Constructing and validating pan-apoptosis-related features for predicting prognosis and immunotherapy response in hepatocellular carcinoma.

The study aimed to develop a prognostic model for Hepatocellular Carcinoma (HCC) based on pan-apoptosis-related genes, a novel inflammatory programmed cell death form intricately linked to HCC progression. Utilizing transcriptome sequencing and clinical data from the TCGA database, we identified six crucial pan-apoptosis-related genes through statistical analyses. These genes were then employed to construct a prognostic model that accurately predicts overall survival rates in HCC patients. Our findings revealed a strong correlation between the model's risk scores and tumor microenvironment (TME) status, immune cell infiltration, and immune checkpoint expression. Furthermore, we screened for drugs with potential therapeutic efficacy in high- and low-risk HCC groups. Notably, PPP2R5B gene knockdown was found to inhibit HCC cell proliferation and clonogenic capacity, suggesting its role in HCC progression. In conclusion, this study presents a novel pan-apoptosis gene-based prognostic risk model for HCC, providing valuable insights into patient TME status and guiding the selection of targeted therapies and immunotherapies.

The dose-dependent dual effects of alpha-ketoglutarate (AKG) on cumulus oocyte complexes during in vitro maturation.

In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology.

Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction.

The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.

Study on the performance of biochar prepared from walnut shell and traditional graphene electrode plate in the treatment of domestic sewage in microbial fuel cells.

As a new pollutant treatment technology, microbial fuel cell (MFC) has a broad prospect. In this article, the devices assembled using walnut shells are named biochar-microbial fuel cell (B-MFC), and the devices assembled using graphene are named graphene-microbial fuel cell (G-MFC). Under the condition of an external resistance of 1,000 Ω, the B-MFC with biochar as the electrode plate can generate a voltage of up to 75.26 mV. The maximum power density is 76.61 mW/m2, and the total internal resistance is 3,117.09 Ω. The removal efficiency of B-MFC for ammonia nitrogen (NH3-N), chemical oxygen demand (COD), total nitrogen (TN), and total phosphorus (TP) was higher than that of G-MFC. The results of microbial analysis showed that there was more operational taxonomic unit (OTU) on the walnut shell biochar electrode plate. The final analysis of the two electrode materials using BET specific surface area testing method (BET) and scanning electron microscope (SEM) showed that the pore size of walnut shell biochar was smaller, the specific surface area was larger, and the pore distribution was smoother. The results show that using walnut shells to make electrode plates is an optional waste recycling method and an electrode plate with excellent development prospects.

Effects of Insulin-degrading enzyme on the proliferation of swine Sertoli cells.

Sertoli cells, the only somatic cells in testis seminiferous tubules, provide a supporting microenvironment for male germ cells and play essential roles in spermatogenesis. The insulin-degrading enzyme (IDE), a ubiquitous zinc peptidase of the inverzincin family, plays crucial role in sperm production, as IDE-knockout mice presented decreased testis weight and impaired sperm viability and morphology. However, whether and how IDE affects swine Sertoli cell proliferation remains unclear. Thus, in the present study, we aimed to evaluate the effects of IDE on the proliferation of swine Sertoli cells, as well as its underlying molecular mechanism. After knocking down IDE expression with small interfering RNA transfection, we analyzed the proliferation of swine Sertoli cells as well as the expression of related regulatory factors (WT1, ERK, and AKT). The results showed that IDE knockdown promoted swine Sertoli cell proliferation and increased WT1 expression, possibly through activating ERK and AKT. Overall, our findings suggest that IDE may be involved in male reproduction by regulating Sertoli cell proliferation, which provides new information to better understand the regulatory mechanisms of swine Sertoli cells and improve the reproductive traits of male pigs.

Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.

The Effects of Mammary Gland ATIII Overexpression on the General Health of Dairy Goats and Their Anti-Inflammatory Response to LPS Stimulation.

Antithrombin III is an important anticoagulant factor with anti-inflammatory properties. However, few studies have explored its anti-inflammatory actions in ATIII overexpressed transgenic animals. In this study, the dairy goats with mammary overexpression of ATIII were used to investigate their general health, milk quality and particularly their response to inflammatory challenge. The results showed that transgenic goats have a normal phenotype regarding their physiological and biochemical parameters, including whole blood cells, serum protein levels, total cholesterol, urea nitrogen, uric acid, and total bilirubin, compared to the WT. In addition, the quality of milk also improved in transgenic animals compared to the WT, as indicated by the increased milk fat and dry matter content and the reduced somatic cell numbers. Under the stimulation of an LPS injection, the transgenic goats had elevated contents of IGA, IGM and superoxide dismutase SOD, and had reduced proinflammatory cytokine release, including IL-6, TNF-α and IFN-ß. A 16S rDNA sequencing analysis also showed that the transgenic animals had a similar compositions of gut microbiota to the WT goats under the stimulation of LPS injections. Mammary gland ATIII overexpression in dairy goats is a safe process, and it did not jeopardize the general health of the transgenic animals; moreover, the compositions of their gut microbiota also improved with the milk quality. The LPS stimulation study suggests that the increased ATIII expression may directly or indirectly suppress the inflammatory response to increase the resistance of transgenic animals to pathogen invasion. This will be explored in future studies.

Enhancing Animal Disease Resistance, Production Efficiency, and Welfare through Precise Genome Editing.

The major goal of animal breeding is the genetic enhancement of economic traits. The CRISPR/Cas system, which includes nuclease-mediated and base editor mediated genome editing tools, provides an unprecedented approach to modify the mammalian genome. Thus, farm animal genetic engineering and genetic manipulation have been fundamentally revolutionized. Agricultural animals with traits of interest can be obtained in just one generation (and without long time selection). Here, we reviewed the advancements of the CRISPR (Clustered regularly interspaced short palindromic repeats)/Cas (CRISPR associated proteins) genome editing tools and their applications in animal breeding, especially in improving disease resistance, production performance, and animal welfare. Additionally, we covered the regulations on genome-edited animals (GEAs) and ways to accelerate their use. Recommendations for how to produce GEAs were also discussed. Despite the current challenges, we believe that genome editing breeding and GEAs will be available in the near future.

2'-Fucosyllactose Suppresses Angiogenesis and Alleviates Toxic Effects of 5-Fu in a HCT116 Colon Tumor-Bearing Model.

The present study was aimed at examining the anti-tumor effects and molecular mechanisms of 2'-fucosyllactose (2'-FL). At the beginning, the viabilities of four types of colon cancer cells were analyzed after exposure to increasing concentrations of 2'-FL, and HCT116 cells were selected as the sensitive ones, which were applied in the further experiments; then, interestingly, 2'-FL (102.35 µM) was found to induce apoptosis of HCT116 cells, which coincides with significant changes in VEGFA/VEGFR2/p-PI3K/p-Akt/cleaved Caspase3 proteins. Next, in a tumor-bearing nude mouse model, HCT116 was chosen as the sensitive cell line, and 5-fluorouracil (5-Fu) was chosen as the positive medicine. It was noteworthy that both 2'-FL group (2.41 ± 0.57 g) and 2'FL/5-Fu group (1.22 ± 0.35 g) had a significantly lower tumor weight compared with the control (3.87 ± 0.79 g), suggesting 2'-FL could inhibit colon cancer. Since 2'-FL reduced the number of new blood vessels and the malignancy of tumors, we confirmed that 2'-FL effectively inhibited HCT116 tumors, and its mechanism was achieved by regulating the VEGFA/VEGFR2/PI3K/Akt/Caspase3 pathway. Moreover, though HE staining and organ index measurement, 2'-FL was validated to alleviate toxic effects on liver and kidney tissue when combining with 5-Fu. In conclusion, 2'-FL had certain anti-tumor and detoxification effects.

[Progress in the clinical treatment of alcoholic hepatitis].

Alcoholic hepatitis is a severe and life-threatening systemic inflammatory response syndrome, which has a high incidence and mortality rate worldwide. The severity ranges from asymptomatic liver biochemical disturbances to fulminant liver failure or death; however, there are few effective therapeutic interventions. Maddrey discriminant function not only predicts short-term mortality, but it also guides clinicians to choose appropriate alcoholic hepatitis-specific treatments. Alcohol abstinence, nutritional support, psychological counseling, and infection prevention remain the cornerstones for alcoholic hepatitis treatment. Corticosteroids remain the mainstay of treatment when patients have a good appetite and normal serum creatinine levels, but early liver transplantation is the only life-saving option for steroid-unresponsive patients. New studies have found that gut microbiota is an important therapeutic targets in patients with alcohol hepatitis, and N-acetylcysteine, granulocyte colony-stimulating factor, and metadoxine as adjunctive therapy have a positive effect on patient survival.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

Correlation between low-level viremia and hepatitis B-related hepatocellular carcinoma and recurrence: a retrospective study.

BACKGROUND: Low-level viremia generally refers to detectable HBV DNA levels lower than 2000 IU/mL. Studies show that low-level viremia is a risk factor for hepatocellular carcinoma. The aim of this study was to explore the characteristics of low-level viremia patients with hepatitis B-related hepatocellular carcinoma and identify prognostic factors after curative hepatectomy. METHODS: Data from chronic hepatitis B patients with hepatocellular carcinoma receiving curative hepatectomy for the first time in the first hospital of China Medical University were studied. Patients were divided into two groups based on preoperative HBV DNA levels: group 1 (low-level viremia group, HBV DNA < 2000 IU/mL) and group 2 (HBV DNA ≥ 2000 IU/mL). RESULTS: Of the 212 patients, 104 patients were in group 1 and 108 patients were in group 2. There was a lower proportion of patients with HBsAg levels > 250 IU/mL (the upper limit of detection in our laboratory) in group 1 than in group 2 (71.2% vs. 86.1%, P < 0.01). The percentage of patients with a tumor diameter < 5 cm was 67.3% in group 1 and 37.0% in group 2 (P < 0.000). The percentage of tumor recurrence was 40.4% (42) in group 1 and 54.6% (59) in group 2 (P < 0.05). Median recurrence-free survival was 30.1 months in group 1 and 17.6 months in group 2 (P < 0.01). Multivariate analysis showed that a tumor diameter ≥ 5 cm (hazard ratio [HR] = 1.819, 95% confidence interval [CI] 1.193-2.775, P = 0.005), intrahepatic metastasis (HR = 1.916, 95% CI 1.077-3.407, P = 0.027), and an HBV DNA level ≥ 100 IU/mL (the lower limit of detection in our laboratory, HR = 2.943, 95% CI 1.916-4.520, P < 0.000) were independent prognostic factors associated with an increased risk of hepatocellular carcinoma recurrence. CONCLUSION: Preoperative low-level viremia was related with a long tumor recurrence interval and complete virologic response after curative hepatectomy was associated with a lower risk of hepatocellular carcinoma recurrence.

Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey.

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.

Integrative Proteomic and Phosphoproteomic Profiling of Testis from Wip1 Phosphatase-Knockout Mice: Insights into Mechanisms of Reduced Fertility.

Mice lacking wild-type p53-induced phosphatase 1 (Wip1) display male reproductive defects including smaller testes, subfertility and spermatogenesis defects at the round- and elongating-spermatid stages. However, the molecular mechanisms underlying these abnormalities remain unclear. Here we examined the proteome and phosphoproteome of testes from Wip1-knockout mice using a quantitative proteomic approach. From a total of 6872 proteins and 4280 phosphorylation sites identified, 58 proteins and 159 phosphorylation sites were found to be differentially regulated compared with wild type mice. Pathway enrichment analyses revealed that these regulated proteins and phosphosites were mainly involved in adherens/tight junctions, apoptosis, inflammatory response, spermatogenesis, sperm motility, and cytoskeletal assembly and depolymerization. Wip1-knockout mice showed decreased expression of junction-associated proteins (occludin, ZO-1, and N-cadherin) and impaired integrity of the blood-testis barrier. In addition, Wip1 deficiency was associated with elevated levels of cytokines and germ cell apoptosis in the testis. These results suggest that proinflammatory cytokines may impair the blood-testis barrier dynamics by decreasing the expression of junction-associated proteins, which could lead to subfertility and spermatogenesis defects. Collectively, these findings help to explain the low reproductive function caused by Wip1 deletion and provide novel insights into our understanding of causes of male infertility.

Dose-response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies.

BACKGROUND: We conducted a systematic review and meta-analysis from published cohort studies to examine the association of adult height and all-cause mortality and to further explore the dose-response association. METHODS: PubMed, The Cochrane Library, The Ovid, CNKI, CQVIP and Wanfang databases were searched for articles published from database inception to 6 February 2018. We used the DerSimonian-Laird random-effects model to estimate the quantitative association between adult height and all-cause mortality and the restricted cubic splines to model the dose-response association. RESULTS: We included 15 articles, with 1 533 438 death events and 2 854 543 study participants. For each 5-cm height increase below the average, the risk of all-cause mortality was reduced by 7% [relative risk (RR) = 0.93, 95% confidence interval (CI), 0.89-0.97] for men and 5% (RR = 0.95, 95% CI, 0.90-0.99) for women. All-cause mortality had a U-shaped association with adult height, the lowest risk occurring at 174 cm for men and 158 cm for women (both Pnonlinearity < 0.001). Relative to the shortest adult height (147 cm for men and 137 cm for women), men at 174 cm had a 47% lower likelihood of all-cause mortality and women at 158 cm a 33% lower risk of all-cause mortality. CONCLUSIONS: Our study suggests that the relation between adult height and all-cause mortality is approximately U-shaped in both men and women.

Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS: We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION: A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

The Effects of Flavonoid Apigenin on Male Reproductive Health: Inhibition of Spermatogonial Proliferation through Downregulation of Prmt7/Akt3 Pathway.

Apigenin, a common dietary flavonoid abundantly present in a variety of fruits and vegetables, has promising anticancer properties. As an effector of apigenin in myoblasts, protein arginine methyltransferase 7 (Prmt7) is required for male germ cell development. However, whether apigenin may influence male reproductive health through Prmt7 is still unclear. To this end, mouse spermatogonia were treated with different concentrations (2.5 to 50 µM) of apigenin for 48 h, which showed that apigenin could cause reduced cell proliferation in conjunction with longer S phase and G2/M phase (with concentrations of 10 and 20 µM, respectively), and increased apoptosis of spermatogonia (with concentration of 20 µM). Reduced Prmt7 expression was found in 20 µM apigenin-treated spermatogonia. Moreover, siRNA-induced Prmt7 knockdown exhibited similar influence on spermatogonia as that of apigenin treatment. In mechanistic terms, transcriptome analysis revealed 287 differentially expressed genes between Prmt7-downregulated and control spermatogonia. Furthermore, rescue experiments suggested that the effects of apigenin on spermatogonia might be mediated through the Prmt7/Akt3 pathway. Overall, our study supports that apigenin can interfere with mouse spermatogonial proliferation by way of the downregulated Prmt7/Akt3 pathway, which demonstrates that the concentration should be taken into account in future applications of apigenin for cancer therapy of men.

Race- and sex-specific association between alcohol consumption and hypertension in 22 cohort studies: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The alcohol-hypertension relation has been well documented, but whether women have protective effect or race and type of beverage consumed affect the association remain unclear. To quantify the relation between total or beverage-specific alcohol consumption and incident hypertension by considering the effect of sex and race. METHODS AND RESULTS: Articles were identified in PubMed and Embase databases with no restriction on publication date. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random effects models. Restricted cubic splines were used to model the dose-response association. This study involved 22 articles (31 studies) and included 414,477 participants. The hypertension risk was different among liquor, wine, and beer at 5.1-10 g/d of ethanol consumption (P-across subgroups = 0.002). The hypertension risk differed between men (RR: 1.14, 95% CI: 1.07, 1.20) and women (RR: 0.98, 95% CI: 0.89, 1.06) at 10 g/d (P-across subgroups = 0.005). We found a linear alcohol-hypertension association among white (P-linearity = 0.017), black people (P-linearity = 0.035), and Asians (P-linearity<0.001). With 10 g/d increment of consumption, the RRs for hypertension were 1.06 (95% CI: 1.04, 1.08), 1.14 (95% CI: 1.01, 1.28), and 1.06 (95% CI: 1.01, 1.10) for Asians, black, and white people, respectively. CONCLUSION: Sex modifies the alcohol-hypertension association at low level of alcohol consumption and we did not find evidence of a protective effect of alcohol consumption among women. Black people may have higher hypertension risk than Asians and white people at the same ethanol consumption.

Wild-type p53-induced phosphatase 1 (WIP1) regulates the proliferation of swine Sertoli cells through P53.

Wild-type p53-induced phosphatase 1 (WIP1) plays an oncogenic function by increasing cell proliferation in various cancer types. Deficiency in WIP1 expression leads to male infertility, possibly by impairing the blood-testis barrier and spermatogenesis. However, how WIP1 functions in the Sertoli cells to affect male reproduction remains unclear. Thus, in the present study we used a swine Sertoli cell line to investigate whether WIP1 regulated the proliferation of Sertoli cells to participate in male reproduction. The WIP1 inhibitor GSK2830371, WIP1-short interference (si) RNAs and an upstream microRNA (miR-16) were used to inhibit the expression of WIP1, after which the proliferation of swine Sertoli cells, P53 expression and the levels of P53 phosphorylation were determined. Inhibiting WIP1 expression suppressed swine Sertoli cell proliferation, increased P53 expression and increased levels of P53 phosphorylation. In addition, overexpression of miR-16 in swine Sertoli cells resulted in a decrease in WIP1 expression and increases in both P53 expression and P53 phosphorylation. Together, these findings suggest that WIP1 positively regulates the proliferation of swine Sertoli cells by inhibiting P53 phosphorylation, and the miR-16 is likely also involved by targeting WIP1.

The p66shc-mediated Regulation of Hepatocyte Senescence Influences Hepatic Steatosis in Nonalcoholic Fatty Liver Disease.

BACKGROUND Recent studies have suggested that hepatocyte senescence could contribute to hepatic steatosis and its progression in nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism causing hepatocyte senescence in this pathological condition is still unclear. A thorough understanding of the mechanism could provide a new target for therapeutic intervention. The purpose of this study was to investigate the role of p66shc in hepatocyte senescence and hepatocyte damage in NAFLD progression. MATERIAL AND METHODS We examined the expression levels of hepatic p66shc and senescence markers in rats and humans with NAFLD, and we assessed the effect of p66shc knockdown or overexpression on senescence and steatosis in human liver cells. RESULTS In this study, we showed that increased hepatic p66shc expression was consistent with upregulated expression of the following senescence markers in NAFLD rats: heterochromatin protein-1-beta (HP1ß), p16, p21, and p53. Furthermore, senescence and steatosis could be induced in hepatoblastoma cell line (HepG2) cells when cells were stimulated with a low concentration of H2O2, and this effect was significantly alleviated by knockdown of p66shc. However, overexpression of p66shc could promote senescence and steatosis in L02 cells. Finally, increased hepatic p66shc protein levels correlated with enhanced expression of the senescence marker p21 and mirrored the degree of disease severity in NAFLD patients. CONCLUSIONS Our findings indicated that the increase in hepatocyte senescence and steatosis in NAFLD may be caused by the upregulation of p66shc expression, implying that strategies for p66shc-mediated regulation of hepatocyte senescence may provide new therapeutic tools for NAFLD.