Delgadoellison1891
Genetic and epigenetic mechanisms regulate antimicrobial immunity against
(Mtb) infection.
The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages.
The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy-associated protein LC3-II production in Mtb-infected macrophages. circTRAPPC6B-enhanced autophagy aggregation or sequestration was also observed in fluorescence
hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR-874-3p, as shown by bioinformatics, dual-luciferase reporter gene analysis and pull-down assay, respectively. Notably, miR-874-3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3'-untranslated region (UTR) in Mtb-infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb-infected macrophages by blocking the ability of miR-874-3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of
to suppress
expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages.
The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.
The current findings suggested that both circTRAPPC6B and miR-874-3p mechanisms can be explored as potential therapeutics against Mtb infection.
Histone methyltransferase G9a, also known as Euchromatic Histone Lysine Methyltransferase 2 (EHMT2), mediates H3K9 methylation which is associated with transcriptional repression. It possesses immunomodulatory effects and is overexpressed in multiple types of cancer. In this study, we investigated the role of G9a in the induction of trained immunity, a
innate immune memory, and its effects in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical Bacillus Calmette-Guérin (BCG).
EHMT2 expression was assessed upon induction of trained immunity by RNA sequencing and Western blotting. G9a inhibitor BIX-01294 was used to investigate the effect on trained immunity responses
. Subsequent cytokine production was measured by ELISA, epigenetic modifications were measured by ChIP-qPCR, Seahorse technology was used to measure metabolic changes, and a luminescence assay was used to measure ROS release. RNA sequencing was performed on BIX-01294-treated monocytes
.
The expression of EHMT2 mRNA and protein decreased in monocytes during induction of trained immunity. G9a inhibition by BIX-01294 induced trained immunity and amplified trained immunity responses evoked by various microbial ligands
. This was accompanied by decreased H3K9me2 at the promoters of pro-inflammatory genes. G9a inhibition was also associated with amplified
trained immunity responses in circulating monocytes of NMIBC patients. Additionally, altered RNA expression of inflammatory genes in monocytes of NMIBC patients was observed upon
G9a inhibition. Furthermore, intravesical BCG therapy decreased H3K9me2 at the promoter of pro-inflammatory genes.
Inhibition of G9a is important in the induction of trained immunity, and G9a may represent a novel therapeutic target in NMIBC patients.
Inhibition of G9a is important in the induction of trained immunity, and G9a may represent a novel therapeutic target in NMIBC patients.
Transbronchial lung cryobiopsy (TBLC) is a new technique that enables larger tissue collection than can be obtained by conventional transbronchial lung biopsy. TBLC is becoming popular worldwide and is performed for diffuse lung disease and lung cancer. However, only a few reports of TBLC have been published in Japan. This study was performed to evaluate the efficacy and safety of TBLC at our hospital and compare these findings with past reports.
From April 2018 to January 2020, 38 patients who underwent TBLC for diffuse lung disease at our hospital were evaluated with respect to age, sex, biopsy site, biopsy size, diagnostic disease, and complications.
The patients who underwent TBLC were 20 men and 18 women with an average age of 63.7 years. The average sample size was 5.7 mm, and the diagnostic rate was 65.7% (25/38). Grade ≥2 complications included bleeding (15.8%), pneumothorax (2.6%), and atrial fibrillation (2.6%).
TBLC was considered to be useful for the diagnosis of diffuse lung disease and could be safely performed.
TBLC was considered to be useful for the diagnosis of diffuse lung disease and could be safely performed.Vascular endothelial cells have a variety of functions such as the control of blood coagulation, vascular permeability, and tone regulation, as well as quiesce of immune cells. Endothelial dysfunction is a cardiovascular events predictor, which is considered the initial stage in atherosclerosis development. It is characterized by alterations in endothelium functions due to imbalanced vasodilators and vasoconstrictors, procoagulant and anticoagulant mediators, as well as growth inhibitor and promotor substances. Chlorogenic acid (CGA) is the primary polyphenol in coffee and some fruits. It has many health-promoting properties, especially in the cardiovascular system. Many studies investigated the efficacy and mechanism of this compound in vascular health. CGA has several vascular benefits such as anti-atherosclerosis, anti-thrombosis, and anti-hypertensive. find more This review focuses on the molecular mechanism of CGA in vascular health.Background In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%-0.53%; I 2 =89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%-1.22%; I 2 =94.07%) among 58,104 COVID-19 patients.
