Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 287
Filtrar
1.
J Affect Disord ; 296: 189-197, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34607060

RESUMO

BACKGROUND: The symptoms that patients with major depressive disorder (MDD) experience are the dominant contributing factors to its heavy disease burden. This study sought to identify key symptoms leading to disability in patients with MDD. METHODS: Subjects consisted of patients who had a 12-month MDD diagnosis based on the China Mental Health Survey (CMHS). World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was used to assess the degree of disability. The associations between depressive symptoms and disability were analyzed using a linear regression and logistic regression with a complex sampling design. RESULTS: Of the 32,552 community residents, 655 patients were diagnosed with 12-month MDD. The disability rate due to MDD was 1.06% (95% CI: 0.85%-1.28%) among adults in Chinese community and 50.7% (95% CI: 44.3%-57.1%) among MDD patients. Depression was associated with all functional losses measured by the WHODAS. Feelings of worthlessness in life or inappropriate guilt, and psychomotor agitation or retardation were the key symptoms related to disability. Economic status, co-morbidity of physical diseases or anxiety disorders were correlates of disability scores. LIMITATIONS: The disability rate might be underestimated due to the exclusion of MDD patients living in hospitals. The effect of treatments on disability was excluded. CONCLUSIONS: Psychological symptoms, not somatic symptoms, contribute to disability in MDD patients. Disability worsens when physical diseases or anxiety disorders are present. More attention could be paid to psychological symptoms, physical diseases, and anxiety disorders in MDD patients with disabilities.

2.
Cardiovasc Toxicol ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34674150

RESUMO

Ciliary neurotrophic factor (CNTF), which is a neural peptide, has been reported to confer cardioprotective effects. However, whether CNTF-based gene delivery could prevent cardiac remodeling in diabetes mellitus remains unknown. In this study, we used adeno-associated viral vector serotype 9 (AAV9)-based cardiac gene delivery to test the effects of CNTF overexpression on adverse ventricular remodeling in streptozotocin-induced type 1 diabetic mice models. Postnatal (P3-P10) mice were peritoneally injected with AAV9 recombinant virus carrying the CNTF gene or EGFP gene. Then, type 1 diabetic models were established by peritoneal injection of streptozotocin (200 mg/kg) in 7-week-old female mice injected with AAV9. 4 weeks later after the establishment of type 1 diabetes mellitus, mouse hearts were removed to assess the degree of cardiac remodeling. We found that CNTF overexpression in mouse cardiomyocytes exacerbated cell apoptosis and cardiac fibrosis coupled with an increased inflammatory response in the heart tissue of diabetic female mice. Taken together, our results suggested that cardiac CNTF gene delivery may not be beneficial in alleviating adverse cardiac remodeling in type 1 diabetes female mice.

3.
Front Cardiovasc Med ; 8: 716219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712704

RESUMO

Introduction: Myocardial infarction (MI) triggers structural and electrical remodeling. CC chemokine receptor 9 (CCR9) mediates chemotaxis of inflammatory cells in MI. In our previous study, CCR9 knockout has been found to improve structural remodeling after MI. Here, we further investigate the potential influence of CCR9 on electrical remodeling following MI in order to explore potential new measures to improve the prognosis of MI. Methods and Results: Mice was used and divided into four groups: CCR9+/+/Sham, CCR9-/-/Sham, CCR9+/+/MI, CCR9-/-/MI. Animals were used at 1 week after MI surgery. Cardiomyocytes in the infracted border zone were acutely dissociated and the whole-cell patch clamp was used to record action potential duration (APD), L-type calcium current (I Ca,L ) and transient outward potassium current (I to ). Calcium transient and sarcoplasmic reticulum (SR) calcium content under stimulation of Caffeine were measured in isolated cardiomyocytes by confocal microscopy. Multielectrode array (MEA) was used to measure the conduction of the left ventricle. The western-blot was performed for the expression level of connexin 43. We observed prolonged APD90, increased I Ca,L and decreased I to following MI, while CCR9 knockout attenuated these changes (APD90: 50.57 ± 6.51 ms in CCR9-/-/MI vs. 76.53 ± 5.98 ms in CCR9+/+/MI, p < 0.05; I Ca,L : -13.15 ± 0.86 pA/pF in CCR9-/-/MI group vs. -17.05 ± 1.11 pA/pF in CCR9+/+/MI, p < 0.05; I to : 4.01 ± 0.17 pA/pF in CCR9-/-/MI group vs. 2.71 ± 0.16 pA/pF in CCR9+/+/MI, p < 0.05). The confocal microscopy results revealed CCR9 knockout reversed the calcium transient and calcium content reduction in sarcoplasmic reticulum following MI. MEA measurements showed improved conduction velocity in CCR9-/-/MI mice (290.1 ± 34.47 cm/s in CCR9-/-/MI group vs. 113.2 ± 14.4 cm/s in CCR9+/+/MI group, p < 0.05). Western-blot results suggested connexin 43 expression was lowered after MI while CCR9 knockout improved its expression. Conclusion: This study shows CCR9 knockout prevents the electrical remodeling by normalizing ion currents, the calcium homeostasis, and the gap junction to maintain APD and the conduction function. It suggests CCR9 is a promising therapeutic target for MI-induced arrhythmia, which warrants further investigation.

4.
J Transl Med ; 19(1): 400, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34551785

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. METHODS: Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. RESULTS: LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. CONCLUSION: Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.


Assuntos
MicroRNAs , Neoplasias Pancreáticas , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Chaperonas Moleculares , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética
5.
Lancet Psychiatry ; 8(11): 981-990, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34559991

RESUMO

BACKGROUND: In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. METHODS: The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. FINDINGS: 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. INTERPRETATION: Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. FUNDING: National Health Commission and Ministry of Science and Technology of People's Republic of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Transtorno Depressivo Maior/epidemiologia , Transtorno Distímico/epidemiologia , Serviços de Saúde Mental/estatística & dados numéricos , Vigilância da População/métodos , Adulto , Distribuição por Idade , Idoso , China/epidemiologia , Estudos Transversais , Transtorno Depressivo Maior/tratamento farmacológico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtorno Distímico/tratamento farmacológico , Carga Global da Doença , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos , Inquéritos e Questionários
6.
Cancer Discov ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479870

RESUMO

Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially-driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which includes the human pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine-aspartic acid dyad. Injected via the Type III Secretion System (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection-accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependant genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection-accelerated colon tumorigenesis in mice.

7.
Biomed Pharmacother ; 141: 111826, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328121

RESUMO

Spinal cord injury (SCI) may cause long-term physical impairment and bring a substantial burden to both the individual patient and society. Existing therapeutic approaches for SCI have proven inadequate. This is mainly owing to the incomplete understanding of the cellular and molecular events post-injury. Circular RNAs (circRNAs) represent a new class of non-coding RNAs with a covalently closed annular structure that participates in regulating the transcription of certain genes and are linked to various biological processes and diseases. Mounting evidence is indicative that circRNAs are highly expressed in the spinal cord and they play key roles in multiple processes of neurological diseases. Recently, a role for circRNAs as effectors of SCI has emerged, leading to the continuity of relevant research. In this review, we presented current studies with regards to the abnormality of circRNAs mediating SCI by affecting mechanisms of autophagy, apoptosis, inflammation, and neural regeneration. Furthermore, the potential clinical value of circRNAs as therapeutic targets of SCI was also analyzed.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34286429

RESUMO

CuxO/Bi2O3 oxides grown on nickel foam were synthesized via an electrodeposition method to degrade indoor HCHO under visible light irradiation and fully characterized by XRD, SEM, FT-IR, and UV-Vis technologies. The characterization results showed that the CuxO/Bi2O3 oxides were successfully loaded on nickel foam and the visible light response spectrum was expanded to 740 nm. Plackett-Burman design combined with central composite design has been used to optimize factors that affect HCHO removal performance. The results demonstrated that bismuth nitrate content, polyethylene glycol 600 content, sintering time, and lactic acid concentration were the four most important factors affecting the HCHO removal performance over CuxO/Bi2O3 sample. The optimum CuxO/Bi2O3 sample could degrade 88.796% of HCHO in 300 min at the conditions of 4.28 mol/L lactic acid, 4.86% polyethylene glycol 600, 194.03 min sintering time, and 45.83 g bismuth nitrate, and the HCHO removal rate remained 82.3% after five cycles. A plausible mechanism for the degradation of HCHO under visible light irradiation was proposed. This work provides a feasible solution for removing indoor formaldehyde in the field of photocatalysis.

9.
Mol Biol Rep ; 48(5): 3893-3901, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34032975

RESUMO

Fluvastatin, a traditional fat-decreasing drug, is widely used for curing cardiovascular disease. Previous reports demonstrated that fluvastatin pretreatment protected against myocardial ischemia/reperfusion (I/R) by inhibiting TLR4 signaling pathway and/or reducing proinflammatory cytokines. However, whether fluvastatin has a cardioprotective effect against apoptosis and autophagy remains unknown. This study aims to evaluate whether the cardioprotective role of fluvastatin in I/R is mediated by high-mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4) pathway via anti-apoptotic and anti-autophagic functions. Sprague-Dawley rats were anesthetized, artificially ventilated and subjected to 30 min of coronary occlusion, followed by 4 h of reperfusion. The animals were randomized into four groups: (i) Sham operation; (ii) I/R; (iii) I/R + low-dosage fluvastatin (10 mg/kg); and (iv) I/R + high-dosage fluvastatin (20 mg/kg). After reperfusion, the hemodynamic parameters, myocardial infarct size, structural alteration of myocardium, apoptosis index, pro-inflammatory cytokine production, Beclin-1, Light chain 3 (LC3), HMGB1, TLR4 and Nuclear factor kappa B (NF-κB) protein levels were measured and recorded. It was found that fluvastatin preconditioning improved left ventricular dysfunction, reduced HMGB1/TLR4/NF-κB expressions, and inhibited cardiomyocyte apoptosis, autophagy, and inflammation reaction. Moreover, treatment with fluvastatin ameliorated myocardial injury by reducing infarct size, causing less damage to cardiac structure, downregulating autophagy-related protein expression and releasing pro-inflammation mediators. Our findings indicate that fluvastatin exerts beneficial effects on cardiac ischemic damage, which may be associated with its anti-autophagic and anti-apoptotic functions via inhibition of HMGB1/TLR4-related pathway during I/R injury.

10.
ESC Heart Fail ; 8(4): 2698-2712, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33991175

RESUMO

AIMS: Skeletal muscle (SkM) abnormalities may impact exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). We sought to quantify differences in SkM oxidative phosphorylation capacity (OxPhos), fibre composition, and the SkM proteome between HFpEF, hypertensive (HTN), and healthy participants. METHODS AND RESULTS: Fifty-nine subjects (20 healthy, 19 HTN, and 20 HFpEF) performed a maximal-effort cardiopulmonary exercise test to define peak oxygen consumption (VO2, peak ), ventilatory threshold (VT), and VO2 efficiency (ratio of total work performed to O2 consumed). SkM OxPhos was assessed using Creatine Chemical-Exchange Saturation Transfer (CrCEST, n = 51), which quantifies unphosphorylated Cr, before and after plantar flexion exercise. The half-time of Cr recovery (t1/2, Cr ) was taken as a metric of in vivo SkM OxPhos. In a subset of subjects (healthy = 13, HTN = 9, and HFpEF = 12), percutaneous biopsy of the vastus lateralis was performed for myofibre typing, mitochondrial morphology, and proteomic and phosphoproteomic analysis. HFpEF subjects demonstrated lower VO2,peak , VT, and VO2 efficiency than either control group (all P < 0.05). The t1/2, Cr was significantly longer in HFpEF (P = 0.005), indicative of impaired SkM OxPhos, and correlated with cycle ergometry exercise parameters. HFpEF SkM contained fewer Type I myofibres (P = 0.003). Proteomic analyses demonstrated (a) reduced levels of proteins related to OxPhos that correlated with exercise capacity and (b) reduced ERK signalling in HFpEF. CONCLUSIONS: Heart failure with preserved ejection fraction patients demonstrate impaired functional capacity and SkM OxPhos. Reductions in the proportions of Type I myofibres, proteins required for OxPhos, and altered phosphorylation signalling in the SkM may contribute to exercise intolerance in HFpEF.


Assuntos
Insuficiência Cardíaca , Tolerância ao Exercício , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Humanos , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Proteômica , Volume Sistólico
11.
Chin Med J (Engl) ; 134(8): 927-934, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33879755

RESUMO

BACKGROUND: Acute type A aortic dissection (ATAAD) and acute type A intramural hematoma (ATAIMH) are life-threatening diseases with high mortality. To better understand their clinical features in the Chinese population, we analyzed the data from the first Registry of Aortic Dissection in China (Sino-RAD) to promote the understanding and management of the diseases. METHODS: All patients with ATAAD and ATAIMH enrolled in Sino-RAD from January 1, 2012 to December 31, 2016 were involved. The data of patients' selection, history, symptoms, management, outcomes, and postoperation complications were analyzed in the study. The continuous variables were compared using the Student's t test for normal distributions and the Mann-Whitney U test for non-normal distributions. Categorical variables were compared using the Chi-square test or Fisher exact test. RESULTS: A total of 1582 patients with ATAAD and 130 patients with ATAIMH were included. The mean age of all patients was 48.4 years. Patients with ATAAD were significantly younger than patients with ATAIMH (48.9 years vs. 55.6 years, P < 0.001). For the total cohort, males were dominant, but the male ratio of patients with ATAAD was significantly higher compared to those with ATAIMH (P = 0.01). The time range from the onset of symptom to hospitalization was 2.0 days. More patients of ATAIMH had hypertension than that of ATAAD (82.3% vs. 67.6%, P < 0.05). Chest and back pain were the most common clinical symptoms. Computerized tomography (CT) was the most common initial diagnostic imaging modality. 84.7% received surgical treatment and in-hospital mortality was 5.3%. Patients with ATAAD mainly received surgical treatment (89.6%), while most patients with ATAIMH received medical treatment (39.2%) or endovascular repair (35.4%). CONCLUSIONS: Our study suggests that doctors should comprehensively use clinical examination and genetic background screening for patients with ATAAD and ATAIMH and further shorten the time range from symptoms onset to intervention, achieving early diagnosis and treatment, thereby reducing the mortality rate of patients with aortic dissection in China. We should standardize the procedures of aortic dissection treatment and improve people's understanding. Meanwhile, the curing and transferring efficiency should also be improved.


Assuntos
Aneurisma Dissecante , Doença Aguda , Aneurisma Dissecante/diagnóstico , China , Hematoma , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Cell Signal ; 84: 110025, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33915247

RESUMO

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.

13.
Macromol Biosci ; 21(5): e2000399, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33656279

RESUMO

Designing skin decontaminating materials with outstanding therapeutic effects, adhesiveness, and suitable mechanical property has great practical significance in radionuclide-contaminated skin wound healing. Here, a physically crosslinked hydrogel is constructed via hydrogen bonding of poly acrylamide, sodium alginate (SA), and the complexing agent diethylene triamine pentaacetic acid (DTPA). The physical and chemical properties of the poly(AAm-SA-DTPA) hydrogel (PASD) are detected according to established methods. The decontaminating property and skin wound healing of the PASD are investigated to confirm multi-functions of wound dressing. The physical and chemical properties results show that the synthesis of the PASD hydrogel is effective and that DTPA is present in the hydrogel. The hydrogel also shows great mechanical and swelling properties. In vitro tests find that PASD shows significant scavenging abilities for strontium and cerium. In vivo experiments show that the PASD hydrogel can remove radioactive strontium from the skin wounds of mice, and can effectively prevent the absorption of radioactive strontium through the skin wound. Furthermore, the PASD hydrogel can effectively promote the formation of granulation tissue in a radioactive contaminated wound. Taken together, the PASD hydrogels, which has good mechanical properties and radionuclides decontamination, is expected to be used as a dressing for radionuclide-contaminated skin wound healing.

14.
Aging Clin Exp Res ; 33(11): 3073-3080, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33743170

RESUMO

AIMS: To investigate the longitudinal association of metabolic syndrome (MetS) and its components with disability outcomes. METHODS: A total of 5875 participants aged 60 and above completed the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS). MetS at baseline was measured by the National Cholesterol Education Program Adult Treatment Panel III criteria. Logistic regressions were conducted to analyze the associations between baseline MetS and incident disability, measured as the onset of limitations regarding instrumental activities of daily living (IADL) and activities of daily living (ADL) 4 years later. Linear regression was adopted to analyze the longitudinal impact of baseline MetS on the number of IADL and ADL limitations in 2015. A comprehensive list of baseline covariates was adjusted in all regression analyses. RESULTS: Baseline MetS was related to increased odds of incident IADL disability (OR = 1.28, 95% CI 1.05-1.55) and incident ADL disability (OR = 1.27, 95% CI 1.05-1.53) among disability-free participants at baseline. Baseline MetS was also associated with an increase in the number of IADL (beta = 0.15, 95% CI 0.07-0.23) and ADL limitations (beta = 0.10, 95% CI 0.01-0.18), while adjusting for baseline functional performance. Significant MetS component predictors of disability outcomes include abdominal obesity, high blood pressure, and a low level of high-density lipoprotein cholesterol. CONCLUSIONS: Our findings suggest an increased risk of incident disability and deteriorated functional performance over 4 years, associated with the presence of MetS and its components.


Assuntos
Atividades Cotidianas , Síndrome Metabólica , Idoso , China/epidemiologia , Humanos , Estudos Longitudinais , Síndrome Metabólica/epidemiologia , Aposentadoria
15.
J Cell Mol Med ; 25(8): 4040-4052, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33621431

RESUMO

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas de Membrana/antagonistas & inibidores , MicroRNAs/genética , Proteínas de Neoplasias/antagonistas & inibidores , Neovascularização Patológica/prevenção & controle , Fosfatidilinositol 3-Quinases/química , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteína 2 de Ligação ao Retinoblastoma/antagonistas & inibidores , Idoso , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína 2 de Ligação ao Retinoblastoma/genética , Proteína 2 de Ligação ao Retinoblastoma/metabolismo , Taxa de Sobrevida , Células Tumorais Cultivadas
16.
PLoS Biol ; 19(2): e3001041, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524014

RESUMO

The capacity for T cells to become activated and clonally expand during pathogen invasion is pivotal for protective immunity. Our understanding of how T cell receptor (TCR) signaling prepares cells for this rapid expansion remains limited. Here we provide evidence that the E3 ubiquitin ligase Cullin-4b (Cul4b) regulates this process. The abundance of total and neddylated Cul4b increased following TCR stimulation. Disruption of Cul4b resulted in impaired proliferation and survival of activated T cells. Additionally, Cul4b-deficient CD4+ T cells accumulated DNA damage. In T cells, Cul4b preferentially associated with the substrate receptor DCAF1, and Cul4b and DCAF1 were found to interact with proteins that promote the sensing or repair of damaged DNA. While Cul4b-deficient CD4+ T cells showed evidence of DNA damage sensing, downstream phosphorylation of SMC1A did not occur. These findings reveal an essential role for Cul4b in promoting the repair of damaged DNA to allow survival and expansion of activated T cells.


Assuntos
Linfócitos T CD4-Positivos/fisiologia , Reparo do DNA/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteínas de Transporte/metabolismo , Proliferação de Células/fisiologia , Proteínas Culina/genética , Proteínas Culina/metabolismo , Dano ao DNA , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Antígenos de Linfócitos T , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética
17.
Stem Cell Res Ther ; 12(1): 36, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413653

RESUMO

The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs.Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry, and function must be overcame. Notably, the pro-inflammatory and anti-inflammatory effects of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes, and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit.Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSC transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering. MSC transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influence implant integration by improving the healing process. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses.Here, we review the advances in combinatorial biomaterial scaffolds and MSC transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSC transplantation and its future direction for neuronal regeneration will be presented.


Assuntos
Materiais Biocompatíveis , Traumatismos da Medula Espinal , Axônios , Comunicação Celular , Humanos , Regeneração Nervosa , Medula Espinal , Traumatismos da Medula Espinal/terapia
18.
Can J Microbiol ; 67(2): 138-146, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32841574

RESUMO

The SCUEC4 strain of Ochrobactrum intermedium is a newly isolated bacterium that degrades nicotine can use nicotine as the sole carbon source via a series of enzymatic catalytic processes. The mechanisms underlying nicotine degradation in this bacterium and the corresponding functional genes remain unclear. Here, we analyzed the function and biological properties of the ocnE gene involved in the nicotine-degradation pathways in strain SCUEC4. The ocnE gene was cloned by PCR with total DNA of strain SCUEC4 and used to construct the recombinant plasmid pET28a-ocnE. The overexpression of the OcnE protein was detected by SDS-PAGE analysis, and study of the function of this protein was spectrophotometrically carried out by monitoring the changes of 2,5-dihydroxypyridine. Moreover, the effects of temperature, pH, and metal ions on the biological activities of the OcnE protein were analyzed. The optimal conditions for the biological activities of OcnE, a protein of approximately 37.6 kDa, were determined to be 25 °C, pH 7.0, and 25 µmol/L Fe2+, and the suitable storage conditions for the OcnE protein were 0 °C and pH 7.0. In conclusion, the ocnE gene is responsible for the ability of 2,5-dihydroxypyridine dioxygenase. These findings will be beneficial in clarifying the mechanisms of nicotine degradation in O. intermedium SCUEC4.


Assuntos
Proteínas de Bactérias/metabolismo , Genes Bacterianos , Nicotina/metabolismo , Ochrobactrum/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Concentração de Íons de Hidrogênio , Ferro/metabolismo , Peso Molecular , Ochrobactrum/genética , Piridinas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Temperatura
19.
Oncol Lett ; 20(6): 377, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33154775

RESUMO

Approximately 500,000 new head and neck squamous cell carcinoma (HNSCC) cases are detected every year around the world, and its incidence ranks sixth among all cancer types globally. Among these cases, oral squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC) are HNSCC subtypes with high incidence rates, especially in China. The present study examines the association between the apolipoprotein L1 (APOL1) mRNA and protein expression and clinical parameters in HNSCC. The two most common types (oral and larynx) of HNSCC were selected for subgroup analyses. Immunohistochemistry (IHC) was used to detect APOL1 protein expression levels in HNSCC clinical specimens. It was demonstrated that APOL1 protein expression in 221 cases of HNSCC was higher compared with that in normal tissues. Consistent upregulation of APOL1 protein was also found in subgroups of OSCC and LSCC. Through mining the ArrayExpress, The Cancer Genome Atlas and the Gene Expression Omnibus databases, microarrays and RNA sequencing data for HNSCC were retrieved, which were used to analyze APOL1 mRNA expression levels. The results showed that APOL1 expression was higher in both OSCC and LSCC subtypes, as well as in HNSCC, compared with that in non-cancerous squamous epithelium. The summary receiver operating characteristic analysis showed that APOL1 had potential as a diagnostic biomarker for HNSCC, OSCC and LSCC. Thus, upregulation of APOL1 may contribute to the tumorigenesis of HNSCC.

20.
IEEE Trans Cybern ; PP2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33095726

RESUMO

In this article, the consensus of networked underactuated robotic systems subject to fixed and switched communication networks is discussed by developing some novel event-triggered control algorithms, which can synchronously guarantee the convergence of the active states, the boundedness of the velocities of passive actuators, and the exclusion of Zeno behaviors. In the cases of fixed networks, the sufficient criteria are established for the presented distributed event-triggered mechanisms with and without using neighbors' velocities, in order to achieve a better tradeoff between the communication load and system performance. Besides, in the situation of switched networks, the sufficient criterion is established by assuming that the union of the network has a spanning tree. A distributed sampled-data rule is constructed to decide when to update its own and neighbors' estimated positions, and thus further reduces the unnecessary control cost. Finally, by further extending the main results to three other sampled-data control algorithms, several examples with performance comparisons are provided to validate the efficiency and advantages of the theoretical results.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...