Multi-omics profiling reveals microRNA-mediated insulin signaling networks.

BACKGROUND: MicroRNAs (miRNAs) play a key role in mediating the action of insulin on cell growth and the development of diabetes. However, few studies have been conducted to provide a comprehensive overview of the miRNA-mediated signaling network in response to glucose in pancreatic beta cells. In our study, we established a computational framework integrating multi-omics profiles analyses, including RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) data analysis, inverse expression pattern analysis, public data integration, and miRNA targets prediction to illustrate the miRNA-mediated regulatory network at different glucose concentrations in INS-1 pancreatic beta cells (INS-1), which display important characteristics of the pancreatic beta cells. RESULTS: We applied our computational framework to the expression profiles of miRNA/mRNA of INS-1, at different glucose concentrations. A total of 1437 differentially expressed genes (DEGs) and 153 differentially expressed miRNAs (DEmiRs) were identified from multi-omics profiles. In particular, 121 DEmiRs putatively regulated a total of 237 DEGs involved in glucose metabolism, fatty acid oxidation, ion channels, exocytosis, homeostasis, and insulin gene regulation. Moreover, Argonaute 2 immunoprecipitation sequencing, qRT-PCR, and luciferase assay identified Crem, Fn1, and Stc1 are direct targets of miR-146b and elucidated that miR-146b acted as a potential regulator and promising target to understand the insulin signaling network. CONCLUSIONS: In this study, the integration of experimentally verified data with system biology framework extracts the miRNA network for exploring potential insulin-associated miRNA and their target genes. The findings offer a potentially significant effect on the understanding of miRNA-mediated insulin signaling network in the development and progression of pancreatic diabetes.

Fasting before or after wound injury accelerates wound healing through the activation of pro-angiogenic SMOC1 and SCG2.

Healing of the chronic diabetic ulceration and large burns remains a clinical challenge. Therapeutic fasting has been shown to improve health. Our study tested whether fasting facilitates diabetic and burn wound healing and explored the underlying mechanism. Methods: The effects of fasting on diabetic and burn wound healing were evaluated by analyzing the rates of wound closure, re-epithelialization, scar formation, collagen deposition, skin cell proliferation and neovascularization using histological analyses and immunostaining. In vitro functional assays were conducted to assess fasting and refeeding on the angiogenic activities of endothelial cells. Transcriptome sequencing was employed to identify the differentially expressed genes in endothelial cells after fasting treatment and the role of the candidate genes in the fasting-induced promotion of angiogenesis was demonstrated. Results: Two times of 24-h fasting in a week after but especially before wound injury efficiently induced faster wound closure, better epidermal and dermal regeneration, less scar formation and higher level of angiogenesis in mice with diabetic or burn wounds. In vitro, fasting alone by serum deprivation did not increase, but rather reduced the abilities of endothelial cell to proliferate, migrate and form vessel-like tubes. However, subsequent refeeding did not merely rescue, but further augmented the angiogenic activities of endothelial cells. Transcriptome sequencing revealed that fasting itself, but not the following refeeding, induced a prominent upregulation of a variety of pro-angiogenic genes, including SMOC1 (SPARC related modular calcium binding 1) and SCG2 (secretogranin II). Immunofluorescent staining confirmed the increase of SMOC1 and SCG2 expression in both diabetic and burn wounds after fasting treatment. When the expression of SMOC1 or SCG2 was down-regulated, the fasting/refeeding-induced pro-angiogenic effects were markedly attenuated. Conclusion: This study suggests that fasting combined with refeeding, but not fasting solely, enhance endothelial angiogenesis through the activation of SMOC1 and SCG2, thus facilitating neovascularization and rapid wound healing.

Enterotype-based Analysis of Gut Microbiota along the Conventional Adenoma-Carcinoma Colorectal Cancer Pathway.

The dysbiosis of human gut microbiota is strongly associated with the development of colorectal cancer (CRC). The dysbiotic features of the transition from advanced polyp to early-stage CRC are largely unknown. We performed a 16S rRNA gene sequencing and enterotype-based gut microbiota analysis study. In addition to Bacteroides- and Prevotella-dominated enterotypes, we identified an Escherichia-dominated enterotype. We found that the dysbiotic features of CRC were dissimilar in overall samples and especially Escherichia-dominated enterotype. Besides a higher abundance of Fusobacterium, Enterococcus, and Aeromonas in all CRC faecal microbiota, we found that the most notable characteristic of CRC faecal microbiota was a decreased abundance of potential beneficial butyrate-producing bacteria. Notably, Oscillospira was depleted in the transition from advanced adenoma to stage 0 CRC, whereas Haemophilus was depleted in the transition from stage 0 to early-stage CRC. We further identified 7 different CAGs by analysing bacterial clusters. The abundance of microbiota in cluster 3 significantly increased in the CRC group, whereas that of cluster 5 decreased. The abundance of both cluster 5 and cluster 7 decreased in the Escherichia-dominated enterotype of the CRC group. We present the first enterotype-based faecal microbiota analysis. The gut microbiota of colorectal neoplasms can be influenced by its enterotype.

Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes.

The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)2] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe2(µ-SR)2(NO)4] (1) as a universal platform for the O2-triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-ßgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology.

Haptoglobin expression correlates with tumor differentiation and five-year overall survival rate in hepatocellular carcinoma.

Elevated serum haptoglobin (Hp) is identified as a prognostic marker in multiple types of solid tumors, which is correlated with poor prognosis. HCC is one of the major causes of cancer deaths in worldwide, which remains poor prognosis and is clinically urgent for discovering early diagnostic markers. However, except for serum Hp, the correlation of tumor Hp expression with hepatocellular carcinoma (HCC) progression is still unclear. In this study, we evaluated and identified the tissue Hp expression as a prognostic marker to predict the survival rate of HCC patients. To evaluate the prognostic value of Hp expression for HCC, two cohorts were enrolled in our study, including total 130 matched pair tissue sections (both adjacent non-tumorous and tumor tissue derived from same patient) of HCC patients from Changhua Christian Hospital (CCH) and total 316 RNA-seq data with clinical information of HCC patients from The Cancer Genome Atlas (TCGA) database. In contrast to other types of cancers, HCC tumor tissues have lower Hp protein expression in CCH cohort and have lower Hp mRNA expression in TCGA cohort as compared with adjacent non-tumorous tissues (p < 0.001). Moreover, lower Hp expression is significantly correlated with different stages of HCC cancer differentiation in CCH cohort (one-way ANOVA, p < 0.001). Most importantly, lower Hp expression is highly correlated with poor five-year overall survival rate in TCGA cohort (p < 0.01). Based on our data, we conclude that tissue Hp expression positively correlates with better HCC tumor differentiation and increased five-year overall survival rate of HCC patients. The results indicated that tissue Hp is potentially a prognostic marker for HCC patients. Our findings may further provide a new insight of effective treatments along with biopsy diagnosis of HCC patients.

Identity and intimacy crises and their relationship to internet dependence among college students.

In an attempt to test Kandell's proposition that internet dependents used the internet as a coping mechanism against underlying psychological issues, this study investigated the extent to which the fifth and sixth Eriksonian crises (identity, intimacy), were related to internet dependence (online chatting, gaming) among college students. Students spending more than 10 hours per week on chatting/gaming were classified as dependents. On the basis of a national sample of freshmen in Taiwan, this study found that the dependents scored significantly lower on most of the measures that reflected the successful resolution of the crises, and higher on the measures that reflected unsuccessful resolution of the crises. Kandell's proposition was supported.