Patients with heart failure (HF) have structural and functional changes of the gut as a result of microcirculatory disturbances. A disrupted gut epithelial barrier may lead to translocation of microbial products into systemic circulation, possibly aggravating HF by inducing inflammatory responses. Gut microbiota play an essential role in the maintenance of host homeostasis because large quantities of their gene products complement host physiological processes. Emerging evidence has suggested the potential clinical significance of gut microbiota in the pathophysiology of HF. Imbalances of gut microbe-derived metabolites can contribute to cardiac dysfunction and other morbidities in patients with HF. Therapeutic research for HF through targeting microbiota is under way. Thus, the novel concept of a heart-gut axis may lead to breakthroughs in the development of innovative diagnostics and therapeutic approaches for HF.
Complement System Proteins ; Dysbiosis ; Gastrointestinal Microbiome ; Heart Failure* ; Heart* ; Homeostasis ; Humans ; Microbiota ; Physiological Processes ; Therapeutic Human Experimentation

BACKGROUND: Various treatments for hepatocellular carcinoma (HCC) are utilized in clinical practice; however, the prognosis is still poor on account of high recurrence rates. DNA methylation levels of CpG islands around promoters (promoter CpGis) inversely regulate gene expression and closely involved in carcinogenesis. As a new strategy, several chemicals globally inhibiting DNA methylation have been developed aiming at reducing DNA methylation levels and maintaining the expression of tumor suppressor genes. On the other hand, since these drugs nonspecifically modify DNA methylation, they can cause serious adverse effects. In order to ameliorate the methods by targeting specific CpGs, information of cancer-related genes that are regulated by DNA methylation is required. METHODS: We searched candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and which are involved in HCC cases. To do so, we first identified genes whose expression were changed in HCC by comparing gene expressions of 371 HCC tissues and 41 non-tumor tissues using the Cancer Genome Atlas (TCGA) database. The genes were further selected for poor prognosis by log-rank test of Kaplan-Meier plot and for cancer relevance by Pubmed search. Expression profiles of upregulated genes in HCC tissues were assessed by Gene Ontology (GO) analysis. Finally, using DNA methylation data of TCGA database, we selected genes whose promoter DNA methylation levels were inversely correlated with gene expression. RESULTS: We found 115 genes which were significantly up- or downregulated in HCC tissues and were associated with poor prognosis and cancer relevance. The upregulated genes were significantly enriched in cell division, cell cycle, and cell proliferation. Among the upregulated genes in HCC, we identified hypomethylation of CpGis around promoters of FANCB, KIF15, KIF4A, ERCC6L, and UBE2C. In addition, TCGA data showed that the tumor suppressor gene P16 is unexpectedly overexpressed in many types of cancers. CONCLUSIONS We identified five candidate genes whose expressions were regulated by DNA methylation of promoter CpGi and associate with cancer cases and poor prognosis in HCC. Modification of site-specific DNA methylation of these genes enables a different approach for HCC treatment with higher selectivity and lower adverse effects.
Carcinoma, Hepatocellular ; genetics ; metabolism ; Cell Proliferation ; CpG Islands ; genetics ; DNA Methylation ; Databases as Topic ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; genetics ; metabolism ; Promoter Regions, Genetic

BACKGROUND: Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice. METHODS: Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method. RESULTS: The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice. CONCLUSIONS These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.
Animals ; Arsenic/toxicity* ; Arsenites/toxicity* ; Behavior, Animal/drug effects* ; Environmental Pollutants/toxicity* ; Female ; Gene Expression/drug effects* ; Genetic Markers ; Male ; Maternal Exposure/adverse effects* ; Mice ; Mice, Inbred C3H ; Oxidative Stress/genetics* ; Prefrontal Cortex/drug effects* ; Pregnancy ; Prenatal Exposure Delayed Effects/psychology* ; Reverse Transcriptase Polymerase Chain Reaction ; Serotonin/metabolism* ; Social Behavior ; Sodium Compounds/toxicity*

BACKGROUND: Particulate matter (PM) is recognized as the most harmful air pollutant to the human health. The Yangon city indeed suffers much from PM-related air pollution. Recent research has interestingly been focused on the novel subject of changes in the air quality associated with the restrictive measures in place during the current coronavirus disease-2019 (COVID-19) pandemic. The first case of COVID-19 in Myanmar was diagnosed on March 23, 2020. In this article, we report on our attempt to evaluate any effects of the COVID-19-restrictive measures on the ambient PM pollution in Yangon. METHODS: We measured the PM concentrations every second for 1 week on four occasions at three study sites with different characteristics; the first occasion was before the start of the COVID-19 pandemic and the remaining three occasions were while the COVID-19-restrictive measures were in place, including Stay-At-Home and Work-From-Home orders. The Pocket PM RESULTS: The results showed that there was a significant reduction (P < 0.001) in both the PM CONCLUSIONS We concluded that the restrictive measures which were in effect to combat the COVID-19 pandemic had a positive impact on the ambient PM concentrations. The changes in the PM concentrations are considered to be largely attributable to reduction in anthropogenic emissions as a result of the restrictive measures, although seasonal influences could also have contributed in part. Thus, frequent, once- or twice-weekly Stay-At-Home or Telework campaigns, may be feasible measures to reduce PM-related air pollution. When devising such an action plan, it would be essential to raise the awareness of public about the health risks associated with air pollution and create a social environment in which Telework can be carried out, in order to ensure active compliance by the citizens.
Air Pollution/analysis* ; COVID-19/epidemiology* ; Humans ; Myanmar/epidemiology* ; Pandemics ; Particulate Matter/analysis* ; SARS-CoV-2