Objective To explore the potential risk factors to Ymman endemic sudden cardiac death (YESCD) and provide evidence for prevention. Methods Twenty-two cases and 24 controls were randomly selected from YESCD areas and non-YESCD areas, respectively. Both cases and controls were interviewed with unified questionnaires. Univatiate X2 test and multivariate conditional logistic stepwise regression was conducted with SPSS 13.0. The optimal regression model was established and evaluated. Results The univariate X2 teat revealed that presence or absence of 5 potential factors might possibly be associated to YESCD: appropriate places for storing dining utensils, pens for livestock, consumption of mushrooms, exposure to any pesticides, and sudden climate changes before onset(X2=12.206,4.779,5.741,6.120,10.754, P<0.05). Multivariate conditional logistic stepwise regression demonstrated that consumption of mushrooms was a protective factor(OR=0.115, P<0.05) and sudden climate change was a risk factor(OR=36.592, P<0.01). Conclusions Sudden climate change might be a risk factor contributing to YESCD, and eating mushrooms before the prevalence seasons may provide some protection.
Key words:
Death, sudden; Risk factors; Case-control studies
Cervical cancer is the second most common female malignancy worldwide. The metabolic profile of plasma associated with the prognosis of cervical cancer remains poorly understood. In this cross-sectional study, plasma samples were collected from three groups of patients with CSCC, namely primary patients before treatment (BT group), patients with a poor prognosis (PP group, including patients with distant metastasis and local recurrence), and patients with a good prognosis within two years after the first treatment (GP group). The plasma metabolomics was conducted to detect the dynamic changes of metabolites via ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Multivariate analyses, including principle component, partial least square-discriminant, and orthogonal projection to latent structure-discriminant analyses, were performed to compare each pair of the three groups. The differential metabolites were identified by comparison of the exact m/z values and mass spectrometry (MS)/MS spectra with the structural information of the metabolites obtained from the Human Metabolome Database (http://www.hmdb.ca/) and LIPID MAPS (http://www.lipidmaps.org/). To screen for potential markers, receiver operating characteristic curve analysis of the differential metabolites. Finally, thirty plasma samples were collected from each group. Multivariate analyses showed that 31 metabolites were significantly different among the 3 groups studied. Of those, the 5 metabolites phosphatidyl choline (15:0/16:0), phosphatidyl glycerol (12:0/13:0), actosylceramide (d18:1/16:0), D-Maltose, and phthalic acid, with an area under the curve above 0.75, were identified as potential biomarkers. The present findings provide evidence for biomarkers to monitor prognosis of patients with CSCC, which may help in better managing the disease.
Abstract Background: Metformin is the first-line drug for type II diabetes, and recent studies indicate that metformin plays an inhibitory role in multiple cancers. Metformin can also enhance the effect of chemotherapy. Although head and neck squamous cell carcinoma cells are sensitive to metformin, the mechanisms related to the metformin response and the chemosensitization effect have not been fully studied. Results: In this study, we aimed to elucidate the molecular mechanisms of metformin in HNSCC by transcriptome analysis and to reveal the underlying mechanisms of the sensitizing effects of metformin by combined online dataset analysis. mRNA sequencing and functional analysis of HNSCC samples after metformin treatment and functional analysis of mRNAs with opposite metformin-induced effects in chemosensitive versus chemoresistant cells revealed the molecular pathways, mainly the base excision repair pathway, by which this small molecule drug sensitizes HNSCC cells to treatment. Conclusions: These findings indicate that metformin exerts a hypersensitization effect by regulating the BER pathway in tumour cells, reducing their self-repair capacity after chemotherapy-induced DNA damage. In addition, the genes identified by transcriptome analysis are candidates for further investigation into the effector targets of metformin in the inhibition of HNSCC and could be applied to improve the treatment in HNSCC patients who develop resistance after advanced chemotherapy.
Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.
COVID-19 is an infectious disease caused by SARS-CoV-2, with respiratory symptoms as primary manifestations. It can progress to severe illness, leading to respiratory failure and multiple organ dysfunction. Recovered patients may experience persistent neurological, respiratory, or cardiovascular symptoms. Mitigating the multi-organ complications of COVID-19 has been highlighted as a crucial part of fighting the epidemic. Ferroptosis is a type of cell death linked to altered iron metabolism, glutathione depletion, glutathione peroxidase 4 (GPX4) inactivation, and increased oxidative stress. Cell death can prevent virus replication, but uncontrolled cell death can also harm the body. COVID-19 patients with multi-organ complications often exhibit factors related to ferroptosis, suggesting a possible connection. Ferroptosis inhibitors can resist SARS-CoV-2 infection from damaging vital organs and potentially reduce COVID-19 complications. In this paper, we outline the molecular mechanisms of ferroptosis and, based on this, discuss multi-organ complications in COVID-19, then explore the potential of ferroptosis inhibitors as a supplementary intervention for COVID-19. This paper will provide a reference for the possible treatment of SARS-CoV-2 infected disease to reduce the severity of COVID-19 and its subsequent impact.
Objective To acquaint the situation of selenium nutrition level and coxsakievirus B(CVB) infection in Keshan disease(KD)patients in Heilongjiang province,and provide the evidence for taking the direction mell811rement$of KD contr01.Methods The subjeets were divided into three groups:disease area KD group, disease area control group,and non-disease area control group.We collected soil,food and blood,which were used to detect selenium content,and assay IgN antibody of CVB in plasma.The selenium content of blood was determined with hydride generation atomic fluorometry spectrometrie.The lgM antibody of CVB was measured with ELISA test Kit.Results Compared with those in non-disease areas,selenium content of soil,maize,wheat and bean(0.092 ±0.011,0.003±0.001,0.005±0.003,0.006±0.001)μg/L in disease area Welre significantly lower(t=17.007.8.551,15.842,12.109;all P 0.05).Conclusions Selenium deficiency and CVB infection still exist in KD area,Heilongjiang Province.
Key words:
Keshan disease(KD); Selenium; Enterovinls B.Human
Prunetin (PRU) is an O-methylated flavonoid that is present in various natural plants and a primary significant compound found in isoflavone. Liver cancer creates major carcinogenic death despite recently advanced therapies. Hepatocellular carcinoma (HCC) treatment and prognosis are better in people with secure liver function. In the present study, we evaluated the action of PRU on diethylnitrosamine (DEN) alone HCC in a rat model through inflammation-mediated cell proliferative phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway analysis. Male Wistar rats were divided into four groups of six rats each. Group I, normal rats; Group II, DEN alone; Group III, DEN + PRU, and Group IV, PRU-alone. All groups of rats carried out hepatic cancer development by hypothesis antioxidant, biochemical, cell proliferative, apoptosis, cytokines protein, and gene expression status profiles. In tumor incidence DEN + PRU, 100% delayed the tumor growth disappearance of the lesion, and reversal of normal liver architecture was observed. Liver marker enzymes levels decreased when antioxidant levels (superoxidase dismutase, catalase, glutathione peroxidase, and glutathione reductase) were in Group III. Proinflammatory markers nuclear factor-κB, interleukin (IL)-6, IL-1β, and tumor necrosis factor α, were elevated in the rat's serum in Group III. Cell proliferative markers proliferating cell nuclear antigen and Cyclin-D1 protein expressions were downregulated; in contrast, Bcl-2, Bax, caspase-3, and caspase-9 gene expressions were upregulated and then it followed that protein expression of PI3K/AKT was downregulated in PRU-treated groups. PRU assisted reversal of liver damage, antioxidant enzyme restoration cytokine balance, protein, and gene expression to control levels. Taken together, PRU improves functions of the liver, and as such prevents HCC. PRU can be used together with chemopreventives for HCC.
We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes. We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8+ T cells, CD4+ memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.
Calcium entry through CaV2.2 calcium channels clustered at the active zone (AZ) of the presynaptic nerve terminal gates synaptic vesicle (SV) fusion and the discharge of neurotransmitters, but the mechanism of channel scaffolding remains poorly understood. Recent studies have implicated the binding of a PDZ ligand domain (PDZ-LD) at the tip of the channel C terminal to a partner PDZ domain on RIM1/2, a synaptic vesicle-associated protein. To explore CaV2.2 scaffolding, we created intracellular region fusion proteins and used these to test for binding by 'fishing' for native CaV2.2 channels from cell lysates. Fusion proteins mimicking the distal half of the channel C terminal (C3strep) reliably captured CaV2.2 from whole brain crude membrane or purified synaptosome membrane lysates, whereas channel I-II loop or the distal half of the II-III loop proteins were negative. This capture could be replicated in a non-synaptic environment using CaV2.2 expressed in a cell line. The distal tip PDZ-LD, DDWC-COOH, was confirmed as the critical binding site by block of pull-down with mimetic peptides. Pull-down experiments using brain crude membrane lysates confirmed that RIM1/2 can bind to the DDWC PDZ-LD. However, robust CaV2.2 capture was observed from synaptosome membrane or in the cell line expression system with little or no RIM1/2 co-capture. Thus, we conclude that CaV2.2 channels can scaffold to each other via an interaction that involves the PDZ-LD by an inter-channel linkage bridged by an unknown protein.
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