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Objective: To determine whether insulin resistance is associated with all-cause mortality in subjects without diabetes. Methods: A total of 505 participants without diabetes, 198 with normal glucose tolerance (NGT) and 307 with impaired glucose tolerance (IGT), were recruited from the Daqing Diabetes Study. The participants were followed up for 30 years. They were stratified into three groups (tertiles) according to baseline homeostasis model assessment of insulin resistance(HOMA-IR) levels, as the HOMA-IR 0, the HOMA-IR 1 and the HOMA-IR 2 groups, to assess the predictive effect of insulin resistance on risk of all-cause mortality. Results: During the 30-year follow-up, 52, 56 and 78 participants died across the three HOMA-IR groups, respectively. The corresponding mortality per 1 000 person-years (95%CI) were 12.12 (9.56-15.01), 13.10 (10.46-16.03) and 19.91 (16.73-23.15), respectively. Participants in the HOMA-IR 2 group had a significantly higher risk of death than those in the HOMA-IR 0 group after adjustment of age, sex and smoking status (HR=1.97,95%CI 1.38-2.81, P<0.001). Cox analyses showed that a one standard deviation increase in HOMA-IR was associated with a 22% increase in the mortality after adjustment of potential confounders (HR=1.22, 95%CI 1.08-1.39, P=0.002). Conclusions: Insulin resistance is associated with increased risk of all-cause death in Chinese people without diabetes, suggesting that improving insulin resistance could be beneficial for people without diabetic in reducing risk of long-term all-cause mortality.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia , Estudios de Seguimiento , Prueba de Tolerancia a la Glucosa , Humanos , InsulinaRESUMEN
Objective: To investigate the effect of dexmedetomidine on remifentanil-induced hyperalgesia and its underlying mechanism through a prospective cohort study. Methods: From July 2018 to July 2019, 80 patients who underwent day surgery in Taizhou Central Hospital (including patients with laparoscopic cholecystectomy and oophorocystectomy) were selected, there were 46 males and 34 females with a mean age of (28.8±4.3) years. The patients were divided into dexmedetomidine group and control group with random number table, 40 cases in each group. After anesthesia induction, the dexmedetomidine group was managed with intravenous infusion of dexmedetomidine (1 µg/kg) within 10 minutes, while the control group was treated with an equal volume of normal saline. The patient's general information and the intraoperative data were recorded. The visual analogue scale (VAS) was evaluated before the operation and 1, 6 and 12 h after the surgery. The Von Frey cilia method was conducted to determine the mechanical pain threshold of the patient's non-surgical body parts. The vein blood was extracted at the corresponding time point to evaluate the expression level of miR-183 via the RT-PCR method. The demographic and preoperative parameters were comparable between the two groups. Results: Compared with the control group, the mechanical pain threshold in the dexmedetomidine group increased significantly at 1, 6, and 12 h after surgery (all P<0.05), and the VAS score at the corresponding time point declined significantly (all P<0.05). At the same time points, the serum miR-183 levels in the dexmedetomidine group were all significantly higher than those in the control group after surgery (2.07±0.41 vs 1.68±0.60, 1.99±0.33 vs 1.74±0.54, 1.88±0.36 vs 1.67±0.54, respectively, all P<0.05). Conclusion: A perioperative dose of dexmedetomidine in day surgery can significantly improve the remifentanil-related hyperalgesia, and it may be related to up-regulation of the expression of miR-183 in the blood.
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Dexmedetomidina , MicroARNs , Adulto , Femenino , Humanos , Hiperalgesia/inducido químicamente , Masculino , Estudios Prospectivos , Remifentanilo , Adulto JovenRESUMEN
Based on Yichang health big data platform, 850 608 patients from September 2018 to September 2019 were included in this study. According to the date of birth, the participants were divided into early childhood famine exposure group, fetal famine exposure group and non-famine exposure group. The incidence of adult herpes zoster (HZ) in Yichang city was analyzed, and the correlation between early life famine exposure and adult HZ was analyzed. In 2019, the crude incidence rate of adult HZ in Yichang was 6.83. The crude incidence rate of adult HZ in females (7.26) was higher than that in males (6.40). Compared with the non-famine exposure group, fetal famine exposure was associated with the incidence of adult HZ (OR=1.21; 95%CI: 1.01-1.45, P=0.041). After stratification by sex, fetal famine exposure was only found to be associated with the onset of adult HZ in females (OR=1.28, 95%CI:1.02-1.61, P=0.034).
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Herpes Zóster , Efectos Tardíos de la Exposición Prenatal , Adulto , Preescolar , Hambruna , Femenino , Herpes Zóster/epidemiología , Humanos , Incidencia , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiologíaRESUMEN
Objective: To explore the relationship between exposure to famine in early life and the risk of hypertension in adulthood. Methods: The medical data of Yichang Health Management Big Data Center from 2018 to 2019 were analyzed. A retrospective cohort study design was adopted, with hypertension as the study outcome, and different life periods exposed to the Great Famine in China were divided into groups. Multivariate logistic regression model was used to analyze the relationship between famine exposure in early life and hypertension in adulthood. At the same time, the interaction between gender and famine exposure was analyzed. Results: The age of 142 016 subjects was (60. 56±4.43). Among them, men accounted for 46.36% (65 845/142 016) and women accounted for 53.64% (76 171/142 016). There are 42 575(29.98%), 19 644(13.83%), 28 405(20.00%), 28 305(19.93%), 23 087 (19.93%) in non-famine exposure group, fetal famine exposure group, early childhood famine exposure group and late childhood famine exposure group, respectively. The prevalence of hypertension was 17.57% (24 947 cases). Multivariate logistic regression model analysis showed that after adjusting for related confounding factors, compared with non-famine exposure group, the risk of hypertension in fetal, early childhood, middle childhood and late childhood famine exposure group was higher and the OR (95%CI) values were 1.16 (1.11-1.22), 1.27 (1.21-1.33), 1.54 (1.47-1.60) and 1.84 (1.76-1.92), respectively. There was an interaction between sex and famine exposure group (P<0.001). The above association is stronger among women than among men. Conclusion: Famine exposure in early life may increase the risk of hypertension in adulthood, and the risk of women is greater than that of men.
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Hipertensión , Efectos Tardíos de la Exposición Prenatal , Inanición , Adulto , Niño , Preescolar , China/epidemiología , Hambruna , Femenino , Humanos , Hipertensión/epidemiología , Hipertensión/etiología , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/epidemiología , Estudios RetrospectivosRESUMEN
Objective: To determine the opening and closing action of the external muscle, the projection pathway of the axon terminal of trigeminal motor nucleus (Vmo) neuron to the lateral pterygoid muscle was revealed. Methods: In this study, 10 SD rats of 8 weeks old were included. The left lateral pterygoid muscle of SD rats was surgically exposed, and the wound was closed after intramuscular injection of hydroxystilbamidine/fluorogold (FG) 3-5 µl. Seven days after the operation, the experimental animals were perfused, samples collected and sectioned for immunofluorescence staining. After FG injection into the lateral pterygoid muscle, the FG reversed in the Vmo neurons. Results: In the Vmo neurons on the FG injection side (left side), a large number of FG reversed neurons were found in the corpus luteum and dendrites. These neurons were not only distributed in the dorsolateral part of the trigeminal motor nucleus that innervated the closed muscle, but also in the ventral medial portion of the trigeminal nucleus of the open muscle. Conclusions: The neuronal conduction pathway between the Vmo and the lateral pterygoid muscle innervates the lateral pterygoid muscle. The neurons are distributed both in the dorsolateral and in the nucleus of the ventral ventricle. It is concluded that the lateral pterygoid muscle involve in the jaw closing and opening movement.
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Músculos Pterigoideos , Núcleo Motor del Nervio Trigémino , Animales , Femenino , Maxilares , Movimiento , Neuronas , Músculos Pterigoideos/anatomía & histología , Músculos Pterigoideos/inervación , Ratas , Ratas Sprague-Dawley , Núcleo Motor del Nervio Trigémino/anatomía & histología , Núcleos del TrigéminoRESUMEN
Loss of bone mineral density and skeletal muscle area are linked in lung transplant patients. This loss is greater in patients with restrictive compared with obstructive lung diseases. INTRODUCTION: Sarcopenia and osteoporosis are associated with aging and chronic illnesses and may be linked in patients with advanced lung disease. Pectoralis muscle index (PMI) quantitated on computed tomography (CT) of the chest can be used to measure skeletal muscle mass. This study aimed to determine the relationship of PMI to clinical parameters including bone mineral density (BMD) in candidates for lung transplantation. METHODS: A retrospective review of transplant candidates at a single center was performed. Demographic, anthropomorphic, and clinical data were recorded. Pectoralis muscle area (PMA) was determined on an axial slice from a chest CT. PMI was calculated as the PMA divided by height squared. BMD was obtained from routine dual-energy X-ray absorptiometry (DXA) scan. RESULTS: In 226 included patients, mean PMI was 8.2 ± 3.0 cm2/m2 in males and 6.1 ± 2.1 cm2/m2 in females. Osteopenia was present in 44.4%, and 23.2% of patients had osteoporosis. Patients with obstructive lung disease had lower body mass index (22.0 ± 4.9 versus 27.9 ± 4.9 kg/m2, p < 0.001), PMI (6.0 ± 2.3 versus 8.2 ± 2.8 cm2/m2, p < 0.001), and BMD (- 2.3 ± 1.1 versus - 1.3 ± 1.1, p < 0.001) compared with patients with restrictive lung disease. PMI was a significant predictor of BMD (ß = 0.16, p < 0.001). CONCLUSION: The association between muscle area and BMD in lung transplant candidates suggests that similar mechanisms may underlie the development of both. Differences in PMI and BMD in patients with obstructive versus restrictive lung disease may result from differences in respiratory physiology or disease processes.
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Densidad Ósea , Trasplante de Pulmón , Absorciometría de Fotón , Femenino , Humanos , Pulmón , Trasplante de Pulmón/efectos adversos , Masculino , Músculos Pectorales/diagnóstico por imagen , Fenómenos Fisiológicos Respiratorios , Estudios RetrospectivosRESUMEN
Objective: Analyze the genetic characteristic of Hemagglutinin(H) gene of measles viruses isolated in Henan Province in 2017. Methods: Swab samples collected from 7 lab confirmed measles cases, and we got the measles virus by Vero/Slam inoculation. Fragment of H genes were amplified by reverse transcription polymerase chain reaction(RT-PCR), then the PCR products were sequenced and analyzed. Results: The age of the 7 measles confirmed cases were between 1 and 50 years old, and all of them were males. All the 7 measles viruses were identified as H1a genotype, and the average distance of the nucleotides and the amino acids was 0.005, respectively. Compared with the Shanghai-191/China-vaccine, there were some changes in isolated virus, such as 240(th), 397(th) and 381(st) sites in the amino acid sequence. Conclusion: The measles genotype which isolated in Henan Province in 2017 was H1a. There were some difference from Shanghai-191/China-vaccine in the nucleotides sequence of H gene, which suggested that it's necessary to strengthen the monitor the variation of measles virus.
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Hemaglutininas , Virus del Sarampión , Sarampión/virología , Adolescente , Adulto , Niño , Preescolar , China , Genotipo , Hemaglutininas/genética , Humanos , Lactante , Masculino , Vacuna Antisarampión/genética , Virus del Sarampión/genética , Persona de Mediana Edad , Filogenia , Adulto JovenRESUMEN
Objectives: To evaluate the effectiveness and safety of peramivir trihydrate in patients with influenza. Methods: This was a randomized, double-blind, double-dummy, placebo and positive control, multicenter clinical trial, comparing peramivir trihydrate with oseltamivir and placebo. The inclusive criteria were 15-70 years old, onset within 48 h, positive rapid influenza antigen test, and febrile (>38â) accompanied with at least two associated symptoms. The severe cases complicated with chronic pulmonary and cardiac diseases, malignancies, organ transplantation, hemodialysis, uncontrolled diabetes, immunocompromised status, pregnancy and coexistence of bacterium infections were excluded. All patients were randomized 2â¶2â¶1 to receive peramivir, oseltamivir and placebo respectively. The primary endpoint was the disease duration, the secondary endpoints included time to normal axillary temperature and normal living activities, viral response, and adverse effects. Results: Following informed consent, 133 patients were included in this study. Four patients were exclude due to missing medical records, not fitting inclusion or exclusion criteria and poor compliance. A total of 129 patients were finally analyzed, including 49 cases, 54 cases and 26 cases in peramivir group, oseltamivir group and placebo group. The median disease duration were 96 (76, 120) hours, 105 (90,124) hours, and 124 (104, 172) hours in three groups respectively (P>0.05) . The time to normal axillary temperature, normal living activities and viral response were not significantly different in three groups (P>0.05) . Conclusion: The value of antiviral therapy in patients with mild influenza needs to be further determined.
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Antivirales/uso terapéutico , Ciclopentanos/uso terapéutico , Guanidinas/uso terapéutico , Gripe Humana/tratamiento farmacológico , Oseltamivir/uso terapéutico , Ácidos Carbocíclicos , Adolescente , Adulto , Anciano , Método Doble Ciego , Humanos , Gripe Humana/diagnóstico , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: This study aims to explore the regulatory effect of microRNA-193a-3p on rheumatoid arthritis (RA) and its underlying mechanism. PATIENTS AND METHODS: Expression level of microRNA-193a-3p in synovial tissues extracted from 30 RA patients and healthy controls was detected by quantitative Real-time polymerase chain reaction (qRT-PCR). MH7A cells were subjected to TNF-α induction for constructing the in vitro RA model. After transfection of microRNA-193a-3p inhibitor in MH7A cells, proliferation and apoptosis were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine levels of interleukin 6 (IL-6) and IL-8 in MH7A cells. Subsequently, the dual-luciferase reporter gene assay was carried out to verify the binding condition between microRNA-193a-3p and IGFBP5. Rescue experiments were conducted to evaluate the proliferation and apoptosis of MH7A cells with knockdown of microRNA-193a-3p and IGFBP5. RESULTS: MicroRNA-193a-3p was highly expressed in synovial tissues of RA patients and TNF-α-induced MH7A cells than those of controls. TNF-α induction significantly increased the proliferative rate of MH7A cells, reaching the peak at 96 h. After knockdown of microRNA-193a-3p, the promoted proliferation by TNF-α induction was significantly inhibited. In addition, TNF-α induction significantly inhibited the apoptosis of MH7A cells. After inhibition of microRNA-193a-3p expression, the inhibited apoptosis by TNF-α induction remarkably increased. TNF-α induction upregulated levels of IL-6 and IL-8 in MH7A cells, which were remarkably reduced after the microRNA-193a-3p knockdown. Dual-luciferase reporter gene assay confirmed that IGFBP5 could bind to microRNA-193a-3p, and its expression was negatively regulated by microRNA-193a-3p. The regulatory effects of microRNA-193a-3p on proliferation and apoptosis of MH7A cells were reversed by IGFBP5 knockdown. CONCLUSIONS: MicroRNA-193a-3p is highly expressed in the synovial tissues and cells of rheumatoid arthritis. MicroRNA-193a-3p participates in the process of rheumatoid arthritis by regulating the proliferation, apoptosis and inflammatory response of MH7A cells through targeting IGFBP5.
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Artritis Reumatoide/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , MicroARNs/metabolismo , Membrana Sinovial/patología , Apoptosis/efectos de los fármacos , Artritis Reumatoide/inmunología , Artritis Reumatoide/patología , Línea Celular , Movimiento Celular , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Interleucina-6/inmunología , Interleucina-6/metabolismo , Interleucina-8/inmunología , Interleucina-8/metabolismo , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Membrana Sinovial/inmunología , Sinoviocitos , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunologíaRESUMEN
Objective: To explore the influence of lifestyle intervention on long-term diabetes in subjects with impaired glucose tolerance (IGT) returned to normal glucose tolerance (NGT) within 6 years. Methods: A total of 577 subjects (aged 25-74 years old) with IGT in Daqing were enrolled and randomly assigned to control, and diet, exercise and diet plus exercise groups in a six-year intervention trial in 1986. Subjects who were non-diabetic at the end of the intervention were followed up for additional 14 years. Results: Among all the subjects, 41.38% of them who had returned to NGT from IGT within 6 years maintained NGT status after 20 years, and had a lower incidence of diabetes than subjects maintained IGT status (46.55% vs. 75.25%). Of note, in the intervention group, the percentage of participants developed diabetes in the NGT subjects was significantly lower than that in the IGT group (43.71% vs. 76.25%) after 20 years. There was high long-term risk for diabetes in the IGT subjects after the adjustment of age, sex and baseline glucose (HR=1.81, 95%CI 1.27-2.58, P=0.001), whereas in the non-intervention group, no significant difference could be viewed in long-term diabetic risk between subjects maintained IGT status and those returned to NGT (71.43% vs. 65.22%) after adjusting of the same confounders (HR=1.03, 95%CI 0.45-2.35, P=0.94). Conclusions: IGT subjects who had returned to NGT in early years had lower risk for future diabetes than those who remained IGT. However, this beneficial effect could only be viewed in the intervention group, but not in the non-intervention group.
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Diabetes Mellitus Tipo 2/prevención & control , Intolerancia a la Glucosa/prevención & control , Insulina/metabolismo , Adulto , Anciano , Glucemia/análisis , Diabetes Mellitus Tipo 2/diagnóstico , Ejercicio Físico , Estudios de Seguimiento , Intolerancia a la Glucosa/complicaciones , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/diagnóstico , Persona de Mediana Edad , Conducta de Reducción del RiesgoRESUMEN
OBJECTIVE: miR-630 has been reported as a tumor suppressor or tumor promoter in various types of cancer. However, the effect of miR-630 in osteosarcoma (OS) has not been investigated. The purpose of this study was to investigate the expression patterns, clinical value, and functional role of miR-630 in OS. PATIENTS AND METHODS: miR-630 levels in 147 paired OS tissues and corresponding normal bone tissues were investigated by RT-PCR. The clinical data were interpreted by chi-square test, Kaplan-Meier analysis, univariate analysis, and multivariate analysis. The functional role of miR-630 was verified using cell experiments. The regulation of Proteasome 26S subunit ATPase 2 (PSMC2) by miR-630 was detected by Western blotting, dual luciferase reporter assays and rescue experiments. RESULTS: We found that miR-630 expression was decreased in OS tissues and cell lines. A low level of miR-630 was associated with advanced clinical stage and distant metastasis. Clinical assay indicated that downregulation of miR-630 strongly correlated with poor prognosis and was an independent prognostic indicator for overall survival of OS patients. Functional investigation showed that miR-630 overexpression inhibited cell growth, colony formation, migration, invasion and EMT pathway, and promoted apoptosis in OS. Mechanistically, miR-630 was identified as direct targets of miR-630 and its overexpression significantly suppressed the levels of PSMC2. In addition, overexpression of PSMC2 recuperated the effects of miR-630 overexpression. CONCLUSIONS: Our data indicated that miR-630 targets PSMC2 in OS and inhibited OS cell proliferation, which may offer a new mechanism underlying the development and progression of OS.
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ATPasas Asociadas con Actividades Celulares Diversas/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , MicroARNs/genética , Osteosarcoma/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Adulto , Estudios de Casos y Controles , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Invasividad Neoplásica , Osteosarcoma/metabolismo , Osteosarcoma/mortalidad , Osteosarcoma/patología , Pronóstico , Adulto JovenRESUMEN
OBJECTIVES: The role of mechanical stress and transforming growth factor beta 1 (TGF-ß1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. METHODS: In this study, TGF-ß1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-ß1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. RESULTS: A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-ß1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. CONCLUSION: Mechanical stress-induced overexpression of TGF-ß1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-ß1 inhibitor can inhibit articular cartilage degradation.Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-ß1). Bone Joint Res 2018;7:587-594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1.
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OBJECTIVE: In liver transplantation, long-time portal vein blocking causes the occurrence of ischemic liver injury. Dexmedetomidine, a widely admired anesthetic, has been reported as a protective agent on organs under ischemic condition. The objective of this study was to reveal the role and underlying mechanism of dexmedetomidine in ischemic liver injury. MATERIALS AND METHODS: L-02 cells were treated with dexmedetomidine during 6 h of oxygen-glucose deprivation (OGD) exposure. The expression of microRNA-711 (miR-711) in cell was overexpressed by miRNA transfection. Then, the following parameters were observed: cell viability, apoptosis, the expression of apoptosis-related proteins, and the expression and the release of Interleukin 1 beta (IL-1ß) and Tumor necrosis factor alpha (TNF-α). RESULTS: Apoptosis and inflammation were induced following OGD exposure in L-02 cells, as cell viability was impaired, apoptotic cell rate was increased, caspase-3, and caspase-9 was cleaved, and the expression and release of TNF-α and IL-1ß were increased. Dexmedetomidine attenuated OGD-induced apoptosis and inflammation, and dexmedetomidine down-regulated the expression of miR-711. Also, dexmedetomidine blocked the activation of p38 mitogen-activated protein kinase (p38MAPK) and Janus kinase (JAK)/signal transducer and activator of transcription protein (STAT) signaling upon OGD. Moreover, when miR-711 was overexpressed, dexmedetomidine did not protect L-02 cells against OGD, and did not block p38MAPK and JAK/STAT signaling pathways. CONCLUSIONS: Dexmedetomidine ameliorated OGD-induced cell apoptosis and inflammation in L-02 cells, exerting protective activities in ischemic liver injury. The anti-OGD effects of dexmedetomidine might be realized by down-regulation of miR-711 and suppression of p38MAPK and JAK/STAT signaling pathways.
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Apoptosis/efectos de los fármacos , Dexmedetomidina/farmacología , Glucosa/deficiencia , Isquemia/prevención & control , Hepatopatías/prevención & control , Hígado/efectos de los fármacos , MicroARNs/metabolismo , Oxígeno/metabolismo , Hipoxia de la Célula , Línea Celular , Citocinas/metabolismo , Citoprotección , Regulación hacia Abajo , Humanos , Isquemia/genética , Isquemia/metabolismo , Isquemia/patología , Janus Quinasa 1/metabolismo , Hígado/metabolismo , Hígado/patología , Hepatopatías/genética , Hepatopatías/metabolismo , Hepatopatías/patología , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Objective: To investigate the mechanisms of telmisartan on delaying the course of type 2 diabetes. Methods: 3T3-L1 preadipocytes were induced to 80% mature adipocytes (control group) and stimulated with 50 ng/ml tumor necrosis factor (TNF-α) for 1 hour (TNF-α group). Then 0.1, 5, 10 µmol/L telmisartan was added to the culture medium for 24 h, respectively(T(0.1, )T(5) and T(10) group). The cells from each group was collected to detect peroxisome proliferator-activated receptors γ (PPARγ) and its phosphorylation level, as well as upstream kinase cell cycle dependent kinase 5 (CDK5) by Western blot. Adiponectin in the culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA). PPARγ or CDK5 of undifferentiated 3T3-L1 adipocytes were silenced by using targeted short hairpin RNA (shRNA). Through infection of the cells with the retrovirus, stabled PPARγ or CDK5 knockdown cell lines were set up and screened by incubation with puromycin. 3T3-L1 adipocyte cell lines expressing serine mutant PPARγ (S273A, S112A, S186A) were obtained and thus their phosphorate sites were further determined. CDK5 knockdown cell lines were detected by oil red O staining to measure the lipid accumulation and differentiation efficiency. The 10 µmol/L telmisartan was used to treat mature CDK5 knockdown 3T3-L1 adipocytes, Western blot was used to detect PPARγ and its phosphorylation level, and ELISA was used to detect the release of adiponectin in the culture supernatant. Results: The TNF-α stimulation had no significant effect on the expression of PPARγ in each group (all P>0.05), but it could up-regulate the phosphorylation of PPARγ in the TNF-α group and down-regulate the release of adiponectin (all P<0.05). Compared with TNF-α group, telmisartan can reduce PPARγ phosphorylation levels and up-regulate adiponectin release in different degrees, among which T(5) group and T(10) group had statistically significant differences (all P<0.05), but for T(0.1) group, the difference was not significant (P>0.05). Compared with the 3T3-L1 wild type (WT) adipocytes, adiponectin in cell line with only S273A mutant did not respond to TNF-α stimulation and telmisartan intervention. Oil red O staining showed that silencing of CDK5 did not affect the differentiation of 3T3-L1 preadipocytes. Western blot results showed that silencing of CDK5 (shCDK5 group) had no significant effect on PPARγ expression (P>0.05), but it could down-regulate the phosphorylation of PPARγ and up-regulate release of adiponectin, compared with the randomized control group (shCon group) and the differences were statistically significant (all P<0.05). Conclusions: Telmisartan can alleviate the increased PPARγ phosphorylation and up-regulation of adiponectin content due to TNF-α stimulation. CDK5 mediates the effect of telmisartan on PPARγ signaling pathway in 3T3-L1 adipocytes. Additonally, it also demonstrated the action site of telmisartan was PPARγ Ser 273, and CDK5 is upstream kinases of PPARγ.
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Adipocitos , Células 3T3-L1 , Animales , Diferenciación Celular , Diabetes Mellitus Tipo 2 , Ratones , PPAR gamma , TelmisartánRESUMEN
BACKGROUND: Dopamine (DA) is a negative modulator of gut motility. Monoamine oxidase-B (MAO-B) is an important metabolic enzyme degrading DA. Rasagiline, an irreversible MAO-B inhibitor, is used to treat Parkinson's disease because of its neuroprotective effect and increasing central DA. However, it is unclear whether MAO-B exists in the colon and rasagiline increases colonic DA, thereby affecting colonic motility. METHODS: Immunohistochemistry, western blotting, enzyme activity assay, colonic motility recording, gut transit test, and high-performance liquid chromatography-electrochemical detection were employed in this study. KEY RESULTS: Monoamine oxidase-B was distributed in the colonic muscular layers including neurons and glias of rat and human. When oral treatment of rats with rasagiline for 4 weeks, in vitro colonic motility was significantly reduced, but it was greatly reversed by SCH-23390, an antagonist of DA D1 receptor. The rasagiline-treated rats also manifested decreased MAO-B activity and increased DA content in the colonic muscular layer, but no alterations were detected in the protein expressions of D1 and D2 receptors, and MAO-A and MAO-B, as well as in the content of 5-hydroxytryptamine and noradrenaline. Moreover, acute administration of rasagiline did not affect the colonic motility in vitro and the colonic DA level in rats, although MAO-B activity was significantly inhibited. CONCLUSIONS & INFERENCES: Monoamine oxidase-B is abundant in the colonic muscular layer including myenteric plexus of rat and human. Long-term administration of rasagiline can increase colonic DA thereby inhibiting colonic motility, suggesting that colonic MAO-B could be a potential drug target for colonic dysmotility.
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Colon/efectos de los fármacos , Dopamina/metabolismo , Motilidad Gastrointestinal/efectos de los fármacos , Indanos/farmacología , Inhibidores de la Monoaminooxidasa/farmacología , Animales , Colon/metabolismo , Humanos , Masculino , Monoaminooxidasa/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Objective: To observe the influence of exogenous insulin-like growth factor-â (IGF-â ) on the expression of myocyte differentiation factor 5 (Myf5) and transforming growth factor ß1(TGF-ß1) in medial rectus muscle of cat model with strabismus. Methods: Experiment research. Twenty-seven kittens which were in sensitive period of visual development (4-6 weeks old), were randomly divided into experimental, control and blank control groups by random numbers table method. Each experimental group was further divided into 3 sub-groups (4 weeks, 8 weeks and 12 weeks) based on drug intervention time, hence 3 kittens in each sub-group. The control group and the blank control group were also divided into 3 sub-groups respectively. Exotropia treatment models were set up through surgical methods and injection of IGF-â (0.05 ml,0.1 g/L). The internal rectus muscles of 4 weeks sub-group, 8 weeks sub-group and 12 weeks sub-group were taken respectively after the treatment model had been set up. The internal rectus muscles of the control group and the blank control group were also taken according to corresponding time. The expressions of Myf5 and TGF-ß1 were tested with immunohistochemistry staining method, and optical density analysis method were employed to measure the average optical density value. The expression of Myf5 and TGF-ß1 was analyzed by Kruskal-Wallis and Bonferroni test. The correlation between the expression of Myf5 and TGF-ß1 and the time of drug intervention was analyzed by simple linear regression. Results: (1) In the experimental group, the expression of the Myf5 of the 4 weeks sub-group, 8 weeks sub-group and 12 weeks sub-group were 33.34±17.16, 39.24±15.25 and 47.70±19.39, which were higher than the control group (21.30±7.44, 19.43±4.75, 4.82±2.66) and the blank control group (18.95±6.59, 18.00±7.29, 5.86±2.61) at the same time point, and the differences were statistically significant in 8 weeks sub-group and 12 weeks sub-group (χ(2)=21.864, 31.814, both P<0.01). The expression of Myf5 in the experimental group increased with the extension of IGF-â intervention time (R(2)=0.99, P<0.05). But there were negative correlation between expression of Myf5 and drug intervention times in the control group and the blank control group (R(2)=0.81, 0.80, both P<0.05). (2) In the experimental group, the expression of the TGF-ß1 of the 4 weeks sub-group, 8 weeks sub-group and 12 sub-weeks group were 0.80±0.12, 0.53±0.09, 0.42±0.08, which were higher than the control group (1.91±0.23, 2.30±1.03, 1.82±0.72) and the blank control group (2.01±0.31, 2.62±1.11, 1.83±0.67) at the same time point, and the differences were statistically significant (χ(2)=30.801, 40.278, 35.177, all P<0.01). The expression of TGF-ß1 in the experimental group decreased with the extension of IGF-â intervention time (R(2)=0.83, P<0.05). The average optical density value regression equation of TGF-ß1 in the sterile water control group and the blank control group was 0.04 and 0.06, respectively, and the fitting degree was very poor. Therefore, there was no correlation trend with time. Conclusions: Exogenic IGF-â could enhance the expression of Myf5 in medial rectus muscle of cat model with strabismus. Exogenic IGF-â could inhibit the expression of TGF-ß1 in medial rectus muscle of cat model with strabismus. Repeated injection of exogenous IGF-â may continuously enhance the expression of Myf5 and inhibit the expression of TGF-ß1. (Chin J Ophthalmol, 2018, 54: 375-382).
Asunto(s)
Factor I del Crecimiento Similar a la Insulina , Factor 5 Regulador Miogénico , Músculos Oculomotores , Estrabismo , Factor de Crecimiento Transformador beta1 , Animales , Gatos , Diferenciación Celular , Femenino , Factor I del Crecimiento Similar a la Insulina/fisiología , Factor 5 Regulador Miogénico/metabolismo , Músculos Oculomotores/metabolismo , Distribución Aleatoria , Estrabismo/metabolismo , Factor de Crecimiento Transformador beta1/metabolismoAsunto(s)
Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/epidemiología , Eritema Nudoso/epidemiología , Psoriasis/epidemiología , Piodermia Gangrenosa/epidemiología , Estomatitis Aftosa/epidemiología , Adulto , China/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Adulto JovenRESUMEN
AIM: To evaluate the value of the aspartate aminotransferase-to-platelet ratio index (APRI) for hepatocellular carcinoma (HCC) patients who underwent transarterial chemoembolisation (TACE). MATERIALS AND METHODS: A total of 315 patients were enrolled, who were randomly divided into the training cohort (n=158) and the validation cohort (n=157). The optimal cut-off value of the APRI was determined using the X-tile software in the training cohort, and was validated in the validation cohort. Several serum-based markers, neutrophil-to-lymphocyte (N/L) and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratios were included to compare with the APRI. To predict individual survival rate, independent predictors were included to build a nomogram. RESULTS: Using the X-tile, a cut-off value of the APRI as 0.40 was yielded to distinguish patients with distinct outcomes in the training cohort, but failed for the N/L and ALT/AST ratios. In the training cohort, 66 patients with high APRI had poorer survival (p<0.001) than did 92 patients with low APRI. Using the same cut-off value of APRI, 61 patients with high APRI had poorer survival (p<0.001) than did 96 patients with low APRI in the validation cohort. Furthermore, a nomogram, including the APRI, TACE cycles, tumour size, and tumour number, was built based on the training cohort, and validated well in the validation cohort (concordance index [C-index] 0.713). CONCLUSION: The APRI is a promising marker to predict treatment response and outcome for HCC patients after TACE treatment.