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1.
Zhonghua Yi Xue Za Zhi ; 103(17): 1316-1322, 2023 May 09.
Artigo em Chinês | MEDLINE | ID: mdl-37150681

RESUMO

Objective: To investigate the effect of Liraglutide on platelet distribution width(PDW) and carotid intima-media thickness(cIMT) in type 2 diabetic mellitus patients with obesity. Methods: Randomized controlled trial. A total of 80 type 2 diabetes mellitus (T2DM) obese patients with unsatisfactory glucose control were prospectively enrolled in this study from the Department of Endocrinology of Yuhuangding Hospital Affiliated to Qingdao University from January to December 2021. All the participants were treated with metformin or sulfonylureas. They were randomly divided into two groups: Liraglutide treatment group (Li group, n=40) and Control group (Con group, n=40).The Li group started the treatment with Liraglutide on the basis of the original hypoglycemic agents and the Con group was treated with metformin and sulfonylurea. After 16 weeks of treatment, the changes of PDW, cIMT and body mass index (BMI) in the two groups were observed, multiple linear regression was uesd to analyze the influencing factors of cIMT variation, and the effect of liraglutide on PDW and cIMT in obese patients with type 2 diabetes was analyzed. Results: Finally, 38 patients completed the study in Li group, including 23 males and 15 females, aged 30-69(56±11) years. All 40 patients in Con group completed the study, including 18 males and 22 females, aged 39-67(59±7) years. After 16 weeks of treatment, the levels of PDW and cIMT in Li group were (12.8±1.6) fl and (0.85±0.08) mm, respectively, lower than those before treatment (15.0±1.6) fl and (1.14±0.10) mm (t=18.61 and 20.37, respectively, both P<0.001); The PDW and cIMT in Con group were (13.6±1.5) fl and (1.05±0.10) mm, respectively, lower than those before treatment (15.0±1.5) fl and (1.13±0.13) mm (t=17.42 and 9.65, respectively, both P<0.001). The levels of fasting plasma glucose (FPG) and total cholesterol (TC) in both groups were lower than those before treatment(all P<0.001). After the treatment, the levels of PDW, cIMT, FPG and TC in Li group were lower than those in Con group (all P<0.05). The changes of PDW and cIMT before and after the treatment in Li group were (2.2±0.7) fl and (0.30±0.09) mm, respectively, higher than those in the Con group [(1.4±0.5) fl and (0.09±0.06) mm], with a statistically significant difference (both P<0.001). The changes of FPG and TC in Li group were significantly higher than those in Con group (all P<0.05). Multiple linear regression analysis showed that liraglutide, the changes of TC and systolic blood pressure (SBP) were the influencing factors for the changes of cIMT [ß (95%CI) were 0.20 (0.17-0.23), 0.03 (0.01-0.06), 0.01 (0.00-0.01), respectively, all P<0.05] Conclusion: Liraglutide treatment could reduce PDW and cIMT, thus contributing to cardiovascular benefits.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Feminino , Humanos , Masculino , Glicemia , Espessura Intima-Media Carotídea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Obesidade , Compostos de Sulfonilureia
2.
Eur Rev Med Pharmacol Sci ; 27(2): 818-825, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36734723

RESUMO

OBJECTIVE: Transplant recipients have a higher risk of SARS-CoV-2 infection owing to the use of immunosuppressive drugs like tacrolimus (FK506). FK506 and nirmatrelvir (NMV) (an anti-SARS-CoV-2 drug) are metabolized by cytochrome P450 3A4 and may have potential drug-drug interactions. It is important to determine the effect of NMV on FK506 concentrations. PATIENTS AND METHODS: Following protein precipitation from blood, FK506 and its internal standard (FK506-13C,2d4) were detected by ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). Total 22 blood samples (valley concentrations) from two coronavirus disease 2019 (COVID-19) patients were collected and analyzed for FK506 concentrations. RESULTS: Blood levels of FK506 (0.5-100 ng/mL) showed good linearity. The UHPLC-MS/MS method was validated with intra- and inter-batch accuracies of 104.55-107.85%, and 99.52-108.01%, respectively, and precisions of < 15%. Mean blood FK506 concentration was 12.01 ng/mL (range, 3.15-33.1 ng/mL). Five-day co-administration with NMV increased the FK506 concentrations from 3.15 ng/mL to 33.1 ng/mL, returning to 3.36 ng/mL after a 9-day-washout. CONCLUSIONS: We developed a simple quantification method for therapeutic drug monitoring of FK506 in patients with COVID-19 using UHPLC-MS/MS with protein precipitation. We found that NMV increased FK506 blood concentration 10-fold. Therefore, it is necessary to re-consider co-administration of FK506 with NMV.


Assuntos
COVID-19 , Tacrolimo , Humanos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , SARS-CoV-2 , Lactamas , Leucina , Reprodutibilidade dos Testes , Monitoramento de Medicamentos
3.
Eur Rev Med Pharmacol Sci ; 22(9): 2671-2679, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29771418

RESUMO

OBJECTIVE: To investigate the expression of human long non-coding ribonucleic acid (RNA) small nucleolar RNA host gene 15 (SNHG15) in non-small cell lung cancer (NSCLC) tissues and its prognostic significance, and to study the influencing mechanism of SNHG15 on biological functions in lung cancer cell lines. PATIENTS AND METHODS: The expression levels of SNHG15 in 49 pairs of lung cancer tissues and para-carcinoma tissues were detected via quantitative real-time polymerase chain reaction (qRT-PCR). The lung cancer cells were transiently transfected with small-interfering (si)-SNHG15 using RNA interference technique. The effect of si-SNHG15 on the proliferation of lung cancer cells was observed via methyl thiazolyl tetrazolium (MTT) assay, its effect on apoptosis of A549 cells was detected via Hoechst 33342 staining and flow cytometry, and its effects on invasion and migration of A549 cells were studied via wound healing assay and transwell assay. RESULTS: Results of qRT-PCR showed that the expression of SNHG15 in cancer tissues was increased compared with that in para-carcinoma tissues. Results of cell counting kit-8 (CCK-8) assay showed that knocking down SNHG15 could significantly inhibit the proliferation of lung cancer A549 cells. Hoechst 33342 staining and flow cytometry revealed that knocking down SNHG15 could significantly promote apoptosis of A549 cells. Wound healing assay and transwell assay revealed that knocking down SNHG15 could significantly inhibit the invasion and metastasis capacities of lung cancer A549 cells. Results of Western blotting showed that knocking down SNHG15 could inhibit the invasion and metastasis of A549 cells through inhibiting the expressions of epithelial-mesenchymal transition (EMT), matrix metalloproteinase-2 (MMP-2) and MMP-9 in cells. CONCLUSIONS: The expression of SNHG15 in lung cancer tissues is significantly higher than that in para-carcinoma tissues, the prognosis of patients accompanied with a high expression of SNHG15 is poor, and knockdown of SNHG15 in A549 cells can inhibit cell proliferation, invasion, and metastasis, and promote apoptosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Pulmonares/metabolismo , RNA Longo não Codificante/metabolismo , Células A549 , Idoso , Apoptose , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/secundário , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Longo não Codificante/genética , Transdução de Sinais , Regulação para Cima
4.
Eur Rev Med Pharmacol Sci ; 21(9): 2232-2237, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28537659

RESUMO

OBJECTIVE: To study the effects of metformin on streptozotocin-induced type 2 diabetes mellitus (T2DM) in rats. MATERIALS AND METHODS: Wistar male rats were divided into two groups: standard diet (SD, n = 20) group and high-fat diet (HFD, n = 80) group. Twenty rats in HFD group were randomly treated with metformin (EI group). After 6 weeks, among rats in HFD group, 20 rats were intraperitoneally injected with citrate buffered saline (IR group), 20 rats treated with metformin per day for 4 weeks (LI group), and 20 rats were given nothing (DM group). Rats in SD group were injected with citrate buffered saline as normal control (NC) group. Moreover, streptozotocin (STZ) was used for inducing diabetes. The metabolic parameters, such as body weight, fasting blood glucose (FBG), fasting insulin concentration (FINS), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDLC) and total bile acid (TBA) were measured. RESULTS: Compared with SD group, the levels of body weight, FBG, TC, LDLC, TBA and FINS and AUC (glucose) were significantly higher in HFD group. After administration of metformin, the levels of FBG, TG, TC, LDLC and TBA in DM and LI group were higher than NC group. Besides, the FBG, TG, TC, TBA and LDLC levels in EI group were higher than DM group. CONCLUSIONS: Metformin may help to improve the glucose and lipid metabolism by influencing the level of serum total bile acids. A combination of HFD and metformin could be effective in the treatment of rats with T2DM.


Assuntos
Ácidos e Sais Biliares/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Hipoglicemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metformina/farmacologia , Animais , Masculino , Ratos , Ratos Wistar , Estreptozocina
5.
Surg Endosc ; 31(11): 4617-4624, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28409375

RESUMO

INTRODUCTION: Prior studies show promising results of the gastric peroral endoscopic pyloromyotomy (G-POEM) procedure for treatment of refractory gastroparesis. One major technical challenge involved in this procedure is identifying the pyloric muscular ring (PMR). The aim of this study is to establish a reliable method for identification of the PMR during G-POEM. METHODS: Fluoroscopy-guided G-POEM was performed by placing an endoclip at the 9 to 11'o clock position at the pylorus for identification of PMR. Conventional G-POEM was performed by observation of blue colored mucosa at the pylorus area as an indirect marker for PMR. The degree of the PMR identification was graded into well identified, identified, and not identified based on the appearance of the PMR. Procedure times were accurately documented. Gastroparesis cardinal symptoms index and gastric emptying scintigraphy were evaluated before and after the procedure. RESULTS: Fourteen patients were studied, seven underwent fluoroscopy-guided G-POEM, and seven patients underwent conventional G-POEM. All procedures achieved technical success and no adverse events occurred. In the seven patients who underwent fluoroscopy-guided G-POEM, the PMR was well identified in four patients and identified in three patients. In the seven patients who underwent conventional G-POEM, the PMR was identified in four patients and not identified in three patients. The average time to complete the fluoroscopy-guided G-POEM was significantly shorter than that of the conventional G-POEM. CONCLUSIONS: Fluoroscopy-guided G-POEM by placement of an endoclip at the pylorus was a reliable and safe method to direct the orientation of the submucosal tunnel, to facilitate the location of the PMR, and to shorten the procedure time.


Assuntos
Fluoroscopia/métodos , Gastroparesia/cirurgia , Gastroscopia/métodos , Piloromiotomia/métodos , Adulto , Estudos de Coortes , Feminino , Seguimentos , Esvaziamento Gástrico , Humanos , Masculino , Pessoa de Meia-Idade , Piloro/diagnóstico por imagem , Piloro/cirurgia , Estudos Retrospectivos , Instrumentos Cirúrgicos , Resultado do Tratamento
6.
Scand J Immunol ; 85(3): 166-174, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27491503

RESUMO

Macrophages hold a critical position in the pathogenesis of liver injury and repair, in which their infiltrations is regarded as a main feature for both acute and chronic liver diseases. It is noted that, based on the distinct phenotypes and origins, hepatic macrophages are capable of clearing pathogens, promoting/or inhibiting liver inflammation, while regulating liver fibrosis and fibrolysis through interplaying with hepatocytes and hepatic stellate cells (HSC) via releasing different types of pro- or anti-inflammatory cytokines and growth factors. Macrophages are typically categorized into M1 or M2 phenotypes by adapting to local microenvironment during the progression of liver injury. In most occasions, M1 macrophages play a pro-inflammatory role in liver injury, while M2 macrophages exert an anti-inflammatory or pro-fibrotic role during liver repair and fibrosis. In this review, we focused on the up-to-date information about the phenotypic and functional plasticity of the macrophages and discussed the detailed mechanisms through which the phenotypes and functions of macrophages are regulated in different stages of liver injury and repair. Moreover, their roles in determining the fate of liver diseases were also summarized. Finally, the macrophage-targeted therapies against liver diseases were also be evaluated.


Assuntos
Células de Kupffer/imunologia , Cirrose Hepática/patologia , Fígado/lesões , Fígado/patologia , Ativação de Macrófagos/imunologia , Cicatrização/fisiologia , Animais , Citocinas/imunologia , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Humanos , Inflamação/imunologia , Fígado/citologia
7.
Mol Cell Endocrinol ; 423: 77-86, 2016 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-26773730

RESUMO

The classic renin-angiotensin system (RAS) is a complex system in which angiotensin II (Ang II) has been identified as an important endogenous regulator that influences both smooth muscle contraction and cell growth. Although a local RAS is known to exist in the gastrointestinal tract, it is unclear whether Ang II is involved in the loss of gastric interstitial cells of Cajal (ICC) in diabetic mice. The present study was designed to investigate the effect of Ang II on ICC survival in streptozotocin (STZ)-induced diabetic mice. Western blot, immunofluorescence, isometric muscle recording, enzyme-linked immunosorbent assay (ELISA) and a cell counting kit-8 were used in this research. Our results demonstrate that the c-Kit and membrane-bound stem cell factor (mSCF) protein expression levels in gastric smooth muscle were decreased in STZ-induced diabetic mice. However, the angiotensin receptor type 1 (AT1R) expression levels in gastric smooth muscle and angiotensin-converting enzyme (ACE) expression levels in gastric mucosa were increased. The effect of Ang II on the tonic contraction of gastric smooth muscle was potentiated in diabetic mice, and the plasma Ang II level was enhanced. Ang II increased mSCF expression, cell proliferation, and Akt-Ser473 phosphorylation in cultured gastric smooth muscle cells (GSMCs). These effects were reduced by specific inhibitors ZD7155 (an AT1R antagonist) and LY294002 (a PI3-kinase inhibitor). Our results suggest that Ang II increases mSCF expression and cell proliferation in cultured GSMCs in a PI3K/Akt signaling-dependent manner. ACE and AT1R up-regulation in the stomach may help compensate for ICC loss in STZ-induced diabetic mice.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Células Intersticiais de Cajal/fisiologia , Receptor Tipo 1 de Angiotensina/metabolismo , Angiotensina II/fisiologia , Animais , Proliferação de Células , Células Cultivadas , Diabetes Mellitus Experimental/patologia , Mucosa Gástrica/metabolismo , Masculino , Camundongos Endogâmicos ICR , Miócitos de Músculo Liso/fisiologia , Peptidil Dipeptidase A/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antro Pilórico/patologia , Receptor Tipo 1 de Angiotensina/genética , Transdução de Sinais , Estreptozocina , Regulação para Cima
8.
Eur J Gynaecol Oncol ; 37(5): 674-677, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29787009

RESUMO

OBJECTIVE: To investigate the effect of exemestane on HHUA human endometrial carcinoma cells. MATERIALS AND METHODS: The HHUA human endometrial carcinoma cells were treated with various concentrations of exemestane, and its effects on cell growth and apoptosis were investigated in vitro. The cell apoptosis was analyzed by flow cytometry and RT-PCR was used to investigate the expression of CD44s. The invasion ability of HHUA human endometrial carcinoma cells which treated with exemestane were assessed using transwell chamber model. RESULTS: At increasing doses of exemestane, a simultaneous increase in apoptotic subpopulations was detected when compared with group A (p < 0.05); the CD44s expression was found to be suppressed after the exemestane treatment. The decrease was a dose-dependent with exemestane treatment. CONCLUSION: 6x108 mol/L exemestane is an optimal dose to inhibit the expression of CD44s mRNA and inhibit the invasive growth of the endometrial carcinoma HHUA cells.


Assuntos
Androstadienos/farmacologia , Antineoplásicos/farmacologia , Inibidores da Aromatase/farmacologia , Neoplasias do Endométrio/tratamento farmacológico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/patologia , Feminino , Humanos , Receptores de Hialuronatos/genética
9.
Biosens Bioelectron ; 66: 559-64, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25522084

RESUMO

In this work, a double-probe based immunoassay was developed for rapid and sensitive determination of ß-casein in bovine milk samples. In the method, magnetic beads (MBs), employed as supports for the immobilization of anti-ß-casein polyclonal antibody (PAb), were used as the capture probe. Colloidal gold nanoparticles (AuNPs), employed as a bridge for loading anti-ß-casein monoclonal antibody (McAb) and horseradish peroxidase (HRP), were used as the amplification probe. The presence of ß-casein causes the sandwich structures of MBs-PAb-ß-casein-McAb-AuNPs through the interaction between ß-casein and the anti-ß-casein antibodies. The HRP, used as an enzymatic-amplified tracer, can catalytically oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB), generating optical signals that are proportional to the quantity of ß-casein. The linear range of the immunoassay was from 6.5 to 1520ngmL(-1). The limit of detection (LOD) was 4.8ngmL(-1) which was 700 times lower than that of MBs-antibody-HRP based immunoassay and 6-7 times lower than that from the microplate-antibody-HRP based assay. The recoveries of ß-casein from bovine milk samples were from 95.0% to 104.3% that had a good correlation coefficient (R(2)=0.9956) with those obtained by an official standard Kjeldahl method. For higher sensitivity, simple sample pretreatment and shorter time requirement of the antigen-antibody reaction, the developed immunoassay demonstrated the viability for detection of ß-casein in bovine milk samples.


Assuntos
Técnicas Biossensoriais/métodos , Caseínas/análise , Imunoensaio/métodos , Leite/química , Animais , Anticorpos Imobilizados , Benzidinas , Técnicas Biossensoriais/estatística & dados numéricos , Caseínas/imunologia , Bovinos , Ouro , Peroxidase do Rábano Silvestre , Imunoensaio/estatística & dados numéricos , Fenômenos Magnéticos , Nanopartículas Metálicas/ultraestrutura
10.
Neurogastroenterol Motil ; 26(12): 1705-16, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25292410

RESUMO

BACKGROUND: Hydrogen sulfide (H2 S) has been shown to have an excitatory effect on gastric motility, but the underlying molecular mechanism is unclear. In this study, we aimed to investigate the possible targets of H2 S and determine how H2 S affects its target proteins during H2 S-induced contraction. METHODS: Patch-clamp and potentiometric fluorescence dye were utilized to measure the electrophysiological changes. The Biotin-switch assay was utilized to detect the protein S-sulfhydration. The isometric tension measurement was conducted too. KEY RESULTS: Exogenous H2 S enhanced the tonic contraction of gastric antral smooth muscle, and voltage-dependent potassium channel (KV ) blocker and Dithiothreitol (DTT, a reducing agent) abolished the excitatory effect of NaHS. Exogenous H2 S inhibited the fast inactivation component of the voltage-dependent potassium channel current (IKVfast ) in isolated gastric antral smooth muscle cells. H2 S inhibited the KV 4.3 current in H293 cells with heterologous expression of KV 4.3, but did not inhibit the KV 4.1 and KV 4.2 currents, which together contribute greatly to IKVfast . NaHS significantly decreased the membrane potential in cultured gastric smooth muscle cells, but the NaHS-induced depolarization was suppressed by knockdown of KV 4.3 and N-ethylamaleimide (NEM), a free thiol group blocker. In addition, NaHS sulfhydrated KV 4.3 in H293 cells and in gastric smooth muscle tissue. However, this S-sulfhydration was inhibited by NEM and DTT. Meanwhile the NaHS-induced inhibition of IKVfast and KV 4.3 was also blocked by NEM and DTT. CONCLUSIONS & INFERENCES: These results suggest that exogenous H2 S sulfhydrates KV 4.3 to decrease the membrane potential, thereby enhancing the basal tension of gastric antral smooth muscle.


Assuntos
Mucosa Gástrica/metabolismo , Sulfeto de Hidrogênio/metabolismo , Tono Muscular/fisiologia , Músculo Liso/metabolismo , Canais de Potássio Shal/metabolismo , Animais , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/fisiologia , Células HEK293 , Humanos , Sulfeto de Hidrogênio/farmacologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Tono Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Técnicas de Patch-Clamp , Estômago/efeitos dos fármacos
11.
Food Chem ; 158: 445-8, 2014 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24731368

RESUMO

An immunomagnetic beads-based enzyme-linked immunosorbent assay (IMBs-ELISA) was developed for the detection of ß-casein in bovine milk. Immunomagnetic beads (IMBs) were employed as the solid phase. The anti-ß-casein monoclonal antibody (McAb) bound to IMBs was used as capture probe and an anti-ß-casein polyclonal antibody (PcAb), labelled with horseradish peroxidase (HRP), was employed as detector probe. Three reaction and two washing steps were needed. Each reaction needed 10 min or less, which significantly shortened detection compared with classic sandwich ELISA. ß-Casein in bovine milk was detected across a linear range (2-128 µg mL(-1)). Application results were in accordance with the Kjejdahl method, which suggests the IMBs-ELISA is rapid and reliable for the detection of ß-casein in bovine milk.


Assuntos
Caseínas/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Leite/química , Animais , Caseínas/análise , Bovinos , Ensaio de Imunoadsorção Enzimática/instrumentação
12.
Diabetologia ; 56(3): 663-74, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23292313

RESUMO

AIMS/HYPOTHESIS: As microRNA-21 (miR-21) plays a pathological role in fibrosis, we hypothesised that it may be a therapeutic target for diabetic nephropathy. METHODS: Abundance of miR-21 was examined in diabetic kidneys from db/db mice. The therapeutic potential of miR-21 in diabetic kidney injury was examined in db/db mice by an ultrasound-microbubble-mediated miR-21 small hairpin RNA transfer. In addition, the role and mechanisms of miR-21 in diabetic renal injury were examined in vitro under diabetic conditions in rat mesangial and tubular epithelial cell lines by overexpressing or downregulating miR-21. RESULTS: In db/db mice, a mouse model of type 2 diabetes, renal miR-21 at age 20 weeks was increased twofold compared with db/m (+) mice at the same age, and this increase was associated with the development of microalbuminuria and renal fibrosis and inflammation. More importantly, gene transfer of miR-21 knockdown plasmids into the diabetic kidneys of db/db mice at age 10 weeks significantly ameliorated microalbuminuria and renal fibrosis and inflammation at age 20 weeks, revealing a therapeutic potential for diabetic nephropathy by targeting miR-21. Overexpression of miR-21 in kidney cells enhanced, but knockdown of miR-21 suppressed, high-glucose-induced production of fibrotic and inflammatory markers. Targeting Smad7 may be a mechanism by which miR-21 regulates renal injury because knockdown of renal miR-21 restored Smad7 levels and suppressed activation of the TGF-ß and NF-κB signalling pathways. CONCLUSIONS/INTERPRETATION: Inhibition of miR-21 might be an effective therapy for diabetic nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Rim/patologia , MicroRNAs/metabolismo , Animais , Linhagem Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/fisiopatologia , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Ratos , Proteína Smad7/genética , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
13.
Immunopharmacol Immunotoxicol ; 33(4): 645-51, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21428715

RESUMO

OBJECTIVE: Lipopolysaccharides (LPS) activates several signaling pathways in macrophages including mitogen-activated protein kinases (MAPK). Previous studies have investigated effect of LPS on MAPK activation in macrophage of normal rats. In the current study, we investigated the effect of LPS exposure on activation of MAPK in alveolar macrophage (AM) of chronic bronchitis (CB) rats and researched the corresponding cyclooxygenase-2 (COX-2), prostaglandins-2 (PGE(2)) and transforming growth factor- ß (TGF-ß) production and their MAPK signal pathways. METHODS: CB model was established by injection of Bacillus Calmette-Guerin (BCG) and LPS in rats. Special inhibitors of p38, extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinases (JNK) MAPK signal pathways were used to determine the effect of MAPK activation on COX-2, PGE(2), TGF-ß production in AM of CB rats via RT-PCR, western blotting, radioimmunoassay and ELISA. KEY FINDINGS: Synthesis of PGE(2) from AM of CB rats was increased and suppressed by either PD98059 or SB203580. SB203580 and PD98059, (inhibitors of ERK and p38 MAPK), could significantly inhibit COX-2 mRNA and protein expression. Moreover, ERK and p38 MAPK had synergistic effect on COX-2 expression. Inhibitor of ERK MAPK signal transduction could inhibit TGF-ß expression in AM. CONCLUSION: These results demonstrated COX-2, PGE(2) and TGF-ß productions in AM of CB rats were significantly increased, which might be regulated by the different MAPK signaling pathway.


Assuntos
Bronquite Crônica/imunologia , Ciclo-Oxigenase 2/imunologia , Dinoprostona/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos Alveolares/imunologia , Fator de Crescimento Transformador beta/imunologia , Animais , Bronquite Crônica/induzido quimicamente , Bronquite Crônica/patologia , Lipopolissacarídeos/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos Alveolares/patologia , Masculino , Mycobacterium bovis/imunologia , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia
14.
Horm Metab Res ; 42(7): 507-13, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20225169

RESUMO

The proliferation of cardiac fibroblasts (CFs) and excessive extracellular matrix protein accumulation are the basic pathological processes of myocardial fibrosis. Visfatin is a novel adipokine involved in the regulation of inflammatory cytokines, however, the effects of visfatin on proliferation and collagen synthesis of CFs are unclear. The aim of this study was to determine whether visfatin has any effect on the proliferation and collagen synthesis in rat CFs. Incorporation of [ (3)H]-thymidine and [ (3)H]-proline were used for evaluating DNA and collagen synthesis. Flow cytometry techniques were adopted to analyze cell cycle. Enzyme-linked immunosorbent assay was used for measuring collagen type I and III production. RT-PCR and Western blot analysis were used for determining procollagen I and III mRNA expression and protein production. The inhibitors used for pathway determination were: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK)1/2)], and JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin significantly increased DNA and collagen synthesis in a dose- and time-dependent manner. Cell cycle analysis showed that visfatin increased S-stage percentage and proliferation index in a dose- and time-dependent manner. It was also found that visfatin upregulated collagen I and III production, procollagen I and III mRNA expression and protein production. These effects were diminished by SB203580, wortmannin, and PD98059, but not by JNK inhibitor II. These results suggest that visfatin promote CFs proliferation and collagen synthesis via p38MAPK, PI3K, and ERK 1/2 pathways rather than JNK pathways, which also indicate that visfatin might play a role in myocardial fibrosis.


Assuntos
Proliferação de Células/efeitos dos fármacos , Colágeno/biossíntese , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Miocárdio/metabolismo , Nicotinamida Fosforribosiltransferase/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/citologia , Coração/efeitos dos fármacos , Miocárdio/citologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Br J Dermatol ; 162(4): 843-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20105167

RESUMO

BACKGROUND: There are racial differences in the prevalence and types of androgenetic alopecia (AGA). The prevalence of AGA has been studied in Caucasians and in some Asian people. In China, although there have been some epidemiological studies carried out in single cities or regions, no multicentre population-based study has been reported. OBJECTIVES: To study the prevalence and types of AGA in China and to compare the results with those previously reported in Caucasians and in other Asian people. METHODS: A community-based study was carried out in six cities of China. Subjects were interviewed face-to-face and completed questionnaires. The degree of AGA was classified according to the Norwood and Ludwig classifications. RESULTS: In total 17 886 subjects were interviewed and 15 257 completed the questionnaires. In men, the overall prevalence of AGA was 21.3%, with 2.8% in men aged 18-29 years, 13.3% in those aged 30-39 years, 21.4% in those aged 40-49 years, 31.9% in those aged 50-59 years, 36.2% in those aged 60-69 years and 41.4% in those aged 70 years and over. The most common type was frontal and vertex hair loss. A small number of subjects (3.7%) showed 'female pattern' hair loss. In women, the prevalence of AGA was 6.0%, with 1.3% in women aged 18-29 years, 2.3% in those aged 30-39 years, 5.4% in those aged 40-49 years, 7.5% in those aged 50-59 years, 10.3% in those aged 60-69 years and 11.8% in those aged 70 years and over. Ludwig grade I was the most common type. The prevalence of AGA varied between cities. A positive family history was present in 29.7% of men and 19.2% of women with AGA. CONCLUSIONS: The prevalence of AGA in Chinese men and women was lower than in Caucasians and similar to that in Koreans.


Assuntos
Alopecia/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alopecia/genética , Povo Asiático/genética , China/epidemiologia , Cidades/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , População Branca/genética , Adulto Jovem
16.
Am J Chin Med ; 37(6): 1099-111, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19938219

RESUMO

The goal of this study was to investigate the possible therapy mechanism of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. Leaf (TAL) in alveolar macrophage (AM) of chronic bronchitis (CB) rats. CB model was established by injection of bacillus calmette guein (BCG) plus lipopolisacharide (LPS) in rats. TAL significantly inhibited the increased NO concentration, iNOS expression and phosphorylation of p38 MAPK in alveolar macrophages (AMs) of CB rats. Using in vivo test, we found that SB203580, a p38 MAPK inhibitor, (10 muM) significantly inhibited inducible nitric oxide synthase (iNOS) mRNA expression in AM. This data indicate that TAL highly decreases excessive iNOS expression and NO induction, and p38 MAPK signal transduction participates in iNOS expression and NO induction in AM of CB rats. The effect of TAL on iNOS expression in AM may be related to its inhibition of p38 MAPK signal transduction.


Assuntos
Bronquite Crônica/metabolismo , Eriobotrya/química , Macrófagos Alveolares/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Bronquite Crônica/tratamento farmacológico , Bronquite Crônica/microbiologia , Inibidores Enzimáticos , Imidazóis , Lipopolissacarídeos , Masculino , Modelos Animais , Mycobacterium bovis , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Fosforilação , Fitoterapia , Extratos Vegetais/uso terapêutico , Folhas de Planta , Piridinas , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Triterpenos/uso terapêutico
17.
Gen Physiol Biophys ; 26(2): 104-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17660584

RESUMO

Molecular cloning of cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac-specific protein kinase containing seven N-terminal ankyrin (ANK) repeats followed by a protein kinase domain and a C-terminal Ser-rich domain, has previously been reported. In the present study, we show that the C-terminal functional region of TNNI3K negatively regulates the kinase activity, and the N-terminal ANK domain is necessary for autophosphorylation. An in vitro kinase assay shows that TNNI3K exhibits dual-specific kinase activity and forms dimers or oligomers that may be necessary for its activation.


Assuntos
MAP Quinase Quinase Quinases/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases , Motivos de Aminoácidos , Linhagem Celular Transformada , Clonagem Molecular , Dimerização , Ativação Enzimática , Regulação da Expressão Gênica , Humanos , MAP Quinase Quinase Quinases/química , Miócitos Cardíacos/enzimologia , Fosforilação , Multimerização Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Terciária de Proteína , Proteínas Tirosina Quinases/metabolismo , Serina/química , Serina/metabolismo , Relação Estrutura-Atividade , Especificidade por Substrato
18.
Nano Lett ; 6(9): 1887-92, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16967996

RESUMO

The photoconductive characteristics of CdS single nanoribbons were investigated. The device characteristics, including spectral response, light intensity response, and time response, were studied systematically. It is found that CdS nanoribbon has the response speed substantively faster than those ever reported for conventional film and bulk CdS materials and the size of nanoribbons has a significant influence on the response speed with smaller CdS nanoribbons showing higher response speed. The high photosensitivity and high photoresponse speed are attributable to the large surface-to-volume ratio and high single-crystal quality of CdS nanoribbons and the reduction of recombination barrier in nanostructures. Measurements in a different atmosphere demonstrate that the absorption of ambient gas (mainly oxygen) can significantly change the photosensitivity of CdS nanoribbons through trapping electrons from the nanoribbons.


Assuntos
Cristalização/métodos , Eletroquímica/métodos , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Nanotecnologia/métodos , Fotoquímica/métodos , Relação Dose-Resposta à Radiação , Condutividade Elétrica , Eletroquímica/instrumentação , Luz , Nanoestruturas/ultraestrutura , Nanotecnologia/tendências , Fotoquímica/instrumentação , Doses de Radiação , Transdutores
19.
Int J Oral Maxillofac Surg ; 34(4): 350-6, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16053841

RESUMO

The authors reviewed 24 cases of familial or nonfamilial cherubism. The age at onset was between 6 and 10 years. It was characterized by bilateral painless swelling of jaws and eyes-to-heaven appearance was visible when the maxillae were affected as well. Radiographs showed well-defined multilocular radiolucencies and with age, thick sclerotic borders were visible. A malocclusive and abnormal dentition, worse in the mandible can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. Multinucleated giant cells were positive for osteoclastic specific markers, tartrate-resistant acid phosphatase and human alphaV beta3 integrin, 23C6. Results after follow-up were available for 14 cases. Of these, no treatment was carried out in five cases, cherubism resolved (three cases) or grew slowly (two cases); curettage or surgical contouring was performed in seven cases, during the rapid growth of the lesions. This not only gave good immediate results, but also arrested active growth of remnant cherubic lesions and even stimulated bone regeneration. Segmental mandibulectomy followed by reconstruction was performed in two cases with extensive lesion and the risk of pathologic fracture of the mandible, and excellent results were obtained.


Assuntos
Querubismo/patologia , Arcada Osseodentária/patologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idade de Início , Substituição de Aminoácidos , Querubismo/sangue , Querubismo/genética , Querubismo/cirurgia , Criança , Pré-Escolar , Feminino , Genes Dominantes , Células Gigantes/patologia , Humanos , Imuno-Histoquímica , Arcada Osseodentária/diagnóstico por imagem , Masculino , Procedimentos Cirúrgicos Ortognáticos , Linhagem , Radiografia Panorâmica
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