short neck, measuring 0.48 of the trunk length, compared to > 0.8 from the Middle Triassic onwards. Comparative phylogenetic analysis shows that neck elongation occurred rapidly in all Triassic eosauropterygian lineages, probably driven by feeding pressure in a time of rapid re-establishment of new kinds of marine ecosystems.

Pan-Cancer Study of the Prognosistic Value of Selenium Phosphate Synthase 1.

Objective: This study sought to determine the mean prognostic usefulness of seleniumphosphate synthase (SEPHS1) by investigating its expression in 33 human malignancies and its relationship to tumor immunity.Methods: The expression of selenophosphate synthase 1 (SEPHS1) in 33 human malignant tumors was examined using the Genotype-Tissue Expression (GTEx), Cancer Genome Atlas (TCGA), and TIMER databases. Furthermore, the TCGA cohort was used to investigate relationships between SEPHS1 and immunological checkpoint genes (ICGs), tumor mutation burden (TMB), microsatellite instability (MSI), and DNA mismatch repair genes (MMRs). To establish independent risk factors and calculate survival probabilities for liver hepatocellular carcinoma (LIHC) and brain lower-grade glioma (LGG), Cox regression models and Kaplan-Meier curves were utilized. Eventually, the Genomics of Cancer Drug Sensitivity (GDSC) database was used to evaluate the drug sensitivity in LGG and LIHC patients with high SEPHS1 expression.Results: Overall, in numerous tumor tissues, SEPHS1 was highly expressed, and it significantly linked with the prognosis of LGG, ACC, and LIHC (P < .05). Furthermore, in numerous cancers, SEPHS1 expression was linked to tumor-infiltrating immune cells (TIICs), TMB, MSI, and MMRs. According to univariate and multivariate Cox analyses, SEPHS1 expression was significant for patients with LGG and LIHC.Conclusion: High SEPHS1 expression has a better prognosis for LGG, while low SEPHS1 expression has a better prognosis for LIHC. Chemotherapy was advised for LGG patients, particularly for those with high SEPHS1 expression because it can predict how responsive patients will be to 5-Fluorouracil and Temozolomide. This interaction between SEPHS1 and chemoradiotherapy has a positive clinical impact and may be used as evidence for chemotherapy for LGG and LIHC patients.

Mitochondria-derived H2O2 triggers liver regeneration via FoxO3a signaling pathway after partial hepatectomy in mice.

Reactive oxygen species (ROS) can induce oxidative injury and are generally regarded as toxic byproducts, although they are increasingly recognized for their signaling functions. Increased ROS often accompanies liver regeneration (LR) after liver injuries, however, their role in LR and the underlying mechanism remains unclear. Here, by employing a mouse LR model of partial hepatectomy (PHx), we found that PHx induced rapid increases of mitochondrial hydrogen peroxide (H2O2) and intracellular H2O2 at an early stage, using a mitochondria-specific probe. Scavenging mitochondrial H2O2 in mice with liver-specific overexpression of mitochondria-targeted catalase (mCAT) decreased intracellular H2O2 and compromised LR, while NADPH oxidases (NOXs) inhibition did not affect intracellular H2O2 or LR, indicating that mitochondria-derived H2O2 played an essential role in LR after PHx. Furthermore, pharmacological activation of FoxO3a impaired the H2O2-triggered LR, while liver-specific knockdown of FoxO3a by CRISPR-Cas9 technology almost abolished the inhibition of LR by overexpression of mCAT, demonstrating that FoxO3a signaling pathway mediated mitochondria-derived H2O2 triggered LR after PHx. Our findings uncover the beneficial roles of mitochondrial H2O2 and the redox-regulated underlying mechanisms during LR, which shed light on potential therapeutic interventions for LR-related liver injury. Importantly, these findings also indicate that improper antioxidative intervention might impair LR and delay the recovery of LR-related diseases in clinics.

Biological Functions of Selenoprotein Glutathione Peroxidases (GPXs) and their Expression in Osteoarthritis.

Purpose: In order to further study the biological functions of glutathione peroxidases (GPXs) and their expression level in patients with osteoarthritis (OA), we fully explored the potential relationship between GPXs and OA. This will provide new ideas for basic biological studies and therapeutic strategies for OA patients. Patients and Methods: In this study, bioinformatics techniques were used to explore the biological functions of five GPXs. The core genes related to the biological functions of GPXs were identified by constructing a protein-protein interaction network (PPI). In addition, we utilized microarray data in public databases to analyze the expression levels of GPXs in OA patients and healthy controls. Finally, we used quantitative real-time polymerase chain reaction (qRT-PCR) to detect the expression of GPXs in OA patients and controls to validate our bioinformatic analysis results. Results: Enrichment analysis showed GPXs were mainly enriched in the glutathione metabolic pathway and participate in the biological process of oxidative stress response, and further play an antioxidant role. The PPI network indicated that superoxide dismutase 1 (SOD1), superoxide dismutase 2(SOD2) and catalase (CAT) were the core proteins of this network. GPX1 was regulated by the greatest number of miRNAs. Experiments showed that the expression of GPX1 was elevated in OA patients compared with controls. Conclusion: GPXs play an important antioxidant role in oxidative stress response. The expression of GPX1 was elevated in peripheral blood mononuclear cells (PBMCs) of OA patients. The changes of GPXs in OA patients may regulate the level of oxidative stress, which may influence synovial lesions and chondrocyte apoptosis.

Benefits of successful percutaneous coronary intervention in chronic total occlusion patients with diabetes.

BACKGROUND: Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes. METHODS: Consecutive patients undergoing elective CTO-PCI were prospectively enrolled from Apr. 2018 to May 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. These data were analyzed accordingly for risk predictors of clinical outcome in patients who have diabetes and received successful CTO-PCI. RESULTS: A total of 1076 patients underwent CTO-PCI attempts. Diabetes was present in 374 (34.76%) patients, who had more hypertension, previous PCI and stroke. Regarding the coronary lesions, diabetic patients suffered more LCX lesion, multivessel disease, number of lesions per patient, blunt stump, calcification and higher J-CTO score (p < 0.05). In-hospital major adverse cardiac event (MACE) (4.13% vs. 5.35%; p = 0.362) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, the incidence of MACE and all-cause mortality were also similar in the two groups (p > 0.05). Number of lesions per patient was an independent risk factor of MACE and all-cause mortality (p < 0.001) 1 year after successful CTO-PCI. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, patients with diabetes showed similar degrees of improvement to those without diabetes (P > 0.05). CONCLUSIONS: Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptoms and QOL in CTO patients with diabetes.

A comparison of NAFLD and MAFLD diagnostic criteria in contemporary urban healthy adults in China: a cross-sectional study.

BACKGROUND: A recently proposed diagnostic criteria of metabolic dysfunction-associated fatty liver disease (MAFLD) is more available for various clinical situations than nonalcoholic fatty liver disease (NAFLD), but understanding about differences between NAFLD and MAFLD in clinical practice remains limited in the general adult urban population in China. METHODS: A total of 795 subjects were recruited from Wu Song Branch of Zhongshan Hospital who participated in the general health assessment. Examination results was obtained through analysis of blood samples and abdominal ultrasonography. Participants were divided into four subgroups according to whether they had NAFLD or MAFLD (NAFLD- MAFLD-, NAFLD + MAFLD-, NAFLD- MAFLD + and NAFLD + MAFLD+). RESULTS: Among the urban healthy adults investigated, 345 people (43.4%) were diagnosed with NAFLD and 356 people (44.8%) with MAFLD. No significant differences in the prevalence, age, fasting blood glucose, glycosylated hemoglobin, liver enzyme examination, percentage of overweight, hypertension or dyslipidaemia were found between NAFLD and MAFLD patients. Patients with MAFLD had worse metabolic disorders than NAFLD + MAFLD- patients. The NAFLD fibrosis score (NFS) of the NAFLD- MAFLD + group was higher than that of the NAFLD + MAFLD- group. Higher proportion of patients in the NAFLD- MAFLD + group have NFS ≥-1.455. CONCLUSION: MAFLD criteria have similar prevalence and patient characteristics compared with previous NAFLD but help to identify a group of patients with high risks of metabolic disorders and liver fibrosis who have been missed with NAFLD, and has superior utility.

GANT61 exerts anticancer cell and anticancer stem cell capacity in colorectal cancer by blocking the Wnt/ß­catenin and Notch signalling pathways.

The present study aimed to assess the anticancer cell and anticancer stem cell (CSC) effects of GANT61, and its regulatory influence on the Wnt/ß­catenin and Notch signalling pathways in colorectal cancer (CRC). HT­29 and HCT­116 cells were treated with 0, 2.5, 5, 10, 20 or 40 µM GANT61, after which relative cell viability and the expression of Gli1, ß­catenin and Notch1, as well as the percentage of CD133+ cells, were detected. Subsequently, HT­29/HCT­116 cells and CSCs were treated with 20 µM GANT61, 10 mM of the Wnt/ß­catenin pathway agonist HLY78, and 30 mM of the Notch pathway agonist JAG1 (alone or in combination), which was followed by the assessment of cell viability and apoptosis. In both cell lines, GANT61 reduced relative cell viability in a time­ and dose­dependent manner, inhibited Gli1, ß­catenin and Notch1 expression, and decreased the percentage of CD133+ cells in a dose­dependent manner. Furthermore, HLY78 and JAG1 were both found to improve the relative viability, while downregulating the apoptosis of untreated and GANT61­treated HT­29 and HCT­116 cells. Moreover, Wnt/ß­catenin and Notch signalling pathway activity were upregulated in CSCs isolated from HT­29 and HCT­116 cells, compared with the associated control groups. GANT61 also reduced the viability of HT­29 and HCT­116 cells and increased apoptosis, whereas HLY78 and JAG1 treatment resulted in the opposite effect. Moreover, both HLY78 and JAG1 attenuated the effects of GANT61 on cellular viability and apoptosis. In conclusion, GANT61 was found to effectively eliminate cancer cells and CSCs by blocking the Wnt/ß­catenin and Notch signalling pathways in CRC.

Mapping of Global Research on Electronic Cigarettes: A Bibliometric Analysis.

Electronic cigarettes (E-cigarettes) use has increased rapidly in the past decades and has been widely studied by scholars worldwide, whereas the research topics and development trends in this field are still unclear. This study aimed to explore the landscape of research relating to e-cigarettes. The data outputted from the Web of Science Core Collection database was used for bibliometric analysis. Frequencies and percentages were used to describe the publications' characteristics. Visualizing maps were designed using VOSviewer 1.6.9 and CiteSpace 5.8 R2. Overall, a total of 7,979 records were identified in the database and the number of researches increased rapidly since 2010. All publications involved 19837 authors, with the top ten authors contributing to 8.71% (695) of all documents. The most productive country and institution were the United States of America and the University of California San Francisco, respectively. Nicotine & Tobacco Research was not only the journal with the most published papers but also the most co-cited journal. The main research domains in this field were the prevalence, awareness, reasons for using e-cigarettes; e-cigarettes use for tobacco harm reduction; exposure in the population; and the relationship between e-cigarettes and tobacco and nicotine. E-cigarettes researches have become a popular field for scholars. The hot topics on e-cigarette research were extensive and changed over the past decade.

A novel model for detecting advanced fibrosis in patients with nonalcoholic fatty liver disease.

AIMS: The study aimed to develop a novel noninvasive model to detect advanced fibrosis based on routinely available clinical and laboratory tests. MATERIALS AND METHODS: A total of 309 patients who underwent liver biopsy were randomly divided into the estimation group (n = 201) and validation group (n = 108). The model was developed using multiple regression analysis in the estimation group and further verified in the validation group. Diagnostic accuracy was evaluated using the receiver operating characteristic (ROC) curve. RESULTS: The model was named NAFLD Fibrosis Index (NFI): -10.844 + 0.046 × age - 0.01 × platelet count + 0.19 × 2h postprandial plasma glucose (PG) + 0.294 × conjugated bilirubin - 0.015 × ALT + 0.039 × AST + 0.109 × total iron binding capacity -0.033 × parathyroid hormone (PTH). The area under the ROC curve (AUC) of NFI was 0.86 (95% CI: 0.79-0.93, p < 0.001) in the estimation group and 0.80 (95% CI: 0.69-0.91, p < 0.001) in the validation group, higher than NFS, FIB4, APRI, and BARD, and similar to FibroScan (NFI AUC = 0.77, 95% CI: 0.66-0.89, p = 0.001 vs. FibroScan AUC = 0.76, 95% CI: 0.62-0.90, p = 0.002). By applying the low cut-off value (-2.756), advanced fibrosis could be excluded among 49.3% and 48% of patients in the estimation group (sensitivity: 93.1%, NPV: 97.9%, specificity: 55.2%, and PPV: 26.0%) and validation group (sensitivity: 81.3%, NPV: 94.2%, specificity: 53.3%, and PPV: 23.2%), respectively, allowing them to avoid liver biopsy. CONCLUSIONS: The study has established a novel model for advanced fibrosis, the diagnostic accuracy of which is superior to the current clinical scoring systems and is similar to FibroScan.

[Clinical Investigation of Key Parameter Range of AMG Muscle Relaxant Monitor].

The accelerometry(AMG) muscle relaxant monitor is the most widely used quantitative muscle relaxant monitor to assess the degree of neuromuscular at present. In this study, the ulnar nerve was stimulated by using train of four stimulation(TOF) mode of the AMG muscle relaxant monitor, and the movement of the adductor pollicis muscle was monitored. In this way, the distribution range of key parameters (acceleration peak value, response time, and TOF ratio) of the adductor pollicis muscle during the use of muscle relaxant in clinical practice is analyzed and will provide a practical basis for the development and improvement of the muscle relaxant monitor.

Biological Functions of Selenoprotein Iodothyronine Deiodinase and its Expression in Osteoarthritis.

Objective Iodothyronine deiodinases (DIOs) are important selenoproteins that play a key role in the bone and joint diseases. Osteoarthritis (OA) is the most prevalent joint disease especially in elders. This bioinformatic analysis was performed to explore the role of DIOs in OA pathogenesis. Methods The biological functions of selenoprotein DIOs were analyzed by bioinformatic techniques, including GenCLip 3.0, Database for Annotation, Visualization and Integrated Discovery (DAVID), STRING, Cytoscape, and Network Analyst. The expression of DIOs in the healthy individuals and OA patients was determined by mining OA-related microarray data in the gene expression omnibus (GEO) database of National Center for Biotechnology Information and performing a Meta-analysis of the data with Review Manager 5.3. Results Cluster analysis revealed that the function of the DIOs was associated with thyroid hormone receptor and iodothyronine; GO analysis showed that DIOs were mainly involved in biological processes, such as ethanol metabolism and phenol-containing compound metabolism and primarily involved in the cytochrome P450 metabolism of exogenous organisms and thyroid hormone signaling; SULT1A1 was the core node of the PPI network; miRNAs and thyroid hormones had some iterations with DIO1and DIO2; Meta-analysis showed that DIO3 expression was significantly up-regulated in OA patients (SMD = 0.31, 95%CI: 0.03, 0.59, P = 0.03). Conclusions The main biological functions of DIOs were closely associated with the regulation of thyroid hormone. And the up-regulated expression of DIO3 may have crucial impact on the occurrence of OA.

Isolation and Quantification of the Hepatoprotective Flavonoids From Scleromitron diffusum (Willd.) R. J. Wang With Bio-Enzymatic Method Against NAFLD by UPLC-MS/MS.

Flavonoids were the major phytochemicals against hepatic peroxidative injury in Scleromitron diffusum (Willd.) R. J. Wang with an inventive bio-enzymatic method by our group (LU500041). Firstly, the total flavonoids from Scleromitron diffusum (Willd.) R. J. Wang were extracted by reflux, ultrasonic, ultrasound-assisted enzymatic methods (TFH), and the bio-enzymatic method (Ey-TFH). Then 24 flavonoid compounds were isolated and quantified in the extracts by UPLC-MS/MS. Next, six representative differential compounds in Ey-TFH were further screened out by multivariate statistical analysis compared with those in TFH. In a further step, Ey-TFH presented a higher protective rate (59.30 ± 0.81%) against H2O2-damaged HL-02 hepatocytes than TFH. And six representative differential compounds at 8 and 16 µmol/L all exerted significant hepatoprotective effects (p < 0.05 or p < 0.01). Finally, the therapeutic action of Ey-TFH for nonalcoholic fatty liver disease (NAFLD) was processed by a rat's model induced with a high-fat diet. Ey-TFH (90, 120 mg/kg) significantly ameliorated the lipid accumulation in the rat model (p < 0.05). Meanwhile, Ey-TFH relieved liver damage. The levels of ALT, ALP, AST, LDH, and γ-GT in rats' serum were also significantly reduced (p < 0.05 or p < 0.01). In addition to this, the body's antioxidant capacity was improved with elevated SOD and GSH levels (p < 0.05) and down-regulated MDA content (p < 0.01) after Ey-TFH administration. Histopathological observations of staining confirmed the hepatic-protective effect of Ey-TFH.

Glutathione peroxidase family and survival prognosis in patients with renal cell carcinoma. / è°·èƒ±ç”˜è‚½è¿‡æ°§åŒ–ç‰©é ¶å®¶æ—ä¸Žè‚¾ç»†èƒžç™Œæ‚£è€ ç”Ÿå­˜é¢„åŽçš„å ³ç³».

OBJECTIVES: Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. METHODS: The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. RESULTS: The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. CONCLUSIONS: GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

[Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients].

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Clinical Characteristics, Transmissibility, Pathogenicity, Susceptible Populations, and Re-infectivity of Prominent COVID-19 Variants.

In addition to the rapid, global spread of SARS-CoV-2, new and comparatively more contagious variants are of considerable concern. These emerging mutations have become a threat to the global public health, creating COVID-19 surges in different countries. However, information on these emerging variants is limited and scattered. In this review, we discuss new variants that have emerged worldwide and identify several variants of concern, such as B.1.1.7, B.1.351, P.1, B.1.617.2 and B.1.1.529, and their basic characteristics. Other significant variants such as C.37, B.1.621, B.1.525, B.1.526, AZ.5, C.1.2, and B.1.617.1 are also discussed. This review highlights the clinical characteristics of these variants, including transmissibility, pathogenicity, susceptible population, and re-infectivity. It provides the latest information on the recent variants of SARS-CoV-2. The summary of this information will help researchers formulate reasonable strategies to curb the ongoing COVID-19 pandemic.