Publications by authors named "Min Yu"

1,028 Publications

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Ambient Temperature and Years of Life Lost: A National Study in China.

Innovation (N Y) 2021 Feb 16;2(1):100072. Epub 2020 Dec 16.

School of Medicine, Griffith University, Gold Coast, 4214, Australia.

Although numerous studies have investigated premature deaths attributable to temperature, effects of temperature on years of life lost (YLL) remain unclear. We estimated the relationship between temperatures and YLL, and quantified the YLL per death caused by temperature in China. We collected daily meteorological and mortality data, and calculated the daily YLL values for 364 locations (2013-2017 in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces, and 2006-2011 in other locations) in China. A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates (YLL/100,000 population), and a multivariate meta-analysis model was used to pool location-specific associations. Then, YLL per death caused by temperatures was calculated. The temperature and YLL rates consistently showed U-shaped associations. A mean of 1.02 (95% confidence interval: 0.67, 1.37) YLL per death was attributable to temperature. Cold temperature caused 0.98 YLL per death with most from moderate cold (0.84). The mean YLL per death was higher in those with cardiovascular diseases (1.14), males (1.15), younger age categories (1.31 in people aged 65-74 years), and in central China (1.34) than in those with respiratory diseases (0.47), females (0.87), older people (0.85 in people ≥75 years old), and northern China (0.64) or southern China (1.19). The mortality burden was modified by annual temperature and temperature variability, relative humidity, latitude, longitude, altitude, education attainment, and central heating use. Temperatures caused substantial YLL per death in China, which was modified by demographic and regional characteristics.
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http://dx.doi.org/10.1016/j.xinn.2020.100072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454660PMC
February 2021

Superficialization of dilated radial artery for vascular access: A case report.

J Vasc Access 2021 Sep 23:11297298211047090. Epub 2021 Sep 23.

Long Hua Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Successful hemodialysis treatment need a well functioning vascular access (VA) allowing two cannulation sites with enough blood flow have minimum adverse events. The expectations, age of the HD population are rising as well as the lack of conventional methods due to central venous exhaustion, we have to choose some complex access, including complex or tertiary vascular access mentioned in 2018 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS) and the option to abandon the venous circuit in instead of arterial system, including arterial-arterial graft and arterial superficialization. This article report a complicated case of AVF dysfunction, central venous stenosis due to central venous catheter and aortic dissection stent as well as lower extremity arteriosclerosis occlusion, using the simple method of superficialization of enlarged radial artery to maintain hemodialysis.
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http://dx.doi.org/10.1177/11297298211047090DOI Listing
September 2021

A Comparison of Preterm Birth Rate and Growth from Birth to 18 Years Old between in Vitro Fertilization and Spontaneous Conception of Twins.

Twin Res Hum Genet 2021 Sep 20:1-6. Epub 2021 Sep 20.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

The aim of the present study was to compare the rate of preterm birth (PTB) and growth from birth to 18 years between twins conceived by in vitro fertilization (IVF) and twins conceived by spontaneous conception (SC) in mainland China. The retrospective cohort study included 1164 twins resulting from IVF and 25,654 twins conceived spontaneously, of which 494 from IVF and 6338 from SC were opposite-sex twins. PTB and low birth weight (LBW), and growth, including length/height and weight, were compared between the two groups at five stages: infancy (0 year), toddler period (1-2 years), preschool (3-5 years), primary or elementary school (6-11 years), and adolescence (10-18 years). Few statistically significant differences were found for LBW and growth between the two groups after adjusting for PTB and other confounders. Twins born by IVF faced an increased risk of PTB compared with those born by SC (adjusted odds ratio [aOR] 8.21, 95% confidence interval [CI] [3.19, 21.13], p < .001 in all twins and aOR 10.12, 95% CI [2.32, 44.04], p = .002 in opposite-sex twins). Twins born by IVF experienced a similar growth at five stages (0-18 years old) when compared with those born by SC. PTB risk, however, is significantly higher for twins conceived by IVF than those conceived by SC.
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http://dx.doi.org/10.1017/thg.2021.33DOI Listing
September 2021

Cadmium-induced changes in composition and co-metabolism of glycerolipids species in wheat root: Glycerolipidomic and transcriptomic approach.

J Hazard Mater 2021 Sep 4;423(Pt B):127115. Epub 2021 Sep 4.

Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtze River), Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan 430070, China; State Environmental Protection Key Laboratory of Soil Health and Green Remediation, Wuhan 430070, China. Electronic address:

Lipids are the structural constituents of cell membranes and play crucial roles in plant adaptation to abiotic stresses. The aim of this study was to use glycerolipidomic and transcriptomic to analyze the changes in lipids metabolism induced by cadmium (Cd) exposure in wheat. The results indicated that Cd stress did not decrease the concentrations of monogalactosyldiacyglycerol (MGDG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and phosphatidic acid at 6 h, but decreased digalactosyldoacylglycerol (DGDG), MGDG, PC, phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS) and LPC concentrations in wheat root at 24 h. Although the concentrations of highly abundant glycerolipids PC and PE were decreased, the ratios of PC/PE increased thus contributing to wheat adaptation to Cd stress. Cd did not reduce the extent of total lipid unsaturation due to the unchanged concentrations of high abundance species of C36:4, C34:2, C34:3 and C36:6 at 6 h, indicative of their roles in resisting Cd stress. The correlation analysis revealed the glycerolipids species experiencing co-metabolism under Cd stress, which is driven by the activated expression of genes related to glycerolipid metabolism, desaturation and oxylipin synthesis. This study gives insights into the changes of glycerolipids induced by Cd and the roles in wheat adaptation to Cd stress.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127115DOI Listing
September 2021

Phosphoinositidies: emerging players in plant salinity stress tolerance.

Mol Plant 2021 Sep 13. Epub 2021 Sep 13.

International Research Centre for Environmental Membrane Biology, Foshan University, Foshan 528041, China. Electronic address:

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http://dx.doi.org/10.1016/j.molp.2021.09.007DOI Listing
September 2021

The Impact of Catastrophic Medical Insurance in China: A five-year patient-level panel study.

Lancet Reg Health West Pac 2021 Aug 5;13:100174. Epub 2021 Jul 5.

Stanford University, Stanford, CA.

In an effort to provide greater financial protection from the risk of large medical expenditures, China has gradually added catastrophic medical insurance (CMI) to the various basic insurance schemes. Tongxiang, a rural county in Zhejiang province, China, has had CMI since 2000 for their employee insurance scheme, and since 2014 for their resident insurance scheme. Compiling and analysing patient-level panel data over five years, we use a difference-in-difference approach to study the effect of the 2014 introduction of CMI for resident insurance beneficiaries in Tongxiang. In our study design, resident insurance beneficiaries are the treatment group, while employee insurance beneficiaries are the control group. We find that availability of CMI significantly increases medical expenditures among resident insurance beneficiaries, including for both inpatient and outpatient spending. Despite the greater financial protection, out-of-pocket expenditures increased, in part because patients accessed treatment more often at higher-level hospitals. Better financial coverage for catastrophic medical expenditures led to greater access and expenditures, not only for inpatient admissions-the category that most often leads to catastrophic expenditures-but for outpatient visits as well. These patterns of expenditure change with CMI may reflect both enhanced access to a patient's preferred site of care as well as the influence of incentives encouraging more care under fee-for-service payment. Stanford University's Freeman Spogli Institute for International Studies' Policy Implementation Lab and a Shorenstein Asia Pacific Research Center faculty research award provided funding for this project. .
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http://dx.doi.org/10.1016/j.lanwpc.2021.100174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358690PMC
August 2021

Effects of calcium dobesilate combined with categlicine and valsartan capsules on inflammation and cellular immunity in patients with diabetic nephropathy.

Minerva Surg 2021 Sep 15. Epub 2021 Sep 15.

Department of Nephrology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China -

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http://dx.doi.org/10.23736/S2724-5691.21.09075-4DOI Listing
September 2021

Overweight and Risk of Type 2 Diabetes: A Prospective Chinese Twin Study.

Diabetes Metab 2021 Sep 11:101278. Epub 2021 Sep 11.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Objectives: This study aimed to estimate the association between overweight and type 2 diabetes mellitus (T2DMM) in twins, and further to explore whether genetic and early-life environmental factors account for this association.

Methods: This study included 31,197 twin individuals from the Chinese National Twin Registry (CNTR). Generalised estimating equation (GEE) models were applied for unmatched case-control analysis. Conditional logistic regressions were used in co-twin matched case-control analysis. Logistic regressions were fitted to examine the differences in odds ratios (ORs) from the GEE models and conditional logistic regressions. Bivariate genetic model was used to explore the genetic and environmental correlation between body mass index (BMI) and T2DM.

Results: In the GEE model, overweight was associated with a higher T2DM risk (OR=2.71, 95% confidence interval (CI): 1.96∼3.73), compared with participants with normal BMI. In the multi-adjusted conditional logistic regression, the association was still significant (OR=2.60, 95% CI: 1.15∼5.87). The ORs from the unmatched and matched analyses were different (P = 0.042). Particularly, overweight could increase T2DM risk in monozygotic (MZ) twins, and the difference in ORs between the unmatched and matched designs was significant (P = 0.014). After controlling for age and sex, the positive BMI-T2DM association was partly due to a significant genetic correlation (rA= 0.31, 95% CI: 0.20∼0.41).

Conclusions: Our findings suggest that genetics and early-life environments might account for the observed overweight-T2DM association. Genetic correlation between BMI and T2DM further provides evidence for the influence of overlap genes on their association.
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http://dx.doi.org/10.1016/j.diabet.2021.101278DOI Listing
September 2021

Measuring the uptake of continuous care among people living with HIV receiving antiretroviral therapy and social determinants of the uptake of continuous care in the southwest of China: a cross-sectional study.

BMC Infect Dis 2021 Sep 11;21(1):943. Epub 2021 Sep 11.

Department of Infectious Diseases, The Third People's Hospital of Kunming City, Kunming, Yunnan, People's Republic of China.

Background: Continuous care is essential for people living with HIV. This study aimed to measure continuous care uptake and investigate the association between higher uptake of continuous care and behavioral and social factors, including HIV-acquisition risk and socioeconomic characteristics.

Methods: A hospital-based cross-sectional study was conducted from April to November 2019 in an HIV treatment center of a specialized hospital in Kunming city, China. Fourteen service indicators were used to calculate composite care scores, which were classified into three levels (low, middle, and high), using principal component analysis. The Behavioral Model for Vulnerable Populations was employed to examine predisposing, enabling, and need factors associated with composite care scores among people living with HIV.

Results: A total of 702 participants living with HIV aged ≥ 18 years (median age: 41.0 years, 69.4% male) who had been on ART for 1-5 years were recruited. Based on ordinal logistic regression modeling, predisposing factors: being employed (adjusted odds ratio (AOR): 1.54, 95% confidence interval (CI): 1.13-2.11), heterosexuals (AOR: 1.58, 95% CI: 1.11-2.25) and men who have sex with men (AOR: 2.05, 95% CI: 1.39-3.02) and enabling factors: Urban Employee Basic Medical Insurance (AOR: 1.90, 95% CI: 1.03-3.54), middle socioeconomic status (SES) (AOR: 1.42, 95% CI: 1.01-2.01), were positively associated with the higher level of continuous care uptake, compared to the unemployed, people who inject drugs, those with no medical insurance and low SES, respectively.

Conclusion: There were large differences in continuous care uptake among people living with HIV. HIV-acquisition risk categories and socioeconomic factors were significant determinants of uptake of continuous care. Our findings could inform the development of evidence-based strategies that promote equitable healthcare for all people living with HIV.
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http://dx.doi.org/10.1186/s12879-021-06644-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436458PMC
September 2021

Characteristics and Role of Neutrophil Extracellular Traps in Asthma.

Inflammation 2021 Sep 4. Epub 2021 Sep 4.

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Asthma is a common chronic respiratory disease that affects millions of people worldwide. The incidence of asthma has continued to increase every year. Bronchial asthma involves a variety of cells, including airway inflammatory cells, structural cells, and neutrophils, which have gained more attention because they secrete substances that play an important role in the occurrence and development of asthma. Neutrophil extracellular traps (NETs) are mesh-like structures composed of DNA, histones, and non-histone molecules that can be secreted from neutrophils. NETs can enrich anti-bacterial substances and limit pathogen migration, thus having a protective effect in case of inflammation. However, despite of their anti-inflammatory properties, NETs have been shown to trigger allergic asthma and worsen asthma progression. Here, we provide a systematic review of the roles of NETs in asthma.
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http://dx.doi.org/10.1007/s10753-021-01526-8DOI Listing
September 2021

The prevalence and clinical features of pulmonary embolism in patients with AE-COPD: A meta-analysis and systematic review.

PLoS One 2021 2;16(9):e0256480. Epub 2021 Sep 2.

Department of Respiratory, First People's Hospital of Yuhang, Hangzhou, China.

Background: The prevalence of pulmonary embolism (PE) in the acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is highly controversial. We conducted a systematic review and meta-analysis to summarize the epidemiology and characteristics of PE with AE-COPD for current studies.

Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases for studies published prior to October 21, 2020. Pooled proportions with 95% confidence intervals (95% CIs) were calculated using a random effects model. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals were used as effect measures for dichotomous and continuous variables, respectively.

Results: A total of 17 studies involving 3170 patients were included. The prevalence of PE and deep vein thrombosis (DVT) in AE-COPD patients was 17.2% (95% CI: 13.4%-21.3%) and 7.1% (95% CI: 3.7%-11.4%%), respectively. Dyspnea (OR = 6.77, 95% CI: 1.97-23.22), pleuritic chest pain (OR = 3.25, 95% CI: 2.06-5.12), lower limb asymmetry or edema (OR = 2.46, 95% CI:1.51-4.00), higher heart rates (MD = 20.51, 95% CI: 4.95-36.08), longer hospital stays (MD = 3.66, 95% CI: 3.01-4.31) were associated with the PE in the AE-COPD patients. Levels of D-dimer (MD = 1.51, 95% CI: 0.80-2.23), WBC counts (MD = 1.42, 95% CI: 0.14-2.70) were significantly higher and levels of PaO2 was lower (MD = -17.20, 95% CI: -33.94- -0.45, P<0.05) in the AE-COPD with PE group. The AE-COPD with PE group had increased risk of fatal outcome than the AE-COPD group (OR = 2.23, 95% CI: 1.43-3.50).

Conclusions: The prevalence of PE during AE-COPD varies considerably among the studies. AE-COPD patients with PE experienced an increased risk of death, especially among the ICU patients. Understanding the potential risk factors for PE may help clinicians identify AE-COPD patients at increased risk of PE.

Prospero Registration Number: CRD42021226568.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256480PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412363PMC
September 2021

Strong Emergence in Biological Systems: Is It Open to Mathematical Reasoning?

Acta Biotheor 2021 Aug 31. Epub 2021 Aug 31.

International Research Centre for Environmental Membrane Biology, Foshan University, Foshan, People's Republic of China.

Complex, multigenic biological traits are shaped by the emergent interaction of proteins being the main functional units at the molecular scale. Based on a phenomenological approach, algorithms for quantifying two different aspects of emergence were introduced (Wegner and Hao in Progr Biophys Mol Biol 161:54-61, 2021) describing: (i) pairwise reciprocal interactions of proteins mutually modifying their contribution to a complex trait (denoted as weak emergence), and (ii) formation of a new, complex trait by a set of n 'constitutive' proteins at concentrations exceeding individual threshold values (strong emergence). The latter algorithm is modified here to take account of protein redundancy with respect to a complex trait ('full redundancy'). Irreducibility is considered a necessary and sufficient criterion for strong biological emergence; if one constitutive protein is missing, or its concentration drops below the threshold the trait is lost. A definition based on 'unpredictability' is dismissed, because this criterion is irrelevant for the evolution of a complex trait, and apparent unpredictability may rather reflect our basic deficits in understanding unless we can provide an unequivocal proof for it. The phenomenological approach advocated here allows to identify hidden rules according to which strongly emergent traits may be organized. This is of high value for understanding the evolution of complex traits which seems to require the saltational advent of all constitutive proteins 'in one turn' to arrive at a functional trait providing for an improved fitness of the organism. Rather than being a purely random process, it may be guided by fundamental structural principles.
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http://dx.doi.org/10.1007/s10441-021-09423-1DOI Listing
August 2021

Association of Red Blood Cell Distribution Width Levels with Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD).

Dis Markers 2021 6;2021:5536360. Epub 2021 Aug 6.

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, No. 321 Zhongshan Road, Nanjing, 210008 Jiangsu, China.

Objective: The aim of this study was to evaluate the diagnostic and prognostic value of red blood cell distribution width (RDW) in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD).

Methods: We retrospectively reviewed 213 CTD-ILD patients and 97 CTD patients without ILD from February 2017 to February 2020. Hospital and office records were used as data sources. CTD-ILD patients were followed up.

Results: Patients with CTD-ILD had significantly higher RDW than those with CTD without ILD ( < 0.001). The area under the receiver operating characteristic curve (AUROC) of RDW for discriminating CTD-ILD from CTD without ILD was 0.64 (95% CI: 0.57-0.70, < 0.001). The cutoff value of RDW for discriminating CTD-ILD from CTD without ILD was 13.95% with their corresponding specificity (55.9%) and sensitivity (70.1%). Correlation analyses showed that the increased RDW was significantly correlated with decreased DLCO%predicted ( = -0.211, = 0.002). Cox multiple regression analysis indicated that RDW (HR = 1.495, < 0.001) was an independent factor in the survival of CTD-ILD. The best cutoff value of RDW to predict the survival of patients with CTD-ILD was 14.05% (AUC = 0.78, 95% CI: 0.72-0.84, < 0.001). The log-rank test showed a significant difference in survival between the two groups (RDW > 14.05% and RDW < 14.05%).

Conclusion: RDW was higher in CTD-ILD patients and had a negative correlation with DLCO%predicted. RDW may be an important serum biomarker for severity and prognosis of patients with CTD-ILD.
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http://dx.doi.org/10.1155/2021/5536360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397563PMC
August 2021

Revealing the Role of the Calcineurin B-Like Protein-Interacting Protein Kinase 9 (CIPK9) in Rice Adaptive Responses to Salinity, Osmotic Stress, and K Deficiency.

Plants (Basel) 2021 Jul 23;10(8). Epub 2021 Jul 23.

International Research Centre for Environmental Membrane Biology, Foshan University, Foshan 528000, China.

In plants, calcineurin B-like (CBL) proteins and their interacting protein kinases (CIPK) form functional complexes that transduce downstream signals to membrane effectors assisting in their adaptation to adverse environmental conditions. This study addresses the issue of the physiological role of CIPK9 in adaptive responses to salinity, osmotic stress, and K deficiency in rice plants. Whole-plant physiological studies revealed that rice mutant lacks a functional CIPK9 gene and displayed a mildly stronger phenotype, both under saline and osmotic stress conditions. The reported difference was attributed to the ability of to maintain significantly higher stomatal conductance (thus, a greater carbon gain). plants contained much less K in their tissues, implying the role of CIPK9 in K acquisition and homeostasis in rice. roots also showed hypersensitivity to ROS under conditions of low K availability suggesting an important role of HO signalling as a component of plant adaptive responses to a low-K environment. The likely mechanistic basis of above physiological responses is discussed.
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http://dx.doi.org/10.3390/plants10081513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399971PMC
July 2021

Development and validation of a population-based model for predicting the regional lymph node metastasis in adolescent differentiated thyroid carcinoma.

Oral Oncol 2021 Oct 24;121:105507. Epub 2021 Aug 24.

Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, No.74, Linjiang Rd, Yuzhong Dist, Chongqing 404100, PR China. Electronic address:

Background: Adolescent differentiated thyroid carcinoma (DTC) is a rare type of thyroid cancer that represents a special entity of all endocrine-related cancer. This study aims to establish the first nomogram for predicting the regional (central and lateral) lymph node metastasis (LNM) in the adolescent population for better surgical management.

Method: We retrospectively reviewed the clinicopathology characteristics of adolescent patients with DTC in the Surveillance, Epidemiology, and End Results database between 2010 and 2015.

Results: A total of 1,930 adolescent patients between the ages of 10 and 24 years from the SEER database were enrolled in this study. Six predictive factors including age, race, histology, multifocality, extrathyroidal invasion (EI) and tumor size were identified to be significantly associated with the regional LNM via univariate and multivariate logistic regression analyses. These indicators were used to construct a nomogram for predicting the regional LNM in adolescent patients with DTC. Moreover, a satisfied predictive ability of the model was determined with a C-index of 0.794, supported by an internal validation group with a C-index of 0.776. The Decision Curve Analysis and calibration curve further conducted a great agreement in our model.

Conclusion: The first predictive model containing multiple factors has been successfully established with good discrimination for predicting the regional LNM in adolescent patients with DTC. This nomogram could effectively help surgeons to make better individualized surgical decision intraoperatively, especially in terms of whether cervical lymph node dissection (LND) is warranted.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105507DOI Listing
October 2021

Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer.

Chem Sci 2021 Aug 6;12(31):10501-10505. Epub 2021 Jul 6.

Hefei National Laboratory for Physical Sciences at the Microscale, Department of Chemistry, Center for Excellence in Molecular Synthesis of CAS, University of Science and Technology of China Hefei 230026 P. R. China

Fe, Co, and Mn hydride-initiated radical olefin additions have enjoyed great success in modern synthesis, yet the extension of other hydrogen radicalophiles instead of olefins remains largely elusive. Herein, we report an efficient Fe-catalyzed intramolecular isonitrile-olefin coupling reaction delivering 3-substituted indoles, in which isonitrile was firstly applied as the hydrogen atom acceptor in the radical generation step by MHAT. The protocol features low catalyst loading, mild reaction conditions, and excellent functional group tolerance.
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http://dx.doi.org/10.1039/d1sc03058bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356753PMC
August 2021

Arsenic transport and interaction with plant metabolism: Clues for improving agricultural productivity and food safety.

Environ Pollut 2021 Aug 17;290:117987. Epub 2021 Aug 17.

International Research Centre for Environmental Membrane Biology, Foshan University, Foshan, 528000, China; Tasmanian Institute of Agriculture, University of Tasmania, Hobart, Tas7001, Australia. Electronic address:

Arsenic (As) is a ubiquitous metalloid that is highly toxic to all living organisms. When grown in As-contaminated soils, plants may accumulate significant amounts of As in the grains or edible shoot parts which then enter a food chain. Plant growth and development per se are also both affected by arsenic. These effects are traditionally attributed to As-induced accumulation of reactive oxygen species (ROS) and a consequent lipid peroxidation and damage to cellular membranes. However, this view is oversimplified, as As exposure have a major impact on many metabolic processes in plants, including availability of essential nutrients, photosynthesis, carbohydrate metabolism, lipid metabolism, protein metabolism, and sulfur metabolism. This review is aimed to fill this gap in the knowledge. In addition, the molecular basis of arsenic uptake and transport in plants and prospects of creating low As-accumulating crop species, for both agricultural productivity and food safety, are discussed.
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http://dx.doi.org/10.1016/j.envpol.2021.117987DOI Listing
August 2021

Modeling the effects of EMT-immune dynamics on carcinoma disease progression.

Commun Biol 2021 08 18;4(1):983. Epub 2021 Aug 18.

Department of Mathematics, University of California, Irvine, CA, USA.

During progression from carcinoma in situ to an invasive tumor, the immune system is engaged in complex sets of interactions with various tumor cells. Tumor cell plasticity alters disease trajectories via epithelial-to-mesenchymal transition (EMT). Several of the same pathways that regulate EMT are involved in tumor-immune interactions, yet little is known about the mechanisms and consequences of crosstalk between these regulatory processes. Here we introduce a multiscale evolutionary model to describe tumor-immune-EMT interactions and their impact on epithelial cancer progression from in situ to invasive disease. Through simulation of patient cohorts in silico, the model predicts that a controllable region maximizes invasion-free survival. This controllable region depends on properties of the mesenchymal tumor cell phenotype: its growth rate and its immune-evasiveness. In light of the model predictions, we analyze EMT-inflammation-associated data from The Cancer Genome Atlas, and find that association with EMT worsens invasion-free survival probabilities. This result supports the predictions of the model, and leads to the identification of genes that influence outcomes in bladder and uterine cancer, including FGF pathway members. These results suggest new means to delay disease progression, and demonstrate the importance of studying cancer-immune interactions in light of EMT.
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http://dx.doi.org/10.1038/s42003-021-02499-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373868PMC
August 2021

Ionomics analysis provides new insights into the co-enrichment of cadmium and zinc in wheat grains.

Ecotoxicol Environ Saf 2021 Oct 10;223:112623. Epub 2021 Aug 10.

Key Laboratory of Arable Land Conservation (Middle and Lower Reaches of Yangtze River), Ministry of Agriculture, Micro-elements Research Center, College of Resource and Environment, Huazhong Agricultural University, Wuhan 430070, China; State Environmental Protection Key Laboratory of Soil Health and Green Remediation, Wuhan 430070, China. Electronic address:

Cadmium (Cd) is present in many soils and, when enter a food chain, represents a major health threat to humans. The existent large variation in grain Cd content amongst wheat genotypes opens prospects for genetic improvement for reduced Cd uptake in this species. However, selecting low-Cd-accumulating varieties comes with a possible caveat of affecting uptake other essential nutrients. In this work, we screened 134 wheat varieties in 3 various field studies and selected 15 high- and 15 low-Cd accumulating varieties in grains for ionomics analysis. Our results showed that high-Cd accumulating varieties also possessed an ability to accumulate mineral elements of calcium, magnesium, manganese, iron and zinc, while varieties with low Cd content were deficient in many essential nutrients and, especially, zinc (Zn). The above data was confirmed in an independent trail involving another 97 wheat varieties. Thus, selecting plants for high Zn accumulation (as a part of biofortification programs) resulted in an inadvertent increase in accumulation of the toxic Cd in wheat. Vice versa, selecting low Cd-accumulating varieties comes with a danger of reducing their Zn content, with major consequences to food quality and human health. We suggest that the above conundrum can be resolved by understanding the structure-function relations of various transporters isoforms involved in Zn and Cd transport and issue-specific mode of their operation, via cell-based phenotyping followed by molecular breeding.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112623DOI Listing
October 2021

Successful treatment of refractory retroperitoneal Epstein-Barr virus-positive diffuse large B-cell lymphoma with secondary hemophagocytic syndrome by sequential combination regimen of PD-1 blockade and chimeric antigen receptor T cells: a case report.

Anticancer Drugs 2021 Aug 11. Epub 2021 Aug 11.

Department of Hematology, The First Affiliated Hospital of Nanchang University Department of Lymphomatous diseases, Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.

Epstein-Barr virus (EBV) is convincingly contributed to the development of several types of lymphomas such as NK/T cell lymphoma, Burkitt lymphoma, plasmablastic lymphoma, and diffuse large B cell lymphoma (DLBCL). Herein, we reported an atypical case of EBV-positive DLBCL in an immunocompetent young male patient who presented with epistaxis due to hypergammaglobulinemia. 2-Deoxy-2-[fluorine-8] fluoro-D-glucose PET/computed tomography showed multiple highly metabolic retroperitoneal tissue masses with the involvement of bilateral adrenal gland. Ultrasonography-guided biopsy revealed a significant number of lymphocytes and plasma-like cells that are immunopositive for plasma-cell markers and partly positive for pan-B cell markers. The Ki-67 proliferation index was 20%. The extensive distribution of EBV-encoded small RNAs was confirmed by in-situ hybridization. Due to atypical/overlapping pathological characteristics, it was initially misdiagnosed as extramedullary plasmacytoma and treated with two cycles of bortezomib, lenalidomide, and dexamethasone. Disease progression occurred and pathology consultation for the retroperitoneal biopsies modified the diagnosis to EBV-positive DLBCL with plasma cell differentiation. The treatment was adjusted to etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab, and lenalidomide (R2-EPOCH), but no response was observed after three cycles of treatment and he developed hemophagocytic syndrome during treatment. A monotherapy of anti-programmed cell death-1 (PD-1) treatment with tiririzumab was administered, successfully controlling hemophagocytic syndrome and EBV infection. The response assessment was partial for EBV-positive DLBCL, subsequent anti-CD19 chimeric antigen receptor-T (CAR-T) cell therapy resulted in complete remission including lumps, immunoglobulins, and negative EBV-DNA 1.5 months later. The present case study proved the possibility of PD-1 blockade in controlling EBV infection and associated hemophagocytic syndrome and offered an example of the combination of CAR-T therapy and PD-1 blockade for refractory EBV-positive DLBCL in clinic.
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http://dx.doi.org/10.1097/CAD.0000000000001187DOI Listing
August 2021

PPOS Protocol Effectively Improves the IVF Outcome Without Increasing the Recurrence Rate in Early Endometrioid Endometrial Cancer and Atypical Endometrial Hyperplasia Patients After Fertility Preserving Treatment.

Front Med (Lausanne) 2021 27;8:581927. Epub 2021 Jul 27.

Shanghai JIAI Genetics and IVF Institute, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

To investigate the effectiveness and recurrence risk of different ovulation stimulation protocols in early-stage endometrioid endometrial cancer (EEC) and atypical endometrial hyperplasia (AEH) patients after successful fertility preserving treatment. A retrospective review of clinical files between June 2012 and July 2018. University hospital. Ninety seven women (74 AEH and 23 early-stage EEC patients) underwent fertilization (IVF) and frozen-thawed embryo transfer (FET) after successful fertility preserving treatment. All patients received megestrol acetate which was initiated immediately after AEH or EEC diagnosis by hysteroscopy. Fertility treatment was initiated after confirmation of complete response by two consecutive hysteroscopic evaluations and endometrium biopsy in a 3-month interval. Women with tubal factors underwent IVF treatment directly. Women who failed to conceive spontaneously within 12 months or after other infertility treatments like ovulation induction for 6 consecutive months or 2 consecutive artificial insemination failures were also offered IVF treatment. The clinical and laboratory embryo data, clinical pregnancy outcomes and endometrial disease recurrence rates. Compared with the standard regimen group, the good-quality embryo rate was higher in progestin primed ovarian stimulation (PPOS) regimen group ( = 0.034). Univariate analysis showed significant differences in age ( = 0.033), treatment time of endometrial lesions ( < 0.001), and duration of Gn treatment ( = 0.018) between the recurrent and non-recurrent groups. In the adjusted model of multivariate logistic regression analysis, the age ( = 0.014) at ovulation induction and treatment time of endometrial lesions ( < 0.001) were significantly correlated with the recurrence of endometrial disease. The PPOS protocol is a feasible and safe strategy to stimulate ovulation during IVF after fertility preservation therapy, and the age at ovulation induction and treatment time of endometrial lesions are two stable predictors of recurrence in endometrial diseases.
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http://dx.doi.org/10.3389/fmed.2021.581927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354380PMC
July 2021

Preoperatively Predicting the Central Lymph Node Metastasis for Papillary Thyroid Cancer Patients With Hashimoto's Thyroiditis.

Front Endocrinol (Lausanne) 2021 22;12:713475. Epub 2021 Jul 22.

Department of Breast and Thyroid Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The preoperative distinguishment of lymph nodes with reactive hyperplasia or tumor metastasis plays a pivotal role in guiding the surgical extension for papillary thyroid carcinoma (PTC) with Hashimoto's thyroiditis (HT), especially in terms of the central lymph node (CLN) dissection. We aim to identify the preparative risk factors for CLN metastasis in PTC patients concurrent with HT.

Materials And Methods: We retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and thyroid function of consecutive PTC patients with HT in our medical center between Jan 2019 and Apr 2021. The Chi-square and Fisher's exact tests were used for comparison of qualitative variables among patients with or without CLN metastasis. Univariate and multivariate logistic regression analyses were used to determine the risk factors for CLN metastasis. The nomogram was constructed and further evaluated by two cohorts produced by 1,000 resampling bootstrap analysis.

Results: A total of 98 in 214 (45.8%) PTC patients were identified with CLN metastasis. In multivariate analysis, four variables including high serum thyroglobulin antibody (TgAb) level (>1,150 IU/ml), lower tumor location, irregular margin of CLN, and micro-calcification in the CLN were determined to be significantly associated with the CLN metastasis in PTC patients with HT. An individualized nomogram was consequently established with a favorable C-index of 0.815 and verified two internal validation cohorts.

Conclusions: Our results indicated that preoperatively sonographic characteristics of the tumor and lymph node condition combined with serum TgAb level can significantly predict the CLN in PTC patients with HT and the novel nomogram may further help surgeons to manage the CLN in this subpopulation.
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http://dx.doi.org/10.3389/fendo.2021.713475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339927PMC
July 2021

Quercetin improves the adipose inflammatory response and insulin signaling to reduce "real-world" particulate matter-induced insulin resistance.

Environ Sci Pollut Res Int 2021 Aug 7. Epub 2021 Aug 7.

Jiangsu Vocational College of Medicine, Yancheng, Jiangsu Province, People's Republic of China.

Numerous epidemiological data and experimental studies support a strong link between fine particulate matter (less than 2.5 mm in aerodynamic diameter, PM) exposure and the development of insulin resistance/type 2 diabetes mellitus (T2DM). Quercetin (Que), a flavonoid compound with anti-inflammatory effects, has been confirmed to improve glucose metabolic disorders in rodents and humans. In this study, we investigated the underlying mechanisms of particulate matter (PM)-induced glucose metabolic disorder and subsequently examined the protective effect and mechanism of quercetin supplementation. Male C57BL/6 mice in the control group and PM group were exposed to ambient filtered air (FA) or PM (6 h/day, 7 days/week) for 18 weeks. Mice in the Que group were exposed to PM for 18 weeks and administered Que (50 or 100 mg/kg bw). Glucose tolerance, insulin sensitivity, and systemic and visceral white adipose tissue (vWAT) inflammatory responses were measured. The expression of proteins involved in insulin signal transduction in vWAT was assessed. Chronic PM exposure caused systemic and vWAT inflammation characterized by an increase in serum IL-6 and TNF-α levels and increased vWAT macrophage filtration, triggering NLRP3 inflammasome activation, impairing the classic glucose metabolism signal in vWAT, and inducing whole-body insulin resistance. Moreover, Que administration significantly alleviated systemic and vWAT inflammation, abolished NLRP3 inflammasome activation, and improved signaling abnormalities characteristic of insulin resistance in vWAT and adipocytes. Based on these findings, chronic PM exposure activated the NLRP3 inflammasome and subsequently caused systemic and WAT inflammation and impaired insulin signaling in vWAT and adipocytes. Most importantly, Que administration inhibited NLRP3 inflammasome-mediated inflammation and insulin signaling in vWAT to improve these adverse effects.
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http://dx.doi.org/10.1007/s11356-021-15829-8DOI Listing
August 2021

Age-specific disparity in life loss per death attributable to ambient temperature: A nationwide time-series study in China.

Environ Res 2021 Aug 4;203:111834. Epub 2021 Aug 4.

School of Public Health, Southern Medical University, Guangzhou, China. Electronic address:

Age-specific discrepancy of mortality burden attributed to temperature, measured as years of life lost (YLL), has been rarely investigated. We investigated age-specific temperature-YLL rates (per 100,000) relationships and quantified YLL per death caused by non-optimal temperature in China. We collected daily meteorological data, population data and daily death counts from 364 locations in China during 2006-2017. YLL was divided into three age groups (0-64 years, 65-74 years, and ≥75 years). A distributed lag non-linear model was first employed to estimate the associations of temperature with age-specific YLL rates in each location. Then we pooled the associations using a multivariate meta-analysis. Finally, we calculated age-specific average YLL per death caused by temperature by cause of death and region. We observed greater effects of cold and hot temperature on YLL rates for the elderly compared with the young population by region or cause of death. However, YLL per death due to non-optimal temperature for different regions or causes of death decreased with age, with 2.0 (95 % CI:1.5, 2.5), 1.2 (1.1, 1.4) and 1.0 years (0.9, 1.2) life loss per death for populations aged 0-64 years, 65-74 years and over 75 years, respectively. Most life loss per death results from moderate temperature, especially moderate cold for all age groups. The effect of non-optimal temperature on YLL rates is smaller for younger populations than older ones, while the temperature-related life loss per death was more prominent for younger populations.
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http://dx.doi.org/10.1016/j.envres.2021.111834DOI Listing
August 2021

Development of bispecific anti-c-Met/PD-1 diabodies for the treatment of solid tumors and the effect of c-Met binding affinity on efficacy.

Oncoimmunology 2021 21;10(1):1914954. Epub 2021 Jul 21.

Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education and Department of Biochemistry and Molecular Biology, School of Basic Medicine Science, Fudan University, Shanghai, China.

Although the blockade of the programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has become a promising treatment strategy for several types of cancers, the constitutive activation of c-Met in tumors may cause a low overall response rate to PD-1 inhibitors. Increasing evidence indicates that the dual inhibition of c-Met and PD-1 could improve the efficacy of anti-PD-1/PD-L1 monoclonal antibodies for tumor immunotherapy. In this study, we developed two bispecific single-chain diabodies targeting c-Met and PD-1 for the treatment of solid tumors based on protein homology modeling, and we identified that the binding affinity of diabody-mp to c-Met was 50-folds higher than that of diabody-pm. The results of studies revealed that both diabodies suppressed HGF-induced proliferation, migration, and invasion of tumor cells, inhibiting the activation of c-Met signaling by antagonizing HGF binding to c-Met. Moreover, they promoted T cell activation by blocking the PD-1 pathway, mediating tumor cellular cytotoxicity through T cell engagement. studies with mice models demonstrated that diabody-mp exhibited higher therapeutic efficacy than other structural antibodies, greatly enhancing the survival of c-Met-positive tumor-bearing mice compared to single or combined c-Met and PD-1 blockade therapy. Furthermore, diabody-mp, which had a higher c-Met binding affinity, showed better anti-tumoral activity than diabody-pm, which had a lower c-Met binding affinity. In conclusion, bispecific anti-PD-1/c-Met diabody-mp, with high c-Met-associated affinity, inhibited tumor growth by activating T cells, suggesting its therapeutic potential for c-Met-positive solid tumors.
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http://dx.doi.org/10.1080/2162402X.2021.1914954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296967PMC
July 2021

Increased levels of serum interleukin-10 are associated with poor outcome in adult hemophagocytic lymphohistiocytosis patients.

Orphanet J Rare Dis 2021 Aug 4;16(1):347. Epub 2021 Aug 4.

Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.

Background: Interleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients.

Methods: This single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits.

Results: Serum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r =  - 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P < 0.001). Univariate analysis indicated that hemoglobin < 8.2 g/dL, platelets < 40 × 10/L, lactate dehydrogenase ≥ 700 IU/L, albumin < 28 g/L, post-treatment ferritin > 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064-8.090, P < 0.001; HR 3.814, 95% CI 2.042-7.126, P < 0.001, respectively).

Conclusions: Our results suggest that higher serum IL-10 levels might be a prognostic marker in adult HLH patients.
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http://dx.doi.org/10.1186/s13023-021-01973-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336343PMC
August 2021

Factors related to age at natural menopause in China: results from the China Kadoorie Biobank.

Menopause 2021 Aug 2. Epub 2021 Aug 2.

Department of Non-Communicable Disease Control and Prevention, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, China Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK Chinese Academy of Medical Sciences, Dong Cheng District, Beijing, China Department of Epidemiology, School of Public Health, Peking University Health Science Center, Haidian District, Beijing, China School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, China.

Objectives: The aim of this study was to investigate the potentially modifiable factors affecting age at natural menopause (ANM) in Chinese women.

Methods: We used cross-sectional data from the China Kadoorie Biobank study which that recruited 0.5 million (0.3 million women) Chinese adults aged 30 to 79 from 2004 to 2008. Multinomial logistic regression models were used to examine the relationships between ANM and various factors recorded at baseline.

Results: Among 87,349 postmenopausal women, the mean ANM (SD) was 48.7 (4.3) years. Older age, being a housewife, earlier menarche, and passive smoking were associated with both premature menopause (PM, ie, ANM <40 years) and early menopause (EM, ie, ANM between 40 and 44 years). A higher odds for EM was observed in women who were widowed (odds ratio: 1.10, 95% confidence interval: 1.04-1.16), had spontaneous abortions (1.33 [1.05-1.69]), current regular smoking (1.19 [1.07-1.37]), and frequent spicy food intake (1.11 [1.05-1.08]). Higher socioeconomic status; later first birth; more live births and induced abortions; longer breastfeeding; tea drinking, as well as intakes of meat, fruits, dairy, and soybean products; and increased body mass index gain were inversely associated with PM and/or EM. In contrast, women who had more pregnancies, occasional alcohol drinking, higher levels of physical activity or body mass index, vitamin intake, and hypertension were more likely to have a later age at menopause (LM, ie, ANM ≥53 years).

Conclusions: This large epidemiological study found a wide range of sociodemographic, lifestyle, dietary, and reproductive factors related to PM, EM, and LM in Chinese women.
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http://dx.doi.org/10.1097/GME.0000000000001829DOI Listing
August 2021

miR221 regulates cell migration by targeting annexin a1 expression in human mesothelial MeT-5A cells neoplastic-like transformed by multi-walled carbon nanotube.

Genes Environ 2021 Aug 2;43(1):34. Epub 2021 Aug 2.

Hangzhou Normal University, School of Public Health, Hangzhou, 310036, China.

Background: Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 μg/cm for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT.

Results: After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration.

Conclusions: Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells.
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http://dx.doi.org/10.1186/s41021-021-00209-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327461PMC
August 2021

Genome wide profiling of miRNAs relevant to the DNA damage response induced by hexavalent chromium exposure (DDR-related miRNAs in response to Cr (VI) exposure).

Environ Int 2021 Jul 28;157:106782. Epub 2021 Jul 28.

School of Public Health (Institute of Occupational Diseases), Hangzhou Medical College (Zhejiang Academy of Medical Sciences), Hangzhou, Zhejiang, China. Electronic address:

Aim: We aimed to explore the expression of miRNAs and their potential roles in the DNA damage response (DDR) induced by Cr (VI) exposure in human B lymphoblast cells (HMy2.CIR cells) and in a population of Cr (VI)-exposed humans.

Methods: Differentially expressed miRNAs were found by a combination of miRNA sequencing and RT-qPCR validation in HMy2.CIR cells treated with KCrO. Differentially expressed miRNAs related to DDR were selected for functional study. The expression levels of differential miRNAs were also investigated in chromate workers.

Results: A total of 214 differentially expressed miRNAs were identified by sequencing, and the expression of 5 miRNAs among 25 associated with DDR was found to be consistent between sequencing and validation studies.Functional studies showed that miR-148a-3p, miR-21-5p, and miR-424-3p might be related to Cr (VI)-induced cell apoptosis, and miR-221-3p might participate in Cr (VI)-induced DDR. We also found that the expression of miR-21-5p and miR-424-3p was upregulated in chromate workers.

Conclusions: Cr (VI) exposure could significantly impact miRNAs expression in vitro and in chromate workers. Functional studies showed that miR-148a-3p, miR-21-5p and miR-221-3p might take a crucial role in the cellular DDR induced by Cr (VI) exposure.
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http://dx.doi.org/10.1016/j.envint.2021.106782DOI Listing
July 2021

Tumor-derived exosomal BCYRN1 activates WNT5A/VEGF-C/VEGFR3 feedforward loop to drive lymphatic metastasis of bladder cancer.

Clin Transl Med 2021 Jul;11(7):e497

Department of Urology, Sun Yat-sen Memorial Hospital, Guangzhou, Guangdong, P. R. China.

Background: Patients with lymph node (LN) metastatic bladder cancer (BCa) present with extremely poor prognosis. BCa-derived exosomes function as crucial bioactive cargo carriers to mediate the signal transduction in tumor microenvironment triggering tumor metastasis. However, the mechanisms underlying exosome-mediated LN metastasis in BCa are unclear.

Methods: We conducted the high-throughput sequencing to explore the expression profile of long noncoding RNA (lncRNA) in urinary exosomes (urinary-EXO) from patients with BCa and further evaluated the clinical relevance of exosomal lncRNA BCYRN1 in a larger 210-case cohort. The functional role of exosomal BCYRN1 was evaluated through the migration and tube formation assays in vitro and the footpad-popliteal LN metastasis model in vivo. RNA pull-down assays, luciferase assays, and actinomycin assays were conducted to detect the regulatory mechanism of exosomal BCYRN1.

Results: LncRNA BCYRN1 was substantially upregulated in urinary-EXO from patients with BCa, and associated with the LN metastasis of BCa. We demonstrated that exosomal BCYRN1 markedly promoted tube formation and migration of human lymphatic endothelial cells (HLECs) in vitro and lymphangiogenesis and LN metastasis of BCa in vivo. Mechanistically, BCYRN1 epigenetically upregulated WNT5A expression by inducing hnRNPA1-associated H3K4 trimethylation in WNT5A promoter, which activated Wnt/β-catenin signaling to facilitate the secretion of VEGF-C in BCa. Moreover, exosomal BCYRN1 was transmitted to HLECs to stabilize the VEGFR3 mRNA and thus formed an hnRNPA1/WNT5A/VEGFR3 feedforward regulatory loop, ultimately promoting the lymphatic metastasis of BCa. Importantly, blocking VEGFR3 with specific inhibitor, SAR131675 significantly impaired exosomal BCYRN1-induced the LN metastasis in vivo. Clinically, exosomal BCYRN1 was positively associated with the shorter survival of BCa patients and identified as a poor prognostic factor of patients.

Conclusion: Our results uncover a novel mechanism by which exosomal BCYRN1 synergistically enhances VEGF-C/VEGFR3 signaling-induced lymphatic metastasis of BCa, indicating that BCYRN1 may serve as an encouraging therapeutic target for patients with BCa.
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http://dx.doi.org/10.1002/ctm2.497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288020PMC
July 2021
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