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1.
J Med Chem ; 67(9): 7470-7486, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38690769

RESUMO

We assessed factors that determine the tissue-specific bioactivation of ProTide prodrugs by comparing the disposition and activation of remdesivir (RDV), its methylpropyl and isopropyl ester analogues (MeRDV and IsoRDV, respectively), the oral prodrug GS-621763, and the parent nucleotide GS-441524 (Nuc). RDV and MeRDV yielded more active metabolite remdesivir-triphosphate (RDV-TP) than IsoRDV, GS-621763, and Nuc in human lung cell models due to superior cell permeability and higher susceptivity to cathepsin A. Intravenous administration to mice showed that RDV and MeRDV delivered significantly more RDV-TP to the lung than other compounds. Nevertheless, all four ester prodrugs exhibited very low oral bioavailability (<2%), with Nuc being the predominant metabolite in blood. In conclusion, ProTides prodrugs, such as RDV and MeRDV, are more efficient in delivering active metabolites to the lung than Nuc, driven by high cell permeability and susceptivity to cathepsin A. Optimizing ProTides' ester structures is an effective strategy for enhancing prodrug activation in the lung.


Assuntos
Adenosina/análogos & derivados , Antivirais , Catepsina A , Pulmão , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Animais , Camundongos , Antivirais/farmacocinética , Antivirais/farmacologia , Antivirais/química , Antivirais/metabolismo , Humanos , Catepsina A/metabolismo , Pulmão/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacocinética , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/química , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/química , Alanina/farmacocinética , Alanina/metabolismo , Alanina/farmacologia , Permeabilidade , Ariloxifosforamidatos
3.
Front Public Health ; 12: 1372146, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510351

RESUMO

Background: Isoniazid-resistant, rifampicin-susceptible tuberculosis (Hr-TB) globally exhibits a high prevalence and serves as a potential precursor to multidrug-resistant tuberculosis (MDR-TB). Recognizing the spatial distribution of Hr-TB and identifying associated factors can provide strategic entry points for interventions aimed at early detection of Hr-TB and prevention of its progression to MDR-TB. This study aims to analyze spatial patterns and identify socioeconomic, demographic, and healthcare factors associated with Hr-TB in Shanghai at the county level. Method: We conducted a retrospective study utilizing data from TB patients with available Drug Susceptible Test (DST) results in Shanghai from 2010 to 2016. Spatial autocorrelation was explored using Global Moran's I and Getis-Ord Gi∗ statistics. A Bayesian hierarchical model with spatial effects was developed using the INLA package in R software to identify potential factors associated with Hr-TB at the county level. Results: A total of 8,865 TB patients with DST were included in this analysis. Among 758 Hr-TB patients, 622 (82.06%) were new cases without any previous treatment history. The drug-resistant rate of Hr-TB among new TB cases in Shanghai stood at 7.20% (622/8014), while for previously treated cases, the rate was 15.98% (136/851). Hotspot areas of Hr-TB were predominantly situated in southwestern Shanghai. Factors positively associated with Hr-TB included the percentage of older adult individuals (RR = 3.93, 95% Crl:1.93-8.03), the percentage of internal migrants (RR = 1.35, 95% Crl:1.15-1.35), and the number of healthcare institutions per 100 population (RR = 1.17, 95% Crl:1.02-1.34). Conclusion: We observed a spatial heterogeneity of Hr-TB in Shanghai, with hotspots in the Songjiang and Minhang districts. Based on the results of the models, the internal migrant population and older adult individuals in Shanghai may be contributing factors to the emergence of areas with high Hr-TB notification rates. Given these insights, we advocate for targeted interventions, especially in identified high-risk hotspots and high-risk areas.


Assuntos
Migrantes , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Idoso , China/epidemiologia , Estudos Retrospectivos , Isoniazida/farmacologia , Isoniazida/uso terapêutico , Teorema de Bayes , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico
4.
BMC Geriatr ; 24(1): 189, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409011

RESUMO

BACKGROUND: There are a variety of determinants that are key to functional disability of older adults. However, little is known regarding the relationship between cognitive frailty and disability among older people. The aims of this study were to examine the associations between cognitive frailty and its six components with instrumental activities of daily living (IADL) functioning in community-dwelling older adults. METHODS: A total of 313 community-dwelling older adults (aged ≥ 65 years) were recruited from eight community centers in central China. Cognitive frailty was operationalized using the Mini-Mental State Examination for the evaluation of cognitive status and the Fried criteria for the evaluation of physical frailty. The outcome was functional disability assessed by the IADL scale. The association between cognitive frailty, as well as its components, and IADL limitations was identified by conducting binary logistic regression analysis. RESULTS: The prevalence of cognitive frailty was 8.9% in this study. The results showed that cognitive frailty (OR = 22.86) and frailty without cognitive impairment (OR = 8.15) were associated with IADL limitations. Subdimensions of cognitive frailty, exhaustion, weakness, low physical activity and cognitive impairment components were independently associated with IADL limitations. CONCLUSION: Cognitive frailty was associated with a higher prevalence of disability. Interventions for improving cognitive frailty should be developed to prevent IADL disability among community-dwelling older adults in China.


Assuntos
Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Idoso Fragilizado/psicologia , Vida Independente/psicologia , Estudos Transversais , Atividades Cotidianas , China/epidemiologia , Cognição , Avaliação Geriátrica/métodos
5.
Front Public Health ; 12: 1354515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38371243

RESUMO

Backgrounds: The diagnostic delay of tuberculosis (TB) contributes to further transmission and impedes the implementation of the End TB Strategy. Therefore, we aimed to describe the characteristics of patient delay, health system delay, and total delay among TB patients in Shanghai, identify areas at high risk for delay, and explore the potential factors of long delay at individual and spatial levels. Method: The study included TB patients among migrants and residents in Shanghai between January 2010 and December 2018. Patient and health system delays exceeding 14 days and total delays exceeding 28 days were defined as long delays. Time trends of long delays were evaluated by Joinpoint regression. Multivariable logistic regression analysis was employed to analyze influencing factors of long delays. Spatial analysis of delays was conducted using ArcGIS, and the hierarchical Bayesian spatial model was utilized to explore associated spatial factors. Results: Overall, 61,050 TB patients were notified during the study period. Median patient, health system, and total delays were 12 days (IQR: 3-26), 9 days (IQR: 4-18), and 27 days (IQR: 15-43), respectively. Migrants, females, older adults, symptomatic visits to TB-designated facilities, and pathogen-positive were associated with longer patient delays, while pathogen-negative, active case findings and symptomatic visits to non-TB-designated facilities were associated with long health system delays (LHD). Spatial analysis revealed Chongming Island was a hotspot for patient delay, while western areas of Shanghai, with a high proportion of internal migrants and industrial parks, were at high risk for LHD. The application of rapid molecular diagnostic methods was associated with reduced health system delays. Conclusion: Despite a relatively shorter diagnostic delay of TB than in the other regions in China, there was vital social-demographic and spatial heterogeneity in the occurrence of long delays in Shanghai. While the active case finding and rapid molecular diagnosis reduced the delay, novel targeted interventions are still required to address the challenges of TB diagnosis among both migrants and residents in this urban setting.


Assuntos
Migrantes , Tuberculose , Feminino , Humanos , Idoso , Diagnóstico Tardio , Teorema de Bayes , China/epidemiologia , Tuberculose/diagnóstico , Tuberculose/epidemiologia
6.
ACS Pharmacol Transl Sci ; 6(10): 1340-1346, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37854623

RESUMO

The ProTide prodrug design is a powerful tool to improve cell permeability and enhance the intracellular activation of nucleotide antiviral analogues. Previous in vitro studies showed that the activation of ProTide prodrugs varied in different cell lines. In the present study, we investigated the activation profiles of two antiviral prodrugs tenofovir alafenamide (TAF) and sofosbuvir (SOF) in five cell lines commonly used in antiviral research, namely, Vero E6, Huh-7, Calu-3, A549, and Caco-2. We found that TAF and SOF were activated in a cell-dependent manner with Vero E6 being the least efficient and Huh-7 being the most efficient cell line for activating the prodrugs. We also demonstrated that TAF was activated at a significantly higher rate than SOF. We further analyzed the protein expressions of the activating enzymes carboxylesterase 1, cathepsin A, histidine triad nucleotide-binding protein 1, and the relevant drug transporters P-glycoprotein and organic anion-transporting polypeptides 1B1 and 1B3 in the cell lines using the proteomics data extracted from the literature and proteome database. The results revealed significant differences in the expression patterns of the enzymes and transporters among the cell lines, which might partially contribute to the observed cell-dependent activation of TAF and SOF. These findings highlight the variability of the abundance of activating enzymes and transporters between cell lines and emphasize the importance of selecting appropriate cell lines for assessing the antiviral efficacy of nucleoside/nucleotide prodrugs.

7.
BMC Geriatr ; 23(1): 242, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085758

RESUMO

PURPOSE: The integral conceptual model of frailty (ICFM) integrates physical, psychological, social aspects of individuals and stresses that frailty is a dynamic state evolving over time. This study aimed to validate the ICMF among community-dwelling older adults in China. METHODS: The study recruited 341 older community-dwelling adults by convenient sampling method between June 1 and August 30, 2019 in Hubei province, China. The data was collected by questionnaire-based survey. Frailty was assessed by the Chinese version of the Tilburg Frailty Index. Participants were assessed for life-course determinants, disease and adverse health outcomes. Hierarchical regression analyses, Bootstrap method and the structural equation model were conducted in data analysis. RESULTS: Both linear and logistic hierarchical regression models were statistically significant. Life-course determinants, disease, and three domains of frailty together explained 35.6% to 50.6% of the variance of disability and all domains of quality of life. The mediation effect of frailty between disease and all adverse outcomes was significant, excluding hospitalization. The structural equation model guided by the ICMF fits the data well. CONCLUSIONS: The ICMF is valid among community-dwelling older adults in China. Therefore, the multidimensional concept of frailty should be widely used in Chinese communities.


Assuntos
Fragilidade , Humanos , Idoso , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/psicologia , Vida Independente/psicologia , Qualidade de Vida/psicologia , Estudos Transversais , Idoso Fragilizado/psicologia , Avaliação Geriátrica/métodos , China/epidemiologia
8.
Nutr Metab Cardiovasc Dis ; 33(4): 698-714, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737357

RESUMO

AIMS: An increasing number of studies on non-traditional lipid profiles have been investigated in recent years. However, the associations between non-traditional lipid profiles and the risk of stroke remained inconsistent. Therefore, this meta-analysis aimed to evaluate the associations between non-traditional lipid profiles and the risk of stroke and clarify the dose-response relations. DATA SYNTHESIS: We performed a systematic literature search in PubMed, Embase, and Web of Science databases until 1 November 2022 for relevant studies. Relative risks and 95% confidence intervals were pooled by random-effects or fixed-effects models. A total of 26 full-text studies with 676678 participants and 18057 stroke cases were eligible for the final study. We found a positive association between the risk of stroke and total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio (RR = 1.19,95%CI = 1.00-1.40, I2 = 74.6%), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio (RR = 1.24,95%CI = 1.10-1.41, I2 = 62.8%) or low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio (RR = 1.24, 95%CI = 1.11-1.39, I2 = 49.4%). When focusing on the stroke subtype, a more significant association was observed between the risk of ischemic stroke and four non-traditional lipid profiles. In dose-response analysis, we found a linear association between TC/HDL-C ratio and the risk of stroke (RR = 1.16,95%CI = 1.07-1.26). CONCLUSIONS: Elevated non-traditional lipid profiles were associated with an increased risk of ischemic stroke. The linear association showed the risk of stroke increased by 16% when the pooled RR of TC/HDL-C ratio per 1-unit increased. REGISTRATION NUMBER IN PROSPERO: CRD42022321251.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Triglicerídeos , HDL-Colesterol , LDL-Colesterol
10.
Nutr Metab Cardiovasc Dis ; 32(12): 2705-2713, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36333200

RESUMO

BACKGROUND AND AIMS: The sedentary behavior in people's daily life has continued to increase in recent years, causing many studies to focus on its relationship with diseases. Several studies have shown that sedentary behavior is an independent risk factor for cardiovascular disease and metabolic disease. Therefore, we performed a meta-analysis to assess the association between sedentary behavior and the risk of stroke. METHODS AND RESULTS: Two independent investigators searched for prospective cohort studies on the association between sedentary behavior and stroke risk, published before February 2022. We pooled adjusted effect size and performed the dose-response analysis by random-effect model. Seven studies with 677,614 participants and 15,135 stroke events during a median follow-up of 12.2 years were included. The pooled hazard ratio (HR) of stroke was 1.16 (95% confidence interval [CI]: 1.09-1.24) with no significant heterogeneity (I2 = 0.0%, p for heterogeneity = 0.983). In dose-response analysis, a nonlinear association between sedentary behavior and stroke risk was discovered. Stroke risk began to increase when sedentary time exceeded 3.7 h/d (HR, 1.01; 95% CI, 0.97-1.05). And when reached 11 h/d, a significantly increased risk of stroke was observed (HR, 1.21; 95% CI 1.12-1.31). CONCLUSION: A nonlinear association was found in the dose-response analysis, with increased risk only when sedentary time exceeded a certain level. Further research is needed to explain the biological mechanisms by which sedentary time above a certain threshold significantly increases stroke risk. (PROSPERO registration number: CRD42022311544).


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Humanos , Comportamento Sedentário , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco
11.
Med Sci Monit ; 28: e938473, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36168877

RESUMO

The figure 3D was published as figure 3E. The correct figure 3E is provided below. Reference: Tiezhu Guo, Yueting Liu, Xinliang Ren, Wei Wang, Hanrui Liu. Promoting Role of Long Non-Coding RNA Small Nucleolar RNA Host Gene 15 (SNHG15) in Neuronal Injury Following Ischemic Stroke via the MicroRNA-18a/CXC Chemokine Ligand 13 (CXCL13)/ERK/MEK Axis. Med Sci Monit 2020; 26:e923610; DOI: 10.12659/MSM.923610.


Assuntos
AVC Isquêmico , MicroRNAs , RNA Longo não Codificante , Linhagem Celular Tumoral , Proliferação de Células/genética , Quimiocina CXCL13 , Quimiocinas CXC/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Ligantes , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética
12.
J Clin Nurs ; 31(1-2): 167-173, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34189796

RESUMO

OBJECTIVE: To evaluate the relationship between insomnia and multidimensional frailty. BACKGROUND: Frailty has major implications on adverse health outcomes of older adults. In recent years, multidimensional nature of frailty has been increasingly recognised. Many frail older adults also suffer from insomnia. METHODS: This was a cross-sectional observational study including 454 community-dwelling adults aged 60 and older. Insomnia was defined as a subjective experience of inadequate sleep duration or quality that affects social functioning during the day, based on the Athens Insomnia Scale (AIS), and multidimensional frailty was based on Tilburg Frailty Indicator (TFI). The STROBE checklist was used to guide the submission. RESULTS: Mean age was 69.1 years old, 211 (46.5%) of participants suffered from insomnia, and 185 (40.7%) of participants were frail. There was a significant relationship between insomnia and multidimensional frailty (physical, psychological and social dimensions). Insomnia was associated with frailty, adjusting for sociodemographic characteristics and comorbidity OR of 6.863 (95% CI: 4.237-11.116). CONCLUSION: Frailty was independently predicted by insomnia. Future researches should determine whether there is a causal relationship between insomnia and multidimensional frailty, with the ultimate goal of providing interventions to reverse or prevent frailty. RELEVANCE TO CLINICAL PRACTICE: This study emphasises the importance of assessment and treatment of insomnia, potentially contributing to the reversion and prevention of frailty in community-dwelling older adults.


Assuntos
Fragilidade , Distúrbios do Início e da Manutenção do Sono , Idoso , Estudos Transversais , Idoso Fragilizado , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Vida Independente , Pessoa de Meia-Idade , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/epidemiologia
13.
Med Sci Monit ; 27: e930688, 2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-33934098

RESUMO

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.


Assuntos
Encefalopatias/diagnóstico , Influenza Humana/diagnóstico , Doença Aguda , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aquaporinas/sangue , Aquaporinas/metabolismo , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Encefalopatias/sangue , Encefalopatias/metabolismo , Líquido Cefalorraquidiano/metabolismo , Pré-Escolar , Feminino , Glucocorticoides/sangue , Glucocorticoides/metabolismo , Humanos , Imunoglobulinas Intravenosas/sangue , Imunoglobulinas Intravenosas/metabolismo , Influenza Humana/sangue , Influenza Humana/metabolismo , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Neuroimagem/métodos , Convulsões/sangue , Convulsões/diagnóstico , Convulsões/metabolismo
14.
Curr Med Sci ; 41(1): 31-38, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33582902

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented threat to health care providers (HCPs) in Wuhan, China, especially for nurses who were frequently exposed to infected or suspected patients. Limited information was available about the working experience of nurses in fighting against the pandemic. To learn the physical and psychological responses of nurses during the pandemic and explore the potential determinants, we conducted a large-scale survey in Wuhan. This multicenter cross-sectional study enrolled 5521 nurses who worked in designated hospitals, mobile cabins, or shelters during the pandemic. A structured online questionnaire was distributed to assess the physical discomforts, emotional distress and cognitive reactions of nurses at work, and the log-binomial regression analysis was performed to explore potential determinants. A considerable proportion of nurses had symptoms of physical discomforts [3677 (66.6%)] and emotional distress [4721 (85.5%)]. Nurses who were directly involved in the care of patients (i.e., care for severe patients: RR, 2.35; 95% CI, 1.95-2.84), with irregular work schedules (RR, 2.36; 95% CI, 1.95-2.87), and working overtime (RR, 1.34; 95% CI, 1.08-1.65) were at a higher risk for physical discomforts. Nurses who were directly involved in the care of patients (i.e., care for severe patients: RR, 1.78; 95% CI, 1.40-2.29), with irregular work schedules (RR, 3.39; 95% CI, 2.43-4.73), and working overtime (RR, 1.51; 95% CI, 1.12-2.04) were at a higher risk for emotional distress. Therefore, formulating reasonable work schedules and improving workforce systems are necessary to alleviate the physical and emotional distress of nurses during the pandemic.


Assuntos
COVID-19/enfermagem , Enfermeiras e Enfermeiros/psicologia , Estresse Ocupacional/psicologia , Carga de Trabalho/psicologia , Adulto , COVID-19/psicologia , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
15.
Med Sci Monit ; 26: e923610, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32862188

RESUMO

BACKGROUND Long-non-coding RNA (lncRNA) SNHG15 has been reported to be an aberrantly expressed lncRNA in patients with ischemic stroke, but its role in neuronal injury following ischemic stroke remains unclear. We hypothesized that this lncRNA is associated with the pathogenesis of ischemic stroke. MATERIAL AND METHODS A mouse model of ischemic stroke was established by middle cerebral artery occlusion (MCAO). A neurogenic mouse cell line Neuro-2a (N2a) was subjected to oxygen-glucose deprivation (OGD) for in vitro experiments. Expression of SNHG15, microRNA-18a (miR-18a), and CXCL13 in mouse brain and in OGD-treated N2a cells was determined. Altered expression of SNHG15 and miR-18a was introduced to detect their roles in N2a cell viability and apoptosis. Targeting relationships between miR-18a and SNHG15 or CXCL13 were validated by luciferase assays. Cells were treated with the ERK/MEK antagonist U0126 to assess the role of the ERK/MEK signaling pathway in N2a cell growth. RESULTS SNHG15 and CXCL13 were overexpressed and miR-18a was underexpressed in MCAO-induced mice and OGD-treated N2a cells. Silencing of SNHG15 or overexpression of miR-18a promoted cell viability, while decreased cell apoptosis induced by OGD; however, subsequent disruption of the ERK/MEK signaling pathway reversed these effects. SNHG15 was found to bind to miR-18a, which could further target CXCL13. CONCLUSIONS Silencing of SNHG15 led to CXCL13 upregulation through sequestering miR-18a and the following ERK/MEK activation, thus enhancing viability while reducing apoptosis of N2a cells. SNHG15 may serve as a novel target for ischemic stroke treatment.


Assuntos
Isquemia Encefálica/genética , Quimiocina CXCL13/metabolismo , MicroRNAs/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , RNA Longo não Codificante/fisiologia , RNA Nucleolar Pequeno/fisiologia , Acidente Vascular Cerebral/genética , Animais , Apoptose/genética , Butadienos/farmacologia , Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitrilas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética
16.
BMC Med Educ ; 20(1): 197, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552703

RESUMO

BACKGROUND: The increasing of older adults has led to enormous demand for medical care. However, as a group with unique needs and characteristics, older adults are often discriminated against in the medical field. In this paper, we aimed to translate the Fraboni Scale of Ageism (FSA) into Chinese and examine its construct validity, content validity, and reliability in Chinese mainland medical students. In order to evaluate the prevalence of ageism in Chinese medical students and prompt medical college to adopt necessary teaching methods to mitigate ageism in medical students. METHODS: By Brislin's translation guidelines, FSA was translated to Chinese. The convenient sampling method was used to select samples for this survey, including 1,974 students from two medical schools in central and north China. Construct validity was verified by the exploratory and confirmatory factor analysis. The content validity index (CVI) was used to assess content validity. The Cronbach's alpha coefficients and intraclass correlation coefficient (ICC) were used to estimate reliability. RESULTS: The alpha coefficients for FSA (Chinese version) was 0.81 and ICC was 0.87. The CVI was 0.93. Three factors were identified by exploratory factor analysis explaining 34.84% of the total variance and a three-factor model was confirmed to fit by confirmatory factor analysis. CONCLUSIONS: FSA (Chinese version) is a reliable and valid scale for measuring discrimination degree against older adults in Chinese medical students.


Assuntos
Etarismo , Estudantes de Medicina/psicologia , Inquéritos e Questionários/normas , Tradução , Adolescente , Adulto , China , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Adulto Jovem
17.
Cancer Sci ; 111(6): 1979-1990, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32259365

RESUMO

Tumor-immune crosstalk within the tumor microenvironment (TME) occurs at all stages of tumorigenesis. Tumor-associated M2 macrophages play a central role in tumor development, but the molecular underpinnings have not been fully elucidated. We demonstrated that M2 macrophages produce interleukin 1ß (IL-1ß), which activates phosphorylation of the glycolytic enzyme glycerol-3-phosphate dehydrogenase (GPD2) at threonine 10 (GPD2 pT10) through phosphatidylinositol-3-kinase-mediated activation of protein kinase-delta (PKCδ) in glioma cells. GPD2 pT10 enhanced its substrate affinity and increased the catalytic rate of glycolysis in glioma cells. Inhibiting PKCδ or GPD2 pT10 in glioma cells or blocking IL-1ß generated by macrophages attenuated the glycolytic rate and proliferation of glioma cells. Furthermore, human glioblastoma tumor GPD2 pT10 levels were positively correlated with tumor p-PKCδ and IL-1ß levels as well as intratumoral macrophage recruitment, tumor grade and human glioblastoma patient survival. These results reveal a novel tumorigenic role for M2 macrophages in the TME. In addition, these findings suggest possible treatment strategies for glioma patients through blockade of cytokine crosstalk between M2 macrophages and glioma cells.


Assuntos
Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Glicerolfosfato Desidrogenase/metabolismo , Macrófagos/metabolismo , Microambiente Tumoral/fisiologia , Animais , Neoplasias Encefálicas/patologia , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Glioma/patologia , Glicólise/fisiologia , Xenoenxertos , Humanos , Interleucina-1beta/metabolismo , Camundongos , Camundongos Nus , Receptor Cross-Talk/fisiologia , Transdução de Sinais/fisiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-30766613

RESUMO

BACKGROUND: Although the effectiveness of auricular plaster therapy (APT) on primary insomnia has been systematically reviewed, no systematic review of studies has focused on the effect on comorbid insomnia. OBJECTIVE: To evaluate the efficacy and safety of APT for comorbid insomnia. METHODS: Fifteen databases were searched from inception to July 2018. Randomized controlled trials (RCTs) of APT as an exclusive intervention for comorbid insomnia against Western medications, sham APT or no treatment were identified. RESULTS: Fourteen studies involving 928 participants were identified. The pooled outcomes revealed that APT was superior to control conditions for the global score on PSQI (SMD = -1.13, and 95% CI = -1.48--0.78) and the effective rate (RR = 1.24, 95% CI = 1.13-1.36, NNT = 5, and 95% CI =4-7). Furthermore, the results of subgroup analyses were similar to the pooled results. Additionally, the pooled results were verified to be stable by sensitivity analyses. Regarding safety, no significant difference was identified between APT and Western medications. CONCLUSIONS: APT appears to be an effective and safe treatment for comorbid insomnia. However, the benefits of APT for comorbid insomnia could not be ascertained due to the paucity of the quantity and quality of the included studies. Large-scale studies using proper methodology are needed to yield a firm conclusion.

19.
Complement Ther Clin Pract ; 34: 185-194, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30712726

RESUMO

BACKGROUND AND PURPOSE: Acupuncture is widely used in the treatment of hypertension, yet its efficacy and safety for hypertension remain controversial. This overview aimed to summarize the evidence on acupuncture for hypertension. METHODS: Eight databases were searched. The Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach were performed. RESULTS: Fifteen systematic reviews (SRs) were identified. Methodological quality and quality of evidence were unsatisfactory. Acupuncture combined with Western medicine (WM) was superior to WM in systolic blood pressure (SBP) and diastolic blood pressure (DBP), efficacy rate, and traditional Chinese medicine (TCM) syndrome. Acupuncture was more effective in treating SBP and DBP than sham acupuncture plus WM. Evidence regarding the benefit of acupuncture alone for SBP and DBP, efficacy rate and TCM syndrome was inconsistent. No serious adverse effects were identified. CONCLUSION: High-quality SRs and randomized controlled trials (RCTs) are required.


Assuntos
Terapia por Acupuntura , Hipertensão/terapia , Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Humanos
20.
Biosci Rep ; 38(2)2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29531015

RESUMO

Mammalian mitochondrial ribosomal proteins are functionally involved in protein synthesis in mitochondrion. Recently numerous studies have illuminated the role of mitochondrion in cancer development. However, the precise function of mitochondrial ribosomal protein L42 (MRPL42) remains unclear. Here in the present study, we identified MRPL42 as a novel oncogene in glioma. By analyzing the Cancer Genome Atlas (TCGA) database, we first found that MRPL42 was significantly up-regulated in glioma tissues compared with normal tissues. Functionally, we silenced MRPL42 in glioma cells and revealed that MRPL42 knockdown largely blunted the proliferation of U251 and A172 cells. Mechanistically, our results suggested that MRPL42 silencing resulted in increased distribution of cell cycle in G1 and G2/M phases, while the S-phase decreased. In addition, the apoptosis and caspase3/7 activity were both activated after MRPL42 knockdown. Taken together, MRPL42 is a novel oncogene in glioma and might help us develop promising targetted therapies for glioma patients.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Técnicas de Silenciamento de Genes , Glioma/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas Ribossômicas/metabolismo , Linhagem Celular Tumoral , Glioma/genética , Glioma/patologia , Humanos , Proteínas Mitocondriais/genética , Proteínas Oncogênicas/genética , Proteínas Ribossômicas/genética
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