Publications by authors named "Ping An"

251 Publications

Genetic discovery and risk characterization in type 2 diabetes across diverse populations.

HGG Adv 2021 Apr 9;2(2). Epub 2021 Mar 9.

Division of Statistical Genomics, School of Medicine, Washington University, St. Louis, MO, USA.

Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 control subjects from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Architecture Genomics and Epidemiology (PAGE) and Diabetes Genetics Replication and Meta-analysis (DIAGRAM) Consortia. In individuals of African ancestry, we discovered a risk variant in the gene (rs11466334, risk allele frequency (RAF) = 6.8%, odds ratio [OR] = 1.27, p = 2.06 × 10), which replicated in independent studies of African ancestry (p = 6.26 × 10). We identified a multiethnic risk variant in the gene (rs13052926, RAF = 14.1%, OR = 1.08, p = 5.75 × 10), which also replicated in independent studies (p = 3.45 × 10). We also observed a significant difference in the performance of a multiethnic genetic risk score (GRS) across population groups (p = 3.85 × 10). Comparing individuals in the top GRS risk category (40%-60%), the OR was highest in Asians (OR = 3.08) and European (OR = 2.94) ancestry populations, followed by Hispanic (OR = 2.39), Native Hawaiian (OR = 2.02), and African ancestry (OR = 1.57) populations. These findings underscore the importance of genetic discovery and risk characterization in diverse populations and the urgent need to further increase representation of non-European ancestry individuals in genetics research to improve genetic-based risk prediction across populations.
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http://dx.doi.org/10.1016/j.xhgg.2021.100029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486151PMC
April 2021

Long Noncoding RNA NR2F1-AS1 Enhances the Migration and Invasion of Hepatocellular Carcinoma via Modulating miR-642a/DEK Pathway.

J Oncol 2021 21;2021:6868514. Epub 2021 Sep 21.

Department of Disinfection Supply Center, The 5th People's Hospital of Ji'nan, Jinan 250022, China.

Purpose: Hepatocellular carcinoma (HCC), a malignant tumor that exists worldwide, has a high morbidity and mortality rate. Previous studies have reported that lncRNA NR2F1-AS1 plays a critical role in several cancers. Here, we aimed to investigate the biological function of NR2F1-AS1 and its molecular mechanism in the migration and invasion of HCC.

Methods: Quantitative real-time PCR (qRT-PCR) was performed to analyze NR2F1-AS1 expression in HCC. The biological function was investigated by transwell invasion and migration assays. The protein level was identified by Western blot. In addition, the downstream targets of NR2F1-AS1 and miR-642a were confirmed by luciferase reporter assays.

Results: NR2F1-AS1 was significantly upregulated in HCC and associated with the poor prognosis of HCC patients. Biological function experiments revealed that the silence of NR2F1-AS1 suppressed cell invasion and migration in HCC. More importantly, NR2F1-AS1 directly interacted with miR-642a and negatively regulated miR-642a. DEK was the target of miR-642a, and NR2F1-AS1 positively regulated DEK expression by suppressing miR-642a.

Conclusion: Taken together, it is the first time we discovered the interaction of NR2F1-AS1 with miR-642a in modulating HCC cell invasion and migration.
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http://dx.doi.org/10.1155/2021/6868514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478570PMC
September 2021

Effect of Nutrient Solution Flow Rate on Hydroponic Plant Growth and Root Morphology.

Plants (Basel) 2021 Sep 5;10(9). Epub 2021 Sep 5.

Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan.

Crop production under hydroponic environments has many advantages, yet the effects of solution flow rate on plant growth remain unclear. We conducted a hydroponic cultivation study using different flow rates under light-emitting diode lighting to investigate plant growth, nutrient uptake, and root morphology under different flow rates. Swiss chard plants were grown hydroponically under four nutrient solution flow rates (2 L/min, 4 L/min, 6 L/min, and 8 L/min). After 21 days, harvested plants were analyzed for root and shoot fresh weight, root and shoot dry weight, root morphology, and root cellulose and hemicellulose content. We found that suitable flow rates, acting as a eustress, gave the roots appropriate mechanical stimulation to promote root growth, absorb more nutrients, and increase overall plant growth. Conversely, excess flow rates acted as a distress that caused the roots to become compact and inhibited root surface area and root growth. Excess flow rate thereby resulted in a lower root surface area that translated to reduced nutrient ion absorption and poorer plant growth compared with plans cultured under a suitable flow rate. Our results indicate that regulating flow rate can regulate plant thigmomorphogenesis and nutrient uptake, ultimately affecting hydroponic crop quality.
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http://dx.doi.org/10.3390/plants10091840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465728PMC
September 2021

Apical-root apoplastic acidification affects cell wall extensibility in wheat under salinity stress.

Physiol Plant 2021 Aug 16. Epub 2021 Aug 16.

Arid Land Research Center, Tottori University, Tottori City, Japan.

Plant salt tolerance is associated with a high rate of root growth. Although root growth is governed by cell wall and apoplastic pH, the relationship between these factors in the root elongation zone under salinity stress remains unclear. Herein, we assess apoplastic pH, pH- and expansin-dependent cell wall extensibility, and expansin expression in the root elongation zone of salt-sensitive (Yongliang-15) and -tolerant (JS-7) cultivars under salinity stress. A six-day 80 mM NaCl treatment significantly reduced apical root apoplastic pH in both cultivars. Using a pH-dependent cell wall extensibility experiment, we found that, under 0 mM NaCl treatment, the optimal pH for cell wall loosening was 6.0 in the salinity-tolerant cultivar and 4.6 in the salinity-sensitive cultivar. Under 80 mM treatment, a pH of 5.0 mitigated the cell wall stiffness caused by salinity stress in the salinity-tolerant cultivar but promoted cell wall stiffening in the salinity-sensitive cultivar. Salinity stress altered expansin expression and differentially affecting cell wall extensibility under pH 5.0 and 6.0. TaEXPA8 might be relative to cell wall loosening at pH 5.0, whereas TaEXPA5 relative to cell wall loosening at pH 6.0. These results elucidate the relationship between expansins and cell wall extensibility in the root elongation zone, with important implications for enhancing plant growth under salinity stress.
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http://dx.doi.org/10.1111/ppl.13527DOI Listing
August 2021

Comparative efficacy and safety of verapamil and triamcinolone in keloid and hypertrophic scar treatment: a meta-analysis.

J Cosmet Laser Ther 2021 Feb 18;23(1-2):26-34. Epub 2021 Jul 18.

Health Management Centre, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Keloids and hypertrophic scars are harmful to physical and psychological health. The study aims to compare the efficacy and safety of verapamil and triamcinolone in the treatment of keloids and hypertrophic scars. Relevant publications were searched from PubMed, Embase, Cochrane library, CNKI, Weipu, and Wanfang databases. Results were expressed as weighted mean differences (WMDs) or the relative ratios (RRs) with 95% confidence interval (CI). Pooled estimates were calculated using random-effects or fixed-effects models according to the heterogeneity among studies. The pooled results indicated that the triamcinolone treatment showed significantly better effectiveness in height (at 12, 15, 18, 21, and 24 weeks), pliability (at 3, 6, 9, 21, and 24 weeks) and vascularity (at 3, 6, 9, and 12 week) than that of verapamil ( < .05). Moreover, the side effects such as skin atrophy (RR = 0.13, 95% CI: 0.04 to 0.42, = .001), telangiectasia (RR = 0.08, 95% CI: 0.02 to 0.28, < .001), and hyperpigmentation (RR = 0.12, 95% CI: 0.03 to 0.44, = .001) of verapamil were significantly less than those in triamcinolone. This meta-analysis showed that triamcinolone had a better therapeutic efficacy than verapamil, while verapamil was more safety.
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http://dx.doi.org/10.1080/14764172.2021.1950765DOI Listing
February 2021

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Circ Genom Precis Med 2021 Aug 9;14(4):e003258. Epub 2021 Jul 9.

Department of Epidemiology (N.F., G.H.), University of North Carolina, Chapel Hill.

Background: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

Methods: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

Results: We replicated 2 loci (rs9369640 and rs9349379 near and rs10757278 near ) for CAC and one locus for cIMT (rs7412 and rs445925 near ) that were previously reported in the general EA populations. We identified one novel CAC locus (rs8000449 near at 13q13.3) at =2.0×10 in EA. No additional loci were identified with the meta-analyses of EA and African ancestry. The expression quantitative trait loci analysis with nearby expressed genes derived from arterial wall and metabolic tissues from the Genotype-Tissue Expression project pinpoints , encoding a matricellular protein involved in bone formation and bone matrix organization, as the potential candidate gene at this locus. In addition, we found significant associations (<3.1×10) for 3 previously reported coronary artery disease loci for these subclinical atherosclerotic phenotypes (rs2891168 near and rs11170820 near for CAC, and rs7412 near for cIMT).

Conclusions: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.
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http://dx.doi.org/10.1161/CIRCGEN.120.003258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435075PMC
August 2021

Identification of a Novel Locus for Gait Speed Decline With Aging: The Long Life Family Study.

J Gerontol A Biol Sci Med Sci 2021 Sep;76(10):e307-e313

Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, USA.

Background: Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30-110 years; 45% men).

Methods: Gait speed was measured over 4 m at baseline and follow-up (7 ± 1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum likelihood methods with logarithm of the odds (LOD) scores greater than 3.0, indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center.

Results: At baseline, 26.9% of individuals had "slow" gait speed less than 1.0 m/s (mean: 1.1 ± 0.2 m/s) and gait speed declined at a rate of -0.02 ± 0.03 m/s per year (p < .0001). Baseline and change in gait speed were significantly heritable (h2 = 0.24-0.32, p < .05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD = 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene.

Conclusion: Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.
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http://dx.doi.org/10.1093/gerona/glab177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436996PMC
September 2021

A Gastrointestinal Endoscopy Quality Control System Incorporated With Deep Learning Improved Endoscopist Performance in a Pretest and Post-Test Trial.

Clin Transl Gastroenterol 2021 06 15;12(6):e00366. Epub 2021 Jun 15.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

Introduction: Gastrointestinal endoscopic quality is operator-dependent. To ensure the endoscopy quality, we constructed an endoscopic audit and feedback system named Endo.Adm and evaluated its effect in a form of pretest and posttest trial.

Methods: Endo.Adm system was developed using Python and Deep Convolutional Neural Ne2rk models. Sixteen endoscopists were recruited from Renmin Hospital of Wuhan University and were randomly assigned to undergo feedback of Endo.Adm or not (8 for the feedback group and 8 for the control group). The feedback group received weekly quality report cards which were automatically generated by Endo.Adm. We then compared the adenoma detection rate (ADR) and gastric precancerous conditions detection rate between baseline and postintervention phase for endoscopists in each group to evaluate the impact of Endo.Adm feedback. In total, 1,191 colonoscopies and 3,515 gastroscopies were included for analysis.

Results: ADR was increased after Endo.Adm feedback (10.8%-20.3%, P < 0.01,
Discussion: Endo.Adm feedback contributed to multifaceted gastrointestinal endoscopic quality improvement. This system is practical to implement and may serve as a standard model for quality improvement in routine work (http://www.chictr.org.cn/, ChiCTR1900024153).
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http://dx.doi.org/10.14309/ctg.0000000000000366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208417PMC
June 2021

Prenatal ultrasound measurements of mild congenital pulmonary airway malformation and long-term prognosis: A retrospective cohort study.

Int J Gynaecol Obstet 2021 Jun 8. Epub 2021 Jun 8.

Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Objective: To investigate the relationship between mild congenital pulmonary airway malformation (CPAM) and its long-term prognosis in childhood and to explore whether surgery is necessary.

Methods: We conducted a retrospective cohort of fetuses with mild CPAM diagnosed prenatally with available long-term outcomes in childhood from 2004 to 2016. The patients were divided into two groups according to the fetal CPAM-to-volume ratio (CVR) of less than 1.0 and 1.0-1.6. The primary outcome was a postnatal composite outcome including CPAM-associated respiratory symptoms and surgical resection of the lesion. The secondary outcomes included neonatal asphyxia, perinatal morbidity and mortality.

Results: Forty-two fetuses were identified as having CVR <1.0 or CVR-1.0-1.6 respectively (n = 37 vs n = 5; 88.1% vs 11.9%), with the median duration of follow up 2.15 years (0.3-10.8 years). Of 42 patients, 32 (76%) remained asymptomatic without recurrent respiratory symptoms or surgical resection; the other 10 with CVR <1.0 had respiratory symptoms. Of 10 symptomatic cases, five recovered after expectant treatment, and five underwent resection, for an increase in lesion size and recurrent respiratory infection.

Conclusion: Patients with CVR <1.0 still need to be closely observed after birth. Conservative management is a reasonable option in asymptomatic cases, but surgery might be necessary in some.
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http://dx.doi.org/10.1002/ijgo.13778DOI Listing
June 2021

Essential Oils from cv. Shatangju Peel: Optimization of Hydrodistillation Extraction by Response Surface Methodology and Evaluation of Their Specific Adhesive Effect to Polystyrene.

ACS Omega 2021 Jun 19;6(21):13695-13703. Epub 2021 May 19.

College of Biology & Food Engineering, Jilin Institute of Chemical Technology, 45 Chengde Street, Longtan District, Jilin City 132002, China.

Essential oil (Eo) from the peel has been widely used, and its adhesive effect on polystyrene (PS) was found accidentally. To analyze the essential oils of cv. Shatangju (CrspEos), the extraction of these oils by steam distillation was optimized using the response surface method. The chemical composition of CrspEos was analyzed by gas chromatography-mass spectrometry. Then, the adhesive effect of these essential oils on PS was evaluated. The adhesion area, the influence of adhesion on the thickness of the essential oil on the materials, the effect of adhesion on the transmittance of PS, the strength of adhesion point, and specificity of adhesion were determined. The optimum extraction conditions resulting in the extraction yield of 47.37 μL g were a ratio of liquid-to-solid of 8.94:1, a soaking time of 199.45 min, and an extraction time of 138.71 min. The major component in the essential oils was d-limonene (56.66%), followed by myrcene (6.62%). CrspEos presented a specific adherence effect on PS without influencing the thickness and transmittance of PS but with stronger tenacity than the parent material. CrspEos can be used as an environmentally friendly specific adhesive for PS.
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http://dx.doi.org/10.1021/acsomega.1c00895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173550PMC
June 2021

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

J Voice 2021 Jun 2. Epub 2021 Jun 2.

Department of Oto-Rhino-Laryngology, and West China Biomedical Big Data Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.. Electronic address:

Background: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux.

Methods: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples.

Results: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring.

Conclusions: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.
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http://dx.doi.org/10.1016/j.jvoice.2021.04.009DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Effect of circular RNA, mmu_circ_0000296, on neuronal apoptosis in chronic cerebral ischaemia via the miR-194-5p/Runx3/Sirt1 axis.

Cell Death Discov 2021 May 29;7(1):124. Epub 2021 May 29.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.

Chronic cerebral ischaemia (CCI) is a common pathological disorder, which is associated with various diseases, such as cerebral arteriosclerosis and vascular dementia, resulting in neurological dysfunction. As a type of non-coding RNA, circular RNA is involved in regulating the occurrence and development of diseases, such as ischaemic brain injury. Here, we found that HT22 cells and hippocampus treated with CCI had low expression of circ_0000296, Runx3, Sirt1, but high expression of miR-194-5p. Overexpression of circ_0000296, Runx3, Sirt1, and silenced miR-194-5p significantly inhibited neuronal apoptosis induced by CCI. This study demonstrated that circ_0000296 specifically bound to miR-194-5p; miR-194-5p bound to the 3'UTR region of Runx3 mRNA; Runx3 directly bound to the promoter region of Sirt1, enhancing its transcriptional activity. Overexpression of circ_0000296 by miR-194-5p reduced the negative regulatory effect of miR-194-5p on Runx3, promoted the transcriptional effect of Runx3 on Sirt1, and inhibited neuronal apoptosis induced by CCI. mmu_circ_0000296 plays an important role in regulating neuronal apoptosis induced by CCI through miR-194-5p/Runx3/Sirt1 pathway.
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http://dx.doi.org/10.1038/s41420-021-00507-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164632PMC
May 2021

Impacts of the SOAT1 genetic variants and protein expression on HBV-related hepatocellular carcinoma.

BMC Cancer 2021 May 26;21(1):615. Epub 2021 May 26.

Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains a major public health problem and its pathogenesis remains unresolved. A recent proteomics study discovered a lipid enzyme Sterol O-acyltransferase (SOAT1) involvement in the progression of HCC. We aimed to explore the association between SOAT1 genetic variation and HCC.

Methods: We genotyped three exonic SOAT1 variants (rs10753191, V323V; rs3753526, L475L; rs13306731, Q526R) tagging most variations in the gene, in 221 HCC patients and 229 healthy individuals, to assess the impact of SOAT1 gene variation on risk of HCC occurrence. We further conducted immunohistochemistry to compare SOAT1 protein expression levels in 42 paired tumor and adjacent non-tumor tissues.

Results: We found that rs10753191 (Odds ratio (OR) = 0.58, P = 0.04) and a haplotype TGA (OR = 0.40, P = 0.01) were associated with reduced HCC risk after adjusting for lipid levels. In the immunohistochemistry experiment, we found that the protein expression of SOAT1 was significantly increased in the tumor compared with adjacent tissue (P < 0.001).

Conclusion: This study revealed for the first time SOAT1 genetic variation that associates with host susceptibility to HCC occurrence. Our results suggest a role of SOAT1 in the HCC development, which warrants further elucidation.
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http://dx.doi.org/10.1186/s12885-021-08245-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152151PMC
May 2021

The Epigenetic Modulation of Cancer and Immune Pathways in Hepatitis B Virus-Associated Hepatocellular Carcinoma: The Influence of HBx and miRNA Dysregulation.

Front Immunol 2021 29;12:661204. Epub 2021 Apr 29.

Hepatitis Virus Diversity Research Unit, School of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa.

Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) pathogenesis is fueled by persistent HBV infection that stealthily maintains a delicate balance between viral replication and evasion of the host immune system. HBV is remarkably adept at using a combination of both its own, as well as host machinery to ensure its own replication and survival. A key tool in its arsenal, is the HBx protein which can manipulate the epigenetic landscape to decrease its own viral load and enhance persistence, as well as manage host genome epigenetic responses to the presence of viral infection. The HBx protein can initiate epigenetic modifications to dysregulate miRNA expression which, in turn, can regulate downstream epigenetic changes in HBV-HCC pathogenesis. We attempt to link the HBx and miRNA induced epigenetic modulations that influence both the HBV and host genome expression in HBV-HCC pathogenesis. In particular, the review investigates the interplay between CHB infection, the silencing role of miRNA, epigenetic change, immune system expression and HBV-HCC pathogenesis. The review demonstrates exactly how HBx-dysregulated miRNA in HBV-HCC pathogenesis influence and are influenced by epigenetic changes to modulate both viral and host genome expression. In particular, the review identifies a specific subset of HBx induced epigenetic miRNA pathways in HBV-HCC pathogenesis demonstrating the complex interplay between HBV infection, epigenetic change, disease and immune response. The wide-ranging influence of epigenetic change and miRNA modulation offers considerable potential as a therapeutic option in HBV-HCC.
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http://dx.doi.org/10.3389/fimmu.2021.661204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117219PMC
October 2021

Electrodeposition immobilized molybdenum disulfide quantum dots and their electrochemiluminescence application in the detection of melamine residues in milk powder.

Anal Methods 2021 05;13(19):2196-2203

The Key Lab of Health Chemistry & Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering & Materials Science, Soochow University, Suzhou 215123, P. R. China.

In this paper, one-step hydrothermal and electrodeposition methods were used to prepare a MoS2 quantum dot (QD) solid-phase electrochemiluminescent (ECL) electrode for the detection of melamine residues in milk powder. With the assistance of chitosan, MoS2 QDs fixed by the one-step electrodeposition method show better ECL performance than those by traditional deposition methods due to better dispersibility and stability. Based on the quenching of the MoS2 QDs ECL signal by melamine, quantitative detection of melamine in the sample was performed. The structure and morphology of a MoS2-CHIT/indium tin oxide (ITO) solid-phase ECL electrode were characterized by TEM and XPS, and melamine was detected by the ECL method using a three-electrode system. The proposed sensor exhibited good linearity in the range of 1.00 × 10-11 to 1.00 × 10-7 mol L-1 (ΔI = 12 100.62 + 1009.93 lg c (mol L-1), R2 = 0.997), and the method shows the advantages of simplicity and sensitivity compared to traditional detection methods. The interference of common ions in milk powder on the modified electrode was within 5%, and the recovery rate of real sample detection was within 97-98%. As a result, the proposed method is suitable for detecting melamine residues in milk powder.
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http://dx.doi.org/10.1039/d1ay00364jDOI Listing
May 2021

Salinity Effects on Morpho-Physiological and Yield Traits of Soybean ( L.) as Mediated by Foliar Spray with Brassinolide.

Plants (Basel) 2021 Mar 13;10(3). Epub 2021 Mar 13.

Department of Soil Science, Faculty of Agriculture, Forestry and Wildlife Resources Management, University of Calabar, Calabar P.M.B. 1115, Nigeria.

Salinity episodes that are common in arid regions, characterized by dryland, are adversely affecting crop production worldwide. This study evaluated the effectiveness of brassinolide (BL) in ameliorating salinity stress imposed on soybean at four levels (control (1.10), 32.40, 60.60 and 86.30 mM/L NaCl) in factorial combination with six BL application frequency (control (BL), application at seedling (BL), flowering (BL), podding (BL), seedling + flowering (BL) and seedling + flowering + podding (BL)) stages. Plant growth attributes, seed yield, and N, P, K, Ca and Mg partitioning to leaves, stems and roots, as well as protein and seed-N concentrations, were significantly ( ≤ 0.05) reduced by salinity stress. These trends were ascribed to considerable impairments in the photosynthetic pigments, photosynthetically active radiation, leaf stomatal conductance and relative water content in the leaves of seedlings under stress. The activity of peroxidase and superoxidase significantly ( ≤ 0.05) increased with salinity. Foliar spray with BL significantly ( ≤ 0.05) improved the photosynthetic attributes, as well as nutrient partitioning, under stress, and alleviated ion toxicity by maintaining a favourable K/Na ratio and decreasing oxidative damage. Foliar spray with brassinolide could sustain soybean growth and seed yield at salt concentrations up to 60.60 mM/L NaCl.
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http://dx.doi.org/10.3390/plants10030541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000651PMC
March 2021

APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection.

Commun Biol 2021 03 5;4(1):284. Epub 2021 Mar 5.

Basic Research Laboratory, Molecular Genetic Epidemiology Section, Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

Apolipoprotein L1 (APOL1), an innate immune factor against African trypanosoma brucei, inhibits HIV-1 in vitro. The impact of APOL1 G1-G2 variants on HIV-1-associated opportunistic infections (OIs) is unknown. Here, we report findings from a metaanalysis of four HIV/AIDS prospective cohorts (ALIVE, LSOCA, MACS, and WIHS) including 2066 African American participants. Using a global test combining all four cohorts, carriage of two APOL1 variant alleles is associated with a 50% reduction in odds of OI (combined OR 0.50, 95% CI 0.33-0.76). Subgroup analysis of OI etiological categories (viral, parasitic, fungal and Mycobacterial) suggests the possibility of specific protection from fungal infections (OR 0.54. 95% CI 0.32-0.93; P = 0.08). We observe an association of APOL1 variant alleles with host protection against OI in HIV-positive individuals. The study suggests a broader role of APOL1 variant alleles in innate immunity in vivo.
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http://dx.doi.org/10.1038/s42003-021-01812-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977062PMC
March 2021

Immunosuppression as a risk factor for COVID-19: a meta-analysis.

Intern Med J 2021 02;51(2):199-205

Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia.

Background: While immunosuppression poses a theoretical increase in the risk of COVID-19, the nature of this relationship is yet to be ascertained.

Aims: To determine whether immunosuppressed patients are at higher risk of COVID-19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic.

Methods: We performed a random-effects meta-analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID-19.

Results: Sixty full-text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID-19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID-19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID-19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID-19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID-19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05-0.27).

Conclusions: Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID-19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID-19.
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http://dx.doi.org/10.1111/imj.15142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014211PMC
February 2021

Effect of Evodiamine on Rat Colonic Hypermotility Induced by Water Avoidance Stress and the Underlying Mechanism.

Drug Des Devel Ther 2021 10;15:441-452. Epub 2021 Feb 10.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People's Republic of China.

Background And Aim: EVO is a natural alkaloid that reportedly has potential value in regulating gastrointestinal motility, but this conclusion remains controversial, and the molecular mechanism is unclear. In this study, we aimed to explore the effect of short-chain fatty acids on rat colonic hypermotility induced by water avoidance stress and the underlying mechanism.

Methods: We constructed a hypermotile rat model by chronic water avoidance stress, and Western blot was used to detect the protein level of nNOS in colon tissue. The organ bath and multichannel physiological signal acquisition systems were used to examine the spontaneous contractions of smooth muscle strips. The whole-cell patch-clamp technique was used to investigate L-type voltage-dependent calcium and BK channel currents in colonic smooth muscle cells.

Results: EVO inhibited the spontaneous contractions of colonic smooth muscle strips in a dose-dependent manner. Moreover, EVO decreased the fecal output induced by chronic water avoidance stress. TTX did not block the inhibitory effect of EVO on spontaneous colon contractions, while L-NNA, a selective nNOS synthase inhibitor, did partially abolish this inhibitory effect. The protein expression of nNOS in the colon tissues of rats administered EVO was significantly increased compared to that in control rats. EVO reversibly inhibited the L-type calcium channel current without changing the steady-state activation or inactivation in colonic smooth muscle cells. EVO significantly inhibited the BK current but did not change the shape of the I-V curves.

Conclusion: EVO inhibits gastrointestinal motility by inhibiting L-type calcium and BK channels in colonic smooth muscle cells and indirectly interacting with nNOS.
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http://dx.doi.org/10.2147/DDDT.S298954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882800PMC
October 2021

CaMKII Mediates TGFβ1-Induced Fibroblasts Activation and Its Cross Talk with Colon Cancer Cells.

Dig Dis Sci 2021 Feb 2. Epub 2021 Feb 2.

Department of Gastroenterology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei, China.

Introduction: Cancer-associated fibroblasts (CAFs), as the activated fibroblasts in tumor stroma, are important modifiers of tumor progression. TGFβ1 has been the mostly accepted factor to fuel normal fibroblasts transformation into CAFs. Ca/calmodulin-dependent protein kinase II (CaMKII) is thought to play an important role in fibroblasts activation induced by TGFβ1. The aim of this study is to investigate the potential role of CaMKII in TGFβ1-induced fibroblasts activation and CAF-like differentiation. Cross talk between CaMKII-dependent fibroblasts and colon cancer in colon cancer progression also was addressed RESULTS: Immunostaining demonstrated that in colon cancer stroma, CaMKII overexpressed in stromal CAFs. In vitro, TGFβ1 increased CAF markers expression in human colon fibroblasts CCD-18Co, but not in CaMKII depletion fibroblasts. CaMKII knockdown by CaMKII shRNA significantly inhibited TGFβ1-induced fibroblasts activation and CAF-like differentiation. Smad3, AKT, and MAPK were targeted in TGFβ1-CaMKII-mediated pathway. Human colon cancer cell line HCT-116 activated fibroblasts directly, whereas CaMKII depletion dragged CCD-18Co fibroblasts undergoing CAF-associated trans-differentiation. Furthermore, increased proliferation, migration, and invasion of colon cancer cells were stimulated when co-cultured with normal fibroblasts, but not with CaMKII depletion fibroblasts.

Conclusions: These findings provide evidence that CaMKII is a critical mediator in TGFβ1-induced fibroblasts activation and is involved in the cross talk with colon cancer cells. CaMKII is a potentially effective target for future treatment of colon cancer.
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http://dx.doi.org/10.1007/s10620-021-06847-0DOI Listing
February 2021

Evaluation of the effects of an artificial intelligence system on endoscopy quality and preliminary testing of its performance in detecting early gastric cancer: a randomized controlled trial.

Endoscopy 2021 Jan 11. Epub 2021 Jan 11.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

Background:  Esophagogastroduodenoscopy (EGD) is a prerequisite for detecting upper gastrointestinal lesions especially early gastric cancer (EGC). An artificial intelligence system has been shown to monitor blind spots during EGD. In this study, we updated the system (ENDOANGEL), verified its effectiveness in improving endoscopy quality, and pretested its performance in detecting EGC in a multicenter randomized controlled trial.

Methods:  ENDOANGEL was developed using deep convolutional neural networks and deep reinforcement learning. Patients undergoing EGD in five hospitals were randomly assigned to the ENDOANGEL-assisted group or to a control group without use of ENDOANGEL. The primary outcome was the number of blind spots. Secondary outcomes included performance of ENDOANGEL in predicting EGC in a clinical setting.

Results:  1050 patients were randomized, and 498 and 504 patients in the ENDOANGEL and control groups, respectively, were analyzed. Compared with the control group, the ENDOANGEL group had fewer blind spots (mean 5.38 [standard deviation (SD) 4.32] vs. 9.82 [SD 4.98];  < 0.001) and longer inspection time (5.40 [SD 3.82] vs. 4.38 [SD 3.91] minutes;  < 0.001). In the ENDOANGEL group, 196 gastric lesions with pathological results were identified. ENDOANGEL correctly predicted all three EGCs (one mucosal carcinoma and two high grade neoplasias) and two advanced gastric cancers, with a per-lesion accuracy of 84.7 %, sensitivity of 100 %, and specificity of 84.3 % for detecting gastric cancer.

Conclusions:  In this multicenter study, ENDOANGEL was an effective and robust system to improve the quality of EGD and has the potential to detect EGC in real time.
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http://dx.doi.org/10.1055/a-1350-5583DOI Listing
January 2021

Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.

Nat Commun 2021 01 5;12(1):24. Epub 2021 Jan 5.

Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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http://dx.doi.org/10.1038/s41467-020-19366-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785747PMC
January 2021

Association Between Perioperative Glycemic Control Strategy and Mortality in Patients With Diabetes Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis.

Front Endocrinol (Lausanne) 2020 17;11:513073. Epub 2020 Dec 17.

Department of Endocrinology, Chinese PLA General Hospital, Beijing, China.

Objective: To analyze association between different perioperative glycemic control strategies and postoperative outcomes in patients with diabetes undergoing cardiac surgery.

Methods: MEDLINE, Cochrane Library, Web of Science, EMBASE, Wanfang Data, China National Knowledge Infrastructure (CNKI) and China Biology Medicine (CBM) databases were searched from inception to January 31, 2019. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias of included studies, and consensus was reached by discussion with a third researcher.

Results: Six RCTs were included in the meta-analysis. We analyzed the effect of liberal (>180 mg/dl or 10.0 mmol/L), moderate (140-180 mg/dl or 7.8-10.0 mmol/L) and strict (<140 mg/dl or 7.8 mmol/L) glycemic control strategies in patients with diabetes undergoing cardiac surgery. The pooled results showed that strict glycemic control strategy was associated with a significant reduction in the risk of atrial fibrillation [OR = 0.48, 95%CI (0.32, 0.72), < 0.001] and sternal wound infection [OR = 0.28, 95%CI (0.14, 0.54), < 0.001], while there was no significant differences in postoperative mortality, stroke, and hypoglycemic episodes when compared with moderate control. In addition, there is no significant difference between moderate and liberal glycemic control strategies in postoperative mortality. However, moderate control was beneficial in reducing atrial fibrillation [OR = 0.28, 95%CI (0.13, 0.60), = 0.001] compared with the liberal glycemic control strategy.

Conclusions: This meta-analysis showed when compared with moderate glycemic control strategy in patients with diabetes undergoing cardiac surgery, maintained strict glycemic control was associated with lower risk of atrial fibrillation and sternal wound infection. No benefit was found with liberal glycemic control strategy, so it could be a poor glycemic control strategy.
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http://dx.doi.org/10.3389/fendo.2020.513073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774648PMC
May 2021

Single-Cell Transcriptomics Reveals a Heterogeneous Cellular Response to BK Virus Infection.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

BK virus (BKV) is a human polyomavirus that is generally harmless but can cause devastating disease in immunosuppressed individuals. BKV infection of renal cells is a common problem for kidney transplant patients undergoing immunosuppressive therapy. In cultured primary human renal proximal tubule epithelial (RPTE) cells, BKV undergoes a productive infection. The BKV-encoded large T antigen (LT) induces cell cycle entry, resulting in the upregulation of numerous genes associated with cell proliferation. Consistently, microarray and transcriptome sequencing (RNA-seq) experiments performed on bulk infected cell populations identified several proliferation-related pathways that are upregulated by BKV. These studies revealed few genes that are downregulated. In this study, we analyzed viral and cellular transcripts in single mock- or BKV-infected cells. We found that the levels of viral mRNAs vary widely among infected cells, resulting in different levels of LT and viral capsid protein expression. Cells expressing the highest levels of viral transcripts account for approximately 20% of the culture and have a gene expression pattern that is distinct from that of cells expressing lower levels of viral mRNAs. Surprisingly, cells expressing low levels of viral mRNA do not progress with time to high expression, suggesting that the two cellular responses are determined prior to or shortly following infection. Finally, comparison of cellular gene expression patterns of cells expressing high levels of viral mRNA with those of mock-infected cells or cells expressing low levels of viral mRNA revealed previously unidentified pathways that are downregulated by BKV. Among these are pathways associated with drug metabolism and detoxification, tumor necrosis factor (TNF) signaling, energy metabolism, and translation. The outcome of viral infection is determined by the ability of the virus to redirect cellular systems toward progeny production countered by the ability of the cell to block these viral actions. Thus, an infected culture consists of thousands of cells, each fighting its own individual battle. Bulk measurements, such as PCR or RNA-seq, measure the average of these individual responses to infection. Single-cell transcriptomics provides a window to the one-on-one battle between BKV and each cell. Our studies reveal that only a minority of infected cells are overwhelmed by the virus and produce large amounts of BKV mRNAs and proteins, while the infection appears to be restricted in the remaining cells. Correlation of viral transcript levels with cellular gene expression patterns reveals pathways manipulated by BKV that may play a role in limiting infection.
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http://dx.doi.org/10.1128/JVI.02237-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094954PMC
February 2021

Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4 mouse model of PFIC3.

J Hepatol 2021 06 17;74(6):1416-1428. Epub 2020 Dec 17.

Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. Electronic address:

Background & Aims: Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation.

Methods: We have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs). We examined their pharmacological effects in a cell-based model and in a new in vivo mouse model resembling human PFIC3 as a result of homozygous disruption of the Abcb4 gene in fibrosis-susceptible BALB/c.Abcb4 mice.

Results: We show that treatment with liver-targeted hABCB4 mRNA resulted in de novo expression of functional hABCB4 protein and restored phospholipid transport in cultured cells and in PFIC3 mouse livers. Importantly, repeated injections of the hABCB4 mRNA effectively rescued the severe disease phenotype in young Abcb4 mice, with rapid and dramatic normalisation of all clinically relevant parameters such as inflammation, ductular reaction, and liver fibrosis. Synthetic mRNA therapy also promoted favourable hepatocyte-driven liver regeneration to restore normal homeostasis, including liver weight, body weight, liver enzymes, and portal vein blood pressure.

Conclusions: Our data provide strong preclinical proof-of-concept for hABCB4 mRNA therapy as a potential treatment option for patients with PFIC3.

Lay Summary: This report describes the development of an innovative mRNA therapy as a potential treatment for PFIC3, a devastating rare paediatric liver disease with no treatment options except liver transplantation. We show that administration of our mRNA construct completely rescues severe liver disease in a genetic model of PFIC3 in mice.
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http://dx.doi.org/10.1016/j.jhep.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188846PMC
June 2021

Association between Neck Circumference and the Risk of Decreased Estimated Glomerular Filtration Rate in the General Population of China: A Cross-Sectional Study.

Biomed Res Int 2020 23;2020:3496328. Epub 2020 Nov 23.

Medical School of Chinese PLA, Beijing, China.

Background: The burden of chronic kidney disease is increasing substantially worldwide. Neck circumference (NC), an anthropometric index for upper-body adiposity, has been recognized as an indicator of cardiometabolic diseases. However, the association between NC and renal dysfunction has not been fully disclosed.

Objectives: The aim of this study was to investigate the association between NC and estimated glomerular filtration rate (eGFR) in the general population in China.

Methods: A total of 8805 participants (3322 men and 5483 women) were enrolled in this study. Logistic regression analysis was conducted to examine the association between NC and eGFR. The male and female subjects were divided into four groups according to the NC quartiles. The primary outcome was defined as an eGFR ≤ 90 mL/min/1.73 m.

Results: Logistic regression analysis revealed that in both sexes, higher NC was significantly associated with a higher risk of decreased eGFR even after fully adjusting for age, other anthropometric indexes, traditional risk factors for chronic kidney diseases, and sociologic risk factors (quartile 1 as a reference; the odds ratios [95% confidence intervals] were as follows: quartile 2, 1.26 [0.99-1.59]; quartile 3, 1.40 [1.07-1.83]; and quartile 4, 1.71 [1.22-2.38], in men; quartile 2, 1.14 [0.95-1.37]; quartile 3, 1.31 [1.03-1.66]; and quartile 4, 1.32 [1.04-1.68], in women). Stratified analyses suggested that the association was significant among subjects with prediabetes or normal serum uric acid levels and those without cardiovascular diseases (CVD). Among subjects with CVD, the association persisted only in males. When the subjects were stratified according to blood pressure or BMI, the association persisted among male subjects with abnormal blood pressure and was strengthened among male subjects who were overweight/obese, while the association disappeared among female subjects.

Conclusions: NC is independently associated with the risk of decreased eGFR in the general population in China, indicating that NC could contribute to renal dysfunction risk assessment.
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http://dx.doi.org/10.1155/2020/3496328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707937PMC
June 2021

Development of Indoleamine 2,3-Dioxygenase 1 Inhibitors for Cancer Therapy and Beyond: A Recent Perspective.

J Med Chem 2020 12 20;63(24):15115-15139. Epub 2020 Nov 20.

Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 211100, People's Republic of China.

Indoleamine 2,3-dioxygenase 1 (IDO1) has received increasing attention due to its immunosuppressive function in connection with various diseases, including cancer. A recent increase in the understanding of IDO1 has significantly contributed to the discovery of numerous novel inhibitors, but the latest clinical outcomes raised questions and have indicated a future direction of IDO1 inhibition for therapeutic approaches. Herein, we present a comprehensive review of IDO1, discussing the latest advances in understanding the IDO1 structure and mechanism, an overview of recent IDO1 inhibitor discoveries and potential therapeutic applications to provide helpful information for medicinal chemists investigating IDO1 inhibitors.
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http://dx.doi.org/10.1021/acs.jmedchem.0c00925DOI Listing
December 2020

Gastrointestinal Symptoms Onset in COVID-19 Patients in Wuhan, China.

Dig Dis Sci 2021 10 12;66(10):3578-3587. Epub 2020 Nov 12.

Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, 430060, Hubei Province, China.

Background: Early detection is critical in limiting the spread of 2019 novel coronavirus (COVID-19). Although previous data revealed characteristics of GI symptoms in COVID-19, for patients with only GI symptoms onset, their diagnostic process and potential transmission risk are still unclear.

Methods: We retrospectively reviewed 205 COVID-19 cases from January 16 to March 30, 2020, in Renmin Hospital of Wuhan University. All patients were confirmed by virus nuclei acid tests. The clinical features and laboratory and chest tomographic (CT) data were recorded and analyzed.

Results: A total of 171 patients with classic symptoms (group A) and 34 patients with only GI symptoms (group B) were included. In patients with classical COVID-19 symptoms, GI symptoms occurred more frequently in severe cases compared to non-severe cases (20/43 vs. 91/128, respectively, p < 0.05). In group B, 91.2% (31/34) patients were non-severe, while 73.5% (25/34) patients had obvious infiltrates in their first CT scans. Compared to group A, group B patients had a prolonged time to clinic services (5.0 days vs. 2.6 days, p < 0.01) and a longer time to a positive viral swab normalized to the time of admission (6.9 days vs. 3.3 days, respectively, p < 0.01). Two patients in group B had family clusters of SARS-CoV-2 infection.

Conclusion: Patients with only GI symptoms of COVID-19 may take a longer time to present to healthcare services and receive a confirmed diagnosis. In areas where infection is rampant, physicians must remain vigilant of patients presenting with acute gastrointestinal symptoms and should do appropriate personal protective equipment.
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http://dx.doi.org/10.1007/s10620-020-06693-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658436PMC
October 2021
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