Publications by authors named "Xuejun Li"

291 Publications

Systematic Analysis of 4-gene Prognostic Signature in Patients with Diffuse Gliomas Based on Gene Expression Profiles.

J Cancer 2021 19;12(14):4295-4306. Epub 2021 May 19.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.

Diffuse gliomas are a group of diseases that contain different degrees of malignancy and complex heterogeneity. Previous studies proposed biomarkers for certain grades of gliomas, but few of them have conducted a systematic analysis of different grades to search for molecular markers. WGCNA was used to find significant genes associated with malignant progression of diffuse glioma in TCGA glioma sequencing expression data and the GEO expression profile-merge meta dataset. Lasso regression was used for potential model building and the best model was selected by CPE, IDI, and C_index. Risk score model was used to evaluate the gene signature prognostic power. Multi-omics data, including CNV, methylation, clinical traits, and mutation, were used for model evaluation. We found out 67 genes significantly associated with malignant progression of diffuse glioma by WGCNA. Next, we established a new 4 gene molecular marker (KDELR2, EMP3, TIMP1, and TAGLN2). Multivariate cox analysis identified the risk score of the 4 genes as an independent predictor of prognosis in patients with diffuse gliomas, and its predictive power was independent of the histopathological grades of glioma. Further, we had confirmed in five independent test datasets and the risk score remained good predictive power. The combination of the prognosis model with specific molecular characteristics possessed a better predictive power. Furthermore, we divided the low-risk group into three subtypes: LowRisk_IDH1, LowRisk_IDH1/ATRX, and LowRisk_IDH1/ATRX by combining IDH1 mutation with ATRX mutation, which possessed obvious survival difference. In further analysis, we found that the 4 gene prognosis model possessed multi-omics features. We established a malignant-related 4-gene molecular marker by glioma expression profile data from multiple microarrays and sequencing data. The four markers had good predictive power on the overall survival of glioma patients and were associated with gliomas' clinical and genetic backgrounds, including clinical features, gene mutation, methylation, CNV, signal pathways.
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http://dx.doi.org/10.7150/jca.54565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176424PMC
May 2021

A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Clin Immunol 2021 May 8;228:108751. Epub 2021 May 8.

Department of Pharmacology and Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.
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http://dx.doi.org/10.1016/j.clim.2021.108751DOI Listing
May 2021

Comparative effectiveness of team-based care with a clinical decision support system versus team-based care alone on cardiovascular risk reduction among patients with diabetes: Rationale and design of the D4C trial.

Am Heart J 2021 May 4;238:45-58. Epub 2021 May 4.

Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, and Xiamen Clinical Medical Center for Endocrine and Metabolic Diseases, the First Affiliated Hospital of Xiamen University, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China.. Electronic address:

Background: Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries (LMICs). Uncontrolled hyperglycemia, hypertension, and dyslipidemia major risk factors for all-cause mortality and cardiovascular disease (CVD) are common in patients with diabetes in China. We propose to compare the effectiveness of team-based care plus a clinical decision support system (CDSS) with team-based care alone on glycemic, blood pressure (BP), and lipid control, and clinical CVD reduction among patients with type-2 diabetes and at high risk for CVD.

Methods: The Diabetes Complication Control in Community Clinics (D4C) study is a cluster-randomized trial conducted among 38 community health centers in Xiamen City, China. Nineteen clinics have been randomly assigned to team-based care plus CDSS and 19 to team-based care alone. Team-based care includes primary care providers, health coaches, and diabetes specialists working collaboratively with patients to achieve shared treatment goals for CVD risk factor reduction. The CDSS integrates guideline-based treatment algorithms for glycemic, BP, and lipid control, along with a patient's medical history and insurance policy, to recommend treatment and follow-up plans. In phase 1, the co-primary outcomes are mean reduction in glycated hemoglobin (HbA1c), systolic BP (SBP), and low-density lipoprotein (LDL)-cholesterol over 18 months, and the proportion of patients with controlled HbA1c, SBP, and LDL-cholesterol at 18 months' between the 2 comparison groups. In phase 2, the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between the 2 comparison groups. Mean reduction in HbA1c, SBP, and LDL-cholesterol levels will be simultaneously modeled for a single overall treatment effect.

Conclusion: The D4C trial will generate evidence on whether a CDSS will further reduce the CVD burden among patients with diabetes beyond team-based care at community clinics. If proven effective, this implementation strategy could be scaled up within primary care settings in China and other LMICs to reduce CVD incidence and mortality among patients with diabetes.
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http://dx.doi.org/10.1016/j.ahj.2021.04.009DOI Listing
May 2021

Benefits and harms of hemithyroidectomy, total or near-total thyroidectomy in 1-4 cm differentiated thyroid cancer.

Clin Endocrinol (Oxf) 2021 May 4. Epub 2021 May 4.

Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Objective: For 1-4 cm differentiated thyroid cancer (DTC), current ATA guideline recommended hemithyroidectomy (HT) as an acceptable alternative initial procedure to total or near-total thyroidectomy (TT). The aim of this study was to evaluate benefits and harms of HT, TT in 1-4 cm DTC.

Design: Retrospective cohort study.

Patients: DTC patients aged 18 years or older who underwent initial thyroidectomy in a tertiary medical centre were included from January 2008 to July 2018.

Measurements: The structural persistent/recurrent disease, reoperation rates and surgical complications were compared using Cox proportional regression and logistic regression. Propensity score matching was performed to adjust for related clinicopathological variables.

Results: Among 1824 DTC patients, 795 patients sized 1-4 cm were included. A total of 286 patients underwent HT and 509 patients underwent TT. In the matched analysis, no significant difference in disease-free survival (DFS) between HT and TT was observed during the median follow-up period of 56.5 months (hazard ratio [HR] 0.86; 95% CI, 0.37-2.00; p = .733). The difference in DFS between two groups was consistent regardless of age, sex, tumour size, follow-up duration. Meanwhile, HT was associated with a decreased risk of surgical complications (odds ratio [OR] 0.47, 95% CI 0.31-0.71, p < .001), as well as lower proportion of levothyroxine replacement (p = .007). Two cases in HT group received reoperation. Further multivariate analysis showed surgical procedure was not associated with structural persistence/recurrence (HR 0.68; 95%CI, 0.29-1.58, p = .367).

Conclusions: For patients with 1-4 cm DTC without clinical evidence of lymph node metastasis or extrathyroidal extension, HT was associated with lower risk of surgical complications than TT while provided similar benefits as TT.
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http://dx.doi.org/10.1111/cen.14495DOI Listing
May 2021

Using real-world data to estimate the changing trends in the prevalence and incidence of type 2 diabetes mellitus in Xiamen of China from 2014 to 2019.

BMC Endocr Disord 2021 May 1;21(1):92. Epub 2021 May 1.

Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.

Background: The prevalence of diabetes is increasing worldwide. Our study aimed to estimate the changing trends in the prevalence and incidence of diagnosed type 2 diabetes mellitus (T2DM) among Xiamen residents and the floating population using real-world data.

Method: We used real-world data from the System of Xiamen Citizens Health Information from 2014 to 2019 to estimate the changing trends in the prevalence and incidence of diagnosed T2DM. The System included the diagnosis of diabetes and the prescription of hypoglycemic drugs. Prevalent cases of T2DM were individuals who were diagnosed with T2DM and/or using hypoglycemic drugs. Incident cases were individuals with diagnosed T2DM and/or using hypoglycemic drugs in 2014 or 2019 who had not been diagnosed and/or did not use hypoglycemic drugs in the past.

Results: In 2014 and 2019, the prevalence of T2DM in Xiamen was 4.04 and 4.84%, respectively. In 2014 and 2019, the incidence rate of T2DM in Xiamen was 14.1 per 1000 person-year and 15.0 per 1000 person-year, respectively. There was a significant increase in both the prevalence (Prevalence difference: 0.80, 95%CI 0.76-0.83%, P < 0.001) and the incidence of T2DM (Incidence difference: 0.9, 95%CI 0.7-1.1, P < 0.001). in Xiamen. The prevalence and incidence of T2DM in people aged 18-39 increased significantly (P < 0.001), while the prevalence and incidence of T2DM in people aged 40-69 reduced significantly (P < 0.001).

Conclusions: There was a significant increase in the prevalence and incidence of T2DM in Xiamen from 2014 to 2019 especially among those with younger age.
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http://dx.doi.org/10.1186/s12902-021-00759-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088665PMC
May 2021

Irx3 and Irx5 in Ins2-Cre cells regulate hypothalamic postnatal neurogenesis and leptin response.

Nat Metab 2021 May 15;3(5):701-713. Epub 2021 Apr 15.

Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Obesity is mainly due to excessive food intake. IRX3 and IRX5 have been suggested as determinants of obesity in connection with the intronic variants of FTO, but how these genes contribute to obesity via changes in food intake remains unclear. Here, we show that mice doubly heterozygous for Irx3 and Irx5 mutations exhibit lower food intake with enhanced hypothalamic leptin response. By lineage tracing and single-cell RNA sequencing using the Ins2-Cre system, we identify a previously unreported radial glia-like neural stem cell population with high Irx3 and Irx5 expression in early postnatal hypothalamus and demonstrate that reduced dosage of Irx3 and Irx5 promotes neurogenesis in postnatal hypothalamus leading to elevated numbers of leptin-sensing arcuate neurons. Furthermore, we find that mice with deletion of Irx3 in these cells also exhibit a similar food intake and hypothalamic phenotype. Our results illustrate that Irx3 and Irx5 play a regulatory role in hypothalamic postnatal neurogenesis and leptin response.
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http://dx.doi.org/10.1038/s42255-021-00382-yDOI Listing
May 2021

Interleukin-6 mediated exercise-induced alleviation of adiposity and hepatic steatosis in mice.

BMJ Open Diabetes Res Care 2021 Apr;9(1)

Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Key Laboratory of Translational Research for Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China

Introduction: Exercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.

Research Design And Methods: To study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).

Results: After 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepatic steatosis. Moreover, a panel of lipolytic-related and thermogenic-related genes, including ATGL, HSL and PGC-1α, was upregulated in the VAT and SAT of WT mice that received exercise training compared with untrained mice, which was not observed in IL-6 KO mice. In addition, exercise training resulted in a significant inhibition of hepatic peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in WT mice, and these effects were not noted in IL-6 KO mice.

Conclusion: These results revealed that IL-6 is involved in the prevention of obesity and hepatic fat accumulation during exercise training. The mechanisms underlying these antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR-γ expression by IL-6.
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http://dx.doi.org/10.1136/bmjdrc-2020-001431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054088PMC
April 2021

Identification of transcriptomic signatures and crucial pathways involved in non-alcoholic steatohepatitis.

Endocrine 2021 Apr 10. Epub 2021 Apr 10.

Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Purpose: Our study aimed to uncover the crucial genes and functional pathways involved in the development of non-alcoholic steatohepatitis (NASH).

Methods: Liver transcriptome datasets were integrated with Robust rank aggregation (RRA) method, and transcriptomic signatures for NASH progression and fibrosis severity in NAFLD were developed. The functions of transcriptomic signatures were explored by multiple bioinformatic analyses, and their diagnostic role was also evaluated.

Results: RRA analyses of 12 transcriptome datasets comparing NASH with non-alcoholic fatty liver (NAFL) identified 116 abnormally up-regulated genes in NASH patients. RRA analyses of five transcriptome datasets focusing fibrosis severity identified 78 abnormally up-regulated genes in NAFLD patients with advanced fibrosis. The functions of those transcriptomic signatures of NASH development or fibrosis progression were similar, and were both characterized by extracellular matrix (ECM)-related pathways (Adjusted P < 0.05). The transcriptomic signatures could effectively differentiate NASH from NAFL, and could help to identify NAFLD patients with advanced fibrosis. Gene set enrichment analysis and weighted gene co-expression network analysis further validated the key role of ECM-related pathways in NASH development. The top 10 up-regulated genes in NASH patients were SPP1, FBLN5, CHI3L1, CCL20, CD24, FABP4, GPNMB, VCAN, EFEMP1, and CXCL10, and their functions were mainly related to either ECM-related pathways or immunity-related pathways. Single cell RNA-sequencing analyses revealed that those crucial genes were expressed by distinct cells such as hepatocytes, macrophages, and hepatic stellate cells.

Conclusions: Transcriptomic signatures related to NASH development and fibrosis severity of NAFLD patients are both characterized by ECM-related pathways, and fibrosis is a main player during NASH progression. This study uncovers some novel key genes involved in NASH progression, which may be promising therapeutic targets.
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http://dx.doi.org/10.1007/s12020-021-02716-yDOI Listing
April 2021

Human growth hormone proteoform pattern changes in pituitary adenomas: Potential biomarkers for 3P medical approaches.

EPMA J 2021 Mar 3;12(1):67-89. Epub 2021 Mar 3.

Science and Technology Innovation Center, Shandong First Medical University, 6699 Qingdao Road, Jinan, Shandong 250117 People's Republic of China.

Relevance: Human growth hormone (hGH) is synthesized, stored, and secreted by somatotroph cells in the pituitary gland, and promotes human growth and metabolism. Compared to a normal pituitary, a GH-secreting pituitary adenoma can secrete excessive GH to cause pathological changes in body tissues. GH proteoform changes would be associated with GH-related disease pathogenesis.

Purpose: This study aimed to elucidate changes in GH proteoforms between GH-secreting pituitary adenomas and control pituitaries for the predictive diagnostics, targeted prevention, and personalization of medical services.

Methods: The isoelectric point (pI) and relative molecular mass (Mr) are two basic features of a proteoform that can be used to effectively array and detect proteoforms with two-dimensional gel electrophoresis (2DGE) and 2DGE-based western blot. GH proteoforms were characterized with liquid chromatography (LC) and mass spectrometry (MS). Phosphoproteomics, ubiquitinomics, acetylomics, and bioinformatics were used to analyze post-translational modifications (PTMs) of GH proteoforms in GH-secreting pituitary adenoma tissues and control pituitaries.

Results: Sixty-six 2D gel spots were found to contain hGH, including 46 spots (46 GH proteoforms) in GH-secreting pituitary adenomas and 35 spots (35 GH proteoforms) in control pituitaries. Further, 35 GH proteoforms in control pituitary tissues were matched with 35 of 46 GH proteoforms in GH-secreting pituitary adenoma tissues; and 11 GH proteoforms were presented in only GH-secreting pituitary adenoma tissues but not in control pituitary tissues. The matched 35 GH proteoforms showed quantitative changes in GH-secreting pituitary adenomas compared to the controls. The quantitative levels of those 46 GH proteoforms in GH-secreting pituitary adenomas were significantly different from those 35 GH proteoforms in control pituitaries. Meanwhile, different types of PTMs were identified among those GH proteoforms. Phosphoproteomics identified phosphorylation at residues Ser77, Ser132, Ser134, Thr174, and Ser176 in hGH. Ubiquitinomics identified ubiquitination at residue Lys96 in hGH. Acetylomics identified acetylation at reside Lys171 in hGH. Deamination was identified at residue Asn178 in hGH.

Conclusion: These findings provide the first hGH proteoform pattern changes in GH-secreting pituitary adenoma tissues compared to control pituitary tissues, and the status of partial PTMs in hGH proteoforms. Those data provide in-depth insights into biological roles of hGH in GH-related diseases, and identify hGH proteoform pattern biomarkers for treatment of a GH-secreting pituitary adenoma in the context of 3P medicine -predictive diagnostics, targeted prevention, and personalization of medical services.

Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-021-00232-7.
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http://dx.doi.org/10.1007/s13167-021-00232-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954920PMC
March 2021

Resistance to thyroid hormone caused by heterozygous mutation of thyroid hormone receptor B gene c.G1378A: Report of one Chinese pedigree and literature review.

Clin Case Rep 2021 Mar 8;9(3):1055-1059. Epub 2021 Feb 8.

Department of Endocrinology and Diabetes The First Affiliated Hospital of Xiamen University Xiamen China.

The same thyroid hormone receptor B gene (THRB) mutation led to thyroid hormone resistance with different clinical manifestations in the kindreds.
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http://dx.doi.org/10.1002/ccr3.3497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981654PMC
March 2021

The NTCP p.Ser267Phe Variant Is Associated With a Faster Anti-HBV Effect on First-Line Nucleos(t)ide Analog Treatment.

Front Pharmacol 2021 24;12:616858. Epub 2021 Feb 24.

Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Sodium taurocholate cotransporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus infection of host hepatocytes. Previously, many studies confirmed that the NTCP p.Ser267Phe variant was a protective factor against HBV-related disease progression. We therefore designed this study to investigate whether the NTCP p.Ser267Phe variant exerts an additive anti-HBV effect in chronic hepatitis B (CHB) patients on mainstream NAs treatment. After propensity score matching (PSM), a total of 136 CHB patients were included, among whom 68 were heterozygous carriers and 68 were wild-type controls. Proportions of primary nonresponse, partial virological response, virological breakthrough and hepatitis B reactivation and the HBV DNA clearance rate at each time point were compared using the chi-square test. Kaplan-Meier analysis and matched t-tests were also performed to estimate the speed of viral clearance and serum HBV DNA reduction, respectively. The proportion of primary nonresponse was significantly lower in heterozygous carriers than in wild-type controls ( < 0.001), especially in patients using entecavir ( = 0.013). Specifically, heterozygous carriers achieved HBV DNA clearance faster than wild-type controls (log-rank = 0.0198). HBV DNA levels were reduced more in heterozygous carriers after 12 weeks ( < 0.001) and 24 weeks ( = 0.006) of treatment, especially among patients using ETV. Here, our study demonstrated that heterozygous mutations in rs2296651 enhanced the antiviral response of first-line NAs and helped to explore the possibility of combining NAs and NTCP blockers for a better anti-HBV effect.
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http://dx.doi.org/10.3389/fphar.2021.616858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943921PMC
February 2021

Enzymatic Hydrolysis of Defatted Antheraea pernyi (Lepidoptera: Saturniidae) Pupa Protein by Combined Neutral Protease Yield Peptides With Antioxidant Activity.

J Insect Sci 2021 Mar;21(2)

Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian, China.

In this study, peptides were prepared from defatted Antheraea pernyi (Lepidoptera: Saturniidae) pupa protein via hydrolysis with combined neutral proteases. Single-factor tests and response surface methodology (RSM) were used to determine the optimal hydrolysis condition suitable for industrial application. Optimal hydrolysis of the defatted pupa protein was found to occur at an enzyme concentration of 4.85 g/liter, a substrate concentration of 41 g/liter, a hydrolysis temperature of 55°C, and a hydrolysis time of 10 h and 40 min. Under these conditions, the predicted and actual rates of hydrolysis were 45.82% and 45.75%, respectively. Peptides with a molecular weight of less than 2,000 Da accounted for 90.5% of the total peptides generated. Some of the peptides were antioxidant peptides as revealed by sequencing and functional analysis. The antioxidant activity of the mixed peptides was subsequently confirmed by an antioxidant activity assay. The results showed that peptides with high antioxidant activity could be obtained from the hydrolysis of A. pernyi pupa protein.
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http://dx.doi.org/10.1093/jisesa/ieab013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947994PMC
March 2021

Analysis of Differentially Expressed Genes in Endothelial Cells Following Tumor Cell Adhesion, and the Role of PRKAA2 and miR-124-3p.

Front Cell Dev Biol 2021 19;9:604038. Epub 2021 Feb 19.

Department of Pharmacology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, China.

Tumor cell adhesion to the endothelium is one pattern of tumor-endothelium interaction and a key step during tumor metastasis. Endothelium integrity is an important barrier to prevent tumor invasion and metastasis. Changes in endothelial cells (ECs) due to tumor cell adhesion provide important signaling mechanisms for the angiogenesis and metastasis of tumor cells. However, the changes happened in endothelial cells when tumor-endothelium interactions are still unclear. In this study, we used Affymetrix Gene Chip Human Transcriptome Array 2.0. and quantitative real-time PCR (qPCR) to clarify the detailed gene alteration in endothelial cells adhered by prostate tumor cells PC-3M. A total of 504 differentially expressed mRNAs and 444 lncRNAs were obtained through chip data analysis. Gene Ontology (GO) function analysis showed that differentially expressed genes (DEGs) mainly mediated gland development and DNA replication at the biological level; at the cell component level, they were mainly involved in the mitochondrial inner membrane; and at the molecular function level, DEGs were mainly enriched in ATPase activity and catalytic activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway analysis showed that the DEGs mainly regulated pathways in cancer, cell cycle, pyrimidine metabolism, and the mTOR signaling pathway. Then, we constructed a protein-protein interaction functional network and mRNA-lncRNA interaction network using Cytoscape v3.7.2. to identify core genes, mRNAs, and lncRNAs. The miRNAs targeted by the core mRNA PRKAA2 were predicted using databases (miRDB, RNA22, and Targetscan). The qPCR results showed that miR-124-3p, the predicted target miRNA of PRKAA2, was significantly downregulated in endothelial cells adhered by PC-3M. With a dual luciferase reporter assay, the binding of miR-124-3p with PRKAA2 3'UTR was confirmed. Additionally, by using the knockdown lentiviral vectors of miR-124-3p to downregulate the miR-124-3p expression level in endothelial cells, we found that the expression level of PRKAA2 increased accordingly. Taken together, the adhesion of tumor cells had a significant effect on mRNAs and lncRNAs in the endothelial cells, in which PRKAA2 is a notable changed molecule and miR-124-3p could regulate its expression and function in endothelial cells.
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http://dx.doi.org/10.3389/fcell.2021.604038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933219PMC
February 2021

Long-term exposure to ambient PM and stroke mortality among urban residents in northern China.

Ecotoxicol Environ Saf 2021 Apr 24;213:112063. Epub 2021 Feb 24.

Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin 300070, China; Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China. Electronic address:

Evidence is still limited for the role of long-term PM exposure in cerebrovascular diseases among residents in high pollution regions. The study is aimed to investigate the long-term effects of PM exposure on stroke mortality, and further explore the effect modification of temperature variation on the PM-mortality association in northern China. Based on a cohort data with an average follow-up of 9.8 years among 38,435 urban adults, high-resolution estimates of PM derived from a satellite-based model were assigned to each participant. A Cox regression model with time-varying exposures and strata of geographic regions was employed to assess the risks of stroke mortality associated with PM, after adjusting for individual risk factors. The cross-product term of PM exposure and annual temperature range was further added into the regression model to test whether the long-term temperature variation would modify the association of PM with stroke mortality. Among the study participants, the annual mean level of PM concentration was 66.3 μg/m ranging from 39.0 μg/m to 100.6 μg/m. For each 10 μg/m increment in PM, the hazard ratio (HR) was 1.31 (95% CI: 1.04-1.65) for stroke mortality after multivariable adjustment. In addition, the HRs of PM decreased gradually as the increase of annual temperature range with the HRs of 1.95 (95% CI: 1.36-2.81), 1.53 (95% CI: 1.06-2.22), and 1.11 (95% CI: 0.75-1.63) in the low, middle, and high group of annual temperature range, respectively. The findings provided further evidence of long-term PM exposure on stroke mortality in high-exposure settings such as northern China, and also highlighted the view that assessing the adverse health effects of air pollution might not ignore the role of temperature variations in the context of climate change.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150861PMC
April 2021

Genome-wide identification and characterization of olfactory receptor genes in common carp (Cyprinus carpio).

Gene 2021 Apr 2;777:145468. Epub 2021 Feb 2.

Fujian Key Laboratory of Genetics and Breeding of Marine Organisms, College of Ocean and Earth Sciences, Xiamen University, Xiamen, China. Electronic address:

The environment contains a large extent of chemical information, which could be detected as olfactory sense. Olfactory in vertebrates plays important roles on many aspects during life time, including localizing prey or food, avoiding predators, mating behavior and social communication. Considering the essential role of olfactory receptors in the specific recognition of diverse stimuli, understanding the evolutionary dynamics of olfactory receptors in teleost means a lot, especially in the allotetraploid common carp, who has undergone the fourth whole-genome duplication event. Here, we identified the whole set of olfactory receptor genes in representative teleosts and found a significant contraction in common carp when compared with other teleosts. Odorant receptor genes (OR) occupy the most among four groups of olfactory receptors, including 33 functional genes and 16 pseudogenes. Furthermore, 6 trace amine-associated receptor (TAAR) genes (including 1 pseudogene), 7 odorant-related-A receptor genes, and 10 olfactory C family receptor genes (including 3 pseudogenes) were identified in common carp. Phylogenetic and motif analysis were performed to illustrate the phylogenetic relationship and structural conservation of teleost olfactory receptors. Selection pressure analysis suggested that olfactory receptor groups in common carp were all under relaxed purifying-selection. Additionally, gene expression divergences for olfactory receptor genes were investigated during embryonic development stages of common carp. We aim to determine the abundance of common carp olfactory receptor genes, explore the evolutionary fate and expression dynamics, and provide some genomic clues for the evolution of polyploid olfactory after whole-genome duplication and for future studies of teleost olfactory.
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http://dx.doi.org/10.1016/j.gene.2021.145468DOI Listing
April 2021

Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study.

Microb Cell Fact 2021 Jan 19;20(1):18. Epub 2021 Jan 19.

Department of Gastroenterology and Hepatology, Second Hospital of Anhui Medical University, Hefei, China.

Background: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).

Results: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.

Conclusions: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.
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http://dx.doi.org/10.1186/s12934-021-01513-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816432PMC
January 2021

Long-term exposure to high particulate matter pollution and incident hypertension: a 12-year cohort study in northern China.

J Hum Hypertens 2021 Jan 18. Epub 2021 Jan 18.

Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, 300070, China.

Numerous cohort studies have reported the association of long-term exposure to particulate matter <10 μm in diameter (PM) and hypertension in American and European countries. However, these results have been inconsistent and subject to various confounding factors. The study aimed to explore the effect of long-term exposure to high-level concentrations of PM on incident hypertension in a large-scale cohort from northern China. A retrospective cohort study of 39,054 participants aged between 23 and 98 years old from four cities in northern China was followed from 1998 to 2009. Excluding those with hypertension, 37,386 non-hypertensive participants (overall population) were followed for self-reported hypertension. The individuals' exposure to PM was the mean concentration during the follow-up period, according to the data of local environmental monitoring centers. Hazard ratios (HRs) were calculated by Cox proportional hazards models. The adjusted potential confounding factors included sociodemographic information, lifestyle, and diet. There were 2619 (7.0%) incident cases of hypertension among the overall population. In multivariable models, the HR (95% CI) of incident hypertension was 1.537 (1.515, 1.560) for each 10 μg/m increase in PM. Stratified analyses showed individuals (age <65) were prone to developing hypertension. Moreover, the effects of PM increased and produced an HR (95% CI) of 1.555 (1.527, 1.584) for the healthy population in the sensitivity analysis. We found that the association between long-term exposure to PM air pollution and incident hypertension was significantly positive.
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http://dx.doi.org/10.1038/s41371-020-00443-xDOI Listing
January 2021

The 48-week safety and therapeutic effects of tenofovir alafenamide in hbv-related acute-on-chronic liver failure: A prospective cohort study.

J Viral Hepat 2021 04 19;28(4):592-600. Epub 2021 Jan 19.

Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.

Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73 m , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.
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http://dx.doi.org/10.1111/jvh.13468DOI Listing
April 2021

Dose-response relationship between serum fibroblast growth factor 21 and liver fat content in non-alcoholic fatty liver disease.

Diabetes Metab 2020 Dec 26:101221. Epub 2020 Dec 26.

Department of Endocrinology and Diabetes, The First Affiliated Hospital of Xiamen University, Xiamen, China; Xiamen Clinical Medical Centre for Endocrine and Metabolic Diseases, Xiamen, China; Fujian Province Key Laboratory of Diabetes Translational Medicine, Xiamen, China; Xiamen Diabetes Institute, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China.

Background & Aim: Although serum fibroblast growth factor 21 (FGF21) levels are associated with liver fat content in non-alcoholic liver fat disease (NAFLD), the precise nature of the association remains undetermined. Therefore, this study aimed to explore the potential dose-response relationship between FGF21 and liver fat content in NAFLD.

Methods: For this exploratory randomized clinical trial, 220 NAFLD patients with central obesity were recruited via community-based screening and randomly assigned to either control, moderate or vigorous-moderate exercise groups for 12 months. After this exercise intervention, patients were followed-up for a further 12 months. Serum FGF21 levels were measured by ELISA. Intrahepatic triglyceride (IHTG) content was determined by proton magnetic resonance spectroscopy.

Results: Of the 220 patients, 149 (67.7%) were female; mean age was 53.9 ± 7.1 years and mean BMI was 28.0 ± 2.9 kg/m2 for all patients. Baseline IHGT increased gradually (P = 0.029 for trend) according to baseline serum FGF21 quartiles 1, 2, 3 and 4 (212.3, 358.9, 538.7 and 793.5 pg/mL, respectively). On grouping the distribution of serum FGF21 level changes into quartiles at month 12, the relative IHTG loss increased as serum FGF21 levels were reduced (P = 0.004 for trend). A similar trend was observed at month 24 (P = 0.006 for trend). Multivariate linear regression analysis revealed that changes in serum FGF21 levels were independently associated with changes in IHTG at both month 12 [β (SE), 0.136 (0.118); P = 0.048] and month 24 [β (SE), 0.152 (0.139); P = 0.041]. Using restricted cubic spline regression, changes in serum FGF21 were strongly and positively associated with their corresponding relative IHTG loss at both month 12 and follow-up (Poverall = 0.017, Pnon-linear = 0.044 and Poverall = 0.020, Pnon-linear = 0.044, respectively, for dose-response).

Conclusion: Serum FGF21 is strongly associated with liver fat content in a dose-response manner in centrally obese NAFLD patients. These findings support the use of serum FGF21 as a biomarker of liver fat content in NAFLD.
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http://dx.doi.org/10.1016/j.diabet.2020.101221DOI Listing
December 2020

Lipid accumulation product (LAP) was independently associatedwith obstructive sleep apnea in patients with type 2 diabetes mellitus.

BMC Endocr Disord 2020 Dec 9;20(1):179. Epub 2020 Dec 9.

The School of Clinical Medicine, Fujian Medical University, Fuzhou, 350000, China.

Background: Lipid accumulation product (LAP) is a new index based on a combination of waist circumference (WC) and serum triglycerides (TG) reflecting lipid accumulation. In this cross-sectional study, we aimed to explore whether LAP was independently associated with obstructive sleep apnea (OSA) in Type 2 diabetes mellitus (T2DM) patients.

Methods: A cross-sectional study of 317 T2DM patients who underwent overnight polysomnography (PSG) tests was conducted. The clinical data between non-OSA group and OSA group were compared. Multivariable linear regression and multivariable logistic regression analyses were performed to determine associations of LAP, with apnea-hypopnea index (AHI) and OSA.

Results: Among 317 patients, 219 (69.1%) were men, and the mean ages (±SD) were 51.4 (±13.5) years for men and 54.6 (±15.1) years for women (p = 0.067). The prevalence rates of OSA were 63.0% for men and 68.4% for women (p = 0.357). LAP (log-transformed) was significantly correlated with AHI (log-transformed), with the Pearson's correlation coefficient of 0.170 (p = 0.002). With adjustment for potential confounding factors, multivariate linear regression analyses showed the association of LAP with AHI was not statistically significant, with the adjusted linear regression coefficients (95% CI) of per SD increase of LAP for AHI (log-transformed) was 0.092 (- 0.011-0.194, p = 0.080). Multivariate logistic regression analyses showed LAP was significantly associated with increased risk of OSA, with the adjusted OR (95%CI) of per SD increase of LAP of 1.639 (1.032-2.604, p = 0.036). However, as constituents of LAP, neither TG nor WC was significantly associated with AHI and OSA.

Conclusion: LAP was independently associated with OSA and might be used as a potential OSA risk marker in T2DM patients, beyond the general index of obesity.
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http://dx.doi.org/10.1186/s12902-020-00661-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727244PMC
December 2020

Effect of WeChat consultation group on residents staying at home in Sichuan and Chongqing regions during the Coronavirus Disease 2019 (COVID-19) outbreak in China: a cross-sectional study.

BMC Public Health 2020 Nov 30;20(1):1815. Epub 2020 Nov 30.

Department of Pharmacy, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Background: After the outbreak of Coronavirus in Wuhan, Hubei, in 2019, the disease rapidly spread to other parts of China as well as outside of China. Since the pandemic outbreak, the general public has been responsive to the national call to stay at home in quarantine. However, since doubts and anxiety related to the disease have been detected in the general public, in this study, we established the WeChat platform "Coronavirus Disease 2019 Voluntary Assistance Group in Sichuan and Chongqing regions" in January 2020, which was committed to providing professional consultation and psychological counseling services for residents in Sichuan and Chongqing during the Coronavirus Disease 2019 outbreak. Our aim was to analyze the consultation practices of residents in the WeChat assistance group and provide a reference for the similar "non-contact" voluntary service platforms aiming to implement consultations during the late pandemic period.

Methods: A cross-sectional study was conducted using the records containing the consultation content from the WeChat assistance groups in Sichuan and Chongqing between January 30 and March 1, 2020. Data on consultation content, changes in a number of consultation items, answers, knowledge on popular science, and expert advice were summarized, and the Pareto chart was used to analyze the primary and secondary factors of consultation content.

Results: The constituent ratio of "respiratory symptoms, masks, and disinfection" in consultation content ranked as the top three factors. Cumulatively, they occupied 49.77% of the content, thus resulting as the primary factors in the consultation content. The number of consultation items suddenly increased from 10 on the first day to 116 on the 7th day, resulting in a 1060% increased rate. There were 151 consultation factors, among which 130 (86.1%) were related to the Coronavirus Disease 2019, and 21 (13.9%) were unrelated to the Coronavirus Disease 2019.

Conclusion: WeChat groups may be used as an effective means for providing assistance services for the public during the Coronavirus Disease 2019 outbreak.
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http://dx.doi.org/10.1186/s12889-020-09951-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702198PMC
November 2020

Transcriptome analysis of common carp (Cyprinus carpio) provides insights into the ovarian maturation related genes and pathways in response to LHRH-A and dopamine inhibitors induction.

Gen Comp Endocrinol 2021 Jan 20;301:113668. Epub 2020 Nov 20.

College of Fisheries, Henan Normal University, Xinxiang 453007, PR China; College of Fisheries, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang 453007, PR China. Electronic address:

Luteinizing hormone-releasing hormone analog (LHRH-A) and dopamine inhibitors have been widely used to induce oocyte maturation and ovulation in domesticated fishes. Although this approach represents a reliable method for regulating fish reproduction, the underlying molecular mechanisms mediating LH action are largely unexplored. The objective of this study was to determine the transcriptional profile of gene programming in hormone-treated common carp. In the present study, female common carp were intraperitoneally injected with LHRH-A together with dopamine inhibitors, and control fish were injected with saline. Ovarian morphological changes were analysed by both light microscopy and scanning electron microscopy. Furthermore, gene expression profiling of the brain and ovarian tissues was performed by Illumina sequencing. Compared to the control carp, hormone treatment resulted in morphological changes including disappearance of nuclear membrane, breakdown of germinal vesicle (GVBD), and fusion of yolk globules, reflecting that hormones significantly promoted oocyte maturation. In comparison to control, we have identified 867 and 9,053 differentially expressed genes in the hormone-treated female brain and ovary, respectively. In the brain, most of the identified genes were significantly enriched in 18 KEGG pathways. In the ovarian tissue, the identified genes were significantly involved in 9 pathways. In the hormone-treated carp, genes were involved in calcium signalling pathway, cAMP signalling pathway, insulin secretion, and oxidative phosphorylation pathway, which showed obvious associations with ovarian maturation. The present study provides transcriptomic information for hormone-treated carp, which might be useful for studying the endocrine regulation and mechanisms of ovarian maturation in domesticated fishes.
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http://dx.doi.org/10.1016/j.ygcen.2020.113668DOI Listing
January 2021

Enhanced protein phosphorylation in Apostichopus japonicus intestine triggered by tussah immunoreactive substances might be involved in the regulation of immune-related signaling pathways.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Mar 4;37:100757. Epub 2020 Nov 4.

Liaoning Ocean and Fisheries Science Research Institute, Liaoning Academy of Agricultural Sciences, Dalian 116024, PR China.

The sea cucumber Apostichopus japonicus is an economically important species owing to its high nutritive and medicinal value. In order to avoid the pollution resulting from the overuse of antibiotics in A. japonicus aquaculture, various immunostimulants have been used as an alternative to improve the efficiency of A. japonicus farming. Our previous proteomic investigation has shown that several proteins participating in the immune-related physiology of A. japonicus were differentially expressed in the intestinal tissue in response to tussah immunoreactive substances (TIS). This study further explored the immunostimulation mechanism of TIS in A. japonicus. Phosphoproteomics technology was used to investigate the effect of TIS on protein phosphorylation in the intestine of A. japonicus following feeding with a TIS-supplemented diet. A total of 213 unique phosphoproteins were detected from 225 unique phosphopeptides. KEGG pathway analysis showed that majority of the phosphoproteins are involved in endocytosis, carbon metabolism and spliceosome functional group. Sixteen of the phosphoproteins exhibited differential phosphorylation in response to TIS and 12 of these were found to associate with biological functions. Of these 12 phosphoproteins, eight exhibited enhanced phosphorylation while four displayed reduced phosphorylation. These 12 proteins were further analyzed and all were found to play a role in regulating some aspects of the immune system and the growth of sea cucumbers, especially in phagocytosis, energy metabolism and disease resistance. The findings of this study could therefore shed new light on the immune pathways of sea cucumber that are affected by TIS. This could help us to better understand the underlying mechanism linked to the immunoenhancement of A. japonicus in response to TIS, one that is associated with the change in protein phosphorylation.
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http://dx.doi.org/10.1016/j.cbd.2020.100757DOI Listing
March 2021

Physiological Ca Transients Versus Pathological Steady-State Ca Elevation, Who Flips the ROS Coin in Skeletal Muscle Mitochondria.

Front Physiol 2020 22;11:595800. Epub 2020 Oct 22.

Department of Kinesiology, College of Nursing and Health Innovation, The University of Texas at Arlington, Arlington, TX, United States.

Mitochondria are both the primary provider of ATP and the pivotal regulator of cell death, which are essential for physiological muscle activities. Ca plays a multifaceted role in mitochondrial function. During muscle contraction, Ca influx into mitochondria activates multiple enzymes related to tricarboxylic acid (TCA) cycle and oxidative phosphorylation, resulting in increased ATP synthesis to meet the energy demand. Pathophysiological conditions such as skeletal muscle denervation or unloading also lead to elevated Ca levels inside mitochondria. However, the outcomes of this steady-state elevation of mitochondrial Ca level include exacerbated reactive oxygen species (ROS) generation, sensitized opening of mitochondrial permeability transition pore (mPTP), induction of programmed cell death, and ultimately muscle atrophy. Previously, both acute and long-term endurance exercises have been reported to activate certain signaling pathways to counteract ROS production. Meanwhile, electrical stimulation is known to help prevent apoptosis and alleviate muscle atrophy in denervated animal models and patients with motor impairment. There are various mechanistic studies that focus on the excitation-transcription coupling framework to understand the beneficial role of exercise and electrical stimulation. Interestingly, a recent study has revealed an unexpected role of rapid mitochondrial Ca transients in keeping mPTP at a closed state with reduced mitochondrial ROS production. This discovery motivated us to contribute this review article to inspire further discussion about the potential mechanisms underlying differential outcomes of physiological mitochondrial Ca transients and pathological mitochondrial Ca elevation in skeletal muscle ROS production.
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http://dx.doi.org/10.3389/fphys.2020.595800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642813PMC
October 2020

Clinical practice guidelines for the management of adult diffuse gliomas.

Cancer Lett 2021 02 6;499:60-72. Epub 2020 Nov 6.

Department of Neurosurgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.
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http://dx.doi.org/10.1016/j.canlet.2020.10.050DOI Listing
February 2021

HFD and HFD-provoked hepatic hypoxia act as reciprocal causation for NAFLD via HIF-independent signaling.

BMC Gastroenterol 2020 Nov 3;20(1):366. Epub 2020 Nov 3.

Siming Branch, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003, China.

Background: The occurrence of non-alcoholic fatty liver disease (NAFLD) is found to be higher in patients with obstructive sleep apnea (OSA), which is characterized by intermittent hypoxia. Activation of hypoxia-inducible factors has been shown in the development and progression of NAFLD, implying a cause and effects relationship between NAFLD and hypoxia. The present study was designed to investigate the interaction of lipotoxicity and hypoxia in the pathogenesis of NAFLD using mice model with high-fat diet (HFD) feeding or hypoxic treatment.

Methods: NAFLD model was induced in mice by HFD feeding, and in cultured primary hepatocytes by administration of palmitate acid. Mouse hypoxic model was produced by placing the mice in a Animal incubator with oxygen concentration at 75% followed by a 21% oxygen supplement. Hypoxic condition was mimicked by treating the hepatocytes with cobalt chloride (CoCl) or 1% oxygen supply. Pimonidazole assay was conducted to evaluate hypoxia. Lipid metabolic genes were measured by real-time polymerase-chain reaction. HIF-1α and HIF-2α genes were silenced by siRNA.

Results: HFD feeding and palmitate acid treatment provoked severe hepatic hypoxia along with TG accumulation in mice and in cultured primary hepatocytes respectively. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured primary hepatocytes. Hypoxic treatment inhibited the expression of lipolytic genes, while increased the expression of lipogenicgenes in mice. Although both lipotoxicity and hypoxia could activate hepatic hypoxia-induced factor 1α and 2α, while neither lipotoxicity- nor hypoxia- induced hepatic steatosis was affected when HIF was knocked down.

Conclusions: HFD resulted in hepatic TG accumulation and concomitant hypoxia. Conversely, hypoxia induced hepatic TG accumulation in mice and in cultured heptocytes. Thus lipotoxicity and hypoxia might work as reciprocal causation and orchestrate to promote the development of NAFLD.
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http://dx.doi.org/10.1186/s12876-020-01515-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640429PMC
November 2020

Invasive sphenoid sinus aspergillosis mimicking sellar tumor: a report of 4 cases and systematic literature review.

Chin Neurosurg J 2020 9;6:10. Epub 2020 Apr 9.

Department of Neurosurgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008 Hunan People's Republic of China.

Background: Invasive sphenoid sinus aspergillosis is a rare but life-threatening condition usually found in immunocompromised patients. When involving cavernous sinus and surrounding structures, patients are frequently misdiagnosed with a neoplasm or sellar abscess. Timely diagnosis and intervention are crucial to patients' outcomes. The objective of this study is to review cases of invasive sphenoid sinus aspergillosis to describe disease manifestations, imaging features, treatment, and outcome.

Case Presentation: We describe four patients with invasive sphenoid sinus aspergillosis misdiagnosed as sellar tumors preoperatively. The mass was completely removed in three patients and partially removed in one patient microscopically. Pathological examinations confirmed in all cases. All four patients received anti-fungal agents postoperatively. There was no recurrence at the time of each patient's follow-up date. One patient with complete resection was lost to follow-up while the other three patients' neurologic function improved. Additionally, we performed a systematic review regarding invasive sphenoid sinus aspergillosis of existing English literature.

Conclusion: With regard to clinical symptoms, headache, vision impairment, and ophthalmoplegia were observed in over half of the patients in the literature. A sellar mass with bone destruction on CT and involvement of cavernous sinus is highly suggestive of invasive fungal sphenoid sinusitis. Immediate surgical removal of the lesion is recommended for invasive sphenoid sinus aspergillosis to preserve nerve function and increase the likelihood of survival.
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http://dx.doi.org/10.1186/s41016-020-00187-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398181PMC
April 2020

Identification of purity and prognosis-related gene signature by network analysis and survival analysis in brain lower grade glioma.

J Cell Mol Med 2020 10 31;24(19):11607-11612. Epub 2020 Aug 31.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, P. R. China.

Tumour microenvironment of brain lower grade glioma (LGG) consists of non-tumour cells including stromal cells and immune cells mainly. These non-tumour cells dilute the purity of LGG and play pivotal roles in tumour growth and development, thereby affecting patient prognosis. Tumour purity is also associated with molecular subtypes of LGG. In this study, we discovered the most relevant module to purity by weighted gene co-expression network analysis (WGCNA) and afterwards performed consensus network analysis and survival analysis to filter 61 significant genes related to both purity and prognosis. In turn, we built a simplified model based on the calculation of purity score, and consensus measurement of purity estimation (CPE), with a satisfactory predictive performance by random forest regression. HLA-E, MSN, GNG-5, MYL12A, ITGB4, PDPN, AGTRAP, S100A4, PLSCR1, VAMP5 were selected as the most relevant genes correlating to both purity and prognosis. The risk score model based on the 10 genes could moderately predict patients' overall survival. These 10 genes, respectively, were positively correlated positively to immunosuppressive cells like macrophage M2, but negatively correlated to patient prognosis, which may explain partially the poor prognosis with low-purity group.
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http://dx.doi.org/10.1111/jcmm.15805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576230PMC
October 2020

Phylogeny of Slc15 family and response to Aeromonas hydrophila infection following Lactococcus lactis dietary supplementation in Cyprinus carpio.

Fish Shellfish Immunol 2020 Nov 23;106:705-714. Epub 2020 Aug 23.

College of Fishery, Henan Normal University, Xinxiang, 453007, China. Electronic address:

Solute carrier 15 family (Slc15) are membrane proteins that utilize the proton gradient and negative membrane protential for the transmembrane transporter of di-/tripeptide and peptide-mimetic molecules, in addition, they also play important roles in immunoreaction. In this study, 10 Slc15 genes were identified in the common carp genome database. Comparative genomics analysis showed considerable expansion of the Slc15 genes and verified the four-round whole genome duplication (WGD) event in common carp. Phylogenetic analysis revealed all Slc15 genes of common carp were clustered into orthologous groups indicating the highly conservative during evolution. Besides, the tissues and temporal expression examined by RT-PCR and qRT-PCR showed that most of the Slc15 genes had a narrow tissue distribution and exhibited tissue-specific expression patterns. Expression divergences were observed between these copies proving function divergence after the WGD. Then, we investigated the dietary supplementation effects of three Lactococcus lactis strains on the expression of Slc15 genes in common carp infected by A. hydrophila to find an effective way to treat aquatic diseases. Almost all of the Slc15 genes had an increased expression trend in the early post-challenge stage, and reached the highest expression level at 12h post-challenge. Then, the expression level showed a bluff descent at the last two stages and the expression level reached the lowest at 48 h post-challenge. Slc15 genes expression is actively up-regulated when stimulated by inflammatory factors, which can "amplify" immune signals, and improve the body's defense against foreign invasion in the early stage of the inflammatory response. So activation of the Slc15 genes may be an effective way for infectious disease treatment. As expected, three strains improved the expression of Slc15 genes variously compared with the control/infection groups. The strain 3 of L. lactis had a better induction of Slc15 genes compared with strain 1 and strain 2. It might be applied as a potential activation of Slc15 genes for disease treatment and adding befitting L. lactis may be a good way to protect aquatilia from bacillosis.
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http://dx.doi.org/10.1016/j.fsi.2020.08.026DOI Listing
November 2020

Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation.

Oncogene 2020 09 31;39(36):5902-5915. Epub 2020 Jul 31.

School of Life Science, Beijing Institute of Technology, Beijing, China.

PI3K/Akt/mTOR signaling pathway activity is highly elevated in glioblastoma (GBM). Although rapamycin is known to inhibit this pathway, GBM patients are resistant to rapamycin monotherapy. This may be related to mutations of tumor suppressor phosphatase and tensin homolog (PTEN). Here, we show that higher expression of E3 ligase Smad ubiquitylation regulatory factor 1 (Smurf1) in GBM is correlated with poor prognosis. Smurf1 promotes cell growth and colony formation by accelerating cell cycle and aberrant signaling pathways. In addition, we show that Smurf1 ubiquitylates and degrades PTEN. We further demonstrate that the oncogenic role of Smurf1 is dependent on PTEN. Upregulated Smurf1 impairs PTEN activity, leading to consistent activation of PI3K/Akt/mTOR signaling pathway; and depletion of Smurf1 dramatically inhibits cell proliferation and tumor growth. Moreover, loss of Smurf1 abolishes the aberrant regulation of PTEN, causing negative feedback on PI3K/Akt/mTOR signaling pathway, and thus leading to rescue of tumor sensitivity to rapamycin in an orthotopic GBM model. Taken together, we show that Smurf1 promotes tumor progression via PTEN, and combined treatment of Smurf1 knockdown with mammalian target of rapamycin (mTOR) inhibition reduces tumor progression. These results identify a unique role of Smurf1 in mTOR inhibitor resistance and provide a strong rationale for combined therapy targeting GBM.
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http://dx.doi.org/10.1038/s41388-020-01400-1DOI Listing
September 2020