Background: Apoptosis of lung structural cells contributes to the process of lung damage and remodeling in chronic obstructive pulmonary disease (COPD). Our previous studies demonstrated that exogenous hydrogen sulfide (H2S) can reduce the lung tissue pathology score, anti-inflammation and anti-oxidation effects in COPD, but the effect of H2S in regulating cigarette smoke (CS) induced bronchial epithelial cell apoptosis and the underlying mechanisms are not clear.Objectives: To investigate the effect of H2S on CS induced endoplasmic reticulum stress (ERS) and bronchial epithelial cell apoptosis.Methods: Male Sprague–Dawley rats randomly divided into four groups for treatment: control, CS, NaHS + CS, and propargylglycine (PPG) + CS. The rats in the CS group were exposed to CS generated from 20 commercial unfiltered cigarettes for 4 h/day, 7 days/week for 4 months. Since the beginning of the third month, freshly prepared NaHS (14 μmol/kg) and PPG (37.5 mg/kg) were intraperitoneally administered 30 min before CS-exposure in the NaHS and PPG groups. 16HBE cells were pretreated with Taurine (10 mM), 5 mmol/L 4-phenylbutyric acid (4-PBA) or NaHS (100, 200, and 400 μM) for 30 min, and then cells were exposed to 40 μmol/L nicotine for 72 h. ERS markers (GRP94, GRP78) and ERS-mediated apoptosis markers 4-C/EBP homologous protein (CHOP), caspase-3 and caspase-12 were assessed in rat lung tissues and human bronchial epithelial cells. The apoptotic bronchial epithelial cells were detected by Hoechst staining in vitro and TUNEL staining in vivo.Results: In CS exposed rats, peritoneal injection of NaHS significantly inhibited CS induced overexpression ERS-mediated apoptosis markers and upregulation of apoptotic rate in rat lungs, and inhibiting the endogenous H2S production by peritoneal injection of PPG exacerbated these effects. In the nicotine-exposed bronchial epithelial cells, appropriate concentration of NaHS and ERS inhibitors taurine and 4-PBA inhibited nicotine-induced upregulation of apoptotic rate and overexpression of ERS-mediated apoptosis markers.Conclusion: H2S inhibited lung tissue damage by attenuating CS induced ERS in rat lung and exogenous H2S attenuated nicotine induced ERS-mediated apoptosis in bronchial epithelial cells.
Glycosylation changes are key molecular events in tumorigenesis, progression and glycosyltransferases play a vital role in the this process. FUT8 belongs to the fucosyltransferase family and is the key enzyme involved in N-glycan core fucosylation. FUT8 and/or core fucosylated proteins are frequently upregulated in liver, lung, colorectal, pancreas, prostate,breast, oral cavity, oesophagus, and thyroid tumours, diffuse large B-cell lymphoma, ependymoma, medulloblastoma and glioblastoma multiforme and downregulated in gastric cancer. They can be used as markers of cancer diagnosis, occurrence, progression and prognosis. Core fucosylated EGFR, TGFBR, E-cadherin, PD1/PD-L1 and α3β1 integrin are potential targets for tumour therapy. In addition, IGg1 antibody defucosylation can improve antibody affinity, which is another aspect of FUT8 that could be applied to tumour therapy.
Introduction:Tumor-infiltrating lymphocytes (TILs) have been shown to be of prognostic significance in patients with gastric cancer. This study aims to investigate the association between density of TILs and prognoses of patients with gastric cancer.Methods:The relative studies of tumor-infiltrating lymphocytes in tumor tissue from patients with gastric cancer were systematically searched from PubMed and Embase until October 31, 2017. The pooled hazard ratios (HRs) and their 95% confidence intervals (95%CI) for overall survival (OS) were estimated.Results:Twenty-nine studies involving 4,942 patients were included into analyses. Subset of TILs included CD8+, CD3+, CD4+, and FOXP3+ T cell density. Results from meta-analyses revealed that high density of intratumoral CD8+ T cells (HR = 0.77, 95% CI 0.63–0.95) and CD3+ (HR = 0.62, 95% CI 0.49–0.77) were associated with significantly higher OS than those with low density in patients with gastric cancer. Moreover, a larger number of general TILs density also suggested a favorable prognosis (HR 0.75, 95% CI 0.67–0.84). However, patients with high density of intratumoral FOXP3+ T or CD4+ T cells were not statistically associated with higher or lower OS than those with low density (HR 1.41, 95% CI 0.97–2.05; HR = 0.86, 95% CI 0.47–1.57). Sample size and follow-up period seemed to influence study outcomes.Conclusion:The present study revealed that high density of intratumoral CD8+ and CD3+ T cells were associated with better OS in patients with gastric cancer.
Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear. In peripheral lung tissue samples from 24 patients, we found that compared with nonsmokers, the protein level of cystathionine-γ-lyase (CSE) was decreased in smokers and COPD patients. CSE mRNA increased but cystathionine-β-synthase (CBS) mRNA decreased in COPD patients. H2S donors increased glutathione and superoxide dismutase in CS exposed U937 cells and inhibited CS-induced TNF-α and IL-8 secretion. Dexamethasone alone had no effect on lipopolysaccharide (LPS) induced TNF-α release by alveolar macrophages from CS exposed rats, however the combination of dexamethasone and H2S donor significantly inhibited TNF-α release. Thus, H2S metabolism is altered in lung tissue of smokers and COPD patients. Supplementation of H2S protects against CS-induced oxidative stress and inflammation in macrophages and H2S on steroid sensitivity deserves further investigation.
In the process of cancer EMT, some subgroups of cancer cells simultaneously exhibit both mesenchymal and epithelial characteristics, a phenomenon termed partial EMT (pEMT). pEMT is a plastic state in which cells coexpress epithelial and mesenchymal markers. In squamous cell carcinoma (SCC), pEMT is regulated, and the phenotype is maintained via the HIPPO pathway, NOTCH pathway and TGF-β pathways and by microRNAs, lncRNAs and the cancer microenvironment (CME); thus, SCC exhibits aggressive tumorigenic properties and high stemness, which leads collective migration and therapy resistance. Few studies have reported therapeutic interventions to address cells that have undergone pEMT, and this approach may be an effective way to inhibit the plasticity, drug resistance and metastatic potential of SCC.
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