Publications by authors named "Hua Meng"

117 Publications

Effects of polycyclic aromatic hydrocarbons and multiple metals co-exposure on the mosaic loss of chromosome Y in peripheral blood.

J Hazard Mater 2021 Feb 24;414:125519. Epub 2021 Feb 24.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Mosaic loss of chromosome Y (mLOY) is an indicator of genome instability, but the environmental stressors of mLOY remained largely unknown. In this study, we detected the internal exposure levels of 11 polycyclic aromatic hydrocarbon (PAH) metabolites and 22 metals among 888 coke-oven workers, and calculated their blood mLOY based on genome-wide SNP genotyping data and presented as median log R ratio (mLRR-Y). The generalized linear model (GLM), LASSO, and Bayesian kernel machine regression (BKMR), were used to select mLOY-relevant chemicals. The results of these models consistently suggested the negative dose-response relationships of urinary 1-hydroxynaphthalene (1-OHNa), antimony (Sb), and molybdenum (Mo) with mLRR-Y. There were no pairwise interactions between these three chemicals (P > 0.05), but subjects with high exposure to ≥ 2 kinds of these chemicals showed reducing mLRR-Y [β(95%CI) = - 0.015(- 0.023, - 0.008)], increasing oxidative DNA damage (marked by 8-hydroxydeoxyguanosine) [β(95%CI) = 0.625(0.454, 0.796)] and chromosome damage (marked by micronucleus frequency in lymphocytes) [frequency ratio (FR) and 95%CI = 1.146(1.047, 1.225)] than those with low exposure to all these chemicals. The combined effects of 1-OHNa, Sb, and Mo on elevating DNA damage may partly explain their joint effects on increased blood mLOY. These results provided a new insight into environmental hazards co-exposure on chromosome-Y deletions.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125519DOI Listing
February 2021

Effects of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy on Bone Mineral Density in Zucker Diabetic Fatty Rats: A Short-Term Comparative Study.

Obes Facts 2021 Mar 4:1-12. Epub 2021 Mar 4.

Department of General Surgery, China-Japan Friendship Hospital, Beijing, China,

Background: While bariatric surgery could result in weight loss as well as glycaemia improvement, the short-term impact on bone health in a high glycemic environment following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remains intriguing.

Objective: The aim of this study was to compare the short-term effects of RYGB and SG procedures on bone health in Zucker diabetic fatty (ZDFfa/fa) rats.

Methods: Thirty age-matched male ZDFfa/fa rats were randomized into RYGB, SG, and sham groups after establishment of the diabetic model. Body weight, blood glucose, bone mineral density (BMD), the level of bone turnover markers (BTM), vitamin D, and serum calcium and phosphorus were measured 4 weeks after the operation.

Results: The RYGB procedure brought about lower blood glucose, BMD, serum calcium and phosphorus levels, as well as a relatively higher bone turnover rate and 1,25(OH)2VD level, compared to the SG and sham groups, while the influences of the SG procedure were not significant. 25(OH)VD demonstrated no significant difference among the 3 groups.

Conclusions: Despite its excellent ability to provide short-term glycemic control, the RYGB procedure could led to more severe impairment of bone health compared to the SG procedure. Bone health should be procured after bariatric surgery, especially with the RYGB procedure. Early detection of BMD and BTM may help to avoid deterioration of bone.
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http://dx.doi.org/10.1159/000514426DOI Listing
March 2021

Pseudogenes in Cardiovascular Disease.

Front Mol Biosci 2020 10;7:622540. Epub 2021 Feb 10.

Department of Cardiology, Henan Province People's Hospital and People's Hospital of Zhengzhou University, Zhengzhou, China.

Cardiovascular disease is the main disease that affects human life span. In recent years, the disease has been increasingly addressed at the molecular levels, for example, pseudogenes are now known to be involved in the pathogenesis and development of cardiovascular diseases. Pseudogenes are non-coding homologs of protein-coding genes and were once called "junk gene." Since they are highly homologous to their functional parental genes, it is somewhat difficult to distinguish them. With the development of sequencing technology and bioinformatics, pseudogenes have become readily identifiable. Recent studies indicate that pseudogenes are closely related to cardiovascular diseases. This review provides an overview of pseudogenes and their roles in the pathogenesis of cardiovascular diseases. This new knowledge adds to our understanding of cardiovascular disease at the molecular level and will help develop new biomarkers and therapeutic approaches designed to prevent and treat the disease.
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http://dx.doi.org/10.3389/fmolb.2020.622540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902774PMC
February 2021

Increased Prolactin is an Adaptive Response to Protect Against Metabolic Disorders in Obesity.

Endocr Pract 2021 Jan 15. Epub 2021 Jan 15.

Department of Endocrinology, Beijing Chao-yang Hospital, Capital Medical University, Beijing, China. Electronic address:

Objective: Prolactin (PRL) is a polypeptide hormone named for its crucial role in lactation. Recently, PRL has been recognized as a metabolic hormone that regulates energy metabolism. The current study aimed to investigate the relationship between circulating PRL and metabolic alterations in overweight/obese patients and the effect of weight loss through bariatric surgery on circulating PRL.

Methods: A total of 448 overweight/obese patients aged between 18 and 40 years and 120 age- and sex-matched healthy controls with normal weight were enrolled. Among all participants, 156 obese patients underwent bariatric surgery.

Results: Circulating PRL levels were significantly increased in the overweight (15.27 ± 9.58 μg/L) and obese (17.75 ± 9.15 μg/L) groups compared with the normal weight (13.57 ± 9.03 μg/L) group. Multiple regression analyses demonstrated that the adipose tissue insulin resistance (adipo-IR) level was an independent predictor for PRL (β = -0.451, P < .01). Despite comparable anthropometric parameters, the overweight/obese patients with a higher PRL tertile had decreased levels of triglycerides, nonesterified fatty acids, homeostasis model assessment of insulin resistance, and adipo-IR compared with the patients in the moderate and lower PRL tertiles. Serum PRL levels were significantly decreased following the alleviation of metabolic parameters after bariatric surgery (from 17.12 ± 8.27 to 13.00 ± 5.78 μg/L, P < .05), and the decrease in PRL levels was significantly greater in the lower adipo-IR group than in the higher adipo-IR group (P < .01).

Conclusion: An increased serum PRL level might be an adaptive response for protecting against metabolic disorders in obesity.
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http://dx.doi.org/10.1016/j.eprac.2021.01.002DOI Listing
January 2021

A randomized controlled trial protocol of the cardiovascular safety and efficacy of liraglutide in the treatment of type 2 diabetes.

Medicine (Baltimore) 2021 Jan;100(3):e23948

Department of Research Office, The Second Affiliated Hospital of Xingtai Medical College, Hebei 054000, China.

Background: Recently, many clinical experiments have evaluated the influences of liraglutide in the treatment of type 2 diabetes. However, the outcomes of these studies are inconsistent, and the number of high-quality prospective trials that conducted to assess the cardiovascular safety is limited. Hence, for this research, it was implemented for the assessment of the cardiovascular effectiveness and safety of liraglutide in type 2 diabetes patients.

Methods: This research was a 26-week active controlled and randomized trial. Our research protocol follows the guidelines of Good Clinical Practice issued via the Helsinki Declaration and International Conference on Coordination. All the patients will receive the written informed consent in order to involve in our clinical experiment. The participants with type 2 diabetes aged from 18 years to 80 years, patients with 45.0 kg/m2 body-mass index or less, and with glycosylated hemoglobin of 7.5 to 10.0 percent, and received metformin (daily 1500 mg or more) for 3 months or longer were eligible. All the patients were randomized to 1 of 2 interventions (in the ratio of 1:1): liraglutide placebo once daily (blinded) and liraglutide once daily (blinded), respectively, both combined with the glimepiride and metformin (open-labeled). For the efficacy variable, the major endpoint was the baseline glycated hemoglobin change after treating for 26 weeks. The secondary end points involved: the percentage of participants who achieved the goals of postprandial blood glucose, fasting blood glucose, and glycosylated hemoglobin; the changes of mean postprandial blood glucose, fasting blood glucose, and the body weight, pancreatic B-cell function index, and changes in blood pressure and insulin resistance assessed by homeostasis model.

Conclusions: For this research, the limitations involve the short trial period and the limitation of glimepiride in some countries, thus excluding the maximum doses of glimepiride.

Trial Registration: This study protocol was registered in Research Registry (researchregistry6306).
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http://dx.doi.org/10.1097/MD.0000000000023948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837848PMC
January 2021

Comparative efficacy of pharmacological agents on reducing the risk of major adverse cardiovascular events in the hypertriglyceridemia population: a network meta-analysis.

Diabetol Metab Syndr 2021 Jan 29;13(1):15. Epub 2021 Jan 29.

Department of Cardiology, People's Hospital of Zhengzhou University No, 7, Weiwu Road, Zhengzhou, 450003, China.

Background: Hypertriglyceridemia (HTG) is considered an independent risk factor for major adverse cardiovascular events (MACE).

Methods: This study analyzed the effects of various agents on MACE risk reduction in HTG (serum triglyceride ≥ 150 mg/dl) populations by performing a network meta-analysis. We performed a frequentist network meta-analysis to conduct direct and indirect comparisons of interventions. PubMed, EMBASE, and the Cochrane library were searched for trials until Jul 6, 2020. Randomized controlled trials that reported MACE associated with agents in entire HTG populations or in subgroups were included. The primary outcome was MACE.

Results: Of the 2005 articles screened, 21 trials including 56,471 patients were included in the analysis. The network meta-analysis results for MACE risk based on frequency data showed that eicosapentaenoic acid (EPA) (OR: 1.32; 95% CI 1.19-1.46), gemfibrozil (OR: 1.53; 95% CI 1.20-1.95), niacin plus clofibrate (OR: 2.00; 95% CI 1.23-3.25), pravastatin (OR: 1.32; 95% CI 1.15-1.52), simvastatin (OR: 2.38; 95% CI 1.55-3.66), and atorvastatin (OR: 0.55; 95% CI 0.37-0.82) significantly reduced the risk of MACE compared to the control conditions. In the subgroup analysis of HTG patients with triglycerides ≥ 200 mg/dL, bezafibrate (OR: 0.56; 95% CI 0.33-0.94), EPA (OR: 0.72; 95% CI 0.62-0.82), and pravastatin (OR: 1.33; 95% CI 1.01-1.75) significantly reduced the MACE risk.

Conclusions: Simvastatin had a clear advantage in reducing the risk of MACE in the entire HTG population analyzed in this meta-analysis. EPA, but not omega-3 fatty acid, was considered an effective HTG intervention. Among fibrates, gemfibrozil was most effective, though bezafibrate may significantly reduce the risk of MACE in populations with triglyceride levels of 200-300 mg/dL. Trial registration retrospectively registered in PROSPERO (CRD42020213705).
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http://dx.doi.org/10.1186/s13098-021-00626-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845128PMC
January 2021

Apelin protects against ischemia-reperfusion injury in diabetic myocardium via inhibiting apoptosis and oxidative stress through PI3K and p38-MAPK signaling pathways.

Aging (Albany NY) 2020 12 20;12(24):25120-25137. Epub 2020 Dec 20.

Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Among all diabetes mellitus-associated cardiovascular diseases, morbidity of diabetic myocardium with ischemia reperfusion injury (D-IRI) is increasing year by year. We aimed to discover a therapeutic biomarker and investigate its mechanism in D-IRI. High-fat diet and streptozotocin-induced diabetes rats were operated with IRI or sham. Recombined lentiviral vector encoding Apelin was injected into D-IRI rat via tail vein. Cardiac function, infarct size, cellular death and oxidative stress were major outcome measures. Cardiomyocyte ischemia reperfusion injury was more serious in D-IRI rats than in non-diabetes ischemia reperfusion injury (ND-IRI) rats. The secretion of NTproBNP was increased in D-IRI compared with ND-IRI. Bcl-2 expression was decreased, and Bax and cleaved caspase-3 expression was increased in D-IRI rats compared with ND-IRI rats, which were reversed after treatment with Apelin. Apelin-upregulation improved cardiomyocyte ischemia reperfusion injury and decreased NT-proBNP levels in D-IRI rats. Apelin overexpression enhanced PI3K and eNOS levels while reduced those of p38-MAPK and iNOS in D-IRI rats. Apelin overexpression protected against D-IRI through inhibiting apoptosis and oxidative stress via PI3K and p38MAPK signaling pathways in D-IRI rats. These findings provide critical new insight into understanding of Apelin's cardio-protective effects, which may become a novel therapeutic target for the diabetic IRI patients.
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http://dx.doi.org/10.18632/aging.104106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803490PMC
December 2020

Simultaneous Detection of CNVs and SNVs Improves the Diagnostic Yield of Fetuses with Ultrasound Anomalies and Normal Karyotypes.

Genes (Basel) 2020 Nov 25;11(12). Epub 2020 Nov 25.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, China.

The routine assessment to determine the genetic etiology for fetal ultrasound anomalies follows a sequential approach, which usually takes about 6-8 weeks turnaround time (TAT). We evaluated the clinical utility of simultaneous detection of copy number variations (CNVs) and single nucleotide variants (SNVs)/small insertion-deletions (indels) in fetuses with a normal karyotype with ultrasound anomalies. We performed CNV detection by chromosomal microarray analysis (CMA) or low pass CNV-sequencing (CNV-seq), and in parallel SNVs/indels detection by trio-based clinical exome sequencing (CES) or whole exome sequencing (WES). Eight-three singleton pregnancies with a normal fetal karyotype were enrolled in this prospective observational study. Pathogenic or likely pathogenic variations were identified in 30 cases (CNVs in 3 cases, SNVs/indels in 27 cases), indicating an overall molecular diagnostic rate of 36.1% (30/83). Two cases had both a CNV of uncertain significance (VOUS) and likely pathogenic SNV, and one case carried both a VOUS CNV and an SNV. We demonstrated that simultaneous analysis of CNVs and SNVs/indels can improve the diagnostic yield of prenatal diagnosis with shortened reporting time, namely, 2-3 weeks. Due to the relatively long TAT for sequential procedure for prenatal genetic diagnosis, as well as recent sequencing technology advancements, it is clinically necessary to consider the simultaneous evaluation of CNVs and SNVs/indels to enhance the diagnostic yield and timely TAT, especially for cases in the late second trimester or third trimester.
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http://dx.doi.org/10.3390/genes11121397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759943PMC
November 2020

Arsenic exposure and its joint effects with cigarette smoking and physical exercise on lung function impairment: Evidence from an occupational cohort study.

Environ Res 2020 Oct 31:110419. Epub 2020 Oct 31.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, China. Electronic address:

Background: Arsenic (As) is an established toxic metal, but its effect on longitudinal lung function change among occupational workers is less conclusive.

Methods: 1243 participants were recruited in a coke-oven plant and followed up from 2010 to 2014. Each individual provided 20 mL morning urine sample at baseline, which was then used for urinary levels of As (U-As) and polycyclic aromatic hydrocarbon (PAH) metabolites detecting. Lung function levels at both baseline and the end of follow-up were determined. Multiple linear regression models were used to analyze the associations between U-As with annual lung function changes, and to evaluate the joint effects of U-As with cigarette smoking and regular physical exercise.

Results: Among all participants, each 2-fold increase in U-As was associated with -12.09 (95%CI: -19.37, -4.81) mL, -0.32% (95%CI: -0.54%, -0.10%), -15.04 (95%CI: -24.62, -5.46) mL, and -0.36% (95%CI: -0.64%, -0.08%) annual changes in reduced forced expiratory volume in 1 second (FEV), percent predicted FEV (ppFEV), forced vital capacity (FVC), and percent predicted FVC (ppFVC), respectively. These effects were more pronounced among coke-oven workers with smoking (especially heavy smoking with pack-years≥15) and without regular physical exercise. Compared to low-As-exposed (≤4.70 μg/mmol creatinine) non-smokers with regular physical exercise, the high-As-exposed (>4.70 μg/mmol creatinine) smokers without regular physical exercise had the worst annual declines in FEV [β (95%CI) = -69.01 (-106.67, -31.34) mL], ppFEV [β (95%CI) = -1.94% (-3.02%, -0.87%)], FVC [β (95%CI) = -78.66 (95%CI: -129.46, -27.86) mL], and ppFVC [β (95%CI) = -1.80% (-3.23%, -0.37%)].

Conclusions: The findings in our prospective cohort study suggested the positively linear dose-response relationship of U-As with annual lung function decline. The adverse effects of As could be enhanced by cigarette smoking and attenuated by regular physical exercise. Specific emphasizes on tobacco control and physical exercise were suggested to prevent As exposure induced pulmonary impairment.
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http://dx.doi.org/10.1016/j.envres.2020.110419DOI Listing
October 2020

Neutrophils Enhance Cutaneous Vascular Dilation and Permeability to Aggravate Psoriasis by Releasing Matrix Metallopeptidase 9.

J Invest Dermatol 2021 Apr 2;141(4):787-799. Epub 2020 Sep 2.

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address:

Neutrophil infiltration and papillary vessel dilation are hallmarks of the initiation phase of psoriatic lesions. However, how neutrophils aggravate psoriasis development during transendothelial migration and the interaction between neutrophils and cutaneous vascular endothelial cells are less well-understood. In this study, we reported that neutrophils and cutaneous vascular endothelial cells activated each other when neutrophils migrated through the cutaneous endothelial barrier. In addition, neutrophil infiltration into skin lesions caused vascular remodeling including cutaneous vasodilation and enhanced vascular permeability in vivo and in vitro. Microarray gene profile data showed that matrix metallopeptidase (MMP)-9 was overexpressed in psoriatic neutrophils, and zymography assay further validated the bioactivity of MMP-9 secreted by psoriatic neutrophils. Moreover, MMP-9 activated vascular endothelial cells through the extracellular signal‒regulated kinase 1/2 and p38-MAPK signaling pathways, enhancing CD4 T-cell transmigration in vitro. Correspondingly, an MMP-9 inhibitor significantly reduced cutaneous vasodilation, vascular permeability, and psoriatic symptoms in an imiquimod- or IL-23‒induced psoriasiform mouse model. Overall, our study demonstrates that neutrophil-derived MMP-9 induces cutaneous vasodilation and hyperpermeability by activating cutaneous vascular endothelial cells, thus facilitating psoriatic lesion development, which increases our knowledge on the role of neutrophils in the pathogenesis of psoriasis.
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http://dx.doi.org/10.1016/j.jid.2020.07.028DOI Listing
April 2021

Corrigendum to "Circulating essential metals and lung cancer: Risk assessment and potential molecular effects" [Environ. Int. 127 (2019) 685-693].

Environ Int 2020 Oct 1;143:106072. Epub 2020 Sep 1.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

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http://dx.doi.org/10.1016/j.envint.2020.106072DOI Listing
October 2020

Co-Electrolysis-Assisted Decomposition of Hydroxylammonium Nitrate-Fuel Mixtures Using Stainless Steel-Platinum Electrodes.

ACS Omega 2020 Aug 29;5(31):19525-19532. Epub 2020 Jul 29.

School of Aeronautics and Astronautics, Zhejiang University, Hangzhou 310027, Zhejiang, China.

Hydroxylammonium nitrate (HAN) is a promising green propellant because of its low toxicity, high volumetric specific impulse, and reduced development cost. Electrolytic decomposition of HAN is an efficient approach to prepare it for further ignition and combustion. This paper describes the investigation of a co-electrolysis effect on electrolytic decomposition of HAN-fuel mixtures using stainless steel-platinum (SS-Pt) electrodes. For the first time, different materials were utilized as electrodes to alter the cathodic reaction, which eliminated the inhibition effect and achieved a repeatable and consistent electrolytic decomposition of HAN solution. Urea and methanol were added as fuel components in the HAN-fuel mixtures. When the mass ratio of added urea ≥20%, the electrolytic decomposition of a HAN-urea ternary mixture achieved 67% increment in maximum gas temperature () and 185% increment in overall temperature increasing rate over the benchmark case of HAN solution. The co-electrolysis of urea released additional electrons into the mixtures and enhanced the overall electrolytic decomposition of HAN. In contrast, the addition of methanol did not improve the but only increased the overall temperature increasing rate. This work has important implications in the development of an efficient and reliable electrolytic decomposition system of HAN and its mixtures for propulsion applications.
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http://dx.doi.org/10.1021/acsomega.0c01804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424740PMC
August 2020

Electronic-Grade High-Quality Perovskite Single Crystals by a Steady Self-Supply Solution Growth for High-Performance X-ray Detectors.

Adv Mater 2020 Aug 6;32(33):e2001540. Epub 2020 Jul 6.

MOE Key Laboratory of Advanced Micro-structured Materials, School of Physics Science and Engineering, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

High-quality perovskite single crystals with large size are highly desirable for the fundamental research and high energy detection application. Here, a simple and convenient solution method, featuring continuous-mass transport process (CMTP) by a steady self-supply way, is shown to keep the growth of semiconductor single crystals continuously stable at a constant growth rate until an expected crystal size is achieved. A significantly reduced full width at half-maximum (36 arcsec) of the (400) plane from the X-ray rocking curve indicates a low angular dislocation of 6.8 × 10 cm and hence a higher crystalline quality for the CH NH PbI (MAPbI ) single crystals grown by CMTP as compared to the conventional inverse temperature crystallization (ITC) method. Furthermore, the CMTP-based single crystals have lower trap density, reduced by nearly 200% to 4.5 × 10 cm , higher mobility increased by 187% to 150.2 cm V s , and higher mobility-lifetime product increased by around 450% to 1.6 × 10 cm V , as compared with the ITC-grown reference sample. The high performance of the CMTP-based MAPbI X-ray detector is comparable to that of a traditional high-quality CdZnTe device, indicating the CMTP method as being a cost-efficient strategy for high-quality electronic-grade semiconductor single crystals.
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http://dx.doi.org/10.1002/adma.202001540DOI Listing
August 2020

Inhibition of MicroRNA-302c on Stemness of Colon Cancer Stem Cells via the CARF/Wnt/β-Catenin Axis.

Dig Dis Sci 2020 Jul 2. Epub 2020 Jul 2.

Department of Gastroenterology, Caoxian People's Hospital, Development Zone, Fumin Avenue, Caoxian, 274400, Shandong, People's Republic of China.

Background: Even though the relevance of microRNA (miR)-302c has been studied, little is known about its involvement in colon cancer (CC).

Aims: Our aim here was to investigate the role of miR-302c in the cancer stem cells (CSCs) of CC.

Methods: Firstly, the CSCs were screened out from cultured SW1116 and SW480 cells by flow cytometry, and the differentially expressed miRNAs in cell were obtained by microarray analysis. The expression of miR-302c, collaborator of ARF (CARF), and Wnt/β-catenin-related genes in CSCs was determined by means of RT-qPCR and Western blot. A dual-luciferase reporter assay was conducted to authenticate the binding relationship between miR-302c and CARF. Proliferation, migration, invasion, sphere formation as well as apoptosis of CSCs were assessed by cell counting kit-8, Transwell assay, sphere formation assay as well as flow cytometric analysis, respectively. The roles of miR-302c and CARF in tumor growth were determined in vivo.

Results: The expression of miR-302c in CC cells was reduced versus that in normal cells. The overexpression of miR-302c weakened the stemness, proliferation, invasion, and migration abilities while induced apoptosis of CSCs in CC. Also, miR-302c reduced tumor size and weight in mice, accompanied with lowered CARF expression. The mechanistic analysis manifested that miR-302c bound to CARF and suppressed its expression and disrupted the Wnt/β-catenin signaling.

Conclusion: This study offers a novel characterization of miR-302c function in CSCs in CC, which may be beneficial to the development of capable therapeutic options for CC.
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http://dx.doi.org/10.1007/s10620-020-06435-8DOI Listing
July 2020

Mediation of the association between polycyclic aromatic hydrocarbons exposure and telomere attrition by oxidative stress: A prospective cohort study.

J Hazard Mater 2020 11 27;399:123058. Epub 2020 May 27.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, China. Electronic address:

Previous studies have reported associations between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere attrition, but the underlying mechanisms remain to be elucidated. This study aimed to explore the mediation role of oxidative stress on the effects of PAHs exposure on telomere attrition in a cohort study of 1180 coke-oven workers. We determined baseline urinary concentrations of ten urinary PAH metabolites, two oxidative stress biomarkers [8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-isoPGF2α)] and peripheral leukocytes telomere length (TL) in both baseline and follow-up visits. Mediation analysis was applied to assess effects of oxidative stress biomarkers on the PAHs-TL attrition associations. The baseline 8-OHdG had a significant dose-response relationship with TL decline [β(95 %CI) = 0.07(0.03-0.12), P = 0.001] and TL ratio [β(95 %CI)]=0.07 (0.02-0.12), P = 0.003]. Mediation analyses indicated that 8-OHdG mediated a separate 39.1 %, 47.0 %, 43.3 %, and 58.0 % of the associations between 1-hydroxynaphthalene (1-OHNa), 2-OHNa, ΣOHNa, 1-hydroxypyrene (1-OHP) and TL decline (P = 0.016, 0.008, 0.012, and 0.014, respectively). Additionally, 8-OHdG mediated a separate 44.8 %, 49.4 %, 49.2 %, and 35.5 % of the associations between 1-OHNa, 2-OHNa, ΣOHNa, 1-OHP and TL ratio (P = 0.012, 0.008, 0.012, and 0.046, respectively). Our study proposed the positive association of 8-OHdG with TL attrition and revealed the mediation roles of 8-OHdG in PAHs-TL attrition associations.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123058DOI Listing
November 2020

Lead exposure and its interactions with oxidative stress polymorphisms on lung function impairment: Results from a longitudinal population-based study.

Environ Res 2020 08 8;187:109645. Epub 2020 May 8.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, 430030, Hubei, PR China. Electronic address:

Exposure to lead (Pb) and cadmium (Cd) were related to lung function impairment, and this association may be modified by genetic variants in oxidative stress response. Here we enrolled 1243 coke-oven workers in a prospective cohort who were followed up from 2010 to 2014, assessed the associations of Pb and Cd exposure with 4-year lung function impairment, and further explored the interaction effects of Pb with 2664 single nucleotide polymorphisms (SNPs) in 345 oxidative stress related genes. Urinary levels of Pb, Cd, and two oxidative stress biomarkers [8-iso-prostaglandin F2α (8-iso-PGF2α) for lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative DNA damage] were measured at baseline only and their lung function levels were measured both at baseline and at the end of follow-up. Each 10-fold increase in urinary Pb was associated with -159 (95%CI: -254, -64.2) mL and -3.63% (95%CI: -6.48%, -0.78%) changes in FEV and percent predicted FEV (ppFEV), respectively. But none significant associations were observed for Cd. NQO1 rs2917670 showed significant interaction with Pb on elevated FEV decline after multiple comparison (P=1.54 × 10). In addition, urinary Pb increased with 8-iso-PGF2α and the rs2917670-C could significantly decrease NQO1 expression in normal lung tissues. These findings suggested the gene-environmental interaction of NQO1 rs2917670 and Pb exposure on the reduction of FEV. The effect of Pb exposure on elevated oxidative stress and the decreased expression of antioxidant enzyme NQO1 caused by rs2917670-C allele may partly explain the underlying biological mechanism.
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http://dx.doi.org/10.1016/j.envres.2020.109645DOI Listing
August 2020

Co-exposure to multiple metals, TERT-CLPTM1L variants, and their joint influence on leukocyte telomere length.

Environ Int 2020 07 4;140:105762. Epub 2020 May 4.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Objective: Telomere is required for maintaining chromosome stability and genome integrity, while telomere length is sensitive to environmental stressors. We aimed to identify the effects of multiple metals co-exposure as well as their joint effects with TERT-CLPTM1L variants on leukocyte telomere length (LTL).

Methods: This study included 842 workers from a coke-oven plant, of whom plasma concentrations of 23 metals and LTL were determined. Genetic variations in TERT-CLPTM1L were genotyped by using the Global Screening Array. Multipollutant-based statistical methods, including the Bonferroni-correction, backward elimination procedure, and LASSO penalized regression analysis, were used to select the LTL-associated metals. Generalized linear regression models were used to evaluate the joint effects of TERT-CLPTM1L variants with positive metal on LTL.

Results: Each 1% increase in plasma concentration of manganese (Mn) was significantly associated with a 0.153% increase in LTL [β(95%CI) = 0.153(0.075, 0.230), P < 0.001] in single-metal models after Bonferroni-correction. The multiple-metal models and the LASSO penalized regression analysis both indicated Mn as the sole significant predictor for LTL. Furthermore, 5 tagSNPs (rs33954691, rs6554759, rs465498, rs2455393, and rs31489) in TERT-CLPTM1L with high plasma Mn (>4.21 μg/L) showed joint effects on increasing LTL.

Conclusions: Our study revealed the independent and positive association between plasma Mn and LTL when accounting for co-exposure to other metals. This effect can be further enhanced by TERT-CLPTM1L variants. These results may advance our understanding of the complex interplay between genetic and environmental factors on telomere length. Further experimental studies are warranted to elucidate the underlying mechanisms.
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http://dx.doi.org/10.1016/j.envint.2020.105762DOI Listing
July 2020

A double-network hydrogel for the dynamic compression of the lumbar nerve root.

Neural Regen Res 2020 Sep;15(9):1724-1731

Department of Orthopedic Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Current animal models of nerve root compression due to lumbar disc herniation only assess the mechanical compression of nerve roots and the inflammatory response. Moreover, the pressure applied in these models is static, meaning that the nerve root cannot be dynamically compressed. This is very different from the pathogenesis of lumbar disc herniation. In this study, a chitosan/polyacrylamide double-network hydrogel was prepared by a simple two-step method. The swelling ratio of the double-network hydrogel increased with prolonged time, reaching 140. The compressive strength and compressive modulus of the hydrogel reached 53.6 and 0.34 MPa, respectively. Scanning electron microscopy revealed the hydrogel's crosslinked structure with many interconnecting pores. An MTT assay demonstrated that the number of viable cells in contact with the hydrogel extracts did not significantly change relative to the control surface. Thus, the hydrogel had good biocompatibility. Finally, the double-network hydrogel was used to compress the L4 nerve root of male sand rats to simulate lumbar disc herniation nerve root compression. The hydrogel remained in its original position after compression, and swelled with increasing time. Edema appeared around the nerve root and disappeared 3 weeks after operation. This chitosan/polyacrylamide double-network hydrogel has potential as a new implant material for animal models of lumbar nerve root compression. All animal experiments were approved by the Animal Ethics Committee of Neurosurgical Institute of Beijing, Capital Medical University, China (approval No. 201601006) on July 29, 2016.
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http://dx.doi.org/10.4103/1673-5374.276361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7437591PMC
September 2020

Clinical features of pulmonary mucormycosis in patients with different immune status.

J Thorac Dis 2019 Dec;11(12):5042-5052

Division of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Pulmonary mucormycosis (PM) is a relatively rare but often fatal and rapidly progressive disease. Most studies of PM are case reports or case series with limited numbers of patients, and focus on immunocompromised patients. We investigated the clinical manifestations, imaging features, treatment, and outcomes of patients with PM with a focus on the difference in clinical manifestations between patients with different immune status.

Methods: Clinical records, laboratory results, and computed tomography scans of 24 patients with proven or probable PM from January 2005 to December 2018 in Peking Union Medical College Hospital were retrospectively analyzed.

Results: Ten female and 14 male patients were included (median age, 43.5 years; range, 13-64 years). Common presenting symptoms were fever (70.8%), cough (70.8%), sputum production (54.2%), and hemoptysis (41.7%). Radiological findings included consolidation (83.3%), ground-glass opacities (58.3%), nodules (50.0%), masses (37.5%), cavities (33.3%), mediastinal lymphadenopathy (29.2%), and halo sign (12.5%); one patient had a reversed halo sign. Seven patients (29.2%) had no obvious predisposing risk factors, and 17 (70.8%) had underlying diseases including diabetes, hematological malignancy, and use of immunosuppressants. Compared with immunocompromised patients, immunocompetent patients with PM were younger {23 [13-46] 48 [17-64] years, P=0.023}, comprised a higher proportion of men (100.0% 41.2%, P=0.019), had a longer disease course {34 [8-47] 9 [2-102] weeks, P=0.033}, had a higher eosinophil count [0.66 (0.07-2.00) ×10/L 0.04 (0.00-0.23) ×10/L, P=0.001], and had a lower erythrocyte sedimentation rate {12 [1-88] 74 [9-140] mm/h, P=0.032}.

Conclusions: PM can occur in heterogeneous patients with different immune status, and the clinical phenotype differs between immunocompetent and immunocompromised patients. Because of the lack of specific clinic and imaging manifestations, aggressive performance of invasive procedures to obtain histopathological and microbial evidence is crucial for a definitive diagnosis.
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http://dx.doi.org/10.21037/jtd.2019.12.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988080PMC
December 2019

Obstructive sleep apnea and liver injury in severely obese patients with nonalcoholic fatty liver disease.

Sleep Breath 2020 Dec 30;24(4):1515-1521. Epub 2020 Jan 30.

Department of Pulmonary and Critical Care Medicine, Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.

Objectives: Obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are common in subjects with severe obesity. It has been suggested that insulin resistance and systemic inflammation may play a role in the development of nonalcoholic steatohepatitis (NASH), but the mechanisms remain controversial. The aim of this study was to explore the influence of OSA on liver injury and its potential mechanisms in severely obese patients with NAFLD.

Methods: Severely obese patients requiring bariatric surgery were consecutively recruited between November 2017 and June 2018. Demographic, biochemical, liver ultrasound, and ambulatory polygraph data were collected.

Results: One hundred fifty-three subjects with liver ultrasound-verified NAFLD were classified into three groups according to the apnea-hypopnea index (AHI). The level of serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) tended to increase with more severe OSA (P = 0.024 and P = 0.004, respectively). In the unadjusted analysis, both ALT and GGT were positively correlated with AHI, oxygen desaturation index, percentage of total sleep time spent with oxyhemoglobin saturation below 90%, male sex, homeostasis model assessment of insulin resistance (HOMA-IR), and total cholesterol, while liver enzymes were negatively related to lowest oxygen saturation. In multiple regression analysis, AHI (odds ratio (OR) = 1.052, P = 0.044) and HOMA-IR (OR = 1.135, P = 0.001) were independent risk factors for an elevated ALT level. High-sensitivity C-reactive protein (hs-CRP) was positively associated with BMI and GGT (r = 0.349 and r = 0.164 (P < 0.05), respectively), and no correlation was found between hs-CRP and AHI or other parameters of hypoxia. hs-CRP and GGT remained significantly correlated after adjusting for confounding parameters (OR = 2.509, P = 0.013).

Conclusions: OSA may play a role in liver injury among severely obese individuals with NAFLD. Insulin resistance and systemic inflammation were possible contributing factors in this process.
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http://dx.doi.org/10.1007/s11325-020-02018-zDOI Listing
December 2020

BRCA1 c.5470_5477del, a founder mutation in Chinese Han breast cancer patients.

Int J Cancer 2020 06 22;146(11):3044-3052. Epub 2020 Feb 22.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Breast Center, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China.

The spectrum and frequency of BRCA1/2 pathogenic variants may be ethnicity-specific. Whether high-frequency founder mutations are present in Chinese women remains largely unknown. In the current study, germline pathogenic variants in the BRCA1/2 genes were determined in 9,505 unselected Chinese Han breast cancer (BC) patients by next-generation and/ or Sanger sequencing. Four hundred and seventy-one (5.0%) BC patients carried BRCA1/2 pathogenic variants in this cohort. A total of 25 recurrent pathogenic variants (at least found in four unrelated patients) were identified in this cohort (8 BRCA1 and 17 BRCA2 recurrent pathogenic variants), 161 patients carried one of these recurrent pathogenic variants in this cohort of 9,505 patients. All of these 25 recurrent pathogenic variants were further explored whether they had founder effect through haplotype analysis. The most common pathogenic variant, BRCA1 c.5470_5477del, was found in 30 BC patients from 29 unrelated families. Twenty-seven of these 29 unrelated patients who carried this BRCA1 c.5470_5477del mutation shared an identical haplotype, indicating that BRCA1 c.5470_5477del was a founder mutation in the Chinese Han population. Furthermore, BRCA1 c.5470_5477del mutation carriers had a significantly worse survival than noncarriers (disease-free survival, p = 0.049; overall survival, p = 0.029). Taken together, our data suggested that BRCA1 c.5470_5477del is a founder mutation in the Chinese Han population and BRCA1 c.5470_5477del mutation carriers have a poor survival.
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http://dx.doi.org/10.1002/ijc.32877DOI Listing
June 2020

Cognitive Status of Electrolytic Aluminum Workers: A Cross-sectional Study Using Cognitive Screening Tests.

Biomed Environ Sci 2019 Nov;32(11):869-873

School of Public Health, Shanxi Medical University, Taiyuan 030001, Shanxi, China.

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http://dx.doi.org/10.3967/bes2019.110DOI Listing
November 2019

Two case reports: Early detection of amniotic band syndrome by adhesion between hand and umbilical cord at 11 to 14 weeks' gestation.

Medicine (Baltimore) 2019 Dec;98(50):e18302

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.

Rationale: The significant ultrasonic characteristics of amniotic band syndrome (ABS) are the malformations of fetal affected parts and the band-like echoes in amniotic cavity. This article first suggests that the fetal hand adhered to umbilical cord with restricted movement provides some values in the diagnosis of ABS in early gestational weeks especially when the fetal malformation is not obvious and amniotic band is thin and fine.

Patient Concerns: Two pregnant women had no discomfort and underwent routine ultrasound examination at 11 to 14 gestational weeks.

Diagnosis: Only the fetal hand adhered to umbilical cord with restricted movement was detected during the first ultrasound examination at 11∼14 gestational weeks, and the floating band-like echos were detected in the amniotic cavity with follow-up examinations 2 to 3 weeks later. Both of the 2 fetus were diagnosed as ABS by ultrasound INTERVENTIONS:: The two pregnant women underwent the prenatal counseling and were recommended closely follow-up and further examination.

Outcomes: Two fetuses died in utero between 17 and 19 weeks. After induction of labor, it was found that the hands and umbilical cord of the fetuses were wrapped by amniotic bands, which was proved pathologically as ABS.

Lessons: The adhesion of the fetal hand and umbilical cord is an important ultrasonic sign suggesting ABS with poor prognosis in early pregnancy. We hope that this study can provide some guidance for the early diagnosis of ABS during 11 to 14 week's ultrasound examination.
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http://dx.doi.org/10.1097/MD.0000000000018302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6922433PMC
December 2019

Polycyclic aromatic hydrocarbons exposure and their joint effects with age, smoking, and TCL1A variants on mosaic loss of chromosome Y among coke-oven workers.

Environ Pollut 2020 Mar 27;258:113655. Epub 2019 Nov 27.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, China. Electronic address:

Mosaic loss of chromosome Y (mLOY) is the most common structure somatic event that related to increased risks of various diseases and mortality. Environmental pollution and genetic susceptibility were important contributors to mLOY. We aimed to explore the associations of polycyclic aromatic hydrocarbons (PAHs) exposure, as well as their joint effects with age, smoking, and genetic variants on peripheral blood mLOY. A total of 1005 male coke-oven workers were included in this study and their internal PAHs exposure levels of 10 urinary PAH metabolites and plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts were measured. mLOY was defined by the median log R ratio(mLRR) of 1480 probes in male-specific region of chromosome-Y from genotyping array. We found that the PAHs exposure levels were linearly associated with mLOY. A 10-fold increase in urinary 1-hydroxynaphthalene (1-OHNa), 1-hydroxyphenanthrene (1-OHPh), 2-OHPh, 1-hydroxypyrene (1-OHP), ΣOH-PAHs, and plasma BPDE-Alb adducts could generate 0.0111, 0.0085, 0.0069, 0.0103, 0.0134, and 0.0152 decrease in mLRR-Y, respectively. Additionally, mLOY accelerated with age, smoking pack-years, and TCL1A rs1122138-C allele, and we observed the most severe mLOY among subjects carrying more than 3 of the above risk factors. Our results revealed the linear dose-effect associations between PAHs exposure and mLOY. Elder male smokers carrying rs1122138CC genotype were the most susceptible subpopulations to mLOY, who should be given protections for PAHs exposure induced chromosome-Y aberration.
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http://dx.doi.org/10.1016/j.envpol.2019.113655DOI Listing
March 2020

Prenatal diagnosis of lingual cyst and spontaneous regression before birth: A rare case report and literature review.

Medicine (Baltimore) 2019 Nov;98(46):e17873

Department of Ultrasound, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Rationale: We report a case of fetal lingual cyst that was diagnosed prenatally using 2-dimensional and 3-dimensional images during routine second trimester screening. To the best of our knowledge, this is the first description of a cystic lesion disappearing before birth.

Patient Concerns: A 36-year-old woman at 22 weeks' gestation showed the presence of an oral cystic lesion in routine second trimester ultrasound screening. The lesion measured 18 × 15 × 15 mm.

Interventions: A follow-up ultrasound examination was performed every 4 to 6 weeks.

Outcomes: The cyst disappeared in a follow-up ultrasound examination at 35 and 37 weeks of gestation. A male newborn who weighed 3480 g was delivered with no feeding difficulties. The boy was followed to 6 years after birth. The child had normal growth and development, and there was no recurrence of the cyst.

Lessons: Prenatally diagnosed lingual cysts are uncommon findings that can include many different pathologies with a wide spectrum of severity. Lingual cysts usually have a good prognosis.
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http://dx.doi.org/10.1097/MD.0000000000017873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867743PMC
November 2019

Daily cooking duration and its joint effects with genetic polymorphisms on lung cancer incidence: Results from a Chinese prospective cohort study.

Environ Res 2019 12 16;179(Pt A):108747. Epub 2019 Sep 16.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objectives: In this study, we conducted a prospective cohort study to investigate the joint effects of daily cooking duration with single nucleotide polymorphisms (SNPs) on lung cancer incidence.

Materials And Methods: A total of 33,868 individuals recruited in 2013 from Dongfeng-Tongji cohort study were included in our research, in which 5178 participants were genotyped. Daily cooking duration was accessed by questionnaire, and the incident lung cancer cases were confirmed. Fifteen lung cancer related SNPs were selected according to the previous reports. We used the multiple Cox regression models to evaluate the separate and joint effects of daily cooking duration and SNPs on lung cancer incidence.

Results: Each 1-h increase in daily cooking duration was associated with a 17% elevated risk of lung cancer incidence [hazard ratio (HR) (95%CI) = 1.17(1.03, 1.33)]. Specifically, subjects with daily cooking duration >2 h/day had a 2.05-fold increased incident risk of lung cancer than those without cooking [HR(95%CI) = 2.05(1.20, 3.53)] (P = 0.011). The rs2395185 and rs3817963, both located at 6p21.32, were significantly associated with lung cancer incidence. Compared with no cooking subjects with rs2395185GG or rs3817963TT genotype, subjects with daily cooking >2 h/day and carrying rs2395185GT + TT genotypes had a 2.48-fold increased risk of lung cancer [HR(95%CI) = 2.48(1.03, 5.97)], and there were significant joint effects of rs3817963TC + CC with daily cooking 1-2 and >2 h/day [HR(95%CI) = 2.23(1.07, 4.64) and 2.22(1.05, 4.68), respectively].

Conclusions: Longer daily cooking duration, especially daily cooking >2 h/day, was associated with increased risk of lung cancer. There were significant joint effects of rs2395185 and rs3817963 with daily cooking duration on lung cancer incidence. This study offered a new indicator of cooking related pollution exposure and added new evidence for the joint effects of environment and genetic factors on lung cancer incidence.
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http://dx.doi.org/10.1016/j.envres.2019.108747DOI Listing
December 2019

Circulating essential metals and lung cancer: Risk assessment and potential molecular effects.

Environ Int 2019 06 13;127:685-693. Epub 2019 Apr 13.

Department of Occupational and Environmental Health, State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objective: Essential metals play important roles in the carcinogenic process. However, seldom longitudinal investigations have evaluated their roles in lung cancer development. We aimed to investigate the associations between multiple essential metals and lung cancer incidence and to explore the potential mechanisms.

Methods: A nested case-control study of 440 incident lung cancer cases and 1:3 frequency matched 1320 healthy controls from the Dongfeng-Tongji Cohort was conducted. The baseline plasma concentrations of 11 essential metals (cobalt, copper, iron, manganese, molybdenum, rubidium, selenium, strontium, stannum, vanadium, and zinc) were measured, and their associations with lung cancer incidence were estimated. Effect of positive metal (zinc) on 4-year telomere attrition was then evaluated among an occupational cohort of 724 workers. We also assessed the transcriptional regulation effects of plasma zinc on mRNA expression profiles, and the expressions of zinc-related genes were further compared in pair-wised lung tumor and normal tissues.

Results: Elevated plasma level of zinc was associated with lower incident risk of lung cancer [OR (95% CI) = 0.89 (0.79, 0.99)] and decreased 4-year telomere attrition [β (95% CI) = -0.73 (-1.27, -0.19)]. These effects were pronounced among males. In particularly, zinc could regulate the expressions of 8 cancer-related genes, including SOD1, APE, TP53BP1, WDR33, LAPTM4B, TRIT1, HUWE1, and ZNF813, which were over-expressed in lung tumor tissues.

Conclusions: We propose that high plasma zinc could prevent incident lung cancer, probably by slowing down telomere attrition and regulating the expressions of cancer-related genes. These results provided a new insight into lung cancer prevention.
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http://dx.doi.org/10.1016/j.envint.2019.04.021DOI Listing
June 2019

Effect of thallium exposure and its interaction with smoking on lung function decline: A prospective cohort study.

Environ Int 2019 06 25;127:181-189. Epub 2019 Mar 25.

Department of Occupational and Environmental Health, Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Background: Thallium (Tl) is a cumulative high toxicant in the environment, but few longitudinal studies have investigated the respiratory impairment of Tl exposure.

Objectives: This study aimed to evaluate the effect of Tl and its interaction with smoking on lung function decline, and explore the potential mechanisms.

Methods: The baseline and follow-up lung functions were measured from a prospective cohort study of 1243 workers, who were followed from 2010 to 2014. Their baseline urinary levels of Tl were determined. We also measured the plasma C-reactive protein (CRP) and urinary 8-iso-prostaglandin-F2α (8-iso-PGF2α) in a randomly selected subcohort of 474 subjects.

Results: The results showed that a 2-fold increase in urinary Tl was associated with 29.81 mL (95%CI: 3.83-55.80) increased decline in forced expiratory volume in 1 s (FEV). The effect was more pronounced among heavy-smokers (≥15 pack-years) [β(95%CI) = 56.42 mL (9.66-103.19)]. In particular, compared to never-smokers with low Tl, heavy-smokers with high Tl had a separate 158.44 mL (95%CI: 54.88-262.00) and 4.58% (95%CI: 1.40-7.76) increased declines in FEV and percentage of predicted (ppFEV), respectively. There was a significant interaction between Tl and smoking intensity on ppFEV decline (P = 0.034). More importantly, the increasing level of urinary Tl was correlated with elevated CRP and 8-iso-PGF2α.

Conclusion: Our prospective cohort study identified that exposure to high Tl had a deleterious effect on lung function, and this effect may be enhanced by tobacco smoking. Increased inflammation may partly contribute to the joint effects of Tl and smoking on impaired lung function, but the biological mechanisms need further explorations.
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http://dx.doi.org/10.1016/j.envint.2019.03.034DOI Listing
June 2019

OX40 Regulates Both Innate and Adaptive Immunity and Promotes Nonalcoholic Steatohepatitis.

Cell Rep 2018 12;25(13):3786-3799.e4

Experimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China; Beijing Clinical Research Institute, Beijing, 100050, China; Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing, 100050, China; National Clinical Research Center for Digestive Diseases, Beijing, 100050, China. Electronic address:

Both innate and adaptive immune cells are involved in the pathogenesis of nonalcoholic steatohepatitis (NASH), but the crosstalk between innate and adaptive immunity is largely unknown. Here we show that compared with WT mice, OX40 mice exhibit decreased liver fat accumulation, lobular inflammation, and focal necrosis after feeding with diets that induce NASH. Mechanistically, OX40 deficiency suppresses Th1 and Th17 differentiation, and OX40 deficiency in T cells inhibits monocyte migration, antigen presentation, and M1 polarization. Soluble OX40 stimulation alone upregulates antigen presentation, chemokine receptor expression, and proinflammatory cytokine secretion by liver monocytes. Furthermore, plasma soluble OX40 levels are positively associated with NASH in humans, suggesting clinical relevance of the findings. In conclusion, we show a mechanism for T cell regulation of innate immune cells. OX40 is a key regulator of both intrahepatic innate and adaptive immunity, generates two-way signals, and promotes both proinflammatory monocyte and macrophage and T cell function, resulting in NASH development.
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http://dx.doi.org/10.1016/j.celrep.2018.12.006DOI Listing
December 2018

Annexin A3 gene silencing promotes myocardial cell repair through activation of the PI3K/Akt signaling pathway in rats with acute myocardial infarction.

J Cell Physiol 2019 07 19;234(7):10535-10546. Epub 2018 Nov 19.

Department of Cardiology, Henan Provincial People's Hospital, Fuwai Central China Cardiovascular Hospital, Zhengzhou, China.

Acute myocardial infarction (AMI), as a severe consequence of coronary atherosclerotic heart disease, always contributes to the loss of myocardial cells. Mounting evidence shows that annexin protects the myocardium from ischemic injury. In this study, we examine the inhibition of annexin A3 (ANXA3) on AMI through the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. We selected rats to build an AMI model which was then assigned into different groups. The hemodynamic parameters after transfection were detected by using enzyme-linked immunosorbent assay. The effect of silencing of ANXA3 on inflammatory reaction and the PI3K/Akt signaling pathway was assessed. Rats transfected with ANXA3-short hairpin RNA had alleviated hemodynamics, inflammatory reaction, decreased infarct size, α-smooth muscle actin, Collagen I, and Collagen III as well as an increased vascular endothelial growth factor. Silencing ANAX3 would promote repair and healing of myocardial tissue by activation of the PI3K/Akt signaling pathway. Collectively, our study provides evidence that the downregulation of ANXA3 promotes the repair and healing of myocardial tissues by activating the PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1002/jcp.27717DOI Listing
July 2019