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1.
Chin Med J (Engl) ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32049749

RESUMO

The regeneration capacity of cardiomyocytes (CMs) is retained in neonatal mouse hearts but is limited in adult mouse hearts. Myocardial infarction (MI) in adult hearts usually leads to the loss of large amounts of cardiac tissue, and then accelerates the process of cardiac remodeling and heart failure. Therefore, it is necessary to explore the potential mechanisms of CM regeneration in the neonates and develop potential therapies aimed at promoting CM regeneration and cardiac repair in adults. Currently, studies indicate that a number of mechanisms are involved in neonatal endogenous myocardial regeneration, including cell cycle regulators, transcription factors, non-coding RNA, signaling pathways, acute inflammation, hypoxia, protein kinases, and others. Understanding the mechanisms of regeneration in neonatal CMs after MI provides theoretical support for the studies related to the promotion of heart repair after MI in adult mammals. However, several difficulties in the study of CM regeneration still need to be overcome. This article reviews the potential mechanisms of endogenous CM regeneration in neonatal mouse hearts and discusses possible therapeutic targets and future research directions.

2.
Sci Rep ; 10(1): 2226, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041989

RESUMO

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure. A large proportion of genetic cause remains unexplained, especially in idiopathic DCM. We performed target next-generation sequencing of 102 genes which were known causes or candidate genes for cardiomyopathies and channelpathies in 118 prospectively recruited Han Chinese patients with idiopathic DCM. 41 of the 118 patients carried 40 pathogenic or likely pathogenic variants, providing a molecular diagnosis in 34.7% of patients. 32 of these variants were novel. TTN truncating variants were predominant, with a frequency of 31.0%, followed by variants of LMNA (14.3%), RBM20 (4.8%), and NEXN (4.8%). These 4 genes accounted for over half variants identified. No significant difference in clinical characteristics or rates of reaching the composite end point (cardiac transplantation and death from cardiac causes) between pathogenic or likely pathogenic variant carriers and noncarriers (hazard ratio 1.11, 95% CI: 0.41 to 3.00), or between patients with TTN truncating variants or without (hazard ratio 0.49, 95% CI: 0.36 to 6.10). In our prospective study, we first determined the overall genetic profiles and genotype-phenotype correlations in Han Chinese idiopathic DCM patients, which could provide insight for genetic diagnosis of DCM in this population.

3.
BMC Med Genet ; 21(1): 36, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066403

RESUMO

BACKGROUND: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. METHODS: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. RESULTS: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. CONCLUSIONS: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.

4.
Anal Chim Acta ; 1100: 31-39, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31987150

RESUMO

Herein the sulfur/nitrogen contained groups, serving as the "hooks" for electrochemical determination of Hg(II), were assembled on the reduced graphene oxide (hereafter SN-rGO) via a one-step facile hydrothermal method. The thiourea acts as a precursor for sulfur/nitrogen doping and partial reduction of graphene oxide. The SN-rGO was used to modify the glassy carbon electrode (GCE) for electrochemical detection of Hg(II) by square wave anodic stripping voltammetry (SWASV). The sulfur/nitrogen doping significantly improves the Hg(II) complexation by SN-rGO due to the creation of multifunctional groups on the graphene nanosheet. The SN-rGO modified electrode has excellent sensitivity (20.48 µA/µM) and limit of detection (LOD 8.93 nM) for Hg(II) detection. The newly developed Hg(II) sensing electrode possesses minimal interference for other ions typically found in natural waters. Therefore, it can be used for routine water quality monitoring. The fabrication of the SN-rGO electrode is rapid and low cost; hence, it offers a potential platform for environmental monitoring of toxic metal ions.

5.
Int J Equity Health ; 19(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906960

RESUMO

BACKGROUND: Aging and the chronic non-communicable diseases (NCDs) challenge the Chinese government in the process of providing hospitalization services fairly and reasonably. The Chinese government has developed the basic medical insurance system to solve the problem of "expensive medical cost and difficult medical services" for vulnerable groups and alleviate the unfair phenomenon. However, few studies have confirmed its effect through longitudinal comparison. This study aimed to explore the trend in the inequity of inpatient use among middle-aged and elderly individuals with NCDs in China. METHODS: This longitudinal comparative study was based on CHARLS data in 2011, 2013 and 2015. Concentration index (CI) was used to measure the variation trend of inequity of inpatient services utilization, while the decomposition method of the CI was applied to measure the factors contributing to inequity in inpatient services utilization. The effect of each factor on the change of inequity in inpatient services utilization was divided into the change of the elasticity and the change of inequality using the Oaxaca-type decomposition method. RESULTS: The affluent middle-aged and elderly patients with NCDs used more inpatient services than poor groups. The per capita household consumption expenditure (PCE) and Urban Employee Basic Medical Insurance (UEBMI) contributed to the decline in pro-rich inequality of inpatient use, while the New Rural Cooperative Medical Scheme (NRCMS) contributed to the decline in pro-poor inequality of inpatient use. CONCLUSIONS: There was a certain degree of pro-rich unfairness in the probability and frequency of inpatient services utilization for middle-aged and elderly individuals with NCDs in China. The decrease of pro-wealth contribution of PCE and UEBMI offset the decrease of pro-poor contribution of NRCMS, and improved the equity of inpatient services utilization, favoring poor people.

6.
Biomed Pharmacother ; 122: 109705, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918276

RESUMO

IL-37 was discovered as an anti-inflammatory and immunosuppressive cytokine of the IL-1 family. Significant advancements in the understanding of signaling pathways associated with IL-37 have been made in recent years. IL-37 binds to IL-18R and recruits IL-1R8 to form the IL-37/IL-1R8/IL-18Rα complex. Capase-1 plays a key role in the nuclear transduction of IL-37 signal, processing precursor IL-37 into the mature isoform, and interacting with Smad3. IL-37 exerts its role by activating anti-inflammation pathways including AMPK, PTEN, Mer, STAT3 and p62, and promoting tolerogenic dendritic cells and Tregs. In addition, IL-37 inhibits pro-inflammatory cytokines such as IL-1, IL-6, IL-8, IL-17, IL-23, TNF-α, and IFN-γ, and suppresses Fyn, MAPK, TAK1, NFκB, and mTOR signaling. The final effects of IL-37 depend on the interaction among IL-18R, IL-1R8, IL-37 and IL-18BP. Previous studies have deciphered the role of IL-37 in the development and pathogenesis of autoimmune diseases, chronic infections and cancer. In this review, we discuss the role of IL-37 in psoriasis, atopic dermatitis, Behcet's diseases, systemic lupus erythematosus, and other skin and connective tissue diseases.

7.
ESC Heart Fail ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965727

RESUMO

AIMS: RBP4 is an adipokine with adverse effects on cardiovascular system. Increased circulating retinol-binding protein 4 (RBP4) has been linked to chronic heart failure (CHF). However, whether elevated RBP4 is correlated with a poor prognosis in elderly patients with CHF remains unclear. The aim of this study was to evaluate the prognostic value of serum RBP4 in elderly patients with CHF. METHODS AND RESULTS: We enrolled 934 consecutive elderly patients (aged 60 years and older) with CHF and 138 age-matched and sex-matched control subjects in a prospective cohort study and explored the association of serum RBP4 levels with the clinical outcomes using multivariate Cox regression analyses. Serum RBP4 levels were elevated in CHF patients when compared with controls (46.66 ± 12.38 µg/mL vs. 40.71 ± 7.2 µg/mL, P < 0.001). Patients with the highest RBP4 concentrations had higher N terminal pro brain natriuretic peptide (NT-proBNP) levels but lower left ventricular eject fraction (LVEF) and estimated glomerular filtration rate (P < 0.001). Serum RBP4 levels were increased as the New York Heart Association functional class increased and LVEF decreased (P < 0.001) and were negatively correlated with LVEF (r = -0.154, P < 0.001) but positively correlated with NT-proBNP levels (r = 0.074, P = 0.023). Multivariate Cox regression analysis suggested that log RBP4 was an independent predictor for major adverse cardiac event(s) [hazard ratio (HR) = 2.61, 95% confidence interval (CI) = 1.19-5.70], together with age, male, LVEF, log NT-proBNP, and estimated glomerular filtration rate. Moreover, log RBP4 was also an independent predictor for cardiovascular mortality (HR = 2.24, 95% CI = 1.35-5.39) and CHF rehospitalization (HR = 2.54, 95% CI = 1.09-5.60) even after adjustment for the established adverse prognostic factors for CHF. The Kaplan-Meier survival curves showed that high concentration of RBP4 was a prognostic indicator of major adverse cardiac event(s) in patients with CHF. CONCLUSIONS: Our findings demonstrate for the first time that elevated serum RBP4 is correlated with worse outcome in elderly patients with CHF.

8.
Am J Cardiol ; 125(3): 449-458, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31780077

RESUMO

Transcatheter aortic-valve replacement (TAVR) has emerged as a promising strategy for treating patients with severe aortic stenosis. We aimed to compare TAVR with surgical aortic-valve replacement (SAVR) and determine the performance of TAVR over time and within several subgroups. We included 8 randomized trials comparing TAVR versus SAVR. Compared with SAVR, TAVR was associated with a lower rate of all-cause mortality or disabling stroke at 30-day (odds ratio [OR], 0.72; p = 0.004), 1-year (OR, 0.83; p = 0.01), and 2-year (OR, 0.86; p = 0.02), but not at long-term follow-up (rate ratio [RR], 1.02 [confidence interval 0.92 to 1.13]; p = 0.67). Notably, 5-year data showed numerically higher incidence in TAVR (RR, 1.11 [confidence interval 0.97 to 1.27]; p = 0.12). The risks associated with TAVR versus SAVR increased over time, showing a significant interaction (p for interaction = 0.01), as were for new-onset atrial fibrillation and rehospitalization. Incidences of major bleeding, new-onset fibrillation, and acute kidney injury were lower in TAVR, whereas transient ischemic attack, major vascular complications, permanent pacemaker implantation, reintervention, and paravalvular leak were lower in SAVR. Incidences for all-cause and cardiovascular mortality, myocardial infarction, and stroke were not statistically different. TAVR with transfemoral approach and new-generation valve was associated with reduction in all-cause mortality or disabling stroke compared with corresponding comparators. In conclusion, TAVR was associated with a lower risk for all-cause mortality or disabling stroke within 2 years, but not at long-term follow-up compared with SAVR; the risks seems to increase over time. More data are needed to determine longer-term performance of TAVR.

9.
Anal Bioanal Chem ; 412(2): 343-353, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31776638

RESUMO

There is an urgent need to construct highly selective low-cost sensors for fast detection of toxic metal ions such as cadmium. When compared with 3D bulk materials, 2D layered materials after activation treatments show superior performances for electrochemical metal ion detection. The bulk graphitic carbon nitride (hereafter b-g-C3N4) was prepared by thermal polymerization with urea as a precursor; it was then activated through ultrasonic liquid exfoliation and protonation which resulted in successful fabrication of activated ultrathin g-C3N4 nanosheets (hereafter a-g-C3N4). The a-g-C3N4-modified glassy carbon electrode demonstrates excellent electrochemical performances for Cd2+ detection with 22.668 µA/µM sensitivity and 3.9 nM LOD (S/N = 3) due to high specific surface area and active sites created on the 2D layered structure. The chemical interference of Pb2+, Cu2+, and Hg2+ on Cd2+ detection was minimal. We have also measured Cd2+ in natural water and rice samples using the newly developed a-g-C3N4-modified electrode with high spike recoveries. Our results demonstrate the potential applications of newly developed a-g-C3N4-modified electrode for rapid detection of toxic metal ions in different sample matrixes. Graphical Abstract The activated g-C3N4 nanosheets (a-g-C3N4) were synthesized and used to construct electrochemical sensors with high sensitivity and anti-interference performance.

10.
J Dermatol ; 47(1): 78-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31692010

RESUMO

Port-wine stains (PWS) are capillary malformations associated with mutation in the GNAQ (NM_000441.1) gene. Large vestibular aqueduct syndrome (LVAS), caused by mutation in the SLC26A4 (NM_002072) gene, is an inner ear malformation that can lead to hearing loss. To our knowledge, LVAS in PWS patients has never been reported. Here, we describe a case of a 9-year-old female patient diagnosed with PWS on the face and neck, coexisting with large vestibular aqueduct syndrome. Further analyses revealed a somatic mutation in GNAQ and a compound heterozygous mutation in the SLC26A4 gene. Some PWS patients have associated abnormalities, such as glaucoma and choroidal hemangioma, leptomeningeal angiomas and atrophy or hypertrophy of bone and soft tissue. We present here the first case that reveals the possibility that capillary malformations are associated with inner ear malformation. More case reports and further studies are needed to determine whether these conditions coexist in other patients.

11.
Am J Transl Res ; 11(11): 7115-7125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814914

RESUMO

Circular RNAs (circRNAs) are potential biomarkers and therapeutic targets of coronary artery disease due to their high stability, covalently closed structure. And implied roles in gene regulation. The aim of this study was to identify and characterize circRNAs from human coronary arteries. Epicardial coronary arteries were removed during the autopsy of an 81-year-old man who died from heart attack. The natural history and histological classification of atherosclerotic lesions in coronary artery segments were analyzed by hematoxylin and eosin staining, and their circRNA expression profiles were characterized by RNA sequencing. RNA sequencing identified 1259 annotated and 381 novel circRNAs. Combined with the results of histologic examination, intersection analysis identified 54 upregulated and 12 downregulated circRNAs, representing 4.0% of the total number. Coronary artery segments with or without severe atherosclerosis showed distinctly different circRNA profiles on the basis of hierarchical clustering. Our results suggest that these 66 circRNAs contribute to the pathology underlying coronary artery atherosclerosis and may serve as diagnostic or therapeutic targets in coronary artery disease.

12.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4350-4353, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872644

RESUMO

Kangfu Xiaoyan Suppository is widely used in the treatment of gynecological inflammatory diseases. Long-term clinical application and a certain amount of research evidences show that Kangfu Xiaoyan Suppository can alleviate the clinical symptoms of pelvic inflammatory diseases,reduce the recurrence rate,and relieve sequelae,with a better safety and economic characteristics. As a type of nationally protected traditional Chinese medicine and type B medicine included in medical insurance,it has been selected as a Chinese patent medicine for rectal administration. It was included in the Guidelines for diagnosis and treatment of common gynecological diseases of traditional Chinese medicine published by the Chinese Academy of Traditional Chinese Medicine in 2012,the Pelvic inflammatory diseases diagnosis and treatment guidelines issued by the Infectious Diseases Collaborative Group of the Obstetrics and Gynecology Branch of the Chinese Medical Association in 2014,and the group standard of Single use of traditional Chinese medicine/combined antibiot guidelines for clinical practice-pelvic inflammatory diseases of the Chinese Academy of Traditional Chinese Medicine in 2017. To further enhance clinicians' understanding of the drug and better guide its rational clinical use,experts from the field of gynecology of traditional Chinese and Western medicine were invited to develop and compile this expert consensus. This consensus takes full account of clinical evidences and expert clinical experience,and form recommendations for clinical problems based on evidences and consensus recommendations for clinical problems without evidence by nominal grouping method. The expert consensus is mainly formed in the consideration of six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on clinical research evidences and expert experience,this consensus provides a preliminary reference for the clinical use of the drug in a concise and clear format. However,evidence-based support is still required in a large number of high-quality studies,and this consensus will be revised in the future according to new clinical problems and the update of evidence-based evidence in practical application.


Assuntos
Consenso , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Doença Inflamatória Pélvica/tratamento farmacológico , Feminino , Humanos , Medicamentos sem Prescrição , Supositórios
13.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4962-4974, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872607

RESUMO

To evaluate the efficacy and safety of Kangfu Xiaoyan Suppository in the treatment of pelvic inflammatory disease. Four Chinese databases,namely CNKI,VIP,WanFang and SinoMed,and three English databases Cochrane Library,namely Medline,and ClinicalTrail.gov were systematically and comprehensively retrieved from the establishment of each database to June 2018. The quality of the included studies was evaluated by using the risk assessment tools developed by the Cochrane Collaboration,and RevMan 5. 3 software was used for Meta-analysis. A total of 675 articles were retrieved,and finally 56 studies were included. The total sample size was 6 228,the test group included 3 267 cases,and the control group included 2 961 cases. The overall quality of the included studies was generally low. According to the intervention measures and outcome indicators,the included studies were divided into different subgroups for analysis. The main results of Meta-analysis showed that the recurrence rate of Kangfu Xiaoyan Suppository combined with antibiotics was lower than that of antibiotics alone. Kangfu Xiaoyan Suppository combined with antibiotics was superior to antibiotics alone in terms of abdominal pain,leucorrhea abnormality relief time,mass absorption time and pain relief time. In terms of safety,Kangfu Xiaoyan Suppository combined with antibiotics had a lower incidence of adverse reactions than antibiotics alone. Based on the results of this study,it is indicated that Kangfu Xiaoyan Suppository had a certain effect on the treatment of pelvic inflammatory disease,especially with a lower recurrence rate. The long-term effect is remarkable. No serious adverse reaction was observed. Restricted by the quality of the studies included,the above conclusion need to be further verified in high-quality,largesize,multi-center clinical researches.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença Inflamatória Pélvica/tratamento farmacológico , Antibacterianos , Feminino , Humanos , Supositórios
14.
Clin Respir J ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769181

RESUMO

PURPOSE: To examine the effectiveness of a nurse-led self-management program on outcomes of patients with chronic obstructive pulmonary disease (COPD). DESIGN: A randomized controlled, single-blind trial, carried out from October 2017 to December 2018, included 154 participants admitted with COPD to the Affiliated Hospital of Zunyi Medical University in Guizhou, (randomized into intervention (n = 77) and control groups (n = 77)). MATERIALS AND METHODS: Participants in the intervention group underwent a nurse-led self-management program in addition to routine care, and participants of the control group received only routine care. The main outcome measures were COPD-related readmission and emergency department visits, the 6-minute walk distance (6MWD) test for measurement of exercise capacity, the St George Respiratory Questionnaire (SGRQ) for measurement of health-related quality of life, and the COPD Transitional Care Patient Satisfaction Questionnaire (CTCPSQ) for measurement of satisfaction. Data collection was conducted at baseline (T1) and after 3 (T2), 6 (T3) and 12 mo (T4). Findings Compared to the control group, participants in the intervention group showed significantly fewer COPD-related hospital admissions (P = 0.03) and emergency department visits (P = 0.001) and higher total CTCPSQ scores (P = 0.001) at 12 mo. Meanwhile, analysis of variance showed a significantly greater improvement in exercise capacity and health status over time in the nurse-led program group than in the control group, P < 0.001. CONCLUSIONS: This study demonstrated that the nurse-led self-management program was effective in decreasing hospital readmissions and emergency department visits and improving exercise capacity, health-related quality of life and satisfaction for patients with COPD.

15.
Int J Med Mushrooms ; 21(6): 561-570, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679228

RESUMO

The in vitro antioxidant effects of petroleum ether, ethyl acetate, and ethanol extracts isolated from Hericium coralloides were investigated. Overall, the ethyl acetate extract of H. coralloides (HcEAE) showed better antioxidant activity in vitro than the petroleum ether and ethanol extracts (HcPEE and HcETE, respectively) of H. coralloides. A comprehensive investigation of the antioxidant activity of the HcEAE in vitro indicated that it possessed superior antioxidant activity, with half maximal inhibitory concentration (IC50) values of 0.93, 1.84, 1.59, and 0.6 mg/mL against DPPH, hydroxyl, ABTS+, and superoxide (O2- ) radicals, respectively. To assess in vivo antioxidant activity, three different doses of HcEAE were orally administered in a D-galactose-induced aged mouse model. Administration of HcEAE significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and lowered the levels of malondialdehyde (MDA) in brains and sera of mice in a dose-dependent manner. A histopathology assessment indicated that the HcEAE could ameliorate the anile condition of the model mice. These results suggest that the HcEAE has potent antioxidant activity and could minimize the occurrence of age-associated disorders associated with free radicals.

16.
Org Biomol Chem ; 17(48): 10223-10227, 2019 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777898

RESUMO

A novel, sustainable, environmentally friendly, high substrate scope, efficient, solvent-free and metal catalyst-free method for the cross-dehydrogenative coupling (CDC) reaction between N-hydroxyphthalimide (NHPI) and benzyl/ether compounds is described. This coupling reaction proceeds through ultrasound acceleration. Compared to conventional heating conditions, the use of ultrasound techniques not only improves the reaction efficiency and enhances the reaction rate but also minimizes the side reactions.

17.
Mech Ageing Dev ; 184: 111160, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31634486

RESUMO

Skin is the largest organ of the body, and is prone to be affected by external environmental factors. Skin aging is caused by both genetic and environmental factors. Furthermore, aging skin tissue is known to create a permissive tissue microenvironment that promotes the initiation, progression and resistance of cancer cells by promoting the senescence-associated secretory phenotype (SASP). Therefore, more attention should be paid to skin aging. In this review, we highlight the common Rel proteins and two activation pathways: the canonical activation pathway and the non-canonical activation pathway. Furthermore, we summarize the role of NF-κB in skin aging. The effects of UV on the skin results from the production of ROS. Excessive free radicals activate the NF-κB signaling pathway and MAPK signaling pathway, contributing to the activation of AP-1 and NF-κB. Then it increased the level of TNF-α and the expression of MMPs, which induce the degradation of ECM and accelerated skin aging. We also summarize some reported natural antioxidants and synthetic antioxidants which are related to NF-κB signals. On the other hand, NF-κB plays a key role in SASP. Upon senescence-inducing signals, ATM and ATR block p62-dependent autophagic degradation of GATA4, contributing to NF-κB activation and SASP induction.

18.
Sci Rep ; 9(1): 15340, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653960

RESUMO

To explore the association between methylation of antisense non-coding RNA in the INK4 locus (ANRIL) and coronary artery disease (CAD) development. Methylation levels of ANRIL in 100 subjects with CAD and 100 controls were quantitatively analyzed using Sequenom MassARRAY. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify novel pathways. Our analyses indicated that 7 to 8 CpG sites within the 2nd CpG island located upstream of ANRIL, also known as cyclin-dependent kinase inhibitor 2B - antisense 1 (CDKN2B-AS1), are hyper-methylated in CAD subjects compared to controls (p = 0.034). The 40th CpG site within the 2nd CpG island located upstream of CDKN2B-AS1 was methylated to a lesser extent in CAD subjects compared to controls (p = 0.045). Both Pearson and Spearman analyses indicated that methylation levels were significantly associated with total cholesterol (r = 0.204, p = 0.004), fasting high-density lipoprotein cholesterol (r = 0.165, p = 0.020), and fasting low-density lipoprotein cholesterol (r = 0.265, p = 0.000). KEGG pathway analysis revealed a significant enrichment of genes associated with the tumor necrosis factor (TNF) signaling pathway. Among them, CCAAT/enhancer binding protein (C/EBPß) was identified as a key transcription factor that promotes expression of CDKN2B-AS1 through promotor interaction. DNA methylation of the ANRIL promoter was significantly associated with CAD development in our study. Our analyses suggest that C/EBPß is a key transcription factor that promotes CDKN2B-AS1 expression by directly interacting with the gene promotor mediated by TNF signaling.

19.
Int J Mol Sci ; 20(20)2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31600977

RESUMO

A high incidence of hypersensitivity reactions (HSRs) largely limits the use of paclitaxel injection. Currently, these reactions are considered to be mediated by histamine release and complement activation. However, the evidence is insufficient and the molecular mechanism involved in paclitaxel injection-induced HSRs is still incompletely understood. In this study, a mice model mimicking vascular hyperpermeability was applied. The vascular leakage induced merely by excipients (polyoxyl 35 castor oil) was equivalent to the reactions evoked by paclitaxel injection under the same conditions. Treatment with paclitaxel injection could cause rapid histamine release. The vascular exudation was dramatically inhibited by pretreatment with a histamine antagonist. No significant change in paclitaxel injection-induced HSRs was observed in complement-deficient and complement-depleted mice. The RhoA/ROCK signaling pathway was activated by paclitaxel injection. Moreover, the ROCK inhibitor showed a protective effect on vascular leakage in the ears and on inflammation in the lungs. In conclusion, this study provided a suitable mice model for investigating the HSRs characterized by vascular hyperpermeability and confirmed the main sensitization of excipients in paclitaxel injection. Histamine release and RhoA/ROCK pathway activation, rather than complement activation, played an important role in paclitaxel injection-induced HSRs. Furthermore, the ROCK inhibitor may provide a potential preventive approach for paclitaxel injection side effects.

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