Abstract The DNA methyltransferase-mediated proinflammatory activation of macrophages is causally linked to the development atherosclerosis (AS). However, role DNMT1, a methylation maintenance enzyme, in macrophage polarization and AS remains obscure. Here, we established transgenic mice with macrophage-specific overexpression DNMT1 (Tg ) or PPAR-γ investigate their effects on progression ApoE-knockout fed an atherogenic diet. Primary were extracted study DNMT1/PPAR-γ pathway regulating...

Vascular endothelial cell-derived exosomes are thought to mediate disease progression by regulating macrophage polarization. However, its mechanism in diabetes mellitus (DM)-related atherosclerosis (AS) progress is unclear. High-glucose (HG) and oxLDL were used induce human cardiac microvascular cells (HCMECs) mimic DM-related AS model. The conditioned medium (CM) from HG+oxLDL-induced HCMECs was incubated with THP1-M0 monocytes treated LPS or oxLDL. mRNA levels of M1/M2 polarization...

Abstract Background Celastrol is an active ingredient of the traditional Chinese medicinal plant Tripterygium Wilfordii , which exhibits significant antitumor activity in different cancer models vitro and vivo ; however, lack information on target mechanism action this compound have impeded its clinical application. In study, we sought to determine mode celastrol by focusing processes that mediate anticancer activity. Methods The downregulation heat shock protein 90 (HSP90) client proteins,...

Abstract The prognosis of gastric cancer remains poor due to clinical drug resistance. Novel drugs are urgently needed. Shikonin (SHK), a natural naphthoquinone, has been reported trigger cell death and overcome resistance in anti-tumour therapy. In this study, we investigated the effectiveness molecular mechanisms SHK treatment with cancer. vitro , suppresses proliferation triggers cells but leads minor damage epithelial cells. induces generation intracellular reactive oxygen species (ROS),...

As a regulated form of programmed cell death, necroptosis has the intrinsic initiators, including receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed-lineage domain-like protein (MLKL), which combine to necroptotic signaling pathway mediate induced by various stimuli, tumor necrosis factor (TNF). Although chemical inhibition RIPK1 blocks TNF-induced necroptosis, genetic elimination does not suppress but facilitate triggered TNF. Moreover, been reported...

Celastrol, a tripterine derived from the traditional Chinese medicine plant Tripterygium wilfordii Hook F. ("Thunder of God Vine"), has been reported to have multiple effects, such as anti-inflammation, suppression tumor angiogenesis, inhibition growth, induction apoptosis and protection cells against human neurodegenerative diseases. However, mechanisms that underlie these functions are not well defined. In this study, we for first time Celastrol could induce HIF-1α protein accumulation in...

This double-blind, randomized controlled trial aimed to investigate inhaled budesonide and oral dexamethasone compared with placebo for their prophylactic efficacy against acute mountain sickness after high-altitude exposure.There were 138 healthy young male lowland residents recruited randomly assigned receive (200 μg, twice a day [bid]), (4 mg, bid), or (46 in each group). They traveled 3900 m altitude from 400 by car. Medication started 1 before exposure continued until the third of...

Abstract Background This prospective and observational study aimed to identify demographic, physiological psychological risk factors associated with high-altitude headache (HAH) upon acute exposure. Methods Eight hundred fifty subjects ascended by plane 3700 m above Chengdu (500 m) over a period of two hours. Structured Case Report Form (CRF) questionnaires were used record demographic information, examinations, scale, symptoms including insomnia week before ascending within 24 hours after...

Alboflavusins (AFNs) are a group of cyclohexapeptides with moderate antibacterial and antitumor activities from Streptomyces alboflavus sp. 313. In vivo in vitro studies proposed that AFNs biosynthesized by nonribosomal peptide synthetase machinery, the 6-Cl-L-Trp precursor is supplied tryptophan halogenase gene located outside afn cluster. Guided structure–activity relationship knowledge about AFN-like cyclohexapeptides, two dimeric (di-AFNs) regiospecific biaryl linkages were designed...

Necroptosis is a regulated form of necrotic cell death that mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed-lineage domain-like protein (MLKL), which mediates necroptotic signal transduction induced tumor necrosis factor (TNF). Although many target proteins for necroptosis have been identified, no report had indicated FK506-binding 12 (FKBP12, also known as FKBP1A), an endogenous regulates folding conformation alteration, involved in mediating...

Abstract As a nitric oxide (NO) donor prodrug, JS‐K inhibits cancer cell proliferation, induces the differentiation of human leukaemia cells, and triggers apoptotic death in various models. However, anti‐cancer effect gastric has not been reported. In this study, we found that inhibited proliferation cells vitro vivo triggered mitochondrial apoptosis. Moreover, induced significant accumulation reactive oxygen species (ROS), clearance ROS by antioxidant reagents reversed JS‐K‐induced toxicity...

Abstract Oryzias sinensis , also known as Chinese medaka or ricefish, is a commonly used animal model for aquatic environmental assessment in the wild well gene function validation toxicology research lab. Here, high-quality chromosome-level genome assembly of O. was generated using single-tube long fragment read (stLFR) reads, Nanopore long-reads, and Hi-C sequencing data. The 796.58 Mb, total 712.17 Mb assembled sequences were anchored to 23 pseudo-chromosomes. A final set 22,461 genes...

Depsipeptide FR901228 (FK228) is a new kind of histone deacetylase inhibitors (HDACi) that induces growth arrest and cell death in variety tumor cells. Though its effects on oncogene expression degradation have been documented, the detailed mechanism FK228-induced cytotoxicity still undefined. In this study, differential proteomic analysis was performed to identify proteins associated with human lung cancer Two-dimensional gel electrophoresis (2-DE) revealed distinct protein profile H322...

To investigated the objective indicators and potential genotypes for acute mountain sickness (AMS). 176 male subjects were evaluated symptoms scores physiological parameters at 3700 m. EPAS1 gene polymorphisms explored verified effects of on pulmonary function by inhaled budesonide. The incidence AMS was 53.98% (95/176). individuals who suffered from headache with anxiety greater changes in heart rate (HR), forced vital capacity (FVC), mean flow velocity basilar artery (Vm-BA), all which...

Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating necroptosis induced by tumor necrosis factor alpha (TNFα) L929 cells, so knockdown of RIP3 inhibits TNFα-induced cell necroptosis. However, was shown to switch apoptosis cells other studies. Therefore, whether blocks the death controversial. In this study, TNFα activated caspase pathway and RIP3-independent had been blocked Z-VAD-FMK (pan-caspase inhibitor) or 8 knockdown, demonstrating that switched...

We show that an inducible rpoS antisense RNA complementary to the message can inhibit expression of RpoS in both exponential and stationary phases attenuate regulon Escherichia coli. Plasmids containing DNA expressed under control T7lac promoter T7 polymerase were constructed, was optimized pET system. levels could be manipulated effectively RpoS-dependent genes. inhibited by E. catalase HPII also downregulated, as determined activity assays with native polyacrylamide gels stained for...

Previous studies have shown that histone deacetylase inhibitors (HDACis) can kill cancer cells. In addition, HDACis induce mitotic catastrophe in cells due to insufficient localization of chromosomal passenger complex (CPC) the centromere. However, mechanisms behind these phenomena remain unclear. this study, we found a HDACi, FK228, affected multiple epigenetic modification characteristics centromere, including enhanced acetylation H3 lysine 9 (H3K9), decreased trimethylation H3K9, and...

RpoS, an alternative sigma factor produced by many Gram-negative bacteria, primarily controls genes that are expressed in stationary phase response to nutrient deprivation. To test the idea induction of RpoS exponential phase, when is not normally expressed, increases RpoS-dependent gene expression, we constructed a plasmid carrying rpoS under control IPTG (isopropyl-β-D-thiogalactopyranoside)-inducible T7lac promoter. Northern and Western analyses revealed levels mRNA protein, respectively,...