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1.
Cell Death Dis ; 15(8): 591, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39143050

RESUMO

Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is a novel mitophagy receptor, which harbors the LC3-interacting region (LIR) and is required in mitophagy under stress conditions. Although it does not localize in mitochondria under normal culturing conditions, GPR50 is recruited to the depolarized mitochondrial membrane upon mitophagy stress, which marks the mitochondrial portion and recruits the assembling autophagosomes, eventually facilitating the mitochondrial fragments to be engulfed by the autophagosomes. Mutations Δ502-505 and T532A attenuate GPR50-mediated mitophagy by disrupting the binding of GPR50 to LC3 and the mitochondrial recruitment of GPR50. Deficiency of GPR50 causes the accumulation of damaged mitochondria and disrupts OXPHOS, resulting in insufficient ATP production and excessive ROS generation, eventually impairing neuronal development. GPR50-deficient mice exhibit impaired social recognition, which is rescued by prenatal treatment with mitoQ, a mitochondrially antioxidant. The present study identifies GPR50 as a novel mitophagy receptor that is required to maintain mitochondrial OXPHOS in developing neurons.


Assuntos
Mitocôndrias , Mitofagia , Neurônios , Receptores Acoplados a Proteínas G , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Neurônios/metabolismo , Mitocôndrias/metabolismo , Camundongos , Humanos , Fosforilação Oxidativa , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Espécies Reativas de Oxigênio/metabolismo , Camundongos Knockout , Neurogênese
2.
Zhongguo Zhong Yao Za Zhi ; 48(22): 6216-6224, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114228

RESUMO

This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.


Assuntos
Medicamentos de Ervas Chinesas , Influenza Humana , Faringite , Humanos , Influenza Humana/tratamento farmacológico , Medicamentos de Ervas Chinesas/efeitos adversos , Cápsulas , Tosse/tratamento farmacológico , Tosse/induzido quimicamente , Rinorreia , Estudos Multicêntricos como Assunto
4.
Atherosclerosis ; 371: 32-40, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36990029

RESUMO

BACKGROUND AND AIMS: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to attenuate atherosclerosis. Further, it has been suggested that intestinal flora influences atherosclerosis progression. Herein we aimed to investigate whether SGLT2i can alleviate atherosclerosis through intestinal flora. METHODS: Six-week-old male ApoE-/- mice fed a high-fat diet were gavaged either empagliflozin (SGLT2i group, n = 9) or saline (Ctrl group, n = 6) for 12 weeks. Feces were collected from both groups at the end of the experiment for fecal microbiota transplantation (FMT). Another 12 six-week-old male ApoE-/- mice were fed a high-fat diet and received FMT with feces either from SGLT2i (FMT-SGLT2i group, n = 6) or from Ctrl (FMT-Ctrl group, n = 6) groups. Blood, tissue, and fecal samples were collected for subsequent analyses. RESULTS: In comparison with Ctrl group, atherosclerosis was less severe in the SGLT2i group (p < 0.0001), and the richness of probiotic, such as f_Coriobacteriaceae, f_S24-7, f_Lachnospiraceae, and f_Adlercreutzia, was higher in feces. Besides, empagliflozin resulted in a significant reduction in the inflammatory response and altered intestinal flora metabolism. Interestingly, compared with FMT-Ctrl, FMT-SGLT2i also showed a reduction in atherosclerosis and systemic inflammatory response, as well as changes in the component of intestinal flora and pertinent metabolites similar to SGLT2i group. CONCLUSIONS: Empagliflozin seems to mitigate atherosclerosis partly by regulating intestinal microbiota, and this anti-atherosclerotic effect can be transferred through intestinal flora transplantation.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Masculino , Camundongos , Animais , Transplante de Microbiota Fecal/métodos , Aterosclerose/prevenção & controle , Apolipoproteínas E
5.
Natl Sci Rev ; 10(3): nwac272, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36875785

RESUMO

Simultaneously achieving high electrochemical activity and high loading for solid-state batteries has been hindered by slow ion transport within solid electrodes, in particular with an increase in electrode thickness. Ion transport governed by 'point-to-point' diffusion inside a solid-state electrode is challenging, but still remains elusive. Herein, synchronized electrochemical analysis using X-ray tomography and ptychography reveals new insights into the nature of slow ion transport in solid-state electrodes. Thickness-dependent delithiation kinetics are spatially probed to identify that low-delithiation kinetics originate from the high tortuous and slow longitudinal transport pathways. By fabricating a tortuosity-gradient electrode to create an effective ion-percolation network, the tortuosity-gradient electrode architecture promotes fast charge transport, migrates the heterogeneous solid-state reaction, enhances electrochemical activity and extends cycle life in thick solid-state electrodes. These findings establish effective transport pathways as key design principles for realizing the promise of solid-state high-loading cathodes.

6.
Angew Chem Int Ed Engl ; 62(15): e202300691, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36786065

RESUMO

Free carbene readily causes multiple side reactions due to its high energy, thus its asymmetric transformation is very difficult. We present here our findings of high-pKa Brønsted acid catalysts that enable free carbene insertion into N-H bonds of amines to prepare chiral α-amino acid derivatives with high enantioselectivity. Under irradiation with visible light, diazo compounds produce high-energy free carbenes that are captured by amines to form free ylide intermediates, and then the newly designed high-pKa Brønsted acids, chiral spiro phosphamides, promote the proton transfer of ylides to afford the products. Computational and kinetic studies uncover the principle for the rational design of proton-transfer catalysts and explain how the catalysts accelerate this transformation and provide stereocontrol.

7.
Food Res Int ; 161: 111818, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192890

RESUMO

Cultured meat technology is a promising new technology to solve the negative problems brought by traditional animal husbandry. Cultured meat should be further developed to appear on consumers' tables as alternative protein product. Therefore, this study used food grade peanut wire-drawing protein as scaffold to culture smooth muscle cells (SMCs) in vitro to obtain cultured meat productions containing both animal protein and plant protein. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage, which means that the plasticity of cells decreased in the later stage of passage. SMCs can well adhere to the peanut wire-drawing protein scaffold and produce extracellular matrix protein and muscle protein, so as to form a cultured meat product with rich protein composition. This study provides a theoretical basis for the production of nutrient-rich cultured meat products.


Assuntos
Músculo Liso Vascular , Proteínas de Plantas , Animais , Proteínas da Matriz Extracelular/metabolismo , Carne , Proteínas Musculares/metabolismo , Músculo Liso Vascular/metabolismo , Proteínas de Plantas/metabolismo
8.
Zhongguo Zhong Yao Za Zhi ; 47(1): 259-264, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178932

RESUMO

Since narrative medicine was introduced in China, it has been widely used in medical education and clinical practice. The research on narrative medicine in China is especially characterized by its combination with traditional Chinese medicine(TCM). At present, the research on narrative medicine in China is still in the stage of small-scale practicing and theory advocating. Besides, there is also a lack of guidance on experimental design methodology for clinical application, which leads to few high-quality studies in this field. The present study reviewed the current high-quality research on narrative medicine to discuss the value and prospects of mixed methods research in narrative medicine. In addition, the common design, application procedures, and notes of mixed methods research were explained to provide references for the extensive applications of narrative medicine in the medical field, especially TCM clinical practice, education, and scientific research.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Narrativa , China , Medicina Tradicional Chinesa , Projetos de Pesquisa
9.
J Cell Mol Med ; 25(20): 9784-9795, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34551195

RESUMO

Circular RNA is a newly discovered member of non-coding RNA (ncRNA) and regulates the target gene by acting as a micro-RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non-small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ-WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ-WHSC1 promoted NSCLC proliferation. circ-WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ-WHSC1 could act as a sponge for micro-RNA-7 (miR-7) and regulate the expression of TAB2 (TGF-beta activated kinase one binding protein two). Inhibition of the circ-WHSC1/miR-7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ-WHSC1 in NSCLC. The research suggests that the circ-WHSC1/miR-7/TAB2 axis might be a potential target for NSCLC therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Oncogenes , RNA Circular/genética , Proteínas Repressoras/genética , Animais , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Xenoenxertos , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Camundongos , Interferência de RNA , Proteínas Repressoras/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-31920983

RESUMO

Objective: The efficacy and safety of percutaneous ultrasound-guided microwave and laser ablation (MWA and LA, respectively), for treating benign thyroid nodules (BTNs), were retrospectively compared. Methods: Patients (n = 318) underwent ablation of 328 BTNs. Confounding bias was reduced by propensity-score matching, and finally the MWA and LA groups each comprised 160 nodules. At baseline (before ablation), 3, 6, and 12 months, and every 6 months thereafter, the following were recorded: nodule volume reduction rate (VRR), neck symptom scores, cosmetic scores, complications, and side effects. Results: The baseline characteristics of the MWA and LA groups were comparable. The volumes of all nodules were less at all follow-ups relative to the baseline, as were the symptom and cosmetic scores at postoperative 6 months and thereafter (P < 0.01). At each follow-up, the overall VRRs of the MWA and LA groups were comparable. However, for nodules ≥13 mL, the VRR associated with LA at ≥6 months was significantly greater than that of MWA. The average ablation time for MWA was less than that of LA (P < 0.01). The overall incidences of major complications, minor complications, and side effects were 1.6, 2.2, and 18.4%, respectively, and there were no significant differences between the MWA and LA groups. Conclusion: Percutaneous ultrasound-guided MWA and LA are both safe and effective for the treatment of BTNs. Each can significantly reduce the nodule volume and improve the neck symptoms and appearance of patients, with a low incidence of adverse side effects. The efficiency of MWA is higher than that of LA. For nodules ≥13 mL, MWA may be preferred, but at 6 months and subsequent follow-ups the reduction in volume was greater in patients receiving LA.

11.
Huan Jing Ke Xue ; 39(7): 3033-3041, 2018 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29962123

RESUMO

In this study, PM2.5 samples were collected from October to November of 2015 in the northern suburb of Nanjing. The mass concentrations of organic carbon (OC), elemental carbon (EC), and levoglucosan in the samples were analyzed by thermal optical transmittance (TOT) and ion chromatography. The average concentrations of OC and EC were respectively (11.3±4.9) µg·m-3 and (1.1±0.9) µg·m-3. The average total carbon (TC) was 22.9%, and the OC/EC was 7.4. The quality concentrations of PM2.5, OC, EC, and SOC all reflected daytime features, and the correlation between OC and EC was better during the day than at night (correlation coefficients of 0.86 for day and 0.7 for night). By analyzing the mass concentrations of PM2.5, levoglucosan, and SOC, as well as the data of backward trajectories and fire point data, it was determined that the northern suburb of Nanjing is affected by the long-distance transportation of biomass from Hebei and other places from October 13-16. The correlations between levoglucosan and OC, EC, or SOC were significant (correlation coefficients of 0.78, 0.79, and 0.65, respectively), and the contribution of biomass combustion during sampling to OC was 21.9%.

12.
Echocardiography ; 34(5): 779-781, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28299808

RESUMO

Pneumopericardium is a rare clinical entity which is often complicated by trauma. Pneumoperdicardium resulting after esophagopericardial fistula is much rarer. We present a case of pneumopericardium as the complication of esophagopericardial fistula in a 53-year-old man. After undergoing radiotherapy for 26 times, the patient got a fever and an unspecified thoracic pain. Echocardiography showed the rectilinear echoes in the pericardium. Chest computed tomography revealed pneumopericardium, pericardial effusion, recurrence of lung cancer, and pneumonia in right lower and left lung.


Assuntos
Fístula Esofágica/complicações , Fístula Esofágica/diagnóstico por imagem , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Pneumopericárdio/diagnóstico por imagem , Pneumopericárdio/etiologia , Diagnóstico Diferencial , Ecocardiografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumopericárdio/terapia , Doenças Raras/diagnóstico por imagem , Doenças Raras/etiologia , Tomografia Computadorizada por Raios X/métodos
13.
J Diabetes Investig ; 4(3): 252-60, 2013 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-24843663

RESUMO

AIMS/INTRODUCTION: Zinc-α2-glycoprotein (ZAG) is associated with the loss of adipose tissue in cancer cachexia, and has recently been proposed to be a candidate factor in the regulation of bodyweight. The aim of the study was to investigate the effects of ZAG on the proliferation and differentiation of 3T3-L1 preadipocytes. MATERIALS AND METHODS: 3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative reverse transcription polymerase chain reaction and transient transfection methods were used to explore the action of ZAG. RESULTS: Ectopic ZAG expression significantly stimulates 3T3-L1 cells proliferation in a dose- and time-dependent manner. The maximum influence of ZAG on proliferation was 1.43-fold higher than what was observed in control cells. This effect was observed 144 h after transfection with 0.16 µg of murine ZAG (mZAG) plasmid (P < 0.001). The intracellular lipids content in mZAG over-expressing cells were decreased as much as 37% when compared with the control cells after differentiation (P < 0.05, P < 0.01). The messenger ribonucleic acid levels of peroxisome proliferators-activated receptor-γ (PPARγ), CCAAT enhancer-binding protein-α (C/EBPα) and the critical lipogenic gene, fatty acid synthase (FAS), are also downregulated by up to 50% in fully differentiated ZAG-treated adipocytes. ZAG suppresses FAS messenger ribonucleic acid expression by reducing FAS promoter activity. CONCLUSIONS: Zinc-α2-glycoprotein stimulates the proliferation and inhibits the differentiation of 3T3-L1 murine preadipocytes. The inhibitory action of ZAG on cell differentiation might be a result of the attenuation of the expression of PPARγ, C/EBPα and the lipogenic-specific enzyme FAS by reducing FAS promoter activity.

14.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 32(1): 25-8, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20236584

RESUMO

OBJECTIVE: To investigate the possible effects and roles of bodyweight on the puberty onset in adolescent girls. METHODS: Totally 288 Chinese female children and adolescent girls aged 5 to 16 were followed up yearly for four consecutive years. The height, bodyweight, fat percentage, sexual characteristics, and the serum levels of leptin and insulin-like growth factor-1 (IGF-1) were studied to analyze the influential factors of puberty onset and age of menarche. RESULTS: The serum level of leptin elevated significantly from age 13 [(9.23 +/- 1.25) microg/L] and reached peak at age 16 [(13.19 +/- 1.45) microg/L]. IGF-1 significantly correlated with the timing of puberty onset (r = 0.292, P = 0.016). BMI and fat percentage had no significant effects on the onset of puberty, but were negatively correlated with the age of menarche (r = -0.323, P = 0.037, r = -0.298, P = 0.038 respectively). CONCLUSION: Bodyweight may have effect on puberty onset in female adolescents.


Assuntos
Desenvolvimento do Adolescente , Peso Corporal , Puberdade/fisiologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Adulto Jovem
15.
Chin Med J (Engl) ; 122(23): 2846-50, 2009 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-20092788

RESUMO

BACKGROUND: Many clinical studies suggest the inverse relationship between testosterone levels and insulin sensitivity in men, however the causative relationship of these two events is still not determined. The purpose of this study was to investigate the effects of testosterone replacement therapy (TRT) on insulin sensitivity, body composition, serum lipid profiles and high sensitivity C-reactive protein (hsCRP) in hypogonadotropic hypogonadal (HH) puberty undeveloped male patients. METHODS: In this prospectively designed study, we compared homeostasis model assessment of insulin resistance (HOMA-IR), insulin areas under the curves (AUC) of 3-hour oral glucose tolerance test (OGTT) and other metabolic parameters between 26 HH patients and 26 healthy men. The patients' HOMA-IR, insulin AUC, body composition, lipid profiles, hsCRP and other parameters were compared before and after nine-month TRT. RESULTS: The average levels of total testosterone (TT) in HH and healthy group were (0.9 +/- 0.6) nmol/L and (18.8 +/- 3.4) nmol/L, respectively. HOMA-IR in HH group was significantly higher than the healthy group (5.14 +/- 5.16 vs 2.00 +/- 1.38, P < 0.005). Insulin AUC in 3-hour OGTT in HH group was significantly higher than the healthy group (698.6 +/- 414.7 vs 414.2 +/- 267.5, P < 0.01). Fasting glucose level in HH group was significantly higher than control group ((5.1 +/- 0.6) mmol/L vs (4.7 +/- 0.3) mmol/l, P < 0.005). Height, weight and grasp strength of the patients were significantly increased after 9-month TRT. Significant reductions in HOMA-IR (from 5.14 +/- 5.16 to 2.97 +/- 2.16, P < 0.01), insulin AUC (from 698.6 +/- 414.7 to 511.7 +/- 253.9, P < 0.01) and hsCRP (from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L, P < 0.05) were found after TRT. Serum total cholesterol, LDL-C, HDL-C and triglyceride were all decreased, albeit with no significant difference compared to the level prior to TRT. CONCLUSIONS: HOMA-IR, insulin AUC and fasting glucose level in HH young male patients were significantly higher than those of the control group, which suggests that low level of testosterone in male adolescents might be a risk factor for insulin resistance. TRT can significantly improve patients' insulin sensitivity and suppress serum hsCRP, which in return suggests that TRT may prevent the HH patients from developing diabetes mellitus and cardiovascular diseases (CVD) in future.


Assuntos
Proteína C-Reativa/análise , Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Resistência à Insulina , Testosterona/uso terapêutico , Adolescente , Adulto , Composição Corporal , Humanos , Masculino , Estudos Prospectivos , Puberdade , Adulto Jovem
16.
Zhonghua Yi Xue Za Zhi ; 88(36): 2550-2, 2008 Sep 23.
Artigo em Chinês | MEDLINE | ID: mdl-19080648

RESUMO

OBJECTIVE: To evaluate the effect of testosterone replacement therapy in patients with hypogonadotrophic hypogonadism (HH) on insulin sensitivity and high sensitivity C reactive protein (hsCRP). METHODS: 21 males with HH, aged 15 - 30, and 18 age, and BMI-matched healthy males underwent detection of homeostasis model assessment insulin resistance index (HOMA-IR). Second, the values of weight, abdominal circumstance, grips strength, body composition, total testosterone (TT), fast blood glucose and insulin, serum lipid profile, and hsCRP were compared before and after 9-month testosterone replacement therapy in the HH patient group. RESULTS: (1) Before treatment the TT level of the HH patients WAS (0.9 +/- 0.6) nmol/L, significantly lower than that of the healthy control group (18.8 +/- 3.2) nmol/L. The fast insulin level of the HH patients was (16.0 +/- 9.8) mIU/L, significantly higher than that of the control group [(8.4 +/- 3.3) mIU/L, P = 0.018]. The HOMA-IR of the HH patient was 3.7 +/- 2.4, not significantly different from that of the control group (1.8 +/- 0.7, P = 0.021). (2) After testosterone therapy, the fast insulin level of the HH patients decreased from (16.0 +/- 9.8) mIU/L to (12.1 +/- 7.4) mIU/L (P = 0.03); the HOMA-IR decreased from (3.7 +/- 2.4) to (2.7 +/- 1.7) (P = 0.045); and the total cholesterol, LDL-c, HDL-c, and Triglyceride all decreased, but not significantly (all P > 0.05). The hsCRP decreased from (1.49 +/- 1.18) mg/L to (0.70 +/- 0.56) mg/L (P = 0.025). CONCLUSION: Short period of testosterone replacement therapy in young HH male patients significantly improves the insulin sensitivity and decreases the risk of cardiovascular disease.


Assuntos
Terapia de Reposição Hormonal , Hipogonadismo/tratamento farmacológico , Insulina/metabolismo , Testosterona/uso terapêutico , Adolescente , Adulto , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Humanos , Hipogonadismo/metabolismo , Resistência à Insulina , Masculino , Estudos Prospectivos , Adulto Jovem
17.
Chin Med Sci J ; 23(2): 73-80, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18686625

RESUMO

OBJECTIVE: To investigate the effect of interleukin-6 (IL-6) on the human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. METHODS: The plasmids containing various lengths of hGH gene 5'-promoter fragments were constructed. Stably transfected MtT/S cells were created by cotransfecting the above plasmids and pcDNA3. 1(+) with DMRIE-C transfection reagent After the administration of these cells with IL-6 and/or various inhibitors of signaling transduction pathways, the luciferase activities in MtT/S cells lysis were assayed to demonstrate the effects of IL-6 on hGH gene promoter activity and possibly involved mechanism. RESULTS: The 10(3) U/mL IL-6 stimulated GH secretion and synthesis, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.69 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 micromol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-6. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected IL-6 induction of hGH promoter activity. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-6. The results showed that the stimulatory effect of IL-6 was abolished following deletion of the -196 to - 132 bp fragment. CONCLUSIONS: IL-6 promotes GH secretion and synthesis by rat MtT/S somatotroph cells. The stimulatory effect of IL-6 on hGH gene promoter appears to require the activation of MEK and p38 MAPK, and a fragment of promoter sequence that spans the - 196 to - 132 bp of the gene, but may be unlinked with Pit-1 protein.


Assuntos
Hormônio do Crescimento Humano , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Somatotrofos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular , Regulação da Expressão Gênica , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/metabolismo , Humanos , Interleucina-6/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Regiões Promotoras Genéticas , Ratos , Somatotrofos/citologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética
18.
Chin Med Sci J ; 23(4): 193-201, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19180878

RESUMO

OBJECTIVE: To elucidate the effect of interleukin-1 beta (IL-1 beta) on human growth hormone (hGH) gene expression in a rat somatotropic pituitary cell line MtT/S. METHODS: Stably transfected MtT/S cells were firstly established by transfecting 484-Luc1 plasmid which contained hGH gene promoter -484 to +30 bp and luciferase reporter gene. The effect of IL-1 beta on hGH gene expression was determined by assaying the luciferase activities. RT-PCR method was also used to determine whether IL-1 recepor mRNA was expressed in MtT/S cells. RESULTS: The 10(3) U/mL IL-1 beta stimulated secretion and synthesis of GH, and promoted the 5'-promoter activity of GH gene in stably transfected MtT/SGL cells with the action of 1.38 times above the control. Among inhibitors of signaling transduction pathways, mitogen-activated protein kinase kinase (MAPKK/MEK) inhibitor PD98059 (40 micromol/L) and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 (5 micromol/L) completely blocked the stimulatory effect of IL-1 beta, and phosphatidylinositol-3-kinase (PI3-K) inhibitor LY294002 partly abolished the effect of IL-1 beta. Western blot analysis further confirmed the activation of phosphorylated MEK and p38 MAPK in MtT/SGL cells. Neither over-expression of Pit-1 nor inhibition of Pit-1 expression affected induction of hGH promoter activity by IL-1 beta. A series of deletion constructs of hGH promoter were created to identify the DNA sequence that mediated the effect of IL-1 beta, and results showed that the stimulatory effect of IL-1 beta was abolished following deletion of the -196 to -132 bp fragment. CONCLUSIONS: IL-1 beta promotes GH secretion and synthesis in rat MtT/S somatotroph cells. The stimulatory effect of IL-1 beta on hGH gene promoter appears to require the activation of MEK, p38 MAPK, PI3-K, and a fragment of promoter sequence that spans the -196 to -132 bp of the gene, but it may be unlinked with Pit-1 protein.


Assuntos
Hormônio do Crescimento Humano , Interleucina-1beta/metabolismo , Somatotrofos/fisiologia , Animais , Linhagem Celular , Inibidores Enzimáticos/metabolismo , Hormônio do Crescimento Humano/genética , Hormônio do Crescimento Humano/metabolismo , Humanos , Interleucina-1beta/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Regiões Promotoras Genéticas , Ratos , Receptores de Interleucina-1/genética , Receptores de Interleucina-1/metabolismo , Somatotrofos/citologia , Fator de Transcrição Pit-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
19.
Zhonghua Yi Xue Za Zhi ; 87(16): 1117-9, 2007 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-17672994

RESUMO

OBJECTIVE: To investigate the puberty timing in healthy adolescent boys in Daqing city in northern China. METHODS: A cross-sectional and longitudinal combined survey was performed. On 150 male students aged 6-15. Follow up was conducted for 4 years. The serum levels of luteinizing hormone (LH), Follicular Stimulating Hormone (FSH) and total testosterone (TT) were measured. The puberty timing and anthropometry including the body height, weight, and genital development according to Tanner's stages were all recorded. RESULTS: The mean age of puberty onset in healthy adolescent boys is (12.0+/-1.6) years. The growth velocity in the first year after puberty onset is (6.9+/-0.4) cm/year. The level of plasma TT at the time of puberty onset is (1.0+/-0.3) nmol/L. CONCLUSION: The puberty timing of boys in the Daqing city, northern China is in the range from 8 to 14 years.


Assuntos
Puberdade/sangue , Puberdade/fisiologia , Adolescente , Antropometria , Criança , China , Fenômenos Cronobiológicos , Estudos Transversais , Hormônio Foliculoestimulante/sangue , Humanos , Estudos Longitudinais , Hormônio Luteinizante/sangue , Masculino , Puberdade Precoce/sangue , Puberdade Precoce/fisiopatologia , Testosterona/sangue , Fatores de Tempo
20.
Zhonghua Nan Ke Xue ; 12(7): 612-4, 2006 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-16894938

RESUMO

OBJECTIVE: To investigate the relationship between hypogonadism and insulin resistance in young male. METHODS: Twenty-one hypogonadism young males aged 15 to 30 years were included in the clinical trial group, and 11 healthy young males of similar age and BMI in the control. Height, weight, serum FSH, LH, total testosterone (TT), nuclear type and bone age were measured for all the subjects. Serum glucose and insulin levels were taken through 3 h OGTT at 0, 30, 60, 120 and 180 min. And comparisons were made of the levels of fast glucose and insulin, areas under the curve of glucose and insulin and HOMA insulin resistance indexes (HOMA-IR) between the two groups. RESULTS: (1) In the hypogonadism group the average value of TT was (0.9 +/- 0.6) nmol/L and 5 cases of Klinefelter syndrome had pubertal development with Tanner stage above P3, while the other 16 had no. (2) No significant differences were found in BMI, age, areas under the glucose and insulin secretory curve in OGTT between the two groups. (3) Three patients were diagnosed as IGT by OGTT in hypogonadism group, whose serum glucose levels at 120 min were 8.6, 7.9 and 8.2 mmol/L respectively. The maximal insulin excretion time was 30 min after glucose loading. No IGT or DM was found in the control group. (4) Significant difference was found in HOMA-IR and fast insulin level between the two groups. CONCLUSION: (1) IGT incidence was higher in the hypogonadism group than in the control. (2) HOMA-IR and fast insulin levels were significantly higher in the hypogonadism group than in the control, which suggests that lower serum testosterone may cause insulin resistance in young male patients.


Assuntos
Hipogonadismo/fisiopatologia , Resistência à Insulina , Testosterona/sangue , Adolescente , Adulto , Glicemia/metabolismo , Estudos de Casos e Controles , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Masculino
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