Transcription factors regulate gene expression through binding to specific enhancer sequences. Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. NEUROG3 is expressed in endocrine progenitor cells and controls islet differentiation and regeneration. PDX1 is essential for the development of pancreatic exocrine and endocrine cells including beta cells. PDX1 also binds to the regulatory elements and increases insulin gene transcription. Likewise, MAFA binds to the enhancer/promoter region of the insulin gene and drives insulin expression in response to glucose. In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. Here, we review biological properties of PDX1, NEUROG3, and MAFA, and their applications and limitations for beta cell regenerative approaches. The primary source literature for this review was acquired using a PubMed search for articles published between 1990 and 2017. Search terms include diabetes, insulin, trans-differentiation, stem cells, and regenerative medicine.

Heat causes a rapid and transient suppression of spermatogenesis. TU plus heat resulted in low-sperm output that was maintained by continuous treatment with TU. Addition of an oral progestin accelerated spermatogenesis suppression by TU alone. Increased germ cell apoptosis contributed to suppression of spermatogenesis.

Cardiovascular disease is the leading cause of death in the Chinese population. Although general prevalence estimates of cardiovascular risk factors (CVRFs) are available for Chinese adults, prevalence estimates covering all adult age groups by race/ethnicity have not been reported. The aim of this study is to estimate the current prevalence and clustering of major CVRFs in Chinese adults, including a plurality of ethnic minorities.A cross-sectional survey was conducted in a nationally representative sample of 23,010 adults aged 18 years and older from 2007 to 2011. Questionnaires and physical examinations were performed, and fasting blood was collected for laboratory measurements. The prevalence of traditional CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking, were determined.The prevalence of the major CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking were 24.3%, 4.3%, 49.3%, 32.0%, and 21.7%, respectively. These risk factors were significantly associated with sex, age, region, ethnicity, and education levels. Overall, 70.3%, 40.3%, and 16.7% of Chinese adults had ≥1, ≥2, or ≥3 CVRFs, respectively. Men, northern and rural residents were more likely to have clustered CVRFs compared with women, southern and urban residents, respectively. Compared with Han residents, Hui and Mongolian residents were more likely, and Tujia and Miao residents were less likely, to have ≥1, ≥2, or ≥3 risk factors. The prevalence of Chinese women having ≥1, ≥2, or ≥3 CVRFs decreased with increasing levels of education.The prevalence and clustering of CVRFs is still high in Chinese adults ≥18 years old, especially in men and in individuals living in the northern and rural areas. Of note, there are differences in cardiovascular risk among different ethnic groups. Therefore, targeted and enhanced intervention measures are required to reduce the risk of cardiovascular disease and the corresponding economic burden of disease in China.

Introduction: This study aims to determine whether advanced ROS1 gene-rearranged NSCLC (ROS1þ NSCLC) has a higher than expected thromboembolic event (TEE) rate.Methods: Venous and arterial TEEs within ±365 days of diagnosis of ROS1þ, ALKþ, EGFRþ, or KRASþ advanced NSCLC at five academic centers in the United States and China were captured (October 2002-April 2018). The primary endpoint was incidence of TEE in ROS1þ compared to anaplastic lymphoma kinase (ALK)þ, EGFRþ, and KRASþ NSCLC within ±90 days of diagnosis. Logistic regression was used to assess if the odds of TEE differed among oncogene drivers.Results: Eligible data from 95 ROS1þ, 193 ALKþ, 300 EGFRþ, and 152 KRASþ NSCLC patients were analyzed. The incidence rate of TEE was 34.7% (n ¼ 33), 22.3% (n ¼ 43), 13.7% (n ¼ 41), and 18.4% (n ¼ 28), respectively. In univariate analysis, the odds of a TEE in ROS1þ NSCLC were higher than ALKþ, EGFRþ, and KRASþ cohorts. In multivariable analysis, the odds of a TEE were significantly higher for ROS1þ compared to EGFRþ and KRASþ cohorts, the odds ratio (OR) was 2.44, with a 95% confidence interval of 1.31-4.57 (p ¼ 0.005), and OR: 2.62, with a 95% confidence interval of 1.26-5.46 (p ¼ 0.01), respectively.Although numerically superior, the odds for a TEE with ROS1þ compared to ALKþ was not statistically significant (OR: 1.45, p ¼ 0.229). Overall survival was not significantly

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As a major nutraceutical component of a typical Mediterranean vegetable chicory, chicoric acid (CA) has been well-documented due to its excellent antioxidant and antiobesity bioactivities. In the current study, the effects of CA on lipopolysaccharide (LPS)-stimulated oxidative stress in BV-2 microglia and C57BL/6J mice and the underlying molecular mechanisms were investigated. Results demonstrated that CA significantly reversed LPS-elicited cell viability decrease, mitochondrial dysfunction, activation of NFκB and MAPK stress pathways, and inflammation responses via balancing cellular redox status. Furthermore, molecular modeling study demonstrated that CA could insert into the pocket of Keap1 and up-regulated Nrf2 signaling and, thus, transcriptionally regulate downstream expressions of antioxidant enzymes including HO-1 and NQO-1 in both microglial cells and ip injection of LPS-treated mouse brain. These results suggested that CA attenuated LPS-induced oxidative stress via mediating Keap1/Nrf2 transcriptional pathways and downstream enzyme expressions, which indicated that CA has great potential as a nutritional preventive strategy in oxidative stress-related neuroinflammation.

Hyperuricemia is common in China and the relevance of hyperuricemia and cardiovascular disease (CVD) risk has been highlighted, but to date there has been rarely nation-wide study in China. Here, we aim to estimate the current prevalence of hyperuricemia and evaluate the associations between hyperuricemia and cardiovascular risk factors (CRFs) clustering in a large sample of China adults including a plurality of ethnic minorities. Generally, a nationally representative sample of 22983 adults aged ≥18 years was recruited from 2007 to 2011. Questionnaire data and information on anthropometric characteristics, and laboratory measurements were collected. We define hyperuricemia as SUA ≥416 mmol/L for men and SUA ≥357 mmol/L for women. We found that the prevalence of hyperuricemia was 13.0% (18.5% in men and 8.0% in women). To our estimation, hyperuricemic subjects had higher prevalence rates of CRFs clustering than non-hyperuricemic subjects. Furthermore, there was a dose-response association between the number of CVD risk factors clustering and hyperuricemia. Our study revealed a high prevalence of hyperuricemia and CVD risk factors clustering among Chinese adults, and hyperuricemia was significantly associated with coexistence of more CVD risk factors. Therefore, guidance and effective lifestyle intervention are required to prevent hyperuricemia and CVD risk factors in China.

Alanine aminotransferase (ALT) is the most commonly used marker of liver injury, but normal ALT levels are seen in a proportion of chronic hepatitis B virus (HBV)-infected patients with severe liver injury. Golgi protein 73 (GP73) is a promising alternative marker of liver injury. This study assessed the relation between GP73 levels and liver disease severity, monitored the kinetic changes in GP73 levels in chronic HBV patients receiving entecavir (ETV) therapy, and investigated the potential diagnostic and prognostic values of serum GP73 as a new liver injury biomarker in chronic HBV infections.This study enrolled 1150 patients with chronic HBV infections, 200 of whom were retrospectively enrolled in this study after receiving 1 year of ETV treatment. GP73 expression in liver tissue was detected by immunohistochemistry. GP73 levels in single or serial serum samples were measured by enzyme-linked immunosorbent assay.Immunohistochemical analysis indicated that GP73 protein expression in the liver increased progressively with pathologic progression from nonexistent or mild hepatitis to severe hepatitis and cirrhosis during chronic HBV infection. Serum GP73 levels were positively correlated with the disease severity of chronic HBV infections (r = 0.58, P < 0.001). In patients with normal ALT levels, serum GP73 concentrations were significantly higher in patients with prominent hepatic inflammatory injury and fibrosis than in patients without hepatic inflammatory injury or fibrosis. Serum GP73 concentrations and GP73 protein expression were decreased in the liver tissues of patients whose ALT levels normalized after 1 year of ETV antiviral therapy.Changes in serum GP73 levels were closely associated with changes in liver injury severity, and, therefore, GP73 may be an effective new liver inflammatory injury biomarker, and could be useful for monitoring the prognosis of chronic HBV infectious patients with normal ALT levels.