Effect of Dietary Protein Intake from Different Sources on Maternal and Umbilical Cord Plasma Amino Acid Levels.

SCOPE: To assess the associations of dietary protein intake from different sources during pregnancy with maternal and umbilical cord plasma amino acid levels. METHODS AND RESULTS: The study includes 216 pregnant women and 39 newborns from the Tongji Birth Cohort in Wuhan, China. The study examines the levels of 21 amino acids in maternal and cord plasma samples using ultra-performance liquid chromatography with tandem mass spectrometry. A significant positive relationship is observed between dietary protein intake from refined grains and maternal plasma cysteine levels. Dietary protein intake from dairy products is positively associated with maternal plasma levels of sulfur amino acid (mainly cystine), but negatively associated with maternal plasma levels of glutamic acid. In addition, the study observes that pre-pregnancy body mass index and parity may be potential determinants of maternal plasma amino acid levels, whereas a history of passive smoking during pregnancy is an important factor influencing cord plasma amino acid levels. CONCLUSIONS: These findings suggest that dietary protein intakes from specific sources during pregnancy may affect maternal plasma levels of amino acids.

Effects of traditional Chinese exercise therapy on pain scores, sleep quality, and anxiety-depression symptoms in fibromyalgia patients: a systematic review and meta-analysis.

OBJECTIVE: This study aims to assess the effectiveness of traditional Chinese exercise therapy in alleviating pain, improving sleep quality, and reducing symptoms of anxiety and depression among fibromyalgia patients. METHODS: We conducted a comprehensive search across various databases, including PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge, VIP database, and Wanfang, to identify randomized controlled trials (RCTs) examining the impact of Traditional Chinese Exercise (TCE) interventions on fibromyalgia. Two independent authors extracted data from the selected studies based on predefined inclusion and exclusion criteria. Meta-analyses were performed using RevMan 5.3. RESULTS: The analysis encompassed 15 RCTs, comprising 936 participants. The meta-analysis revealed that TCE significantly surpassed the control group in reducing pain scores for fibromyalgia patients, as evidenced by improvements in FIQ [MD = -3.30, 95% CI (- 5.37, - 0.69), z = 2.53, p = 0.01] and VAS [MD = -1.87, 95% CI (- 2.12, - 1.61), z = 6.98, p < 0.00001]. Additionally, TCE demonstrated notable enhancements in sleep quality (PSQI) [MD = -2.23, 95% CI (- 2.86, - 1.61), z = 6.98, p < 0.0001], as well as in alleviating symptoms of anxiety and depression [MD = - 0.59, 95% CI (- 0.80, - 0.39), z = 5.63, p < 0.0001]. CONCLUSION: Traditional Chinese Exercise (TCE) exhibits significant efficacy in ameliorating pain, enhancing sleep quality, and alleviating symptoms of anxiety and depression in fibromyalgia patients.

Separation and structural elucidation of a novel vardenafil analogue as an adulterant in a natural health care dietary supplement.

A novel vardenafil analogue was identified in dietary supplement as an adulterant in herbal formulations. The structure of this analogue was elucidated using HRMS, NMR after extraction from the pulverized powder. It was named morphardenafil as a morpholine ring has replaced the N-ethyl piperazine ring in vardenafil. A tablet of this dietary supplement contained about 50 mg of unspecified morphardenafil, which is 2.5 - 20-times the prescriptive dosage of Levetra, the commercial formulation of the vardenafil monohydrochloride salt in the market and probably places unwary consumers at risk for potentially serious adverse effects or drug-drug interaction (DDI).

Integration of proteomics and network toxicology reveals the mechanism of mercury chloride induced hepatotoxicity, in mice and HepG2 cells.

Mercury is one heavy metal toxin that could cause severe health impairments. Mercury exposure has become a global environmental issue. Mercury chloride (HgCl2) is one of mercury's main chemical forms, but it lacks detailed hepatotoxicity data. The present study aimed to investigate the mechanism of hepatotoxicity induced by HgCl2 through proteomics and network toxicology at the animal and cellular levels. HgCl2 showed apparent hepatotoxicity after being administrated with C57BL/6 mice (16 mg/kg.bw, oral once a day, 28 days) and HepG2 cells (100 µmol/L, 12 h). Otherwise, oxidative stress, mitochondrial dysfunction and inflammatory infiltration play an important role in HgCl2-induced hepatotoxicity. The differentially expressed proteins (DEPs) after HgCl2 treatment and enriched pathways were obtained through proteomics and network toxicology. Western blot and qRT-PCR results showed acyl-CoA thioesterase 1 (ACOT1), acyl-CoA synthetase short chain family member 3 (ACSS3), epidermal growth factor receptor (EGFR), apolipoprotein B (APOB), signal transducer and activator of transcription 3 (STAT3), alanine--glyoxylate aminotransferase (AGXT), cytochrome P450 3A5 (CYP3A5), CYP2E1 and CYP1A2 may be the major biomarkers for HgCl2-induced hepatotoxicity, which involved chemical carcinogenesis, fatty acid metabolism, CYPs-mediated metabolism, GSH metabolism and others. Therefore, this study can provide scientific evidence for the biomarkers and mechanism of HgCl2-induced hepatotoxicity.

Metabolism and elimination kinetics of mono-hydroxylated PAHs metabolites following single exposure to different combinations of PAH4 in rats.

The metabolism of polycyclic aromatic hydrocarbons (PAHs) and the elimination kinetics of their mono-hydroxylated metabolites (OH-PAHs) following single exposure to different combinations of four PAHs (PAH4) were studied. Male Sprague-Dawley rats were orally exposed to a single dose of benzo[a]pyrene (B[a]P) or PAH2 (B[a]P + chrysene), PAH3 (B[a]P + chrysene + benz[a]anthracene), and PAH4 (B[a]P + chrysene + B[a]A + benzo[b]fluoranthene) with each combination adjusted to the same dose of individual compound. OH-PAHs including 3-hydroxybenzo[a]pyrene, 3-hydroxychrysene, 3-hydroxybenz[a]anthracene, and 1-hydroxypyrene (1-OHP) were detected in serum and urine samples collected at six intervals over a 72-h period post-dosing. The hepatic mRNA levels of cytochrome P450 (CYPs) were determined to ascertain the expression induction of PAHs metabolic enzymes. Results showed OH-PAHs (except 1-OHP) peaked within 8 h in serum and were excreted from urine within 24-48 h. The serum and urinary concentration of 3-hydroxybenzo[a]pyrene was significantly increased after PAH4 exposure compared with other PAHs combinations. Inversely, urinary concentration of 3-hydroxychrysene was decreased after PAH4 exposure, and the kinetics of 3-hydroxybenz[a]anthracene or 1-OHP were not different depending on the PAHs combinations. Also, CYPs were markedly induced by PAHs. Notably, the induction levels of CYP1A1 and CYP1B1 were significantly higher after PAH4 exposure compared with B[a]P exposure. The results indicated the metabolism of B[a]P was accelerated after PAH4 exposure which might be partly due to the induction of CYPs. These results confirmed PAHs are rapidly metabolized and suggested potential interactions of PAHs may happen among PAH4 mixture.

Optimal starting age of endoscopic screening for esophageal cancer in China: A multicenter prospective cohort study.

BACKGROUND: Although endoscopic screening for esophageal cancer has been performed in high-risk areas in China for decades, there is limited and inconsistent evidence regarding the starting age for individuals participating in screening. The aim of this study is to investigate the optimal starting age of esophageal cancer screening. METHODS: This study is based on a multicenter prospective cohort consisting 338,017 permanent residents aged 40-69 years in six high-risk areas of esophageal cancer in China. The participation rate, detection rate, hazard ratios (HRs), cumulative incidence and mortality and number needed to screen (NNS) were calculated in each age group. Screening burden, benefit and risk were compared among screening strategies with different initiation ages to explore the optimal starting age for population-based screening in high-risk areas. RESULTS: Individuals aged 50-69 had a higher participation rate, a higher detection rate and improved screening effectiveness than those aged 40-49. The endoscopic screening had no significant effect on reducing the incidence of esophageal cancer in individuals under 55 and mortality in individuals under 45. Increasing the starting age to 50 years reduced the screening demand and NNS by 40% and 55%, and resulted in 12% of detectable positive cases, 16% of preventable incident cases, and 14% of preventable deaths being missed. CONCLUSIONS: Postponing the starting age of endoscopic screening to 50 years might yield a more-favorable balance between screening benefit and burden in high- risk areas with limited resources.

Hawthorn or semen cassiae-alleviated high-fat diet-induced hepatic steatosis in rats via the reduction of endoplasmic reticulum stress.

Hepatic steatosis is a common pathological change of liver that manifests as abnormal lipid accumulation. Epidemiological findings support that diseases such as obesity, diabetes, and hyperlipidemia are mostly accompanied by the development of hepatic steatosis. By screening the disease targets of several traditional Chinese medicines (TCMs) with lipid-reducing effects (hawthorn, semen cassiae, etc.) through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we found that peroxisome-activated receptor gamma (PPAR-γ) is involved in regulating several lipid metabolism-related signaling pathways. Further experiments confirmed that PPAR-γ was correlated with aggravated endoplasmic reticulum (ER) stress in overnutrition-induced hepatic steatosis. The stimulation of hepatocytes by abnormal lipid metabolism signals causes an imbalance in ER homeostasis, which subsequently exacerbates hepatocyte lipid abnormalities. The inhibition of glucose regulatory protein 78 (GRP78, a master regulator of ER homeostasis) was effective in reducing hepatocyte PPAR-γ and lipid synthesis levels. In fact, the hawthorn/semen cassiae treatment effectively downregulated hepatocyte ER stress in high-fat-diet fed rats and reduced the PPAR-γ expression as well as related lipid synthesis. Herein, we confirmed that TCMs characterized by natural lipid-lowering effectively target hepatic PPAR-γ and GRP78, improve ER stress, and have a protective effect against obesity-related hepatic steatosis.

Glioblastoma stem cell-specific histamine secretion drives pro-angiogenic tumor microenvironment remodeling.

The communication between glioblastoma stem cells (GSCs) and the surrounding microenvironment is a prominent feature accounting for the aggressive biology of glioblastoma multiforme (GBM). However, the mechanisms by which GSCs proactively drive interactions with microenvironment is not well understood. In this study, we interrogated metabolites that are preferentially secreted from GSCs and found that GSCs produce and secrete histamine to shape a pro-angiogenic tumor microenvironment. This histamine-producing ability is attributed to H3K4me3 modification-activated histidine decarboxylase (HDC) transcription via MYC. Notably, HDC is highly expressed in GBM, which is associated with poor survival of these patients. GSC-secreted histamine activates endothelial cells by triggering a histamine H1 receptor (H1R)-Ca2+-NF-κB axis, thereby promoting angiogenesis and GBM progression. Importantly, pharmacological blockage of H1R using antihistamines impedes the growth of GBM xenografts in mice. Our findings establish that GSC-specific metabolite secretion remodels the tumor microenvironment and highlight histamine targeting as a potential strategy for GBM therapy.

Awareness of nutrition and health knowledge and its influencing factors among Wuhan residents.

Background: Nutrition and health knowledge play a crucial role in promoting healthy dietary behaviors, and have been found to be related to sociodemographic characteristics. However, the existing evidence is limited and inconsistent. We aimed to evaluate the awareness level of nutrition and health knowledge and its influencing factors among Wuhan residents, and to provide scientific basis for carrying out targeted nutrition education programmes. Methods: By stratified random sampling, residents aged 18-64 in Wuhan were selected for self-administered questionnaire survey. We adopted the structured questionnaire to investigate respondents' sociodemographic characteristics, nutrition and health knowledge, and the way to acquire knowledge. Among them, nutrition and health knowledge includes the following four parts: dietary guidelines recommendations, food and nutrients, nutrition and disease prevention, and nutrition skills. Chi-square tests were used to analyze the associations between total awareness rate and sociodemographic characteristics. Multiple linear regression models were used to analyze the influencing factors of nutrition and health awareness. Results: A total of 33,436 valid questionnaires were obtained, with a response rate of 97.8%. The total awareness rate was 20.4%, with the highest in nutrition and disease prevention (72.7%) and the lowest in nutrition skills (46.3%). Responders aged 35-44 (23.3%), females (22.8%), educational workers (24.8%), obtaining a master's degree or above (34.1%), living in downtown area (23.1%), and without a history of chronic disease (24.6%) were more likely to have higher awareness rates (all p < 0.001). The multiple linear regression models showed that age, gender, education level, occupation, residential address, and the history of chronic disease were the potential factors affecting individual nutrition awareness. Conclusion: The total awareness rate of nutrition and health knowledge among Wuhan residents was not optimistic. Besides, our findings suggested that sociodemographic characteristics are closely related to nutrition awareness, which may provide important clues for carried out nutrition education campaigns.

Metabolomics Analysis of Chronic Exposure to Dimethylarsenic Acid in Mice and Toxicity Assessment of Organic Arsenic in Food.

Dimethylarsenic acid is a natural organic arsenic in seafood and one of the important metabolites of inorganic arsenic, which is generally considered to have low or no toxicity. However, due to the controversy of the toxicity of organic arsenic, the food safety standard of organic arsenic has not been established until now, and the effects of organic arsenic on chronic toxicity and the overall metabolic level of animals are rarely reported. In our study, 64 female C57BL/6 mice were exposed to different concentrations of dimethylarsenic acid with water intake. Fifteen metabolites in serum were detected to be altered with the increase of arsenic concentration and exposure time. Dimethylarsenic acid exposure significantly affected the overall metabolic level of mice, and the related effects were not recovered shortly after the suspension of arsenic intake. Although arsenic was excreted largely in urine and feces, continued dimethylarsenic acid exposure could still lead to arsenic accumulation in the liver and kidneys and cause mild nephritis in mice.

The Endogenous Metabolite Glycerophosphocholine Promotes Longevity and Fitness in Caenorhabditis elegans.

Metabolism and aging are closely connected. The choline derivative glycerophosphocholine (GPC), an important precursor of the neurotransmitter acetylcholine, plays important roles in brain and nervous system function. Although it has been reported to alleviate cognitive decline in aged mice, whether GPC could promote longevity and other fitness factors remains unclear. Here, we find endogenous GPC level declines in the plasma of ageing humans. In Caenorhabditis elegans (C. elegans), GPC extends lifespan and improves exercise capacity during aging. Likewise, GPC inhibits lipofuscin accumulation. We further show that GPC treatment has no adverse effect on nematodes' reproductive abilities and body length. In addition to its benefits under normal conditions, GPC enhances the stress resistance of C. elegans. Mechanically, we find GPC significantly inhibits the reactive oxygen species (ROS) accumulation in worms. Our findings indicate the health benefits of GPC and its potential application in strategies to improve lifespan and healthspan.

Dietary patterns and severity of symptom with the risk of esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional latent class analysis.

BACKGROUND: Dietary patterns and symptoms research among Chinese with esophageal squamous cell carcinoma (ESCC) and its precursor lesions is limited, especially as it relates to multiple food consumption and multiple co-occurring symptoms. The aim of our study was to identify the dietary patterns and severity of symptom classes with the risk of esophageal squamous cell carcinoma and its histological precursor lesions, and develop a risk prediction model for different stages of esophageal disease. METHODS: We analyzed data from a multicenter cross-sectional study carried out in ESCC high incidence areas between 2017 and 2018, which included 34,707 individuals aged 40-69 years. Dietary patterns and severity of symptom classes were derived by applying a latent class analysis (LCA). A multiple logistic regression model was used to derive the odds ratio (ORs) and corresponding 95% confidence intervals (CIs) for ESCC and the different stages of esophageal disease according to the dietary patterns and severity of symptom classes identified. We built the risk prediction model by using a nomogram. RESULTS: We identified five dietary patterns and three severity of symptom classes. The dietary patterns were classified as follows: "Healthy", "Western", "Lower consumers-combination", "Medium consumers-combination" and "Higher consumers-combination" patterns based on the intake of foods such as red meat, vegetables and fruits. The severity of symptoms was categorized into "Asymptomatic", "Mild symptoms" and "Overt symptoms" classes based on health-related symptoms reported by the participants. Compared to the "Healthy" pattern, the other four patterns were all associated with an increased risk of esophageal disease. Similarly, the other two symptom classes present different degrees of increased risk of esophageal disease compared to the "Asymptomatic". The nomograms reflect the good predictive ability of the model. CONCLUSION: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results supplied that subjects with diets rich in livestock and poultry meat and low in fruits and vegetables and subjects with typical symptoms were at increased ESCC risk. The findings highlight the importance of considering food and symptom combinations in cancer risk evaluation.

Comprehensive kinomic study via a chemical proteomic approach reveals kinome reprogramming in hepatocellular carcinoma tissues.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Kinases are attractive therapeutic targets since they are commonly altered in cancers. Here, to identify kinases of potential therapeutic interest in HCC, a quantitative kinomic study of tumour and adjacent non-tumour liver tissues was performed using a chemical proteomics approach. In total, 124 kinases were found differentially expressed and they were distributed over all nine kinase groups. Exploration of The Cancer Genome Atlas (TCGA) data showed that the dysregulation of 45 kinases was correlated with poor prognosis in HCC patients. We then tested 11 inhibitors targeting 12 crucial protein kinases alone or in combination for their ability to inhibit cell growth in Hep3B and PLC/PRF/5 cell lines. Six inhibitors significantly reduced viability in both cell lines. Combination inhibition of polo-like kinase 1 (PLK1) and casein kinase 1 epsilon (CSNK1E) significantly induced growth arrest in both cell lines synergistically. In summary, our analysis presents the most complete view of kinome reprogramming in HCC and provides novel insight into crucial kinases in HCC and potential therapeutic targets for HCC treatment. Moreover, the identification of hundreds of differentially expressed kinases forms a rich resource for novel drug targets or diagnostic biomarker discovery. Data are available via ProteomeXchange (identifier PXD023806).

Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry for the Analysis of Complex Compounds in Serum and Its Application in Accurate Detection of Early Arsenic Exposure.

With the acceleration of industrialization, environmental arsenic pollution is threatening human health. However, by the time clinical symptoms appear, arsenic toxicity has usually caused irreversible damage to the body, so it is important to establish a rapid and accurate screening method for early arsenic exposure. In this work, 32 female C57BL/6 mice were exposed to different concentrations of inorganic arsenic in drinking water for a week. By analyzing the changes in serum, more than 20 compounds were detected to increase or decrease with the increase of arsenic intake. The abnormal increase in inosine, xanthine, xanthosine, and hypoxanthine and the abnormal purine pathway were found at the same time. Dimethylarsenic acid, an important inorganic arsenic metabolite in the body, was also found in serum. Combined with statistical analysis, early arsenic exposure can be easily and quickly detected, and the potential health risks of short-term exposure can be revealed simultaneously.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study.

BACKGROUND: Despite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions. METHODS: We performed an endoscopic examination of 44,857 individuals aged 40-69 years from five high incidence regions of China in 2017-2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors. RESULTS: We identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52-3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03-3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05-1.37) was essential risk factor of LGIN. CONCLUSIONS: Among individuals aged 40-69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Suppression of mitochondrial ROS by prohibitin drives glioblastoma progression and therapeutic resistance.

Low levels of reactive oxygen species (ROS) are crucial for maintaining cancer stem cells (CSCs) and their ability to resist therapy, but the ROS regulatory mechanisms in CSCs remains to be explored. Here, we discover that prohibitin (PHB) specifically regulates mitochondrial ROS production in glioma stem-like cells (GSCs) and facilitates GSC radiotherapeutic resistance. We find that PHB is upregulated in GSCs and is associated with malignant gliomas progression and poor prognosis. PHB binds to peroxiredoxin3 (PRDX3), a mitochondrion-specific peroxidase, and stabilizes PRDX3 protein through the ubiquitin-proteasome pathway. Knockout of PHB dramatically elevates ROS levels, thereby inhibiting GSC self-renewal. Importantly, deletion or pharmacological inhibition of PHB potently slows tumor growth and sensitizes tumors to radiotherapy, thus providing significant survival benefits in GSC-derived orthotopic tumors and glioblastoma patient-derived xenografts. These results reveal a selective role of PHB in mitochondrial ROS regulation in GSCs and suggest that targeting PHB improves radiotherapeutic efficacy in glioblastoma.

Comprehensive Metabolomic Analysis Reveals Dynamic Metabolic Reprogramming in Hep3B Cells with Aflatoxin B1 Exposure.

Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and development of hepatocellular carcinoma (HCC), but their combined impacts and the potential metabolic mechanisms remain poorly characterized. Here, a comprehensive non-targeted metabolomic study was performed following AFB1 exposed to Hep3B cells at two different doses: 16 µM and 32 µM. The metabolites were identified and quantified by an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based strategy. A total of 2679 metabolites were identified, and 392 differential metabolites were quantified among three groups. Pathway analysis indicated that dynamic metabolic reprogramming was induced by AFB1 and various pathways changed significantly, including purine and pyrimidine metabolism, hexosamine pathway and sialylation, fatty acid synthesis and oxidation, glycerophospholipid metabolism, tricarboxylic acid (TCA) cycle, glycolysis, and amino acid metabolism. To the best of our knowledge, the alteration of purine and pyrimidine metabolism and decrease of hexosamine pathways and sialylation with AFB1 exposure have not been reported. The results indicated that our metabolomic strategy is powerful to investigate the metabolome change of any stimulates due to its high sensitivity, high resolution, rapid separation, and good metabolome coverage. Besides, these findings provide an overview of the metabolic mechanisms of the AFB1 combined with HBV and new insight into the toxicological mechanism of AFB1. Thus, targeting these metabolic pathways may be an approach to prevent carcinogen-induced cancer, and these findings may provide potential drug targets for therapeutic intervention.

Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study.

OBJECTIVES: To estimate the effectiveness of endoscopic screening programme in reducing incidence and mortality of upper gastrointestinal cancer in high risks areas of China. DESIGN: This multicentre population-based cohort study was conducted in six areas in China from 2005 to 2015. All permanent residents aged 40 to 69 years were identified as target subjects. We refer to those who were invited for screening collectively as the invited group. Of these, we classify those who were invited and undertook endoscopic screening as the screened group and those who were invited but did not accept screening as the non-screened group. Target subjects who were not invited to the screening were assigned to the control group. The effectiveness of the endoscopic screening and screening programme were evaluated by comparing reductions in incidence and mortality from upper gastrointestinal cancer in the screened and invited group with control group. RESULTS: Our cohort analysis included 637 500 people: 299 483 in the control group and 338 017 in the invited to screening group, 113 340 (33.53%) of whom were screened eventually. Compared with subjects in the control group, upper gastrointestinal cancer incidence and mortality decreased by 23% (relative risk (RR)=0.77, 95% CI 0.74 to 0.81) and 57% (RR=0.43, 95% CI 0.40 to 0.47) in the screened group, respectively, and by 14% (RR=0.86, 95% CI 0.84 to 0.89) and 31% (RR=0.69, 95% CI 0.66 to 0.72) in the invited group, respectively. CONCLUSION: Among individuals aged 40 to 69 years in high risk areas of upper gastrointestinal cancer, one-time endoscopic screening programme was associated with a significant decrease in upper gastrointestinal cancer incidence and mortality.

Glioma stem-like cells evade interferon suppression through MBD3/NuRD complex-mediated STAT1 downregulation.

Type I interferons (IFNs) are known to mediate antineoplastic effects during tumor progression. Type I IFNs can be produced by multiple cell types in the tumor microenvironment; however, the molecular mechanisms by which tumor cells evade the inhibition of immune microenvironment remain unknown. Here we demonstrate that glioma stem-like cells (GSCs) evade type I IFN suppression through downregulation of STAT1 to initiate tumor growth under inhospitable conditions. The downregulation of STAT1 is mediated by MBD3, an epigenetic regulator. MBD3 is preferentially expressed in GSCs and recruits NuRD complex to STAT1 promoter to suppress STAT1 expression by histone deacetylation. Importantly, STAT1 overexpression or MBD3 depletion induces p21 transcription, resensitizes GSCs to IFN suppression, attenuates GSC tumor growth, and prolongs animal survival. Our findings demonstrate that inactivation of STAT1 signaling by MBD3/NuRD provides GSCs with a survival advantage to escape type I IFN suppression, suggesting that targeting MBD3 may represent a promising therapeutic opportunity to compromise GSC tumorigenic potential.