Notes

LncRNA SNHG12 regulates ox-LDL-induced endothelial cellular damage by the miR-218-5p/IGF2 axis throughout coronary artery disease.
To better understand the cancer risk posed by radiation and the development of radiation therapy resistant cancer cells, we investigated the involvement of the cancer risk factor, APOBEC3B, in the generation of radiation-induced mutations. Expression of APOBEC3B in response to irradiation was determined in three human cancer cell lines by real-time quantitative PCR. Using the hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutation assay, mutations in the HPRT gene caused by irradiation were compared between APOBEC3B-deficient human hepatocellular carcinoma (HepG2) cells [APOBEC3B knocked out (KO) using CRISPR-Cas9 genome editing] and the parent cell line. Then, HPRT-mutated cells were individually cultured to perform PCR and DNA sequencing of HPRT exons. X-Irradiation induced APOBEC3B expression in HepG2, human cervical cancer epithelial carcinoma (HeLa) and human oral squamous cell carcinoma (SAS) cells. Forced expression of APOBEC3B increased spontaneous mutations. By contrast, APOBEC3B KO not only decreased the spontaneous mutation rate, but also strongly suppressed the increase in mutation frequency after irradiation in the parent cell line. Although forced expression of APOBEC3B in the nucleus caused DNA damage, higher levels of APOBEC3B tended to reduce APOBEC3B-induced γ-H2AX foci formation (a measure of DNA damage repair). Further, the number of γ-H2AX foci in cells stably expressing APOBEC3B was not much higher than that in controls before and after irradiation, suggesting that a DNA repair pathway may be activated. This study demonstrates that irradiation induces sustained expression of APOBEC3B in HepG2, HeLa and SAS cells, and that APOBEC3B enhances radiation-induced partial deletions.The purpose of the current study was to investigate the biological effects of protons and photons in combination with cisplatin in cultured cells and elucidate the mechanisms responsible for their combined effects. To evaluate the sensitizing effects of cisplatin against X-rays and proton beams in HSG, EMT6 and V79 cells, the combination index, a simple measure for quantifying synergism, was estimated from cell survival curves using software capable of performing the Monte Carlo calculation. Cell death and apoptosis were assessed using live cell fluorescence imaging. HeLa and HSG cells expressing the fluorescent ubiquitination-based cell cycle indicator system (Fucci) were irradiated with X-rays and protons with cisplatin. Red and green fluorescence in the G1 and S/G2/M phases, respectively, were evaluated and changes in the cell cycle were assessed. The sensitizing effects of ≥1.5 μM cisplatin were observed for both X-ray and proton irradiation (P less then 0.05). In the three cell lines, the average combination index was 0.82-1.00 for X-rays and 0.73-0.89 for protons, indicating stronger effects for protons. In time-lapse imaging, apoptosis markedly increased in the groups receiving ≥1.5 μM cisplatin + protons. The percentage of green S/G2/M phase cells at that time was higher when cisplatin was combined with proton beams than with X-rays (P less then 0.05), suggesting more significant G2 arrest. Proton therapy plus ≥1.5 μM cisplatin is considered to be very effective. When combined with cisplatin, proton therapy appeared to induce greater apoptotic cell death and G2 arrest, which may partly account for the difference observed in the combined effects.Helicobacter pylori is a Gram-negative, spiral shaped bacterium that selectively and chronically infects the gastric mucosa of humans. The clinical course of this infection can range from lifelong asymptomatic infection to severe disease, including peptic ulcers or gastric cancer. The high mutation rate and natural competence typical of this species are responsible for massive inter-strain genetic variation exceeding that observed in all other bacterial human pathogens. The adaptive value of such a plastic genome is thought to derive from a rapid exploration of the fitness landscape resulting in fast adaptation to the changing conditions of the gastric environment. Nevertheless, diversity is also lost through recurrent bottlenecks and H. pylori's lifestyle is thus a perpetual race to maintain an appropriate pool of standing genetic variation able to withstand selection events. Another aspect of H. pylori's diversity is a large and variable repertoire of restriction-modification systems. While not yet completely understood, methylome evolution could generate enough transcriptomic variation to provide another intricate layer of adaptive potential. This review provides an up to date synopsis of this rapidly emerging area of H. pylori research that has been enabled by the ever-increasing throughput of Omics technologies and a multitude of other technological advances.
There is some evidence that loneliness may be linked to poorer health behaviours. Despite this, there has been little research to date on the relationship between loneliness and COVID-19 preventive behaviours. Tripterine We studied these associations in a sample of the Japanese population.

Data were analysed from an online survey of 2000 adults undertaken in April and May 2020. Loneliness was assessed with the Three-Item Loneliness Scale. Information was also collected on 13 COVID-19 preventive behaviours. Regression analyses were used to examine associations.

In linear regression models adjusted for demographic and mental health variables, both dichotomous and continuous loneliness measures were negatively associated with engaging in COVID-19 preventive behaviours. Logistic regression analyses further showed that loneliness was also associated with reduced odds for a variety of individual preventive behaviours including wearing a mask (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62-0.95), disinfecting hands (OR 0.80, 95% CI 0.67-0.94) and social distancing when outdoors (OR 0.75, 95% CI 0.61-0.92).

Loneliness is associated with lower engagement in COVID-19 preventive behaviours. Interventions to prevent or ameliorate loneliness during the ongoing pandemic may be important in combating the spread of the coronavirus.
Loneliness is associated with lower engagement in COVID-19 preventive behaviours. Interventions to prevent or ameliorate loneliness during the ongoing pandemic may be important in combating the spread of the coronavirus.
This study evaluated the underlying factors associated with poor tuberculosis (TB) treatment outcomes among patients attending health care facilities in Galkayo, Puntland, Somalia.

An institution-based cross-sectional study was conducted between 2016 and 2017 in three selected TB clinics. Data were collected from 400TB patients, through medical record review and structured questionnaire. Multivariate logistic regression analyses were performed.

Of the 400TB respondents, 57.3% were new cases, 12.3% had smear-negative TB and 12.5% had extrapulmonary TB. The median age was (35.66±13.16) with majority being male (65.5%). Overall, 85% of patients were successfully treated, 9.7% failed and 5.3% defaulted. Multivariate analysis revealed that patient's body weight (odds ratio [OR] 1.078); diabetes (OR 8.022); family size (OR 3.851); patients' delay in diagnosis (OR 11.946); frequency of receiving anti-TB medication (OR 9.068); smoker (OR 5.723); category of patients (retreatment versus new, OR 5.504; retreatment versus transfer in, OR 4.957); health facilities (OR 6.716) and treatment duration (OR 132.091) were independent factors associated with poor TB outcomes.

Our findings highlight the need to improve TB services for vulnerable groups. They also emphasize the need for health system strengthening, public awareness and risk of treatment interruption. link2 This may reduce both patients' delay in seeking care and TB treatment failure in Galkayo district.
Our findings highlight the need to improve TB services for vulnerable groups. They also emphasize the need for health system strengthening, public awareness and risk of treatment interruption. This may reduce both patients' delay in seeking care and TB treatment failure in Galkayo district.Talaromyces marneffei causes life-threatening opportunistic infections, mainly in Southeast Asia and South China. T. marneffei mainly infects patients with human immunodeficiency virus (HIV) but also infects individuals without known immunosuppression. Here we investigated the involvement of anti-IFN-γ autoantibodies in severe T. marneffei infections in HIV-negative patients. We enrolled 58 HIV-negative adults with severe T. marneffei infections who were otherwise healthy. We found a high prevalence of neutralizing anti-IFN-γ autoantibodies (94.8%) in this cohort. The presence of anti-IFN-γ autoantibodies was strongly associated with HLA-DRB1*1602 and -DQB1*0502 alleles in these patients. link3 We demonstrated that adult-onset acquired immunodeficiency due to autoantibodies against IFN-γ is the major cause of severe T. marneffei infections in HIV-negative patients in regions where this fungus is endemic. The high prevalence of anti-IFN-γ autoantibody-associated HLA class II DRB1*1602 and DQB1*0502 alleles may account for severe T. marneffei infections in Southeast Asia. Our findings clarify the pathogenesis of T. marneffei infection and pave the way for developing novel treatments.Intestinal barrier leakage constitutes a potential therapeutic target for many inflammatory diseases and represents a disease progression marker during chronic viral infections. However, the causes of altered gut barrier remain mostly unknown. Using murine infection with lymphocytic choriomeningitis virus, we demonstrate that, in contrast to an acute viral strain, a persistent viral isolate leads to long-term viral replication in hematopoietic and mesenchymal cells, but not epithelial cells (IECs), in the intestine. Viral persistence drove sustained intestinal epithelial barrier leakage, which was characterized by increased paracellular flux of small molecules and was associated with enhanced colitis susceptibility. Type I IFN signaling caused tight junction dysregulation in IECs, promoted gut microbiome shifts and enhanced intestinal CD8 T cell responses. Notably, both type I IFN receptor blockade and CD8 T cell depletion prevented infection-induced barrier leakage. Our study demonstrates that infection with a virus that persistently replicates in the intestinal mucosa increases epithelial barrier permeability and reveals type I IFNs and CD8 T cells as causative factors of intestinal leakage during chronic infections.Many pathogens subvert intestinal immunity to persist within the gastrointestinal tract (GIT); yet, the underlying mechanisms that enable sanctuary specifically in this reservoir are unclear. Using mass cytometry and network analysis, we demonstrate that chronic LCMV infection of the GIT leads to dysregulated microbial composition, a cascade of metabolic alterations, increased susceptibility to GI disease, and a system-wide recalibration of immune composition that defines viral persistence. Chronic infection led to outgrowth of activated Tbet-expressing T reg cell populations unique to the GIT and the rapid erosion of pathogen-specific CD8 tissue-resident memory T cells. Mechanistically, T reg cells and coinhibitory receptors maintained long-term viral sanctuary within the GIT, and their targeting reactivated T cells and eliminated this viral reservoir. Thus, our data provide a high-dimensional definition of the mechanisms of immune regulation that chronic viruses implement to exploit the unique microenvironment of the GIT and identify T reg cells as key modulators of viral persistence in the intestinal tract.
Homepage: https://www.selleckchem.com/products/Celastrol.html