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1.
Zhonghua Er Ke Za Zhi ; 62(7): 649-654, 2024 Jul 02.
Artigo em Chinês | MEDLINE | ID: mdl-38955683

RESUMO

Objective: To investigate the pathogenic mechanism and clinical characteristics of the novel splicing variant of ATP-binding cassette subfamily B member 4 (ABCB4) and provide a basis for subsequent genetic diagnosis. Methods: The clinical data of a 5-year-old child with cholestatic liver disease admitted to the Beijing Children's Hospital of Capital Medical University was retrospectively analyzed. The pathogenic variations were detected by whole exome sequencing and verified by Sanger sequencing, and bioinformatics was used to predict the pathogenicity of the mutation sites. Possible pathogenic variations were verified in vitro by Minigene assay. The clinical outcome was followed after discharge from hospital. Results: The 5-year-old boy had developed cholestasis at the age of 11 months. His physical examination showed obvious enlargement of the liver and spleen. Cholestatic cirrhosis was diagnosed by liver function tests, abdominal ultrasonography, liver biopsy and pathology. The results of genetic analysis showed that the patient was a complex heterozygote of the ABCB4 gene, with a pathogenic mutation c.2860G>A and a novel mutation c.2065-8T>G, derived from the mother and father respectively. The conservative prediction of the c.2065-8T>G site showed that this region was highly conserved and may affect splicing. Minigene assay results confirmed that the c.2065-8T>G mutation resulted in a 7 bp retention of intron 16 in the mature mRNA. In the absence of nonsense-mediated mRNA decay, the amino acid frameshift forms a truncated protein, which is represented by p.Glu689ValfsTer19. The patient was diagnosed as progressive familial intrahepatic cholestasis type 3 (PFIC3) and treated with ursodeoxycholic acid (UDCA). His clinical symptoms improved during 18 months of follow-up. Conclusions: The c.2065-8T>G variant is confirmed to affect the splicing process and exhibits complex heterozygosity with c.2860G>A, which is identified as the cause of the disease. PFIC3 children with this variant showed cholestatic liver disease as the main manifestation with a slow progression and was sensitive to treatment with UDCA.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Colestase Intra-Hepática , Mutação , Fenótipo , Humanos , Masculino , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/diagnóstico , Pré-Escolar , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/deficiência , Sequenciamento do Exoma , Genótipo , Heterozigoto , Estudos Retrospectivos , Ácido Ursodesoxicólico/uso terapêutico , Fígado/patologia
2.
Artigo em Chinês | MEDLINE | ID: mdl-37805777

RESUMO

At present, effective reconstruction of the integrity and functionality of damaged skin tissue remains an important medical problem in the field of wound repair. In recent years, the rapid development of nanozymes and tissue engineering scaffolds in the field of regenerative medicine has made it possible to develop new skin wound repair materials. Based on the process of skin wound repair and regeneration, this review briefly describes the nanozymes and its catalytic mechanism. At the same time, the common tissue engineering scaffolds loaded with nanozymes and their manufacturing strategies are introduced, the application of tissue engineering scaffolds loaded with nanozymes during the stages of anti-bacteria and anti-inflammation in the process of wound repair is summarized, and their future development direction is discussed.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Pele , Medicina Regenerativa , Transplante de Pele
4.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 40(11): 857-860, 2022 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-36510723

RESUMO

Objective: To establish a purge and trap-gas chromatography-mass spectrometry method based on soil analysis model for the determination of six benzene homologues (benzene, toluene, ethylbenzene, m-xylene, p-xylene and o-xylene) in human blood. Methods: From September 2020 to May 2021, diatomite was used as a dispersant to add 2.0 ml blood sample and fully mixed. The sample was directly injected into the purging and collecting bottle after purging. The gas chromatography column was used for separation. The retention time locking was used for qualitative analysis and the selected ion scanning mode (SIM) was used for detection. The detection limit and recovery rate of the method were analyzed. Results: The linear range of the method for the determination of six benzene homologues in human blood was 0.02-10.00 ng/ml, the correlation coefficient was 0.9927-0.9968, the detection limit was 0.006-0.016 ng/ml, the recovery rate of sample spiking was 84.39%-102.41%, and the precision of the method was 3.06%-6.90%. Conclusion: Purge and trap-gas chromatography-mass spectrometry can simultaneously determine the contents of six benzene homologues in human blood. The pretreatment method is simple, time-saving, and the method has low detection limit, which provides a scientific basis for the detection of benzene homologues in human body.


Assuntos
Benzeno , Xilenos , Humanos , Benzeno/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Xilenos/análise , Derivados de Benzeno/análise , Tolueno/análise
5.
Zhonghua Liu Xing Bing Xue Za Zhi ; 43(11): 1796-1803, 2022 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-36444465

RESUMO

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.


Assuntos
Estudantes de Medicina , Humanos , Estudos Transversais , Comportamento Sedentário , Sono
6.
Artigo em Chinês | MEDLINE | ID: mdl-36052595

RESUMO

Objective: To establish a method for detection of 6 BTEXs in urine by Purge and Trap-Gas Chromatography-Mass Spectrometry. Methods: The urine sample need not be diluted, but directly purge and trap in the bottle, separated by gas chromatography column, then simultaneously analyzed by retention time locking (RTL) method and selective ion scanning mode (SIM) . Results: The linear range of 6 BTEXs in urine was good, the correlation coefficient was between 0.997 4 and 0.998 9. The minimum quantification limits was 0.010-0.036 µg/L. The precision was 1.9%-4.7%, and the recovery was 93.1%-101.9%. Conclusion: The method has the advantages of wide linear range, high sensitivity and recovery. It is suitable for the determination of 6 BTEXs in urine of low level occupational-exposed or non-exposed population.


Assuntos
Exposição Ocupacional , Cromatografia Gasosa-Espectrometria de Massas/métodos
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(6): 1023-1028, 2020 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-33331308

RESUMO

OBJECTIVE: To analyse the clinical and laboratory characteristics of antinuclear antibody (ANA) positive rheumatoid arthritis (RA) patients. METHODS: The clinical and laboratory data of 428 RA cases from Department of of Rheumatology and Immunology Peking University Third Hospital from Jan 2013 to Dec 2018 were collected and used to analyse characters between ANA positive group and ANA negative group. T test was used for the quantitative data in accordance with normal distribution. Wilcoxon rank sum test was used for the quantitative data of non normal distribution. The qualitative data were analyzed by chi square test. But while 1≤theoretical frequency < 5, chi square test of corrected four grid table was used. And Fisher exact probability method was used when theoretical frequency < 1. RESULTS: The number of ANA positive group was 231 (54%). The female rate was obviously higher in ANA positive group (82.7% vs. 63.5%, χ2=20.355, P < 0.01). The rate of metatarsophalangeal joints (MTPJs) involvement was lower in ANA positive group (22.1%) than in ANA negative group (33.0) (χ2=6.414, P < 0.05). The incidence of secondary Sjögren's syndrome (sSS) was much higher in ANA positive group(19.5% vs. 4.1%, χ2=23.300, P < 0.01). The positivity of rheumatoid factor (RF), as well as the positivity of anti-cyclic citrullinated peptide(CCP) antibody was much higher in ANA positive group (77.1% vs. 53.8%, χ2=25.743, P < 0.01, 74.9% vs. 59.4%, χ2=11.694, P < 0.01, respectively). The levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) of ANA positive group were higher [(15.1±5.1) g/L vs. (13.8±5.3) g/L, t=2.359, P < 0.05, 1.25 (0.92) g/L vs. 1.05 (0.65) g/L, Z=-3.449, P < 0.01, respectively]. But the levels of hemoglobin (Hb) and platelet (PLT) was lower in ANA positive group[(109.64±17.98) vs. (114.47±18.48) g/L, t=-2.734, P < 0.01; (266.4×109±104.6×109) vs. (295.9×109±100.1×109) /L, t=-2.970, P < 0.01, respectively]. CONCLUSION: The incidence of sSS was obviously higher in ANA positive group than in ANA negative group. Serum IgG of ANA positive group was higher, but Hb and PLT were lower.


Assuntos
Anticorpos Antinucleares , Artrite Reumatoide , Artrite Reumatoide/epidemiologia , Autoanticorpos , Feminino , Humanos , Laboratórios , Peptídeos Cíclicos , Fator Reumatoide
9.
Zhonghua Yi Xue Za Zhi ; 100(47): 3788-3792, 2020 Dec 22.
Artigo em Chinês | MEDLINE | ID: mdl-33379844

RESUMO

Objective: To compare the clinical and laboratory characteristics and therapy methods of elderly onset rheumatoid arthritis (EORA) and younger onset rheumatoid arthritis (YORA). Methods: The clinical, laboratory and therapeutic data of 481 RA patients in the Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018 were collected and used to analyze the difference of characteristics between EORA group and YORA group, which might be useful for better diagnosis and treatment of EORA patients. Quantitative data of normal distribution were compared with t test between the two groups. Results: There were 481 patients in this cohort, of which 137(28.5%) were EORA, 344(71.5%) were YORA, with a mean age of (59±14) years (19-87 years). There were 358 females (74.4%) and 123 males (25.6%). The percentage of male patients was obviously higher in EORA group (36.5% vs 21.2%, χ(2)=12.012, P<0.01), and the average disease course was obviously shorter (Z=-7.985, P<0.01). Disease Activity Score 28 (DAS28) score was higher in EORA group (5.6±1.3 vs 5.2±1.6, t=2.549, P<0.05), meanwhile the incidences of pleural effusion and interstitial lung disease (ILD) were higher (6.6% vs 1.7%, 29.9% vs 18.3%, respectively; χ(2)=7.550, 7.797, both P<0.05). The incidences of venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, coronary heart disease (CHD), peripheral atherosclerosis and cataract in EORA group were all significantly higher than those in YORA group (all P<0.05). Erythrocyte sedimentation rate (ESR) and D-Dimer in EORA group were all remarkably higher (both P<0.05). The rate of using glucocorticoid in EORA group was higher but the rate of using methotrexate and anti-tumor necrosis factor-α agents were lower (χ(2)=5.271, 8.407, 9.356, all P<0.05). Conclusion: Compared to YORA group, the percentage of male patients and disease activity of EORA group are higher. The occurrence of pleural effusion, ILD, venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, CHD, peripheral atherosclerosis and cataract in EORA group are higher than those in YORA group.


Assuntos
Artrite Reumatoide , Idade de Início , Idoso , Artrite Reumatoide/epidemiologia , Sedimentação Sanguínea , Progressão da Doença , Feminino , Humanos , Masculino , Metotrexato , Pessoa de Meia-Idade
10.
Eur Rev Med Pharmacol Sci ; 24(24): 12963-12970, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33378047

RESUMO

OBJECTIVE: The aim of the study was to clarify the therapeutic mechanism of Dexmedetomidine (DEX) on the chronic obstructive pulmonary disease (COPD) and its regulatory effect on long non-coding RNA (lncRNA) PACER. PATIENTS AND METHODS: Serum level of PACER in COPD patients was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic potential of PACER in COPD was assessed by plotting ROC curves. The in vivo COPD model was generated in rats by cigarette smoking exposure. Primary rat alveolar epithelial cells were isolated, purified and cultured. After overexpression of PACER in primary rat alveolar epithelial cells, proliferative and migratory abilities were assessed by cell counting kit-8 (CCK-8) and transwell assay, respectively. Subsequently, we detected changes in PACER expression, viability and migratory potentials in primary rat alveolar epithelial cells harvested from control rats, and those harvested from COPD rats and induced with either DEX or not. Rescue experiments were conducted to uncover the involvement of PP2A in PACER-regulated cell phenotypes. RESULTS: PACER was upregulated in serum of COPD patients, which was a potential biomarker for diagnosing COPD. Overexpression of PACER in primary rat alveolar epithelial cells enhanced proliferative and migratory abilities. Compared with primary rat alveolar epithelial cells harvested from control rats, proliferative and migratory abilities were stronger in those harvested from COPD rats and induced with either DEX or not. Notably, DEX induction decreased PACER expression, and proliferative and migratory abilities in primary rat alveolar epithelial cells harvested from COPD rats. Overexpression of PP2A could partially abolish the promotive effects of PACER on proliferative and migratory abilities in DEX-induced primary rat alveolar epithelial cells harvested from COPD rats. CONCLUSIONS: PACER drives the proliferative and migratory abilities of alveolar epithelial cells through activating PP2A. Dexmedetomidine is conducive to COPD treatment by downregulating PACER.


Assuntos
Dexmedetomidina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , RNA Longo não Codificante/antagonistas & inibidores , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/metabolismo , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley
11.
Eur Rev Med Pharmacol Sci ; 21(21): 4952-4965, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29164562

RESUMO

OBJECTIVE: To investigate the effects of resveratrol on autophagy in the chronically diabetic nephropathy and to study the effects of the different expression of microRNAs after resveratrol (RSV) treated in db/db mice (diabetic mice). MATERIALS AND METHODS: Db/m (non- diabetic) and db/db mice were randomly divided into intra gastric RSV treatment group or control group. Renal tissues were prepared for HE/PAS staining. In vitro, mouse podocytes cell lines were grown in different mediums with different dose of resveratrol treatment. microRNA (miRNA) gene chips assay was performed for differentially expressed miRNAs screening. Western blot was used to detect protein levels. RESULTS: In vivo, RSV significantly decreased urinary albumin, serum creatinine, mesangial area and glomerular size in db/db mice. After RSV treatment, LC3-II/LC3-I and synaptopodin were increased while cleaved-caspase 3 was decreased in kidney tissues. In vitro, podocytes treated with RSV exhibited significantly increased LC3-II/LC3-I and decreased cleaved caspase 3. Moreover, this effect of RSV can be enhanced by rapamycin (RAPA, an activator of autophagy) but partially reversed by 3-MA (an autophagy inhibitor). Further, we found that miR-18a-5p was significantly upregulated after RSV treatment in db/db mice. Overexpression of miR-18a-5p in podocytes resulted in significant inhibition of cleaved-caspase 3 protein, and increased the ratio of LC3-II/LC3-I. Dual luciferase report assay validated that Atactic telangiectasis mutation (ATM) was a target of miR-18a-5p. In podocytes, downregulation of cleaved caspase 3 and the enhanced ratio of protein LC3-II/LC3-I were detected in cells transfected with ATM siRNA. CONCLUSIONS: Role of miRNA-18a-5p in the regulation of autophagy via targeting ATM may represent a promising therapeutic target for preventing and attenuating diabetic nephropathy.


Assuntos
Autofagia/efeitos dos fármacos , MicroRNAs/metabolismo , Estilbenos/farmacologia , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Caspase 3/metabolismo , Linhagem Celular , Creatinina/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Regulação para Baixo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Obesos , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Resveratrol , Sirolimo/farmacologia , Regulação para Cima/efeitos dos fármacos
12.
Genet Mol Res ; 15(4)2016 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-27966738

RESUMO

Trichomes are derived from the epidermis and constitute an ideal system for studying cell division in plants. Here, a Chinese cabbage doubled haploid (DH) line (FT) without trichomes was crossed with another DH line (PurDH-1) with trichomes to develop an F2 population for fine mapping of trichome control genes. Genetic analysis showed that the trichome phenotype was controlled by a single dominant gene, Brtri1. Using 1226 glabrous individuals in the F2 segregation population, Brtri1 was localized to a 16.84 kb region between markers Pur6-31 and Pur6-39 on chromosome A06. One of the four complete open reading frames within the mapping region, Bra025311, encodes a MYB transcription factor and is highly homologous to the trichome regulatory gene GL1 in Arabidopsis thaliana. It was thus regarded as a candidate gene for Brtri1. Comparative sequencing showed a 5-bp deletion in the third exon of Bra025311 in FT, resulting in a frame-shift mutation. No expression of Bra025311 was detected in FT. A co-dominant indel marker close to this mutation site was developed for marker-assisted selection in Chinese cabbage breeding.


Assuntos
Brassica rapa/genética , Mapeamento Cromossômico/métodos , Fatores de Transcrição/genética , Tricomas/crescimento & desenvolvimento , Brassica rapa/crescimento & desenvolvimento , Cruzamentos Genéticos , DNA de Plantas/análise , Mutação da Fase de Leitura , Marcadores Genéticos , Haploidia , Fenótipo , Análise de Sequência de DNA , Tricomas/genética
13.
Eur Rev Med Pharmacol Sci ; 20(20): 4322-4327, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27831640

RESUMO

OBJECTIVE: To provide selectable microRNA for intervening diabetes mellitus diseases, NOD mice's expression of microRNA in pancreas tissues and blood under the exendin-4 intervention of was observed and the difference of microRNA target gene was screened. MATERIALS AND METHODS: Forty clean NOD mice were randomly divided into four groups (in each group, n = 10): One is blank control group D which is intervened with normal saline, and the other three groups were divided into low-dose group A, middle-dose group B, and high-dose group C according to the different exendin-4 dosage 2, 4, and 8 µg/kg·d. After the 8-week intervention, these four groups were killed, and the pancreatic tissue and blood were left to prepare specimens for morphology and molecular biology analysis. The specimen with differential expression microRNA in pancreas tissue and blood should be screened out after detected with the locked nucleic acid array system (LNATM) microRNA expression profile chip. The primers should be designed, and the ABI7500 real-time fluorescent quantitative PCR should be applied to amplify, analyze, and verify according to the screen results of the microRNA chip in order to screen out the significant differentially expressed microRNA. RESULTS: Histological detection showed that the pancreas of the mice in control group D was fibrosis gradually and the islet frame was relatively disordered and significantly atrophied. Groups A, B, and C have no islet hypertrophy or atrophy and the degree of fibrosis of the pancreas has reduced. According to the gene chip detection, there are four significantly differently expressed microRNAs in pancreas tissue and blood among the group A, B, and C, among which miR-19a, miR-19b, and miR-22 were downregulated expressed while the miRNA-1 was upregulated expressed. Bioinformatics analysis showed that the target genes of 4 differentially regulated microRNA genes were related to cell proliferation, apoptosis, glucose metabolism, and angiogenesis. The expression of microRNA in pancreatic tissue and blood of NOD rats was highly consistent. CONCLUSIONS: MicroRNA expression file of pancreatic tissue and blood can be changed during the intervention of the NOD rat model with exendin-4. MicroRNA that indicates the differential expression may take part in the recovering process of the NOD pancreatic trauma. At the same time, the administration of exendin-4 can protect NOD mice, reduce its pancreatic tissue fibrosis, and regulate molecular markers of pancreatic cells in size and pancreatic mast cells. This may be one of the main mechanisms of pancreatic injury in diabetes prevention.


Assuntos
Diabetes Mellitus , MicroRNAs/genética , Peptídeos , Peçonhas , Animais , Modelos Animais de Doenças , Exenatida , Camundongos , Camundongos Endogâmicos NOD , Pâncreas , Ratos
14.
Eur Rev Med Pharmacol Sci ; 20(17): 3642-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27649665

RESUMO

OBJECTIVE: Growth hormone deficiency (GHD) is the most common cause for childhood dwarfism. Currently, the significance of insulin-like growth factor-1 (IGF-1) in diagnosis of GHD is still debatable. Due to the possible correlation between leptin (LEP) and GHD pathogenesis, this study investigated the gene polymorphism of LEP and its receptor (LEPR) genes, along with serum IGF-1 and LEP levels in GHD patients. This study attempted to illustrate the correlation between gene polymorphism and GHD pathogenesis. PATIENTS AND METHODS: A case-control study was performed using 180 GHD children in addition to 160 healthy controls. PCR-DNA sequencing method was employed for genotyping various polymorphism loci of LEP and LEPR genes in both GHD and healthy individuals. Serum IGF-1 and LEP levels were also determined. RESULTS: Results revealed a statistically significant difference between the levels of IGF-1 and LEP in the serum samples collected from patients in the GHD and the control groups. Both IGF-1 and LEP levels were found to be correlated with polymorphism at rs7799039 loci of LEP gene, in which GG and GA genotypes carriers had higher serum IGF-1 levels when compared to AA genotype carriers. CONCLUSIONS: GHD pathogenesis is well correlated with the LEP and IGF-1 levels in the both of which were mediated by the gene polymorphism at rs7799039 loci of LEP gene.


Assuntos
Hormônio do Crescimento/deficiência , Fator de Crescimento Insulin-Like I/genética , Leptina/sangue , Receptores para Leptina/genética , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Hormônio do Crescimento Humano , Humanos , Masculino
15.
Eur J Obstet Gynecol Reprod Biol ; 203: 279-85, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27400425

RESUMO

OBJECTIVE: To analyse lipoprotein lipase (LPL) expression and lipid levels in placenta and plasma of patients with intrahepatic cholestasis of pregnancy (ICP) and normal pregnancies. METHODS: This prospective study included 30 patients with ICP and 30 gestational-age-matched pregnancies without any complications. Enzyme-linked immunosorbent assays were used to investigate plasma LPL levels from 28 weeks of gestation, at 4-weekly intervals, to 38 weeks of gestation, and data were assessed longitudinally. Immunohistochemistry, Western blotting and real-time polymerase chain reaction were used to detect placental LPL expression and activity. Placental triglyceride and total cholesterol levels were also analysed. The clinical data related to ICP and lipid profiles were collected retrospectively. RESULTS: Plasma LPL concentration increased with gestational age in both groups, but the increase was limited in the ICP group. Immunohistochemistry revealed LPL staining mainly in syncytiotrophoblasts, and 3,3'-diamino-benzidine tetrahydrochloride wt% was lower in ICP placenta compared with normal placenta (p<0.01). LPL protein and mRNA expression in ICP placenta were significantly lower than in normal placenta (p<0.01). LPL activity was not significantly different in both groups. Correlation analysis indicated that the plasma LPL level was negatively associated with the corresponding concentration of total bile acid (r=-0.57) in the ICP group. CONCLUSION: Reduced LPL expression in placenta, limited increase in LPL level in maternal plasma, and abnormal lipid profiles were found in patients with ICP. LPL was possibly related to ICP by participating abnormal lipid metabolism.


Assuntos
Colestase Intra-Hepática/metabolismo , Lipídeos/sangue , Lipase Lipoproteica/metabolismo , Placenta/metabolismo , Complicações na Gravidez/metabolismo , Adulto , Colestase Intra-Hepática/sangue , Feminino , Idade Gestacional , Humanos , Lipase Lipoproteica/sangue , Gravidez , Complicações na Gravidez/sangue , Estudos Prospectivos , Adulto Jovem
16.
Cell Death Dis ; 4: e665, 2013 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-23764846

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a serious progressive and irreversible lung disease with unknown etiology and few treatment options. This disease was once thought to be a chronic inflammatory-driven process, but it is increasingly recognized that the epithelial-mesenchymal transition (EMT) contributes to the cellular origin of fibroblast accumulation in response to injury. During the pathogenesis of pulmonary fibrotic diseases, transforming growth factor-ß (TGF-ß) signaling is considered a pivotal inducer of EMT and fibroblast activation, and a number of therapeutic interventions that interfere with TGF-ß signaling have been developed to reverse established fibrosis. However, efficient and well-tolerated antifibrotic agents are not currently available. Previously, we reported the identification of sorafenib to antagonize TGF-ß signaling in mouse hepatocytes in vitro. In this manuscript, we continued to evaluate the antifibrotic effects of sorafenib on bleomycin (BLM)-induced pulmonary fibrosis in mice. We further demonstrated that sorafenib not only profoundly inhibited TGF-ß1-induced EMT in alveolar epithelial cells, but also simultaneously reduced the proliferation and collagen synthesis in fibroblasts. Additionally, we presented in vivo evidence that sorafenib inhibited the symptoms of BLM-mediated EMT and fibroblast activation in mice, warranting the therapeutic potential of this drug for patients with IPF.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/fisiologia , Fibrose Pulmonar Idiopática/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/fisiologia , Animais , Apoptose , Bleomicina , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/metabolismo , Feminino , Fibroblastos/efeitos dos fármacos , Células HEK293 , Humanos , Fibrose Pulmonar Idiopática/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteínas Smad/metabolismo , Sorafenibe , Fator de Crescimento Transformador beta1/fisiologia
17.
Eur J Med Chem ; 44(8): 3345-9, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19285756

RESUMO

According to the data of structural identification, six capsinoids or their derivatives were successfully synthesized to test for their analgesic activity. Three of them were capsinoids with different acyl chain compared with capsaicin after substitution of ester for amide at C(1) position. The other three could be described as capsinoid derivatives with different alkoxy chain, compared with capsaicin after substitution of ester for amide at C(1) position and alkoxy for hydroxy at C(4) position and synthesis of them was reported first. Compared with capsaicin, experiment results about pungency showed that capsinoids and their derivatives synthesized were all no or only slight pungent; that is, capsinoid derivates synthesized still have the same advantage of nonpungency with capsinoid. Relation between analgesic activity and molecular structure of compounds synthesized was also reported first, which would facilitate finding capsinoid derivatives owning excellent analgesic activity. The experiment results about analgesic activity showed that capsinoids displayed moderate analgesia effect and their antinociceptive activity decreased with the elongation of acyl chain at C(1) position; that antinociceptive activities of capsinoid derivatives synthesized were much stronger not only than those of indomethacin but also than those of their precursor (vanillyl decanoate), which increased with elongation of alkoxyl chain at C(4) position. Especially 4-hexyloxyl-3-methoxybenzyl decanoate showed the best antinociceptive activity in synthesized compounds, which was 9-fold higher than its precursor (vanillyl decanoate) and 6-fold higher than that of indomethacin.


Assuntos
Analgésicos/síntese química , Analgésicos/farmacologia , Ésteres/síntese química , Ésteres/farmacologia , Analgésicos/química , Animais , Desenho de Fármacos , Ésteres/química , Feminino , Masculino , Camundongos , Relação Estrutura-Atividade
18.
Eur J Med Chem ; 44(2): 665-9, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18599159

RESUMO

For slowing down the too fast metabolic velocity and increasing the bioavailability of cordycepin, four N-acyl-(propionyl-, octanoyl-, lauroyl- and stearoyl-) cordycepin derivatives were synthesized chemically and their pharmacokinetic profiles were investigated in this study. The results show that time of maximum concentration (T(max)) and half-life (t(1/2)) would be elongated with the increase of the alkyl chain length, but maximum concentration (C(max)) and area under concentration-time curve (AUC) increased initially, then decreased when the number of alkyl carbon exceeded eight. The T(max), C(max) and AUC of N-octanoyl-cordycepin were nearly 4, 30 and 68 times, respectively, higher than that of cordycepin. All derivatives could be transformed into cordycepin in vivo and the concentration of transformed cordycepin was proportional to that of derivatives. It indicated that N-octanoyl modification could decrease the metabolic velocity and increase the bioavailability of cordycepin to the maximum, thus it might be a promising prodrug of cordycepin.


Assuntos
Desoxiadenosinas/química , Desoxiadenosinas/farmacocinética , Antifúngicos , Antineoplásicos , Área Sob a Curva , Meia-Vida , Taxa de Depuração Metabólica , Farmacocinética , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Relação Estrutura-Atividade
19.
Acta Clin Belg ; 63(6): 376-80, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19170353

RESUMO

BACKGROUND: Controversies exist on the nature of influence of body position on the level of blood pressure. This study was designed to investigate the impact of postures on blood pressures in healthy subjects. METHODS: Blood pressure was measured in 6,485 healthy subjects in both supine and sitting positions, using a standard mercury sphygmomanometer. RESULTS: The average systolic and diastolic blood pressure in all age groups in the supine position was higher than in the sitting position (P < 0.001). There was a reduced systolic pressure increment but enhanced diastolic pressure increment with aging (P < 0.05). The levels of sitting blood pressure were inversely correlated to the pressure increments in supine positions (P < 0.001). Multivariate regression analysis showed that age is an independent factor for the systolic pressure increment in the supine position (P < 0.001), whereas sex, age, body height and body mass index are independent predictors for the increment in diastolic blood pressure (P < 0.001). CONCLUSIONS: In healthy subjects, blood pressure in the supine position is higher than in the sitting position and age plays an important part in this posture-related pressure increment.


Assuntos
Pressão Sanguínea/fisiologia , Postura/fisiologia , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Decúbito Dorsal/fisiologia
20.
J Asian Nat Prod Res ; 9(1): 49-58, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17365190

RESUMO

The relationship between the immunological activities and their surface activities of octadecanoyl acetal sodium sulphite series containing different numbers of double bonds (HOU-C18:n; n = 1, Delta9; n = 2, Delta9,12; n = 3, Delta9,12,15) were studied. The results showed that HOU-C18:n were able to increase the carbon granular clearance rate K, the NK cell activity in spleen and the activity of lysozymes in serum as well as inhibit Staphylococcus aureus and lysozymes in vitro to some degree. As the number of double bonds in HOU-C18:n increased along with the hydrophobic properties and the ability to improve the immune activity, NK cell activity and lysozyme activity decreased, but the bacteriostatic activity increased. It is speculated that HOU-C18:n could improve immunity and bacteriostasis realised by the interaction between the hydrophobic chain and membranes of cells. From the results of the effects of HOU-C18:n on lysozymes in vivo and in vitro, it is speculated that HOU-C18:0 could initiate and greatly enhance lysozyme activity in serum by increasing the amount of lysozymes, while unsaturated HOU-C18:n might do so mainly by increasing the number of lysozymes.


Assuntos
Acetais/farmacologia , Houttuynia/química , Células Matadoras Naturais/efeitos dos fármacos , Sulfitos/farmacologia , Acetais/química , Animais , Ácidos Decanoicos/química , Ácidos Decanoicos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Muramidase/sangue , Muramidase/metabolismo , Distribuição Aleatória , Staphylococcus aureus/efeitos dos fármacos , Sulfitos/química , Tensão Superficial
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