Publications by authors named "Wenjun Fan"

73 Publications

The potential population health impact of treating REDUCE-IT eligible US adults with Icosapent Ethyl.

Am J Prev Cardiol 2022 Jun 28;10:100345. Epub 2022 Apr 28.

MedStar Health Research Institute, Georgetown University, Washington, DC.

Objective: To explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs.

Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59.

Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion).

Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.
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http://dx.doi.org/10.1016/j.ajpc.2022.100345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097618PMC
June 2022

Evaluation Exploration of Atlas-Based and Deep Learning-Based Automatic Contouring for Nasopharyngeal Carcinoma.

Front Oncol 2022 31;12:833816. Epub 2022 Mar 31.

Department of Radiation Oncology, The First Medical Center of the Chinese PLA General Hospital, Beijing, China.

Purpose: The purpose of this study was to evaluate and explore the difference between an atlas-based and deep learning (DL)-based auto-segmentation scheme for organs at risk (OARs) of nasopharyngeal carcinoma cases to provide valuable help for clinical practice.

Methods: 120 nasopharyngeal carcinoma cases were established in the MIM Maestro (atlas) database and trained by a DL-based model (AccuContour), and another 20 nasopharyngeal carcinoma cases were randomly selected outside the atlas database. The experienced physicians contoured 14 OARs from 20 patients based on the published consensus guidelines, and these were defined as the reference volumes (V). Meanwhile, these OARs were auto-contoured using an atlas-based model, a pre-built DL-based model, and an on-site trained DL-based model. These volumes were named V, V, and V, respectively. The similarities between V, V, V, and V were assessed using the Dice similarity coefficient (DSC), Jaccard coefficient (JAC), maximum Hausdorff distance (HD), and deviation of centroid (DC) methods. A one-way ANOVA test was carried out to show the differences (between each two of them).

Results: The results of the three methods were almost similar for the brainstem and eyes. For inner ears and temporomandibular joints, the results of the pre-built DL-based model are the worst, as well as the results of atlas-based auto-segmentation for the lens. For the segmentation of optic nerves, the trained DL-based model shows the best performance (p < 0.05). For the contouring of the oral cavity, the DSC value of V is the smallest, and V is the most significant (p < 0.05). For the parotid glands, the DSC of V is the minimum (about 0.80 or so), and V and V are slightly larger (about 0.82 or so). In addition to the oral cavity, parotid glands, and the brainstem, the maximum Hausdorff distances of the other organs are below 0.5 cm using the trained DL-based segmentation model. The trained DL-based segmentation method behaves well in the contouring of all the organs that the maximum average deviation of the centroid is no more than 0.3 cm.

Conclusion: The trained DL-based segmentation performs significantly better than atlas-based segmentation for nasopharyngeal carcinoma, especially for the OARs with small volumes. Although some delineation results still need further modification, auto-segmentation methods improve the work efficiency and provide a level of help for clinical work.
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http://dx.doi.org/10.3389/fonc.2022.833816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008357PMC
March 2022

Acute coronary syndromes in diabetes: Biomarkers of endothelial injury improve risk stratification and help identify predictors of risk.

Diabetes Metab Syndr 2022 Apr 28;16(4):102476. Epub 2022 Mar 28.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine School of Medicine, Irvine, CA, United States. Electronic address:

Background And Aims: Patients with diabetes mellitus (DM) are at an increased risk of acute coronary syndrome (ACS); however, the factors predicting those at highest risk are not well understood. We identified risk factors in those with DM that best predict high ACS risk based on a multiple endothelial injury biomarker algorithm.

Methods: We studied adults with DM from a clinical registry with measures of a coronary artery disease prediction algorithm (CADPA) score identifying 5-year ACS risk from nine markers. Stepwise logistic regression provided odds ratios for the relationship of age, gender, and individual risk factors not part of the CADPA algorithm with the likelihood of a high risk CADPA score.

Results: We studied 1,613 adults with DM (women: 47.3%, ages 22 to 100, mean age 63.2 years). Of these, 6.1% had a low, 13.2% intermediate, and 80.7% high risk CADPA score. From stepwise logistic regression, women were less likely to have a high risk CADPA score (odds ratio [OR] 0.21, 95% confidence intervals [CI] 0.15-0.29, p<.0001), while age (per standard deviation [SD]) (OR 5.04, [4.12-6.17], p<.0001), body mass index (BMI per SD) (OR 1.34, [1.14-1.58], p = 0.004), hypertension (OR 1.60, [1.15-2.24], p = 0.006), current smoking (OR 2.55, [1.56-4.16], p = 0.0002), hsCRP (per SD) (OR 1.24, [1.01-1.53], p = 0.04), and triglycerides (per SD) (OR 1.26, [1.04-1.54], p = 0.02) were more likely to have a high risk CADPA score.

Conclusions: Age, men, hypertension, BMI, current smoking, hsCRP, and triglycerides are key factors in those with DM associated with higher ACS risk.
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http://dx.doi.org/10.1016/j.dsx.2022.102476DOI Listing
April 2022

Nuclear Aurora kinase A switches mA reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4.

Signal Transduct Target Ther 2022 Apr 1;7(1):97. Epub 2022 Apr 1.

Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.

Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression, yet how this process is regulated by oncogenic signal remains largely unknown. Here, we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by mA reader YTHDC1 in lung cancer. Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing, specifically triggering RBM4 splicing from the full isoform (RBM4-FL) to the short isoform (RBM4-S) in a kinase-independent manner. RBM4-S functions as a tumor promoter by abolishing RBM4-FL-mediated inhibition of the activity of the SRSF1-mTORC1 signaling pathway. Mechanistically, AURKA disrupts the binding of SRSF3 to YTHDC1, resulting in the inhibition of RBM4-FL production induced by the mA-YTHDC1-SRSF3 complex. In turn, AURKA recruits hnRNP K to YTHDC1, leading to an mA-YTHDC1-hnRNP K-dependent exon skipping to produce RBM4-S. Importantly, the small molecules that block AURKA nuclear translocation, reverse the oncogenic splicing of RBM4 and significantly suppress lung tumor progression. Together, our study unveils a previously unappreciated role of nuclear AURKA in mA reader YTHDC1-dependent oncogenic RNA splicing switch, providing a novel therapeutic route to target nuclear oncogenic events.
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http://dx.doi.org/10.1038/s41392-022-00905-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971511PMC
April 2022

TET2 Regulates 5-Hydroxymethylcytosine Signature and CD4 T-Cell Balance in Allergic Rhinitis.

Allergy Asthma Immunol Res 2022 03;14(2):254-272

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Purpose: Previous studies have shown the role of ten-eleven translocation 2 (TET2) in CD4 T cells. However, its function in CD4 T cells under allergic inflammation is unclear. We aimed to investigate the epigenomic distribution of DNA 5-hydroxymethylcytosine (5hmC) and the role of TET2 in CD4 T cells of allergic rhinitis (AR).

Methods: The hMeDIP-seq was performed to identify sequences with 5hmC deposition in CD4 T cells of AR patients. -deficient or wild type mice were stimulated with ovalbumin (OVA) to develop an AR mouse model. The histopathology in nasal mucosae, Th1/Th2/Treg/Th17 cell percentage, concentrations of Th-related cytokines, expression of Tets and differential hydroxymethylated genes (DhMG), and the global deposition of 5hmC in sorted CD4 T cells were detected.

Results: Epigenome-wide 5hmC landscape and DhMG in the CD4 T cells of AR patients were identified. depletion did not led to spontaneous inflammation. However, under the stimulation of allergen, OVA, loss of resulted in the exacerbation of allergic inflammation, which was characterized by severer allergic symptoms, more inflammatory cells infiltrating the nasal lamina propria, sharper imbalances between Th1/Th2 and Treg/Th17 cells, and excessive secretion of OVA-specific IgE and Th2-related cytokines. Moreover, altered mRNA production of several DhMG and sharp decrease in 5hmC deposition were also observed in -deficient OVA-exposed mice.

Conclusions: TET2 may regulate DNA 5hmC, DhMG expressions, and CD4 T cell balance in AR.
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http://dx.doi.org/10.4168/aair.2022.14.2.254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8914607PMC
March 2022

Correlation of common inflammatory cytokines with cognition impairment, anxiety, and depression in acute ischemic stroke patients.

Braz J Med Biol Res 2022 28;55:e11517. Epub 2022 Feb 28.

Nursing Department Office, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Inflammatory cytokines are related to cognitive function and psychiatric disorders in patients with several diseases. However, few relevant studies have been performed on acute ischemic stroke (AIS) patients. Hence, this study aimed to investigate the correlation of common inflammatory cytokines with cognition impairment, anxiety, and depression in AIS patients. Common inflammatory cytokines of 176 AIS patients (including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, and IL-17) were measured using Human Enzyme Linked Immunosorbent Assay Kits. Cognition impairment (Mini-Mental State Examination (MMSE)), anxiety (Hospital Anxiety and Depression Scale for anxiety (HADS-A)), and depression (HADS-D) were evaluated. The incidence of cognition impairment, anxiety, and depression was 43.2, 39.2, and 31.2%, respectively. TNF-α and IL-6 were negatively associated with MMSE score, and high TNF-α, IL-1β, and IL-6 were correlated with cognition impairment occurrence. In addition, TNF-α, IL-1β, and IL-17 were positively associated with HADS-A score, while only high TNF-α was associated with anxiety occurrence. Furthermore, TNF-α, IL-1β, and IL-17 were positively associated with HADS-D score, while high IL-1β, IL-6, and IL-17 correlated with depression occurrence. Multivariate logistic regression revealed that TNF-α and National Institutes of Health Stroke Scale (NIHSS) score ≥5 were associated with high risk of cognition impairment; TNF-α, IL-17, unemployed before surgery, hypertension, and chronic kidney disease (CKD) correlated with high anxiety occurrence. Furthermore, IL-17, divorced/widowed/single status, diabetes, and NIHSS score ≥5 were associated with high risk of depression. In conclusion, common inflammatory cytokines including TNF-α, IL-1β, and IL-17 were related to cognition impairment, anxiety, or depression in AIS patients.
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http://dx.doi.org/10.1590/1414-431X2021e11517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8905669PMC
March 2022

Widespread genetic heterogeneity of human ribosomal RNA genes.

RNA 2022 Apr 2;28(4):478-492. Epub 2022 Feb 2.

Department of Radiation Oncology and Molecular Radiation Sciences, and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

Polymorphism drives survival under stress and provides adaptability. Genetic polymorphism of ribosomal RNA (rRNA) genes derives from internal repeat variation of this multicopy gene, and from interindividual variation. A considerable amount of rRNA sequence heterogeneity has been proposed but has been challenging to estimate given the scarcity of accurate reference sequences. We identified four rDNA copies on chromosome 21 (GRCh38) with 99% similarity to recently introduced reference sequence KY962518.1. We customized a GATK bioinformatics pipeline using the four rDNA loci, spanning a total 145 kb, for variant calling and used high-coverage whole-genome sequencing (WGS) data from the 1000 Genomes Project to analyze variants in 2504 individuals from 26 populations. We identified a total of 3791 variant positions. The variants positioned nonrandomly on the rRNA gene. Invariant regions included the promoter, early 5' ETS, most of 18S, 5.8S, ITS1, and large areas of the intragenic spacer. A total of 470 variant positions were observed on 28S rRNA. The majority of the 28S rRNA variants were located on highly flexible human-expanded rRNA helical folds ES7L and ES27L, suggesting that these represent positions of diversity and are potentially under continuous evolution. Several variants were validated based on RNA-seq analyses. Population analyses showed remarkable ancestry-linked genetic variance and the presence of both high penetrance and frequent variants in the 5' ETS, ITS2, and 28S regions segregating according to the continental populations. These findings provide a genetic view of rRNA gene array heterogeneity and raise the need to functionally assess how the 28S rRNA variants affect ribosome functions.
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http://dx.doi.org/10.1261/rna.078925.121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8925967PMC
April 2022

Longitudinal assessment of anxiety/depression rates and their related predictive factors in acute ischemic stroke patients: A 36-month follow-up study.

Medicine (Baltimore) 2021 Dec;100(50):e28022

Department of Rehabilitation Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract: This study aimed at investigating the longitudinal changes of poststroke anxiety/depression rates, and their potential risk factors in acute ischemic stroke (AIS) patients.A total of 250 first diagnosis of AIS patients were enrolled and followed for 36 months. Anxiety/depression of patients were assessed using hospital anxiety and depression scale (HADS) at month (M) 0 (M0) and then every 3 months till M36.During 36-month follow-up, both HADS-anxiety score (from 6.9 ± 3.1 at M0 to 8.0 ± 3.5 at M36) and anxiety rate (from 41.2% at M0 to 54.0% at M36) (both P < .01) were increased with time longitudinally. Meanwhile, HADS-depression score (from 6.2 ± 3.0 at M0 to 6.9 ± 3.1 at M36) and depression rate (from 32.4% at M0 to 40.4% at M36) (both P > .05) displayed an upward trend with time longitudinally but without statistical significance. By forward multivariate logistic regression analysis, female, diabetes and higher National Institute of Health Stroke Scale (NIHSS) score independently predicted elevated anxiety risk at M0, M12, M24, and M36 (all P < .05); while longer education duration and hypertension independently predicted raised anxiety risk at M0 and M12 (all P < .05), respectively. Regarding depression, diabetes independently predicted increased depression risk at M0, M12, M24, and M36 (all P < .01); longer education duration independently predicted higher depression risk at M0 and M12 (both P < .05); female independently predicted increased depression risk at M24 and M36 (both P < .01); higher NIHSS score independently predicted raised depression risk at M24 and M36 (both P < .01).Poststroke anxiety and depression are frequent, which deteriorate with time; besides, female, diabetes, NIHSS score, hypertension and education duration independently predicted increased poststroke anxiety or depression risk in AIS patients.
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http://dx.doi.org/10.1097/MD.0000000000028022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677976PMC
December 2021

Topological DNA Tetrahedron Encapsulated Gold Nanoparticle Enables Precise Ligand Engineering for Targeted Cell Imaging.

Anal Chem 2021 12 15;93(51):17036-17042. Epub 2021 Dec 15.

Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

Ligand-functionalized plasmonic nanoparticles have been widely used for targeted imaging in living systems. However, ligand presentation and encoding on the nanoparticle's surface in a stoichiometrically controllable manner remains a great challenge. Herein, we propose a method to construct ligand-engineered plasmonic nanoprobes by using nanoparticle encapsulation with topological DNA tetrahedrons, which enables the programmed ligand loading for precise regulation of targeting efficiency of nanoprobes in biorelated applications. With this method, we demonstrated the preparation of functionalized plasmonic nanoprobes by programmed loading of RGD peptides and aptamers onto the DNA tetrahedron encapsulated gold nanoparticles with controllable stoichiometric ratios. The cell imaging and particle counting assays suggested that the targeting efficiency of the nanoprobes could be readily modulated by tailoring the number and stoichiometric ratios of the loaded ligands, respectively. It can be anticipated that this robust strategy could provide new opportunities for the construction of efficacious nanoprobes and delivery systems for versatile bioapplications.
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http://dx.doi.org/10.1021/acs.analchem.1c03682DOI Listing
December 2021

Relevance of the microbial community to Sb and As biogeochemical cycling in natural wetlands.

Sci Total Environ 2022 Apr 22;818:151826. Epub 2021 Nov 22.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, School of Environmental Science and Engineering, Guangzhou University, Guangzhou 510006, China. Electronic address:

Mining activities lead to elevated levels of antimony (Sb) and arsenic (As) in river systems, having adverse effects on the aquatic environment and human health. Microbes inhabiting river sediment can mediate the transformation of Sb and As, thus changing the toxicity and mobility of Sb and As. Compared to river sediments, natural wetlands could introduce distinct geochemical conditions, leading to the formation of different sedimentary microbial compositions between river sediments and wetland sediments. However, whether such changes in microbial composition could influence the microbially mediated geochemical behavior of Sb or As remains poorly understood. In this study, we collected samples from a river contaminated by Sb tailings and a downstream natural wetland to study the influence of microorganisms on the geochemical behavior of Sb and As after the Sb/As-contaminated river entered the natural wetland. We found that the microbial compositions in the natural wetland soil differed from those in the river sediment. The Sb/As contaminant components (Sb(III), As(III), As(V), As) and nutrients (TC) were important determinants of the difference in the compositions of the microbial communities in the two environments. Taxonomic groups were differentially enriched between the river sediment and wetland soil. For example, the taxonomic groups Xanthomonadales, Clostridiales and Desulfuromonadales were important in the wetland and were likely to involve in Sb/As reduction, sulfate reduction and Fe(III) reduction, whereas Burkholderiales, Desulfobacterales, Hydrogenophilales and Rhodocyclales were important taxonomic groups in the river sediments and were reported to involve in Sb/As oxidation and sulfide oxidation. Our results suggest that microorganisms in both river sediments and natural wetlands can affect the geochemical behavior of Sb/As, but the mechanisms of action are different.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151826DOI Listing
April 2022

Nomograms Based on the Advanced Lung Cancer Inflammation Index for the Prediction of Coronary Artery Disease and Calcification.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211060455

117914The Affiliated Hospital of Chengde Medical University, Chengde, HeBei, China.

Aim: To develop and validate 3 nomograms incorporating the advanced lung cancer inflammation index (ALI) that can aid in predicting the risk of coronary artery disease (CAD) and coronary artery calcification (CAC).

Methods: The study enrolled 562 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography between September 2015 and June 2017. Independent risk factors for CAD, CAC, and CAD with CAC were identified via univariate and multivariate analysis, and nomograms were established based on the independent predictors identified. The area under the curve (AUC), calibration curve, and decision curve analysis were used to evaluate the nomograms. Correlations between ALI and other clinical indicators were examined via Spearman correlation analysis.

Results: In total, 549 patients with suspected CAD who underwent coronary computed tomographic angiography were included. Male sex, hypertension, diabetes, dyslipidemia, ischemic stroke, and ALI were independent predictors of both CAD and CAC. Male sex, hypertension, diabetes, dyslipidemia, and ALI were also identified as independent predictors of CAD with CAC. The AUC values for the nomograms developed using these risk factors were 0.739 (95% confidence interval [CI], 0.693-0.785), 0.728 (95% CI, 0.684-0.772), and 0.717 (95% CI 0.673-0.761), respectively. ALI was negatively correlated with neutrophil-to-lymphocyte ratio and CAC score and positively correlated with serum albumin levels and body mass index (all  < .05).

Conclusions: ALI is an independent predictor of CAD, CAC, and CAD with CAC. Our ALI-based nomograms can provide accurate and individualized risk predictions for patients with suspected CAD.
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http://dx.doi.org/10.1177/10760296211060455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619753PMC
March 2022

Activation of Dopamine D2 Receptor Alleviates Neuroinflammation in a Mouse Model of Allergic Rhinitis With Olfactory Dysfunction.

Allergy Asthma Immunol Res 2021 Nov;13(6):882-895

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Purpose: Allergic rhinitis (AR) is a common otolaryngology disease and one of the clinical causes of olfactory dysfunction (OD). The olfactory bulb serves as a transfer station for olfactory information transmission, and alleviating its neuroinflammation may be expected to improve AR-induced OD. Recent studies have suggested that the dopamine D2 receptor acts as a key target in regulating immune functions and neuroinflammatory reaction. However, the effect of dopamine D2 receptor on AR-induced neuroinflammation is still unknown.

Methods: An AR mouse model with OD induced by ovalbumin were constructed. The buried food pellet test was to evaluate the olfactory function of the mice. Immunofluorescence staining, hematoxylin and eosin staining, enzyme-linked immunosorbent assay and western blotting were also used to investigate the molecular mechanisms underlying the anti-inflammatory effects of the dopamine D2 receptor in AR-induced OD.

Results: We found that AR-induced OD has a relationship with inflammatory responses in the olfactory bulb. Nasal administration of quinpirole (Quin, a dopamine D2 receptor agonist, 3 mg/kg) improved olfactory function in mice, inhibited the expression of toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalings and the levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 in the olfactory bulb. , Quin (20 μmol/L) inhibited the release of TLR4/NF-κB signalings-dependent inflammatory cytokines in cultured microglia.

Conclusions: Activation of the dopamine D2 receptor inhibits the release of inflammatory cytokines through TLR4/NF-κB signaling in the olfactory bulb microglia, and protects olfactory function.
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http://dx.doi.org/10.4168/aair.2021.13.6.882DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569020PMC
November 2021

Neuroprotective effects of dopamine D2 receptor agonist on neuroinflammatory injury in olfactory bulb neurons in vitro and in vivo in a mouse model of allergic rhinitis.

Neurotoxicology 2021 12 5;87:174-181. Epub 2021 Oct 5.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Available evidence indicates that dopamine D2 receptor modulates the neurotoxic effects induced by glutamate. However, neurotoxicity mediated by AMPA-subtype glutamate receptor has rarely been studied in the olfactory bulb. This study mainly explores the neuroprotective effects of dopamine D2 receptor agonist on AMPA receptor-mediated neurotoxicity in the olfactory bulb in a mouse model of allergic rhinitis (AR) with olfactory dysfunction (OD). In our study, we found that AR with OD was closely associated with increased surface expression of the AMPA receptor GluR1, reduced surface expression of GluR2, and apoptosis damage in the olfactory bulb in vivo. Quinpirole (a dopamine D2 receptor agonist) improved olfactory function in mice, ameliorated apoptosis injury in the olfactory bulb but not in the olfactory mucosa, and inhibited the internalization of GluR2-containing AMPA receptor in vitro and in vivo. In addition, phosphorylation plays a crucial role in the regulation of AMPA receptor trafficking. Our results showed that quinpirole reduced the phosphorylation of GluR1 S845 and GluR2 S880 in olfactory bulb neurons in vitro, but it had no obvious effect on GluR1 S831. Therefore, dopamine D2 receptor agonist may inhibit the phosphorylation of GluR1 S845 and GluR2 S880, thereby reducing AMPA receptor-mediated neurotoxicity and alleviating neurotoxic injury to the olfactory bulb caused by AR.
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http://dx.doi.org/10.1016/j.neuro.2021.10.001DOI Listing
December 2021

Association of cardiovascular health with mortality among COPD patients: National Health and Nutrition Examination Survey III.

Respir Med Res 2021 Nov 9;80:100860. Epub 2021 Sep 9.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, CA, U SA. Electronic address:

Background: All-cause and cardiovascular disease (CVD) mortality are higher among patients with chronic obstructive pulmonary disease (COPD). We examined the association between American Heart Association's Life's Simple 7 (LS7) metrics and all-cause as well as CVD mortality in patients with COPD.

Methods: We examined 1513 US adults with COPD aged ≥ 40, without prior CVD, from the National Health and Nutrition Examination Survey III. COPD was defined as FEV/FVC<0.7 in absence of asthma. Adjusted Cox regression was used to assess the relation of LS7 metrics with all-cause and CVD mortality.

Results: Overall, only 74 participants (4.9%) had ideal 5-7 LS7 metrics. Over a mean follow-up of 14.2±7.9 years, 1162 individuals died, of which 315 were due to CVD. Age, sex, and ethnicity-adjusted HRs (95% CI) for all-cause mortality were 0.53 (0.41-0.68), 0.45 (0.34-0.59), 0.66 (0.49-0.87) and 0.75 (0.56-1.00) among those with ideal vs poor control of smoking, diet, physical activity and fasting blood glucose, respectively. However, the ideal and intermediate LS7 metrics were not significantly associated with lower risk of CVD mortality, except for a BMI between 25-29.9 kg/m. Those with 5-7 vs 0-1 ideal metrics had adjusted HRs 0.50 (0.40-0.87) for all-cause and 0.53 (0.21-1.36) for CVD mortality.

Conclusion: Ideal levels of multiple behavioral and health factors are associated with substantially lower risks for all-cause mortality, with a trend for lower CVD mortality among US adults with COPD.
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http://dx.doi.org/10.1016/j.resmer.2021.100860DOI Listing
November 2021

Targeting cancer cell plasticity by HDAC inhibition to reverse EBV-induced dedifferentiation in nasopharyngeal carcinoma.

Signal Transduct Target Ther 2021 09 4;6(1):333. Epub 2021 Sep 4.

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China.

Application of differentiation therapy targeting cellular plasticity for the treatment of solid malignancies has been lagging. Nasopharyngeal carcinoma (NPC) is a distinctive cancer with poor differentiation and high prevalence of Epstein-Barr virus (EBV) infection. Here, we show that the expression of EBV latent protein LMP1 induces dedifferentiated and stem-like status with high plasticity through the transcriptional inhibition of CEBPA. Mechanistically, LMP1 upregulates STAT5A and recruits HDAC1/2 to the CEBPA locus to reduce its histone acetylation. HDAC inhibition restored CEBPA expression, reversing cellular dedifferentiation and stem-like status in mouse xenograft models. These findings provide a novel mechanistic epigenetic-based insight into virus-induced cellular plasticity and propose a promising concept of differentiation therapy in solid tumor by using HDAC inhibitors to target cellular plasticity.
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http://dx.doi.org/10.1038/s41392-021-00702-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418605PMC
September 2021

Changes in Resting-State Spontaneous Brain Activity in Patients With Allergic Rhinitis: A Pilot Neuroimaging Study.

Front Neurosci 2021 14;15:697299. Epub 2021 Jul 14.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Allergic rhinitis (AR) is an inflammatory disorder of the nose caused by immunoglobulin E (IgE)-mediated immune response to allergens. Apart from the typical symptoms of sneezing, itching, rhinorrhea, and nasal congestion, behavioral complications were also reported to be associated with the progression of AR, such as cognitive deficits, mood changes, memory decline, attention deficiency, poor school performance, anxiety, and depression. Recent human studies have suggested that alterations in brain function caused by allergen exposure may precipitate high levels of anxiety and emotional reactivity in asthma patients. But until now, there is no direct evidence of the relationship between brain activity and allergic rhinitis.

Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to excavate whether there remain functional changes of brain activity in AR patients. We measured the amplitude of low-frequency fluctuation (ALFF) and the conversion of ALFF (zALFF) in 20 patients with AR and 20 age- and sex-matched healthy controls (HCs) using the rs-fMRI data.

Results: Compared with healthy controls, AR patients exhibited lower ALFF values in the precuneus (PCUN) and higher ALFF values in the anterior cingulate cortex (ACC). The ALFF values of these features were significantly correlated with the visual analog scale (VAS) scores, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores, the subscales of RQLQ, and specific IgE, partly.

Conclusion: We found changes in resting-state spontaneous brain activity in AR patients with hypoactivity in the PCUN and hyperactivity of the ACC. The brain-related symptoms of AR might be another potential clinical intervention target for improving the life quality of AR patients. Further attention to brain activity is essential for a deeper understanding of AR.
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http://dx.doi.org/10.3389/fnins.2021.697299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317644PMC
July 2021

Estimated ASCVD risk according to statin use in US adults with borderline triglycerides: Results from National Health and Nutrition Examination Survey (NHANES) 2007-2014.

Am J Prev Cardiol 2020 Sep 8;3:100087. Epub 2020 Sep 8.

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, USA.

Background: Elevated triglycerides (TGs) are associated with atherosclerotic cardiovascular disease (ASCVD). Despite statin therapy, many US adults have borderline or elevated TG levels. Not characterized is the ASCVD risk associated with borderline TG levels in statin users, including the estimated number of adults who will sustain ASCVD events.

Methods: We studied 4986 US adults (weighted to 113 million) aged 40-74 from the National Health and Nutrition Examination Surveys 2007-2014. The proportion of persons at low (<5%), borderline (5-<7.5%), intermediate (7.5-<20%), and high (≥20%) 10-year ASCVD risk among those on statins was quantified for low (<70 ​mg/dL, 70-<100 ​mg/dL), borderline (100-<135 ​mg/dL and 135-<150 ​mg/dL), borderline high (150-<200 ​mg/dL), and elevated (≥200 ​mg/dL) TGs. Multiple logistic regression examined these TG categories in relation to high risk status.

Results: Overall, 18.6% of participants had TG ​< ​70 ​mg/dL, 24.2% TG 70-<100 ​mg/dL, 22.0% TG 100-<135 ​mg/dL, 6.2% TG 135-<150 ​mg/dL, 15.0% TG 150-<200 ​mg/dL, and 14.0% TG ​≥ ​200 ​mg/dL. Mean 10-year ASCVD risk for these groups were 5.6%, 6.9%, 7.8%, 10.3%, 9.6% and 10.8%, respectively (p ​< ​0.0001). One-fifth or more of statin users with TGs over 135 ​mg/dL were at ≥ 20% 10-year ASCVD risk and ≥60% of persons in all TG groups were at borderline or higher ASCVD risk. Compared to those with TGs <70 ​mg/dL, multiple logistic regression showed odds ratios of 3.1 to 4.6 (p ​< ​0.05 to p ​< ​0.01) for those in TG groups ≥135 ​mg/dL in the overall sample, but 3.4 to 8.1 (p ​< ​0.05 to p < 0.01) for those in TG groups of ≥100 ​mg/dL in statin users, despite adjustment including HDL-C.

Conclusion: Many US adults with borderline levels of TGs are at elevated ASCVD risk despite statin therapy, suggesting the need first for greater lifestyle modification efforts, and when indicated, evidence-based therapies known to reduce this residual ASCVD risk.
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http://dx.doi.org/10.1016/j.ajpc.2020.100087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315641PMC
September 2020

The Prognostic Value of a Derived Neutrophil-Lymphocyte Ratio in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211034579

Department of Cardiology, 117914The Affiliated Hospital of Chengde Medical University, Chengde, HeBei, China.

The systemic immune-inflammatory index (SII) and derived neutrophil-lymphocyte ratio (dNLR) are novel indexes that simultaneously reflect the host inflammatory and immune status and have prognostic value in some cancers. SII was associated with major cardiovascular events in coronary artery disease patients who received percutaneous coronary intervention (PCI). However, dNLR correlations with clinical outcomes in acute coronary syndrome (ACS) patients undergoing PCI remain unclear. This study aimed to elucidate the predictive values of SII and dNLR on the long-term prognosis of patients with ACS undergoing PCI. In total, 1,553 ACS patients undergoing PCI were consecutively enrolled from January 2016 to December 2018. The subjects were divided into high and low SII and dNLR groups for comparison (high vs. low). The SII and dNLR cutoff values for predicting major adverse cardiovascular events (MACE) were calculated using receiver operating characteristic curves, and Kaplan-Meier curves and Cox regression models were used for survival analyses. The endpoint was a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. The Kaplan-Meier curves showed that a higher SII or dNLR value was associated with a higher risk of MACE (all < 0.001). Multivariate Cox regression models showed that SII (hazard ratio [HR]: 2.545; 95% confidence interval [CI]: 1.416-4.574; = 0.002) and dNLR (HR: 2.610, 95% CI: 1.454-4.685, = 0.001) were independent predictors for MACE. dNLR may be a suitable laboratory marker to identify high-risk ACS patients after PCI.
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http://dx.doi.org/10.1177/10760296211034579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299898PMC
November 2021

Novel biomarker panel measuring endothelial injury identifies patients at risk of coronary artery syndrome and discordance with low-density lipoprotein cholesterol.

Coron Artery Dis 2022 01;31(1):e51-e58

Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine School of Medicine.

Background: Individuals with no history of coronary artery disease can develop acute coronary syndrome (ACS), often in the absence of major risk factors including low-density lipoprotein cholesterol (LDL-C). We identified risk factors and biomarkers that can help identify those at discordantly high risk of ACS with normal LDL-C using a novel validated coronary artery disease predictive algorithm (CADPA) incorporating biomarkers of endothelial injury.

Methods: Five-year predicted ACS risk was calculated for 6392 persons using CADPA. Persons were classified as low (<3.5%), intermediate (3.5-<7.5%) or high (≥7.5%) CADPA risk and by LDL-C levels <130 mg/dL (low) and ≥130 mg/dL (high) and whether in the discordantly low LDL-C (but high CADPA risk) or high LDL-C (but low/intermediate CADPA risk) group. Multiple logistic regression identified risk factors and biomarkers that predicted discordance.

Results: 31% were classified as low (<3.5%), 27% at intermediate (3.5-<7.5%) and 42% were at high risk (≥7.5%). 28% of subjects were identified in the low LDL discordant risk group (LDL-C< 130 mg/dL but 5-year CADPA predicted risk ≥7.5%) and 19% in the high LDL discordant risk group (LDL-C ≥ 130 mg/dL but 5-year CADPA risk of <7.5%). Diabetes (odds ratio [OR], 2.84 [2.21-3.66]), male sex (OR, 2.83 [2.40-3.35]), family history (OR, 2.23 [1.88-2.64]) and active smoking (OR, 1.99 [1.50-2.62]) predicted low LDL risk discordance more than other risk factors (all P < 0.01). Increased serum soluble FAS, hemoglobin A1c and interleukin-16 were the biomarkers most independently associated with increased risk.

Conclusions: Discordance between LDL-C levels and ACS risk is common. Males with diabetes and a family history of myocardial infarction who are actively smoking may be at highest risk of developing ACS despite controlled LDL-C. Future studies should examine whether using the CADPA can help identify individuals that could benefit from earlier targeting of risk factor modification for the prevention of ACS.
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http://dx.doi.org/10.1097/MCA.0000000000001076DOI Listing
January 2022

Atherogenic Index of Plasma, Triglyceride-Glucose Index and Monocyte-to-Lymphocyte Ratio for Predicting Subclinical Coronary Artery Disease.

Am J Med Sci 2021 09 12;362(3):285-290. Epub 2021 May 12.

Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, HeBei, China. Electronic address:

Background: The atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, and monocyte-to-lymphocyte ratio (MLR) are strongly associated with atherogenesis of the coronary artery. This study aimed to investigate the association of the AIP, TyG index, and MLR with subclinical coronary artery disease (CAD) and evaluate their ability to predict subclinical CAD.

Methods: A total of 697 asymptomatic patients were enrolled in this study and assigned to the subclinical CAD group (n=332) and control group (n=365). The clinical data, coronary artery calcification score, and calculated AIP, TyG index, and MLR were collected by graduate students in the cardiology division. Multivariate logistic regression models were set up to assess the risk factors for subclinical CAD.

Results: The AIP, TyG index and MLR values were higher in the subclinical CAD group than in the control group (all P<0.05). In addition to the classic independent clinical risk factors, increased AIP, TyG index and MLR values were all independent risk factors for subclinical CAD (all P<0.05). The AUCs were higher after combining clinical risk factors than the AIP, TyG index, or MLR alone (all P<0.05).

Conclusions: The AIP, TyG index and MLR are independent risk factors for subclinical CAD, which can be useful for improving the diagnosis and prevention of CAD.
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http://dx.doi.org/10.1016/j.amjms.2021.05.001DOI Listing
September 2021

Multimodal Treatment With Orbital Organ Preservation in Adult Patients With Locally Advanced Small-Round-Cell Malignancy of the Nasal Cavity and Paranasal Sinus.

Front Oncol 2021 1;11:650385. Epub 2021 Apr 1.

ColIege of Otolaryngology Head and Neck Surgery, Chinese PLA General Hospital, National Clinical Research Center for Otolaryngologic Diseases, Key Lab of Hearing Science, Ministry of Education, Beijing Key Lab of Hearing Impairment for Prevention and Treatment, Beijing, China.

Background: To investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in adult patients with locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.

Methods: The clinical data of 49 patients with orbital involvement of locally advanced small-round-cell malignancy of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between December 2009 and January 2019 were retrospectively analyzed. Treatment efficacy and side effects were assessed. The study included three different pathological types. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 3. The overall survival (OS) rate, progression-free survival (PFS) rate, and orbital preservation rate were calculated using the Kaplan-Meier method.

Results: After multimodal treatment, the 3- and 5-year OS rates of the 49 patients were 63.8% and 54.5%, respectively, and the 3- and 5-year total PFS rates were 66.8% and 63.1%, respectively.

Conclusions: Multimodal treatment can preserve the orbital organs of adult patients with small-round-cell malignancy of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates, and improve quality of life, thus providing a new treatment option for these patients.
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http://dx.doi.org/10.3389/fonc.2021.650385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047626PMC
April 2021

Probing Dynamic Features of Phagosome Maturation in Macrophage using [email protected] @SiO Nanoparticles as pH-Sensitive Plasmonic Nanoprobes.

Chem Asian J 2021 May 31;16(9):1150-1156. Epub 2021 Mar 31.

Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

Phagosome maturation in macrophage is essential to the clearance of pathogenic materials in host defence but the dynamic features remain difficult to be measured in real time. Herein, we reported the multilayered [email protected] @SiO nanoparticle as a robust pH-sensitive plasmonic nanosensor for monitoring the dynamic acidification features over the phagosome maturation process in macrophage under darkfield microscopy. For this multilayered nanosensor, the gold nanoparticle core plays a role of signal reporter, the MnO shell and the outmost SiO act as the sensing layer and the protecting layer, respectively. After subject to the acidic buffer solution, the MnO layer in the multilayered nanoprobe could be decomposed rapidly, resulting in a remarkable spectral shift and color change under darkfield microscopy. We demonstrated this nanosensor for the investigation of single phagosome acidification dynamics by monitoring the color changes of nanoprobes after phagocytosis over time. The nanoprobes after phagocytosized in macrophage displayed a slight color change within the first hour and then cost several minutes to change from red to green in the next stage, indicating the phagosome undergoes a slow first and then fast acidification feature as well as a slow-to-fast acidification translation over the phagosome maturation process. Moreover, we validated that the slow-to-fast acidification translation was dependent on the activation of V-ATPase from the ATP depletion assay. We believed that this nanosensor is promising for studying the dynamic acidification features as well as disorders in phagosome maturation in phagocytic cells, which might provide valuable information for understanding the disease pathogenesis related to phagosome dysfunctions.
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http://dx.doi.org/10.1002/asia.202100031DOI Listing
May 2021

A Risk Prediction Model by LASSO for Radiation-Induced Xerostomia in Patients With Nasopharyngeal Carcinoma Treated With Comprehensive Salivary Gland-Sparing Helical Tomotherapy Technique.

Front Oncol 2021 26;11:633556. Epub 2021 Feb 26.

Department of Radiation Oncology, Medical School of the Chinese People's Liberation Army (PLA), Beijing, China.

Objective: This study aimed to develop a least absolute shrinkage and selection operator (LASSO)-based multivariable normal tissue complication probability (NTCP) model to predict radiation-induced xerostomia in patients with nasopharyngeal carcinoma (NPC) treated with comprehensive salivary gland-sparing helical tomotherapy technique.

Methods And Materials: LASSO with the extended bootstrapping technique was used to build multivariable NTCP models to predict factors of patient-reported xerostomia relieved by 50% and 80% compared with the level at the end of radiation therapy within 1 year and 2 years, R50-1year and R80-2years, in 203 patients with NPC. The model assessment was based on 10-fold cross-validation and the area under the receiver operating characteristic curve (AUC).

Results: The prediction model by LASSO with 10-fold cross-validation showed that radiation-induced xerostomia recovery could be predicted by prognostic factors of R50-1year (age, gender, T stage, UICC/AJCC stage, parotid Dmean, oral cavity Dmean, and treatment options) and R80-2years (age, gender, T stage, UICC/AJCC stage, oral cavity Dmean, N stage, and treatment options). These prediction models also demonstrated a good performance by the AUC.

Conclusion: The prediction models of R50-1year and R80-2years by LASSO with 10-fold cross-validation were recommended to validate the NTCP model before comprehensive salivary gland-sparing radiation therapy in patients with NPC.
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http://dx.doi.org/10.3389/fonc.2021.633556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953987PMC
February 2021

Association between triglyceride glucose index and coronary artery disease with type 2 diabetes mellitus in middle-aged and elderly people.

Medicine (Baltimore) 2021 Mar;100(9):e25025

Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, Hebei, China.

Abstract: This study aimed to investigate the correlation between triglyceride glucose (TyG) index and coronary artery disease (CAD) with type 2 diabetes mellitus (T2DM) and identify the risk associated TyG index in different subgroups.A total of 1665 eligible inpatients (CAD with T2DM group [n = 680], non-coronary artery disease without T2DM [n = 985]) were consecutively enrolled in this study. They were assigned into 4 subgroups: middle-aged, elderly, male, and female subgroups. Receiver operating characteristic curve diagnostic test and a logistic regression model was established to analyze the risk factors for CAD with T2DM.TyG index is an independent risk factor for patients with CAD with T2DM. The risk of increased TyG index is greater in the middle-aged and male subgroups than in the elderly and female subgroups, respectively (all P < .05). The specificity and the positive predictive value of the TyG index is greater than the sensitivity and the negative predictive value, respectively (all P < .05).Increased TyG index is a new independent risk factor for CAD with T2DM, and its risk is higher in the middle-aged and male subgroups than in the elderly and female subgroups, respectively. TyG index may be used as a clinical predictor of CAD with T2DM.
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http://dx.doi.org/10.1097/MD.0000000000025025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939227PMC
March 2021

TAK-242 ameliorates olfactory dysfunction in a mouse model of allergic rhinitis by inhibiting neuroinflammation in the olfactory bulb.

Int Immunopharmacol 2021 Mar 14;92:107368. Epub 2021 Jan 14.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China; Research Institute of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address:

Objective: Olfactory dysfunction (OD) is a common symptom of allergic rhinitis (AR) that can seriously affect patient quality of life; however, the associated pathogenesis remains unclear. This study aimed to explore the relationship between OD and damage of the olfactory bulb (OB) in allergic rhinitis (AR). The therapeutic potential of TAK-242, a selective TLR4 inhibitor, was evaluated for OD.

Method: An AR mouse model was established with ovalbumin (OVA) to test the olfactory function of AR mice using the buried food pellet test (BFPT). Mice with OD were intraperitoneally injected with TAK-242 or 1% DMSO (vehicle). Immunohistochemistry was used to detect microglia and astrocyte activation in the OB. TUNNEL staining was performed to detect apoptosis in the OB. Proteins in the TLR4 signaling pathway were detected by Western blot. The level of proinflammatory factor mRNA in the OB was determined by RT-PCR.

Result: Neuroinflammation was observed in the OB of the OD group, as evidenced by glial cell activation and increased proinflammatory factor expression. The number of apoptotic cells was significantly increased in the OB of the OD group. The expression of TLR4, MyD88, and p-NF-κBp65 was significantly up-regulated in the OB of the OD group. TAK-242 treatment significantly reduced the level of IL-1β, IL-6, and TNF-α mRNA expression, as well as activation of microglia and astrocytes in the OB tissues.

Conclusion: TAK-242 improve olfactory function in AR mice mainly by reducing neuroinflammation and apoptosis in the OB, which may be related to blocking the TLR4/MyD88/NF-κB signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2021.107368DOI Listing
March 2021

Thallium shifts the bacterial and fungal community structures in thallium mine waste rocks.

Environ Pollut 2021 Jan 27;268(Pt A):115834. Epub 2020 Oct 27.

Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, School of Environmental Science and Engineering, Guangzhou University, Guangzhou, 510006, China. Electronic address:

Thallium (Tl) is a highly toxic metalloid and is considered a priority pollutant by the US Environmental Protection Agency (EPA). Currently, few studies have investigated the distribution patterns of bacterial and fungal microbiomes in Tl-impacted environments. In this study, we used high-throughput sequencing to assess the bacterial and fungal profiles along a gradient of Tl contents in Tl mine waste rocks in southwestern China. Our results showed that Tl had an important, but different influence on the bacterial and fungal diversity indices. Using linear regression analysis, we furtherly divided the dominant bacterial and fungal groups into three distinct microbial sub-communities thriving at high, moderate, and low levels of Tl. Furthermore, our results also showed that Tl is also an important environmental variable that regulates the distribution patterns of ecological clusters and indicator genera. Interestingly, the microbial groups enriched in the samples with high Tl levels were mainly involved in metal and nutrient cycling. Taken together, our results have provided useful information about the responses of bacterial and fungal groups to Tl contamination.
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http://dx.doi.org/10.1016/j.envpol.2020.115834DOI Listing
January 2021

Long-Noncoding RNA CASC9 Promotes Progression of Non-Small Cell Lung Cancer by Promoting the Expression of CDC6 Through Binding to HuR.

Cancer Manag Res 2020 25;12:9033-9043. Epub 2020 Sep 25.

China-Neal Friendship Medical Research Center of Rajiv Kumar Jha, School of Clinical Medicine, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, People's Republic of China.

Objective: The long-noncoding RNAs (lncRNAs) have been identified as key players in diverse cellular processes in non-small cell lung cancer (NSCLC). However, the understanding of biological functions and detailed mechanisms of lncRNAs is still limited. Herein, the lncRNA cancer susceptibility candidate 9 (CASC9) on NSCLC progression is investigated.

Materials And Methods: Expressions of CASC9, HuR and cell division cycle 6 (CDC6) in NSCLC tissues were detected with quantitative real-time polymerase chain reaction (qRT-PCR). The cell counting kit-8, transwell assays, and flow cytometry were used to examine cell proliferation, migration, and the cell cycle. Tumor growth in vivo was evaluated by xenograft tumor experiments and immunohistochemistry. RNA-binding protein immunoprecipitation (RIP) was used to identify the interaction between HuR and CDC6, and CASC9 and HuR.

Results: CASC9, CDC6 and HuR expression were found significantly upregulated in NSCLC tissues, which predicted poorer 5-year overall survival in NSCLC patients. Inhibition of CASC9 significantly reduced the malignancy of NSCLC cells, such as proliferation, migration and cell cycle. In vivo experiments further demonstrated that CASC9 knockdown reduced the tumor growth and the Ki-67 expression. Moreover, CASC9 knockdown inhibited the expression of CDC6 which was detected overexpressed in NSCLC tumor tissues. Then, up-regulation of CDC6 could partly reverse the negative effects of CASC9 on cell proliferation, migration and cell cycle. RIP assay and rescue experiment showed that CASC9 regulated CDC via binding to HuR.

Conclusion: Our results indicate that CASC9 conferred an aggressive phenotype in NSCLC and might be a pivotal target for this disease.
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http://dx.doi.org/10.2147/CMAR.S268375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524203PMC
September 2020

REDUCE-IT Eligibility and Preventable Cardiovascular Events in the US Population (from the National Health and Nutrition Examination Survey [NHANES]).

Am J Cardiol 2020 11 16;134:62-68. Epub 2020 Aug 16.

Department of Cardiology,Johns Hopkins University, Baltimore, Maryland.

The reduction of cardiovascular events with icosapent ethyl-intervention (REDUCE-IT) trial showed in persons with prior cardiovascular disease (CVD) or diabetes mellitus (DM) that icosapent ethyl (IPE) reduced CVD events by 25%. We projected the preventable initial and total CVD events if REDUCE-IT trial eligibility criteria were applied to US adults. We identified US adults with available REDUCE-IT inclusion criteria from NHANES Surveys 1999-2016 and estimated primary (CVD death, nonfatal myocardial infarction, stroke, revascularization, or unstable angina) and secondary composite (CVD death, nonfatal MI or stroke) events using REDUCE-IT published event rates in the IPE and placebo groups, the difference being the number of preventable events. From 11,445 adults aged ≥45 years (representing 111.1 million [M]), a total of 319 persons (3.0 M) fit key REDUCE-IT eligibility criteria: triglycerides of 135 to 499 mg/dL, HbA1c <10%, blood pressure <200/100 mm Hg, and on a statin with LDL-C of 40 to 99 mg/dL. 63% had prior CVD and 37% had DM + ≥1 risk factor (primary prevention cohort). If these persons are given IPE for the REDUCE-IT median trial period of 4.9 years, we estimated preventing a total 349,817 (71,391/year) primary CVD outcomes of which 146,011 (29,798/year) were initial events. Most (24,151) preventable events were from the secondary prevention cohort. Using FDA eligibility criteria, an estimated 4.6 million persons would be eligible for IPE, with 60,544 preventable primary CVD outcomes annually from REDUCE-IT USA event rates. In conclusion, many CVD events in US adults with known CVD or DM and well-controlled LDL-C on statin therapy can be prevented with IPE.
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http://dx.doi.org/10.1016/j.amjcard.2020.08.015DOI Listing
November 2020

The imaging anatomy of ethmomaxillary sinus and its impact on chronic rhinosinusitis.

Eur Arch Otorhinolaryngol 2021 Mar 2;278(3):719-726. Epub 2020 Sep 2.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Rd, Wuhan, 430060, China.

Purpose: The aim of this study was to investigate the pneumatization degree of ethmomaxillary sinus (EMS) and adjacent structures, and its impact on chronic rhinosinusitis (CRS).

Methods: A retrospective analysis of paranasal sinus CT scans of 996 patients was conducted. The maximum vertical diameter of EMS in the coronal plane was measured, allowing EMS to be classified, and its impact on ipsilateral CRS were examined.

Results: The prevalence of EMS was 11.9%. The maximum vertical diameter of EMS in the coronal plane ranged from 3.68 to 28.76 mm with a mean (± SD) of 11.32 ± 5.12 mm. The prevalence rates of EMS in CRS sides and non-CRS sides were 12.5% and 9.3%, respectively, which was significantly different (χ = 4.495; p < 0.05). The difference in prevalence between the three types of EMS in ipsilateral CRS was statistically significant (χ = 6.733; p < 0.05). The difference in Lund-Mackay (LM) score of ipsilateral CRS between the three types showed no statistically significant difference (H = 4.033; p > 0.05).

Conclusion: EMS is a common anatomical variation with marked individual differences in shape and pneumatization degree. A higher degree of EMS pneumatization may contribute to the occurrence of CRS; this should be investigated before surgery.
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http://dx.doi.org/10.1007/s00405-020-06322-yDOI Listing
March 2021

Estimating the number of preventable cardiovascular disease events in the United States using the EMPA-REG OUTCOME trial results and National Health and Nutrition Examination Survey.

Diab Vasc Dis Res 2020 Jul-Aug;17(4):1479164120945674

Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA.

Aim: We examined eligibility and preventable cardiovascular disease events in US adults with diabetes mellitus from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME).

Methods: We identified adults with diabetes mellitus eligible for EMPA-REG OUTCOME based on trial eligibility criteria available from the National Health and Nutrition Examination Surveys, 2007-2016. We estimated composite cardiovascular disease endpoints, as well as all-cause deaths, death from cardiovascular disease and hospitalizations for heart failure from trial treatment and placebo event rates, the difference indicating the preventable events.

Results: Among 29,629 US adults aged ⩾18 years (representing 231.9 million), 4672 (27.3 million) had diabetes mellitus, with 342 (1.86 million) meeting eligibility criteria of EMPA-REG OUTCOME. We estimated from trial primary endpoint event rates of 10.5% and 12.1% in the empagliflozin and placebo groups, respectively, that based on the 'treatment' of our 1.86 million estimated EMPA-REG OUTCOME eligible subjects, 12,066 (95% confidence interval: 10,352-13,780) cardiovascular disease events could be prevented annually. Estimated annual preventable deaths from any cause, cardiovascular causes and hospitalizations from heart failure were 17,078 (95% confidence interval: 14,652-19,504), 14,479 (95% confidence interval: 12,422-16,536) and 9467 (95% confidence interval: 8122-10,812), respectively.

Conclusion: Empagliflozin, if provided to EMPA-REG OUTCOME eligible US adults, may prevent many cardiovascular disease events, cardiovascular and total deaths, as well as heart failure hospitalizations.
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http://dx.doi.org/10.1177/1479164120945674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510356PMC
September 2020
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