Synbiotics Supplements Lower the Risk of Hand, Foot, and Mouth Disease in Children, Potentially by Providing Resistance to Gut Microbiota Dysbiosis.

Background: Hand, foot and mouth disease (HFMD) is an acute enterovirus-induced disease. Gut microbiota dysbiosis has been identified as a factor that plays an important role in enteral virus infection, but the gut microbiota profile in hand, foot and mouth disease has rarely been studied in a large population. Methods: A total of 749 children (HFMD: n = 262, healthy control: n = 487) aged 2 to 7 years were recruited from hospitals and communities in the period from May to July, 2017. Clinical and demographical information was collected by trained personnel, and fecal samples were collected and processed for 16S ribosomal RNA(rRNA) gene sequencing. Results: We observed a significant alteration in the microbiota profile of children with HFMD compared with that of control children. Patients with enteroviruses A71(EV71) positive had more dysbiotic gut microbiota than those with coxsackievirus A16 (CAV16) positive. We found that Prevotella and Streptococcus were enriched in children with HFMD, whereas beneficial bacteria, including Bifidobacterium and Faecalibacterium, were depleted. Children with synbiotics supplements had lower risk of HFMD and we observed that the gut microbiota of HFMD patients who were administered synbiotics exhibited potential resistance to the dysbiosis detected in HFMD. Conclusions: This study suggested that the gut microbiota of patients with hand, foot and mouth disease exhibits dysbiosis and that synbiotics supplements potentially helps maintain the homeostasis of the gut flora.

eIF3 regulates migration, invasion and apoptosis in cadmium transformed 16HBE cells and is a novel biomarker of cadmium exposure in a rat model and in workers.

Translation (eukaryotic) initiation factor 3 (eIF3 or TIF3) has been found to be a proto-oncogene in cadmium (Cd) response both in vitro and vivo, but whether eIF3 may serve as a biomarker of Cd exposure is still unclear. This study aimed to investigate whether eIF3 could serve as a novel biomarker of Cd toxicity in cells, animals and workers, and regulate the apoptosis, migration and invasion in human bronchial epithelial cell (16HBE cells) transformation with cadmium chloride (CdCl2). In CdCl2 transformed 16HBE cells, eIF3 expression increased gradually, and sequencing did not identify mutation and methylation of eIF3. In 16HBE cells with eIF3 silencing by siRNA and CdCl2 treated 16HBE cells of the 15th and 35th generations, the apoptosis, migration and invasion were significantly inhibited, and the expressions of relevant genes were also altered (P < 0.05). In CdCl2 treated rats, eIF3 mRNA expression increased to different extents in the blood, liver, kidney, heart and lung, and this increase was dependent on the Cd concentration (P < 0.05). The eIF3 mRNA expression was related to the mRNA expressions of AKT, BAX, BCL-2, E-CADHERIN, CASPASE-3, EGFR, FOXC2, STAT3, TGF-ß1 and VIMENTIN (P < 0.05). In 181 workers with Cd exposure, the eIF3 mRNA expression was positively related to the blood Cd, urine Cd and ß2-microglobulin content (P < 0.05). This study showed that abnormally expressed eIF3 may regulate the apoptosis, migration and invasion of 16HBE cells with Cd toxicity. This suggests that eIF3 may become a novel and valuable biomarker of Cd toxicity and Cd-induced effects, and may regulate apoptosis, migration and invasion of 16HBE cells. Thus, the detection of eIF3 expression is important for the monitoring of Cd toxicity in humans.

Sipuleucel-T and Androgen Receptor-Directed Therapy for Castration-Resistant Prostate Cancer: A Meta-Analysis.

New treatments, such as sipuleucel-T and androgen receptor- (AR-) directed therapies (enzalutamide (Enz) and abiraterone acetate (AA)), have emerged and been approved for the management of castration-resistant prostate cancer (CRPC). There are still debates over their efficacy and clinical benefits. This meta-analysis aimed to investigate the efficacy and safety of sipuleucel-T and AR-directed therapies in patients with CRPC. RevMan 5.1 was used for pooled analysis and analysis of publication bias. Seven studies were included in the meta-analysis, with three studies in sipuleucel-T (totally 737 patients, 488 patients in treatment group, and 249 patients in placebo group) and four in AR-directed therapies (totally 5,199 patients, 3,015 patients in treatment group, and 2,184 patients in placebo group). Treatment with sipuleucel-T significantly improved overall survival in patients with CRPC and was not associated with increased risk of adverse event of grade ≥3 (p > 0.05). However, treatment with sipuleucel-T did not improve time-to-progression and reduction of prostate-specific antigen (PSA) level ≥50% was not significantly different from that with placebo. AR-directed therapies significantly improved overall survival in patients with CRPC and improved time-to-progression and reduction of PSA level ≥50%. AR-directed therapies did not increase risk of adverse event of grade ≥3 (p > 0.05).

MicroRNAs-mRNAs Expression Profile and Their Potential Role in Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cadmium.

BACKGROUND: Our study was designed to elucidate whether there were miRNA and mRNA aberrantly expression profiles and potential role in malignant transformation of 16HBE induced by Cd. METHODS: mRNA and miRNA expression profiles were determined in 35th Cd-induced 16HBE and untreated 16HBE by microarray. A series of bioinformatics analyses such as predicting targets, GO, KEGG were performed to find DEGs, coexpressing networks between miRNAs and mRNAs and its functions. RESULTS: 498 DEGs were found. 8 Cd-responsive novel miRNAs predicted previously were identified, and 5 of them were downregulated. 214 target genes were predicted for the Cd-responsive miRNAs, many of which appeared to regulate gene networks. Target gene CCM2 was showed reciprocal effect by miRNAs. According to the combination analysis, hsa-miR-27b-3p regulated most of the mRNAs, especially upregulated expression genes. The differentially expressed miRNAs are involved in the biological processes and channels, and these GO and KEGG enrichment analyses result were significantly enriched in the Cd-responsive. DISCUSSION: These results provided a tight link for the miRNA-mRNA integrated network and implied the role of novel miRNAs in malignant transformation of 16HBE induced by Cadmium. It is better to understand the novel molecular mechanism of cadmium-induced tumorigenesis.

Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.

Combined therapy of diabetic peripheral neuropathy with breviscapine and mecobalamin: a systematic review and a meta-analysis of Chinese studies.

OBJECTIVE: A meta-analysis on combined therapy of diabetic peripheral neuropathy (DPN) with breviscapine and mecobalamin was performed to evaluate the efficacy of this therapy. METHODS: Six English databases (Medline, Cochrane Library, PubMed, EMBASE, Web of Science, and CINAHL) and four Chinese databases (China National Knowledge Infrastructure, VIP Journals Database, CBM, and Wanfang database) were searched for studies on the clinical trials in which DPN was treated with breviscapine and mecobalamin, and RevMan 5.1 package was employed for analyzing pooled trials and publication bias. RESULTS: A total of 17 articles including 1398 DPN patients were identified. Homogeneity was observed among different studies (P = 0.74). The efficacy of combined therapy with breviscapine and mecobalamin was significantly better than that in control group [P < 0.0001 (OR = 5.01, 95% CI: 3.70-6.78)]. CONCLUSION: Available findings suggest that the therapeutic efficacy of breviscapine combining mecobalamin is superior to mecobalamin alone, and this strategy is required to be popularized in clinical practice.

Health-related quality of life and preferred health-seeking institutions among rural elderly individuals with and without chronic conditions: a population-based study in Guangdong Province, China.

The aim of this study was to examine health-related quality of life (HRQL) as measured by SF-36 and to identify these factors and the preferred health-seeking institutions of 12,800 persons aged 60 and older with and without chronic conditions in rural areas of Guangdong Province by multistage stratified cluster sampling method. HRQL among rural elderly subjects with chronic conditions was lower than that of elderly subjects with no chronic conditions. Multiple linear regression showed that marital status, living with children, cardiovascular disease, osteoporosis, cataract disease, and mental disease were the main affecting factors of HRQL. The main preferred health-seeking institutions selected by the rural elderly were community/town health service institutions, district hospitals, or secondary hospitals. Our findings indicate that the elderly in rural areas of Guangdong Province have a poor HRQL and incorrect health-seeking pathway. The healthcare policymakers should emphasize the need of developing effective and targeted community services strategies to improve the elderly individuals' HRQL in rural areas of China.