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1.
Medicine (Baltimore) ; 99(25): e20831, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32569232

RESUMO

The objective was to investigate the association of different hydration doses and its effect on renal function in patients with primary osteoporosis treated with zoledronic acid.The subjects with primary osteoporosis treated with zoledronic acid at the First Affiliated Hospital of Chongqing Medical University, China, from January 2015 to December 2018 were included in this study. The subjects were classified according to different hydration doses. Renal function indexes before and after treatment were collected and adverse reactions recorded to analyze the changes in renal function associated with different hydration doses.The choice of the hydration dose treated with zoledronic acid deserves attention. The lower hydration dose is, the greater impact on renal function can be caused.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Rim/fisiopatologia , Osteoporose/tratamento farmacológico , Soluções para Reidratação/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Osteoporose/fisiopatologia , Soluções para Reidratação/administração & dosagem , Estudos Retrospectivos , Ácido Zoledrônico/efeitos adversos
2.
Biochem Biophys Res Commun ; 507(1-4): 355-361, 2018 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-30442365

RESUMO

Dexamethasone (DEX) is a commonly used anti-inflammatory drug and an immunosuppressive drug used in clinical practice to treat a variety of diseases. Glucocorticoid-induced osteoporosis (GIOP) is a consequence of high dose, or a long-term low dose use of glucocorticoids (GCs). These treatment regimens can cause a variety of bone-related adverse effects, leading to increased osteoblast and bone cell apoptosis. Evidence suggests that klotho (KL) can inhibit GIOP. It is unknown whether KL attenuates DEX-induced apoptosis in MC3T3-E1 cells or the underlying mechanisms involved. In the present study, we found that MC3T3-E1 cells pretreated with DEX led to the up-regulation of cleaved-caspase-3, and down-regulation of caspase-3, which were inhibited by KL transfection. Furthermore, flow cytometry and western blot analysis revealed that the NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) could restore the DEX-induced caspase-3 decrease and inhibit the DEX-induced cleaved caspase-3 increase. We observed that DEX stimulated the degradation of IκBα(NFκB inhibitor α) and the translocation of NFκB, which were suppressed by KL transfection. These findings therefore, indicate a protective role for KL against osteoblastic cell apoptosis induced by DEX, via the NF-κB signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Dexametasona/farmacologia , Glucuronidase/metabolismo , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Osteoblastos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteólise/efeitos dos fármacos
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 33(6): 731-735, 2017 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28615093

RESUMO

Objective To explore the effect of overexpression of Klotho (KL) on the differentiation of RAW264.7 cells intoosteoclasts induced by soluble receptor activator of nuclear factor-κB ligand ( sRANKL). Methods The RAW264.7 cells were divided into Ad-KL group, Ad-GFP group and control group. Inverted microscope was used to observe KL transfected cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect mRNA and protein expression level of KL, respectively. Tartrate-resistant acidphosphatase (TRAP) staining was applied to observe the osteoclast differentiation and maturation. The qRT-PCR and Western blotting were performed to assess mRNA or protein expression levels of TRAP and cathepsin K (CTSK). Results Klotho gene was transfected into RAW264.7 cells successfully. Compared with Ad-GFP group and control group, KL mRNA and protein expression levels of Ad-KL group increased significantly. TRAP staining showed that the number and volume of TRAP-positive cells in Ad-KL group were less than those in Ad-GFP group and control group. Compared with Ad-GFP group and control group, TRAP and CTSK mRNA and protein expression levels were reduced remarkably in Ad-KL group. Conclusion Overexpression of Klotho inhibits the differentiation of RAW264.7 cells into osteoclasts.


Assuntos
Glucuronidase/fisiologia , Osteoclastos/citologia , Animais , Catepsina K/análise , Catepsina K/genética , Diferenciação Celular , Células Cultivadas , Glucuronidase/genética , Camundongos , Células RAW 264.7 , Fosfatase Ácida Resistente a Tartarato/análise , Fosfatase Ácida Resistente a Tartarato/genética
4.
J Geriatr Cardiol ; 12(4): 439-47, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26347327

RESUMO

The klotho gene has been identified as an aging suppressor that encodes a protein involved in cardiovascular disease (CVD). The inactivation of the klotho gene causes serious systemic disorders resembling human aging, such as atherosclerosis, diffuse vascular calcification and shortened life span. Klotho has been demonstrated to ameliorate vascular endothelial dysfunction and delay vascular calcification. Furthermore, klotho gene polymorphisms in the human are associated with various cardiovascular events. Recent experiments show that klotho may reduce transient receptor potential canonical6 (TRPC6) channels, resulting in protecting the heart from hypertrophy and systolic dysfunction. Fibroblast growth factor23 (FGF23) is a bone-derived hormone that plays an important role in the regulation of phosphate and vitamin D metabolism. FGF23 accelerates urinary phosphate excretion and suppresses 1,25-dihydroxy vitaminD3 (1,25(OH)2D3) synthesis in the presence of FGF receptor1 (FGFR1) and its co-receptor klotho, principally in the kidney. The hormonal affects of circulating klotho protein and FGF23 on vascular and heart have contributed to an understanding of their roles in the pathophysiology of arterial stiffness and left ventricular hypertrophy. Klotho and FGF23 appear to play a critical role in the pathogenesis of vascular disease, and may represent a novel potential therapeutic strategy for clinical intervention.

5.
Mol Med Rep ; 12(1): 45-54, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25695625

RESUMO

The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats. A recombinant adeno-associated virus (rAAV) carrying mouse klotho full-length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate-buffered saline (PBS). The Sprague-Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi-quantitative reverse transcription-polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes-induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho-associated coiled-coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long-term control and renoprotection of diabetes.


Assuntos
Retinopatia Diabética/terapia , Fibrose/terapia , Glucuronidase/genética , Hipertrofia/terapia , Quinases Associadas a rho/biossíntese , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/terapia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Fibrose/etiologia , Fibrose/genética , Regulação da Expressão Gênica , Técnicas de Transferência de Genes , Glucuronidase/uso terapêutico , Humanos , Hipertrofia/etiologia , Hipertrofia/genética , Rim/metabolismo , Rim/fisiopatologia , Camundongos , Ratos , Transdução de Sinais/efeitos dos fármacos , Quinases Associadas a rho/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 29(6): 662-8, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23225045

RESUMO

OBJECTIVE: To assess the effect of Klotho gene transduction on the progression of hypertension and heart damage in spontaneous hypertensive rats (SHRs). METHODS: An adeno-associated virus (AAV) carrying full-length mouse Klotho cDNA (rAAV.mKL) was constructed for in vivo expression of Klotho. Three different groups of male SHRs and a control group of sex and age-matched Sprague Dawley (SD) rats (5 rats per group) were used. The experimental groups of SHRs received an IV injection of phosphate buffered saline (PBS), rAAV.mKL and rAAV.EGFP, respectively. The control group only received equal-volume of PBS. The whole study has spanned 12 weeks. Plasma levels of insulin-like growth factor-1 (IGF-1) and insulin were measured with ELISA. The weight of whole heart was measured to calculate the heart weight index (HWI). EGFP expression of heart frozen sections was observed by fluorescence microscopy. Expression of mRNA and protein of Klotho, IGF-1, IGF-1 receptor (IGF-1R) and p-Akt were determined with RT-PCR, immunohistochemical analysis, and Western blotting. Hypertrophic myocardial cell and collagen fiber were observed by histological examination following Haematoxylin-Eosin and Masson staining. RESULTS: Transduction of rAAV.mKL can significantly prevent the increase of blood pressure in SHRs. Compared with the control group, the levels of Klotho mRNA and protein have both increased, and the plasma levels of IGF-1, insulin and glucose were elevated, whereas the expression of phosphor-Akt (also called Protein Kinase B, PKB) was decreased in the rAAV.mKL group. Furthermore, a decrease of hypertrophic myocardial cells and collagen fibers was noticed in the rAAV.mKL group compared with the control group. CONCLUSION: The Klotho gene can attenuate the progression of hypertension and abolishes myocardial hypertrophy and myocardial fibrosis. The protective effect observed in the rAAV.mKL group of SHRs may be attributed to increased Klotho protein and suppression of insulin and IGF-1 signaling pathways through inhibition of Akt phosphorylation.


Assuntos
Glucuronidase/genética , Hipertensão/genética , Hipertensão/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Animais , Glicemia , Pressão Sanguínea/genética , Expressão Gênica , Glucuronidase/metabolismo , Hipertensão/metabolismo , Insulina/sangue , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Miocárdio/ultraestrutura , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Transdução Genética
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 23(6): 670-2, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17160951

RESUMO

OBJECTIVE: To study the relationship between resting heart rate and single nucleotide polymorphisms (SNP) at 3 sites of nitric oxide synthase (NOS) gene including NOS3 -922A/G, NOS3 894G/T and NOS2 -1173C/T SNPs. METHODS: Genomic DNA was gained from 211 Chinese Han nationality population. The SNPs of NOS3 -922A/G, NOS3 894G/T and NOS2 -1173C/T were genotyped by allele-specific primer-polymerase chain reaction (ASP-PCR) technique. RESULTS: The distribution frequencies of GG, GT and TT genotypes of NOS3 894G/T and AA, AG and GG genotypes of NOS3 -922A/G and CC, CT and TT genotypes of NOS2 -1173C/T were consistent with Hardy-Weinberg equilibrium (P> 0.05). The resting heart rate of Chinese Han nationality population with AA genotypes was higher than that with GG genotype of NOS3 -922A/G (P< 0.01). The resting heart rate of the sub-population with GG genotype was higher than that with TT genotype of NOS3 894G/T (P< 0.05). There were no difference among the resting heart rates of the sub-populations with the allele genotypes of NOS2 -1173C/T. CONCLUSION: The resting heart rate of Chinese Han nationality population with mutated genotype GG of NOS3 -922A/G and with mutated genotype TT of NOS3 894G/T were lower than those with wild genotype of NOS3 -922A/G and NOS3 894G/T. The finding suggests that resting heart rate is associated with SNP of NOS3 -922A/G and NOS3 894G/T.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Frequência Cardíaca , Óxido Nítrico Sintase/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III/genética
9.
Artigo em Chinês | MEDLINE | ID: mdl-16532803

RESUMO

This experiment was carried out to analyze the time-frequency feature of rabbit cortical somatosensory evoked potential (SEP). Rabbit was narcotized and subjected to craniotomy. SEP was from sensory and motor cortex. Stimulation was continuing many times and signal was sampled at 3 800 Hz. The peak latency of each waveform was measured. Power spectrum of SEP was analyzed. The time-frequency feature of single-trial was compared with that of average SEP. It was found that the variability of single-trial SEP latency enlarges with time in a stimulation period. The spectrum of SEP includes three main frequency spectrum packages. The technique of summation makes a lot of signal aberration such as waveform confluence, new waveform emerging and after-discharging components dismissing.


Assuntos
Córtex Cerebral/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Processamento de Sinais Assistido por Computador , Animais , Estimulação Elétrica , Feminino , Análise de Fourier , Masculino , Coelhos
10.
Yi Chuan ; 28(1): 3-10, 2006 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-16469708

RESUMO

To study single nucleotide polymorphisms (SNP) in A-922G, T-786C and G894T of endothelial nitric oxide synthase (NOS3) and to correlate the distribution of their allelic combinations with hypertension in Chinese Han nationality population, genomic DNA was isolated from venous blood leukocytes from 192 unrelated patients with hypertension (95 females and 97 males) and 122 healthy unrelated individuals (46 females and 76 males) as controls. SNPs of NOS3 A-922G, T-786C and G894T were genotyped by allele-specific primer (ASP) PCR. The distribution of genotype combinations of three SNPs was determined by clustering analysis. There were no difference in allele genotype distribution frequency and haplotype frequency of NOS3 G894T, NOS3 A-922G and NOS3 T-786C between the essential hypertension group and the healthy population (P>0.05). According to sex stratification, no association between essential hypertension and SNP of NOS3 A-922G,NOS3 T-786C or NOS3 G894T has been found in either the male subgroup or the female subgroup. In respect of allele genotype combination frequency in the natural distribution of NOS3 A-922 G, NOS3 T-786C and NOS3 G894T SNP, there was significant difference only in the allele genotype combination frequency of NOS3 G894G+A-922G+T-786T between the hypertension group and the healthy group (P<0.05, Chi2=4.5944). According to sex stratification, there were no significant difference in all above allele genotype combination frequency in three sites of NOS3 SNP between the hypertension male subgroup and the healthy male subgroup (P>0.05). There was significant difference in the allele combination frequency of NOS3 G894G +A-922G+T-786C between the hypertension female subgroup and the healthy female subgroup(P<001, Chi2=8.502). There was no association of SNP in NOS3 A-922G, NOS3 T-786C or NOS3 G894T with hypertension in the Chinese Han nationality population, nor was there a sex difference. The combination frequency of allele NOS3 G894G + A-922G + T-786C in the hypertension female subgroup was much lower than that in the healthy female subgroup, suggesting that female population with this combination genotype may be less susceptible to hypertension.


Assuntos
Hipertensão/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
11.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 22(1): 99-103, 2005 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-15762126

RESUMO

DNA was extracted from the peripheral venous blood of 338 subjects using BLOOD DNA MINI KIT. The 5 site SNP in 3 subtypes of Beta-AR were genotyped by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and allele-specific primer PCR techniques. The genotypes combination distribution of SNP at 5 sites in the 3 subtypes of Beta-AR were determined by clustering analysis technique. The natural combination distribution characteristics for SNP at 5 sites in the 3 subtypes of Beta-AR in 338 subjects were obtained. Sixty-seven combinations types were found. The preceding 5 combinations in the natural combination distribution of the SNP were: (1) The genotype combination of forty subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 11.83%. (2) The genotype combination of thirty-three subjects was B1-AR S/S49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 9.76%. (3) The genotype combination of nineteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/Q27+B3-AR W/W64, its probability was 5.62%. (4) The genotype combination of sixteen subjects was B1-AR S/S49+B1-AR R/G389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 4.74%. (5) The genotype combination of thirteen subjects was B1-AR S/G49+B1-AR R/R389+B2-AR R/G16+B2-AR Q/E27+B3-AR W/W64, its probability was 3.85%. The obvious correlations exist among full sample and female or male subgroup, and between female and male subgroups.


Assuntos
Polimorfismo de Nucleotídeo Único/genética , Receptores Adrenérgicos beta/classificação , Receptores Adrenérgicos beta/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 3/genética
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