The activation of histone deacetylases 4 prevented endothelial dysfunction: A crucial mechanism of HuangqiGuizhiWuwu Decoction in improving microcirculation dysfunction in diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: The regulation of epigenetic factors is considered a crucial target for solving complex chronic diseases such as cardio-cerebrovascular diseases. HuangqiGuizhiWuwu Decoction (HGWWD), a classic Chinese prescription, is mainly used to treat various vascular diseases. Although our previous studies reported that HGWWD could effectively prevent vascular dysfunction in diabetic rodent models, the precise mechanism is still elusive. AIM OF THE STUDY: In this study, we investigated the epigenetic mechanisms of modulating the damage of vascular endothelial cells in diabetes by HGWWD. METHODS: We first analyzed common active components of HGWWD by using HPLC-Q-TOF-MS/MS analysis, and predicted the isoforms of histone deacetylase (HDAC) that can potentially combine the above active components by systems pharmacology. Next, we screened the involvement of specific HDAC isoforms in the protective effect of HGWWD on vascular injury by using pharmacological blockade combined with the evaluation of vascular function in vivo and in vitro. RESULTS: Firstly, HDAC1, HDAC2, HDAC3, HDAC4, HDAC6, HDAC7, SIRT2, and SIRT3 have been implicated with the possibility of binding to the thirty-one common active components in HGWWD. Furthermore, the protective effect of HGWWD is reversed by both TSA (HDAC inhibitor) and MC1568 (class II HDAC inhibitor) on vascular impairment accompanied by reduced aortic HDAC activity in STZ mice. Finally, inhibition of HDAC4 blocked the protective effect of HGWWD on microvascular and endothelial dysfunction in diabetic mice. CONCLUSIONS: These results prove the key role of HDAC4 in diabetes-induced microvascular dysfunction and underlying epigenetic mechanisms for the protective effect of HGWWD in diabetes.

Neural function of Bmal1: an overview.

Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the biologic clock. Although Bmal1 is well-established as a major regulator of circadian rhythm, a growing number of studies in recent years have shown that dysfunction of Bmal1 underlies a variety of psychiatric, neurodegenerative-like, and endocrine metabolism-related disorders, as well as potential oncogenic roles. In this review, we systematically summarized Bmal1 expression in different brain regions, its neurological functions related or not to circadian rhythm and biological clock, and pathological phenotypes arising from Bmal1 knockout. This review also discusses oscillation and rhythmicity, especially in the suprachiasmatic nucleus, and provides perspective on future progress in Bmal1 research.

An Accelerating Reduction Approach for Incomplete Decision Table Using Positive Approximation Set.

Due to the explosive growth of data collected by various sensors, it has become a difficult problem determining how to conduct feature selection more efficiently. To address this problem, we offer a fresh insight into rough set theory from the perspective of a positive approximation set. It is found that a granularity domain can be used to characterize the target knowledge, because of its form of a covering with respect to a tolerance relation. On the basis of this fact, a novel heuristic approach ARIPA is proposed to accelerate representative reduction algorithms for incomplete decision table. As a result, ARIPA in classical rough set model and ARIPA-IVPR in variable precision rough set model are realized respectively. Moreover, ARIPA is adopted to improve the computational efficiency of two existing state-of-the-art reduction algorithms. To demonstrate the effectiveness of the improved algorithms, a variety of experiments utilizing four UCI incomplete data sets are conducted. The performances of improved algorithms are compared with those of original ones as well. Numerical experiments justify that our accelerating approach enhances the existing algorithms to accomplish the reduction task more quickly. In some cases, they fulfill attribute reduction even more stably than the original algorithms do.

Role of Beclin1 expression in patients with hepatocellular carcinoma: a meta-analysis.

BACKGROUND AND AIM: Beclin1 has been reported as a vital marker for a number of malignant tumors. However, the role of Beclin1 in hepatocellular carcinoma (HCC) remains inconclusive. Thus, we conducted a meta-analysis to assess the correlation between Beclin1 and its clinicopathological and prognostic values in HCC. METHODS: PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese WanFang databases were searched for published articles on Beclin1 expression in hepatocellular tissues. Standard-compliant articles were screened using the Newcastle-Ottawa Scale for strict quality control of the literature. The correlation of Beclin1 expression with the clinicopathological features and survival outcomes was analyzed. Pooled odds ratios and hazard ratios with 95% confidence intervals were calculated using STATA14.2. RESULTS: Eleven articles with 1,279 patients were included in this meta-analysis. Positive Beclin1 expression was found to be correlated with alpha fetoprotein, liver cirrhosis, and vascular invasion, but not with gender, age, HBsAg, size of tumor, number of tumors, differentiation, and TNM stage. Positive Beclin1 expression was also associated with favorable 5-year overall survival and disease-free survival rates. CONCLUSION: Our meta-analysis indicated that positive Beclin1 expression was negatively related to alpha fetoprotein, liver cirrhosis, and vascular invasion in HCC. Beclin1 could be used as a prognostic biomarker for HCC.

Prognostic and clinicopathological value of Nanog in hepatocellular carcinoma: A meta-analysis.

BACKGROUND AND AIMS: Recently, studies indicate that Nanog is over-expressed in hepatocellular carcinoma (HCC); however, the relationship between Nanog expression and clinicopathological and prognostic value remains controversial. Therefore, we conducted a meta-analysis to explore the role of Nanog in HCC. METHODS: Articles were included from PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and the Chinese WanFang database. The relationships between Nanog expression, clinicopathological features, and survival rate were calculated. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with STATA14.2. RESULTS: A total of 845 patients from 9 articles were enrolled. Positive Nanog expression was correlated with HBsAg, differentiation, and TNM stage, although it was not related to gender, age, alpha-fetoprotein (AFP), tumor size, tumor number, liver cirrhosis, and vascular invasion. Positive Nanog expression indicates a poor 3-year and 5-year overall survival and disease-free survival rate. CONCLUSION: The results show that Nanog expression was related to HBsAg, differentiation, and TNM stage in HCC. Nanog may be an unfavorable prognostic biomarker for HCC.