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Androgen deprivation therapy (ADT), either by medical or surgical castration, is the backbone for standard treatment of locally advanced or metastatic prostate cancer, yet it is also associated with various metabolic and cardiovascular complications. Recent evidence have shown that obesity, insulin resistance, or metabolic disturbances can be associated with changes in the gut microbiome, while animal studies also show that castration is associated with changes in the gut microbiome. This study aims to investigate whether the fecal microbiota in prostate cancer patients who had undergone prostatectomy or ADT are different, and explore changes in phylogeny and pathways that may lead to side effects from ADT. A total of 86 prostate cancer patients (56 patients on ADT and 30 patients with prostatectomy) were recruited. The fecal microbiota was analyzed by the 16S rRNA gene for alpha- and beta-diversities by QIIME2, as well as the predicted metabolic pathways by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2. The alpha-diversity was significantly lower in the ADT group. The beta-diversity was significantly different between the groups, in which Ruminococcus gnavus and Bacteroides spp were having higher relative abundance in the ADT group, whereas Lachnospira and Roseburia were reduced. The Firmicutes-to-Bacteroidetes ratio is noted to be lower in the ADT group as well. The functional pathway prediction showed that the biosynthesis of lipopolysaccharide (endotoxin) and propanoate was enriched in the ADT as well as the energy cycle pathways. This study is limited by the cross-sectional design and the clinical heterogeneity. There is a significant difference in gut microbiome between prostate cancer patients on ADT and prostatectomy. We theorize that this difference may contribute to the development of metabolic complications from ADT. Further longitudinal studies are awaited.

The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) is believed to share similar characteristics with SARS in 2003 and Mediterranean East Respiratory Syndrome (MERS) in 2012. We hypothesized that countries with previous exposure to SARS and MERS were significantly more likely to have fewer cases and deaths from coronavirus disease 2019 (COVID-19). We retrieved the incidence of COVID-19 per 100,000 population within 30 days since the first confirmed case was reported from the 2019 Novel COVID-19 data repository by the Johns Hopkins Centre for Systems Science and Engineering for 94 countries. The association between previous exposure to SARS and/or MERS and the 30-day COVID-19 incidence rate was examined by multivariable linear regression analysis, whilst controlling for potential confounders including the INFORM COVID-19 Risk Index, Testing Policies, Democracy Index, Scientific Citation Index, Gross Domestic Product (GDP), Human Development Index (HDI) and the population density of each country. We found that countries with previous exposure to SARS and/or MERS epidemics were significantly more likely to have lower incidence of COVID-19 (β coefficient - 225.6, 95% C.I. - 415.8,- 35.4, p = 0.021). However, countries being classified as having "full democracy" using Democracy Index had higher incidence of COVID-19 (reference: authoritarian regime; β coefficient 425.0, 95% C.I. 98.0, 752.0, p = 0.011). This implies that previous exposure to global epidemics and Democracy Index for a country are associated its performance in response to COVID-19. We recommend future studies should evaluate the impact of various pandemic control strategies at individual, community, and policy levels on mitigation of the disease.

MicroRNAs are frequently dysregulated in human neoplasms, including gastrointestinal cancers. Nevertheless, the global influence of microRNA dysregulation on cellular signaling is still unknown. Here we sought to elucidate cellular signaling dysregulation by microRNAs in gastrointestinal cancers at the systems biology level followed by experimental validation. Signature dysregulated microRNAs in gastric, colorectal and liver cancers were defined based on our previous studies. Targets of signature dysregulated miRNAs were predicted using multiple computer algorithms followed by gene enrichment analysis to identify biological processes perturbed by dysregulated microRNAs. Effects of microRNAs on endocytosis were measured by epidermal growth factor (EGF) internalization assay. Our analysis revealed that, aside from well-established cancer-related signaling pathways, several novel pathways, including axon guidance, neurotrophin/nerve growth factor signaling, and endocytosis, were found to be involved in the pathogenesis of gastrointestinal cancers. The regulation of EGF receptor (EGFR) endocytosis by two predicted miRNAs, namely miR-17 and miR-145, was confirmed experimentally. Functionally, miR-145, which blocked EGFR endocytosis, prolonged EGFR membrane signaling and altered responsiveness of colon cancer cells to EGFR-targeting drugs. In conclusion, our analysis depicts a comprehensive picture of cellular signaling dysregulation, including endocytosis, by microRNAs in gastrointestinal cancers.

Incidence of Clostridium difficile infection (CDI) is rapidly increasing and it poses a major health burden globally. However, data regarding the epidemiology of CDI in Asia are limited. We aimed to characterize the antimicrobial susceptibility patterns of common ribotypes of toxigenic C. difficile in Hong Kong. Fifty-three PCR ribotypes were identified among 284 toxigenic C. difficile clinical isolates. The five most prevalent ribotypes were 002 (13%), 017 (12%), 014 (10%), 012 (9.2%), and 020 (9.5%). All tested C. difficile strains remained susceptible to metronidazole, vancomycin, meropenem and piperacillin/tazobactam, but highly resistant to cephalosporins. Of the fluoroquinolones, highest resistance to ciprofloxacin was observed (99%), followed by levofloxacin (43%) and moxifloxacin (23%). The two newly emerged PCR ribotypes, 017 and 002, demonstrated high levels of co-resistance towards clindamycin, tetracycline, erythromycin and moxifloxacin. PCR ribotypes 017 and 002 with multi-drug resistance are rapidly emerging and continuous surveillance is important to monitor the epidemiology of C. difficile to prevent outbreaks of CDI.

Background Sepsis coincides with altered gene expression in different tissues. Accumulating evidence has suggested that microRNAs, long non-coding RNAs, and circular RNAs are important molecules involved in the crosstalk with various pathways pertinent to innate immunity, mitochondrial functions, and apoptosis. Methods We searched articles indexed in PubMed (MEDLINE), EMBASE and Europe PubMed Central databases using the Medical Subject Heading (MeSH) or Title/Abstract words (“microRNA”, “long non-coding RNA”, “circular RNA”, “sepsis” and/or “septic shock”) from inception to Sep 2016. Studies investigating the role of host-derived microRNA, long non-coding RNA, and circular RNA in the pathogenesis of and as biomarkers or therapeutics in sepsis were included. Data were extracted in terms of the role of non-coding RNAs in pathogenesis, and their applicability for use as biomarkers or therapeutics in sepsis. Two independent researchers assessed the quality of studies using a modified guideline from the Systematic Review Center for Laboratory animal Experimentation (SYRCLE), a tool based on the Cochrane Collaboration Risk of Bias tool. Results Observational studies revealed dysregulation of non-coding RNAs in septic patients. Experimental studies confirmed their crosstalk with JNK/NF-κB and other cellular pathways pertinent to innate immunity, mitochondrial function, and apoptosis. Of the included studies, the SYRCLE scores ranged from 3 to 7 (average score of 4.55). This suggests a moderate risk of bias. Of the 10 articles investigating non-coding RNAs as biomarkers, none of them included a validation cohort. Selective reporting of sensitivity, specificity, and receiver operating curve was common. Conclusions Although non-coding RNAs appear to be good candidates as biomarkers and therapeutics for sepsis, their differential expression across tissues complicated the process. Further investigation on organ-specific delivery of these regulatory molecules may be useful. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1555-3) contains supplementary material, which is available to authorized users.

Inflammatory bowel diseases occur due to an aberrant immune response to luminal antigens in genetically predisposed individuals. Although specific genetic loci have been identified underlying the predisposition, they have not fully explained the disease etiology. Striking epidemiological observations implicate the critical role of environmental influences on disease penetrance. The emergence of disease consistently observed as a society becomes modernized or developed may be attributed to westernization of diet, changing antibiotic use, or improved hygiene status. These factors are linked with changes in the gastrointestinal microbiota which, in turn, may affect development of the immune system and influence the risk of disease occurrence. Geographic variations within developing countries suggest that the strength of influence by risk factors in a society varies greatly. Studies of IBD in populations of developing countries where there are opportunities to prospectively collect changing exposure data over time may provide clues to the disease etiology.