Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ACS Appl Mater Interfaces ; 11(25): 22164-22170, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31149791

RESUMO

Infectious diseases caused by pathogenic bacteria (such as sepsis and meningitis) seriously threaten public health; therefore, rapid and accurate identification of the target bacteria is urgently needed to prevent and treat bacterial infections. Although technologies including plate-counting and polymerase chain reaction have been established to detect the pathogenic bacteria, they are either time-consuming or sophisticated. Herein, a biomimetic octopus-like structure integrating merits of multiarm and multivalent interaction is designed for ultraspecific capture and detection of pathogens. The flexible polymeric arms and multivalent ligands work together to mimic the arm-sucker coordination of an octopus to effectively grasp the target pathogens, leading to remarkably high capacity and specificity for the target capture (above 98%, 10 CFU mL-1) without a nonspecific absorption of background pathogens. The captured bacteria can be identified as a point of care by the surface-enhanced Raman spectroscopy method with a detection limit of 10 cells mL-1.

2.
Mol Med Rep ; 20(2): 985-994, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173222

RESUMO

As a common degenerative disease, osteoporosis (OS) is characterized by reduced bone mass and microarchitectural deterioration of bone tissue. Both genetic and environmental factors are involved in OS development. To date, ~300 genes have been confirmed to be involved in the pathogenesis of OS, a large majority of which have been independently investigated. As OS is a polygenetic disease, a comprehensive analysis focusing on the biological functions and interactions of OS­related genes would provide valuable information. In this study, OS related research deposited in PubMed was retrieved and genes related to OS were catalogued. Pathways with an enriched biological function for these genes were extracted, and the crosstalk between the enriched pathways was analyzed. A comprehensive network was constructed, and a minimal network was extracted using the Steiner minimal network algorithm. In this study, a total of 294 genes in were retrieved from PubMed. Biological processes found to be enriched included those related to bone metabolism and the immune system. In total, 58 pathways were enriched. Furthermore, the comprehensive network consisting of 3,943 nodes and 7,976 edges was constructed, among which 631 nodes and 2,581 edges contributed to the OS­specific molecular network. In this network, in excess of 300 potential genes associated with OS and two modules were identified. Thus, this study provides a mechanistic insight into OS and suggests more than 300 potential OS­related genes for future research.

3.
Intern Med ; 58(16): 2341-2347, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31118371

RESUMO

Objective Previous studies have suggested that variations in the ABCC8 gene may be closely associated with T2DM susceptibility and repaglinide response. However, these results have not been entirely consistent, and there are no related studies in a Chinese population, suggesting the need for further exploration. The current study investigated the associations of the ABCC8 rs1801261 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. Methods A total of 234 T2DM patients and 105 healthy subjects were genotyped for ABCC8 rs1801261 polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. A total of 70 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take 3 mg repaglinide per day (1 mg each time before meals) for 8 consecutive weeks. The pharmacodynamic parameters of repaglinide and biochemical indicators were then determined before and after repaglinide treatment. Results The frequency of ABCC8 rs1801261 allele was higher in T2DM patients than in the control subjects (22.6% vs.11.0%, p<0.01). After repaglinide treatment, T2DM patients carrying genotype CT showed a significantly attenuated efficacy on FPG (p<0.01) and HbA1c (p<0.01) compared with those with genotype CC. Conclusion These results suggested that the ABCC8 rs1801261 polymorphism might influence T2DM susceptibility and the therapeutic effect of repaglinide in Chinese Han T2DM patients. This study was registered in the Chinese Clinical Trial Register on May 14, 2013 (No. ChiCTR-CCC13003536).

4.
ACS Synth Biol ; 8(5): 989-1000, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-30935202

RESUMO

Classical swine fever (CSF) is a highly contagious swine disease that causes devastating economic losses. However, there are few efficacious therapeutic antibodies against the CSF virus (CSFV). Accordingly, we isolated two whole-porcine anti-CSFV neutralizing antibodies (NAbs) directly from single B cells sorted using the conserved linear epitope of the CSFV E2 protein and goat anti-pig IgG. These mAbs, termed HK24 and HK44, can bind to the E2 protein by recognizing sites within the conserved linear epitope of E2. In addition, these two mAbs can detect virus infection with high specificity and possess potent neutralizing activity. HK24 and HK44 protect PK-15 cells from CSFV infections in vitro with potent IC50 values of 9.3 and 0.62 µg/mL, respectively. We anticipate that these antibodies can be used as diagnostic and antiviral agents for CSFV and that the method we describe here will accelerate the production of therapeutic antibodies for other viruses.

5.
Anal Chem ; 91(9): 6172-6179, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-30995837

RESUMO

Epitope-specific neutralizing antibodies (EsAbs) are of prime importance in the diagnosis and treatment of various serious diseases. However, obtaining EsAbs by the monoclonal antibody technique involves time-consuming and sophisticated multistep procedures, and the epitopes of the resulting antibodies are often not explicit. It is also very challenging to isolate EsAbs from numerous kinds of total immunoglobulins because of nonspecific adsorption and low separation efficiency. Herein, a magnetic core@multiarm shell-epitope (M@A-E) bioconjugate was fabricated to enrich and isolate EsAbs from immune serums. This robust multiarm scaffold exhibits outstanding binding capacity and good resistance to nontarget adsorption and serves as a reservoir for the release and reloading of EsAbs for repeatable applications. The EsAbs yield per milligram of the M@A-E was about 30 µg, which was approximately twice that of commercially available beads (16 µg). After 10 cycles of loading and release in glycine buffer (0.1 M, pH 2.5), the M@A-E bioconjugates still showed relatively high specificity and capture capacity (20 µg) superior to the same amount of new, unused conventional ones. This strategy provides a promising platform for enriching and isolating substantial quantities of EsAbs, which have great potential for applications in the detection and treatment of critical illness.

6.
Drug Dev Res ; 79(6): 249-259, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30222190

RESUMO

Preclinical Research & Development The purpose of the present study is to evaluate the neuroprotective effect of recombinant human glucagon-like peptide-1 (rhGLP-1) as well as to explore corresponding mechanisms in diabetic rats with cerebral ischemia/reperfusion injury induced by middle cerebral artery occlusion (MCAO). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The rats were pretreated with rhGLP-1 (20 µg/kg intraperitoneally, thrice a day) for 14 days. Thereafter, the rats were subjected to MCAO 90 min/reperfusion 24 hr. At 2 and 24 hr of reperfusion, the rats were assessed for neurological deficits and subsequently executed for the evaluation of cerebral infarct volume, oxidative stress parameters, and the expression of excitatory amino acid transporter 2 (EAAT2) and apoptotic markers. Results indicate that rhGLP-1 significantly ameliorated neurological deficits and reduced cerebral infarct volume in diabetic MCAO rats. In addition, oxidative stress parameters in ischemic penumbra were significantly alleviated in rhGLP-1-pretreated diabetic MCAO rats. rhGLP-1 significantly upregulated the ratio of Bcl-2/Bax and EAAT2 expression and downregulated cleaved caspase-3 expression in ischemic penumbra of diabetic MCAO rats. Our results suggest that rhGLP-1 could significantly ameliorate neurological deficits and reduce cerebral infarct volume in diabetic MCAO rats, which may be due to the inhibition of oxidative stress and apoptosis and the promotion of EAAT2 expression.

7.
Soft Matter ; 14(32): 6696-6707, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-30062357

RESUMO

Several additives, including inorganic (NaCl) and organic salts (derivatives of benzoate), were added into aqueous solutions of a gemini cationic surfactant, 2-hydroxypropyl-1,3-bis (myristyldimethylammonium chloride) (abbreviated as 14-3(OH)-14(2Cl)). The mixed systems were investigated using rheological measurement, cryo-TEM and 1H NMR analysis. The results showed that addition of salts induced rich aggregate morphologies in the 14-3(OH)-14(2Cl)/salt systems. The influence of an inorganic salt on the viscoelasticity of 14-3(OH)-14(2Cl) solutions is much weaker than that of organic salts. Furthermore, the ability of three organic salts in enhancing the viscoelasticity of 14-3(OH)-14(2Cl) solutions is in the order sodium m-hydroxybenzoate > sodium o-hydroxybenzoate > sodium p-hydroxybenzoate. The different roles of these organic salt isomers arise from the different types of hydrogen bonding formed between 14-3(OH)-14(2Cl) and the organic counter ions.

8.
Drug Dev Res ; 79(3): 129-135, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29663513

RESUMO

Post-Market Research We aimed to investigate the impact of G protein-coupled receptor kinase 5 (GRK5) rs10886471 polymorphism on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 300 T2DM patients and 210 healthy controls were genotyped for GRK5 rs10886471 on a three-dimensional polyacrylamide gel-based DNA microarray. Eighty-five patients with the same genotypes of cytochrome P450 (CYP) 2C8*3 139Arg and organic anion-transporting polypeptide 1B1 (OATP1B1) 521TT were randomly selected to orally take repaglinide for eight consecutive weeks. Then, the biochemical indicators and pharmacodynamic parameters were measured before and after repaglinide treatment. The T allelic frequency of GRK5 rs10886471 was higher in T2DM patients than in healthy subjects (p < .01). T2DM patients with genotypes CC and CT at GRK5 rs10886471 had a significant reduction in terms of fasting plasma glucose (FPG) compared with those with genotype TT (p < .01). In addition, the carriers of genotypes CC and CT at GRK5 rs10886471 had higher differential values of postprandial serum insulin (PINS) compared with genotype TT carriers (p < .05). These findings suggest that GRK5 rs10886471 polymorphism may influence the therapeutic efficacy of repaglinide in Chinese Han T2DM patients.


Assuntos
Carbamatos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Quinase 5 de Receptor Acoplado a Proteína G/genética , Hipoglicemiantes/uso terapêutico , Piperidinas/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Glicemia/efeitos dos fármacos , Citocromo P-450 CYP2C8/genética , Diabetes Mellitus Tipo 2/sangue , Feminino , Genótipo , Humanos , Insulina/sangue , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Resultado do Tratamento
9.
Arch Psychiatr Nurs ; 32(2): 224-228, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29579516

RESUMO

Quality of life (QOL) throughout menopause has become an outcome variable requiring measurement in clinical care. Staff nurses can provide earlier nursing during the menopausal transition (MT) stage. The purpose of this study was to describe the changes of QOL in different stages of the MT according to The Stages of Reproductive Aging Workshop (STRAW) in Chinese women in community settings. Prospective longitudinal study design was used to analyze QOL of 327 community women age 30-65years old. They were followed up at 1-year. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. A gradual decline in QOL was seen from premenopausal to menopausal transition (MT) and in postmenopausal women. Significant differences were observed in vasomotor, physical and sexual scores at baseline and follow-up (P<0.05). Significant differences in vasomotor scores were observed between baseline and follow-up for women in the premenopausal and Late MT stages (P<0.05). There were significant differences in psychosocial and physical scores between baseline and follow-up in the Late MT stage (P<0.05). Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longer longitudinal studies.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Vida Independente , Menopausa/psicologia , Qualidade de Vida/psicologia , Adulto , Grupo com Ancestrais do Continente Asiático/psicologia , China , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários
10.
Aquat Toxicol ; 188: 1-9, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28437657

RESUMO

The three major hexabromocyclododecane (HBCD) diastereoisomers, i.e. α-, ß- and γ-HBCD, have distinct physical and chemical properties that may potentially result in different levels of bioaccumulation and toxicity in aquatic organisms. To assess the impact of diastereomeric variation in HBCDs, the marine copepod Tigriopus japonicus was exposed to α-, ß- and γ-HBCD in isolation. Results showed that all the three diastereoisomers had a similar potency to cause growth delay in T. japonicas. Variation was observed in the overall survival rate with exposure to α- and ß-HBCD, and this resulted in significantly higher lethal toxicity in T. japonicas than that with exposure to γ-HBCD. Exposure to α-, ß- and γ-HBCD led to the generation of ROS in T. japonicas, a possibly toxic mechanism. Both α- and ß-HBCD showed a higher potential to induce oxidative stress, which may be a factor in the higher lethal toxicity observed with α- and ß-HBCD exposure. It is of note that T. japonicus was found to be more sensitive to all three diastereoisomers in the F1 generation than in the F0 generation. The bioconcentration potential of HBCD diastereoisomers can be ranked in the order α-HBCD>γ-HBCD>ß-HBCD and was found to be higher in T. japonicus than has been reported for fish species.


Assuntos
Copépodes/efeitos dos fármacos , Hidrocarbonetos Bromados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Copépodes/metabolismo , Hidrocarbonetos Bromados/química , Hidrocarbonetos Bromados/farmacocinética , Estresse Oxidativo , Estereoisomerismo , Poluentes Químicos da Água/química , Poluentes Químicos da Água/farmacocinética
11.
Onco Targets Ther ; 10: 1123-1129, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28260926

RESUMO

This study aimed to explore the diagnostic and prognostic values of contrast-enhanced ultrasound (CEUS) in breast cancer. Between September 2009 and October 2011, a total of 143 breast cancer patients and 161 healthy people were selected as case group and control group, respectively. After the identification of lesions by conventional ultrasound, all patients underwent CEUS. The CEUS images were analyzed, and time-intensity curves (TICs) were obtained. Hematoxylin-eosin and immunohistochemistry staining was performed on tissue specimens, according to which the expressions of estrogen receptor (ER), c-erb-B2, p53, and Ki-67 were measured. Multivariate logistic regression analysis was used to compare CEUS and TIC parameters between the two groups. Compared with the control group, cancer patients showed high enhancement, heterogeneous enhancement or defects in the central region, expansion of lesion diameter after enhancement and crab-like blur lesion edges. The peak intensity (PI), relative start time of enhancement, relative PI, and relative area under the curve in the case group were significantly higher than those in the control group. Logistic analysis showed that the uniformity of enhancement, expansion of lesion diameter, and relative PI were significant diagnostic parameters of breast cancer, with area under the curve being 0.798, 0.776, and 0.919, respectively. There were strong associations between CEUS characteristics and expressions of prognostic factors in breast cancer: the heterogeneous enhancement was common in c-erb-B2-positive tumors; the centripetal enhancement occurred more in ER-negative tumors; perforator vessels were often seen in tumors at high histological grade; perfusion defects were common in ER-negative, c-erb-B2-positive, and Ki-67-positive tumors. CEUS is a useful tool for the early diagnosis and prognosis of breast cancer.

12.
J Clin Nurs ; 26(7-8): 1005-1010, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27219501

RESUMO

AIMS AND OBJECTIVES: To investigate the relationship between quality of life and social support in female nurses. BACKGROUND: Nurses play an important role in providing care and managing patients' health in hospitals. However, limited studies have shown an association between quality of life and social support in female nurses in China. DESIGN: Questionnaire survey. METHODS: To investigate 320 full-time female nurses in different departments at four comprehensive hospitals in Harbin with a cross-sectional correlational design using questionnaires. A demographic data questionnaire, menopause-specific quality of life questionnaire and social support scale were used. RESULTS: The scores on the physical (36·93 ± 17·65) and psychological (17·57 ± 9·45) subscales were higher than those of the vasomotor (4·88 ± 3·48) and sexual (4·53 ± 3·23) subscales of quality of life. The average score of objective support (25·12 ± 4·32) was higher than those of subjective support (9·80 ± 3·04) and utilisation of social support (7·80 ± 1·97). A significant association between quality of life and social support was found (p < 0·01). CONCLUSIONS: Social support influenced quality of life. Social support as a buffer for pressure can influence individual stress perception, help individuals cope with pressure and reduce the negative impact of stress on mental and physical health, thus improving different aspects of health. RELEVANCE TO CLINICAL PRACTICE: Enhancing social support in an active environment would allow female nurses to enjoy a better quality of life in their clinical practice.


Assuntos
Esgotamento Profissional/psicologia , Recursos Humanos de Enfermagem/estatística & dados numéricos , Qualidade de Vida/psicologia , Apoio Social , Adaptação Psicológica , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
13.
Chemosphere ; 167: 155-162, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27718427

RESUMO

The brominated flame retardants hexabromocyclododecanes (HBCDs) are ubiquitous environmental contaminants, widely distributed in aquatic systems including the marine environment and marine organisms. HBCDs are toxic to the development of both freshwater and marine fish. However, the impacts of HBCDs on marine invertebrates are not well known. In this study, the marine copepod, Tigriopus japonicus, was used to assess the bioaccumulation and developmental toxicity of technical HBCD (tHBCD) through water-borne exposure. The uptake rate constant of tHBCD by T. japonicus was high, which resulted in high bioaccumulation potential. The bioconcentration factors of tHBCD were 8.73 × 104 and 6.34 × 104 L kg-1 in T. japonicus, calculated using the kinetic and steady-state methods, respectively. Exposure of T. japonicus nauplii to tHBCD caused significant growth delay. The lowest-observable-effect-concentrations of tHBCD induced developmental delay were 30 and 8 µg L-1 for the F0 and F1 generations, respectively, which suggested that the F1 generation was more sensitive to tHBCD than the F0 generation and warranted multiple-generation toxicity tests for future studies. Furthermore, exposure of the adult copepods to tHBCD induced the transcription of oxidative stress response genes and apoptotic genes, e.g., SOD,CAT, GST, OGG1, P53 and Caspase-3. It was therefore speculated that tHBCD exposure induced the generation of reactive oxygen species in T. japonicus, which activated the oxidative stress defense genes and meanwhile resulted in oxidative DNA damage. The damaged DNA activated the transcription of p53 and triggered the caspase-mediated apoptosis pathway, which may be the reason for the tHBCD induced developmental delay in T. japonicus nauplii.


Assuntos
Copépodes/efeitos dos fármacos , Hidrocarbonetos Bromados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Caspase 3/genética , Catalase/genética , Copépodes/genética , Copépodes/crescimento & desenvolvimento , Copépodes/metabolismo , Dano ao DNA , DNA Glicosilases/genética , Glutationa Transferase/genética , Hidrocarbonetos Bromados/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/genética , Proteína Supressora de Tumor p53/genética , Poluentes Químicos da Água/metabolismo
14.
Sci Rep ; 6: 37293, 2016 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-27857189

RESUMO

Repaglinide is an insulin secretagogue that often exhibits considerable interindividual variability in therapeutic efficacy. The current study was designed to investigate the impact of KCNQ1 genetic polymorphism on the efficacy of repaglinide and furthermore to identify the potential mechanism of action in patients with type 2 diabetes. A total of 305 patients and 200 healthy subjects were genotyped for the KCNQ1 rs2237892 polymorphism, and 82 patients with T2DM were randomized for the oral administration of repaglinide for 8 weeks. HepG2 cells were incubated with repaglinide in the absence or presence of a KCNQ1 inhibitor or the pcDNA3.1-hKCNQ1 plasmid, after which the levels of Akt, IRS-2 and PI(3)K were determined. Our data showed that repaglinide significantly decreased HOMA-IR in patients with T2DM. Furthermore, the level of HOMA-IR was significantly reduced in those patients with CT or TT genotypes than CC homozygotes. The KCNQ1 inhibitor enhanced repaglinide efficacy on insulin resistance, with IRS-2/PI(3)K/Akt signaling being up-regulated markedly. As in our clinical experiment, these data strongly suggest that KCNQ1 genetic polymorphism influences repaglinide response due to the pivotal role of KCNQ1 in regulating insulin resistance through the IRS-2/PI(3)K/Akt signaling pathway. This study was registered in the Chinese Clinical Trial Register on May 14, 2013. (No. ChiCTR-CCC13003536).


Assuntos
Carbamatos/administração & dosagem , Diabetes Mellitus Tipo 2 , Resistência à Insulina/genética , Canal de Potássio KCNQ1/genética , Piperidinas/administração & dosagem , Polimorfismo Genético , Transdução de Sinais , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Células Hep G2 , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Canal de Potássio KCNQ1/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
15.
Zhongguo Zhong Yao Za Zhi ; 40(13): 2486-91, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26697667

RESUMO

Synthetic biology research methods which design and build a new artificial biological systems (medicinal plants or microorganisms system) with specific physiological functions through clarifying and simulating the basic law of the biosynthesis of active components of traditional Chinese medicine, is considered to be a potential method to produce an abundant resources of bioactive components. Tanshinones is a kind of diterpene quinone compounds with important pharmacological activities from traditional Chinese medicine Salvia miltiorrhiza. This article systematically introduced the research progress of the synthetic biology of S. miltiorrhiza, in order to provide references for studies on other terpenoid bioactive components of traditional Chinese medicines, and give new research strategies for the sustainable development of traditional Chinese medicine resources.


Assuntos
Diterpenos de Abietano/biossíntese , Medicina Tradicional Chinesa , Salvia miltiorrhiza/metabolismo , Biologia Sintética
16.
Acta Biochim Biophys Sin (Shanghai) ; 47(6): 422-30, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25926140

RESUMO

Osteoarthritis (OA) is an age-related joint disease that is characterized by the degeneration of articular chondrocytes. Nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is associated with inflammation response. We investigated the role of PARP-1 in interleukin-1ß (IL-1ß)-stimulated human articular chondrocytes and its underlying mechanism. Cell viability and apoptosis were evaluated by using 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide assay and flow cytometry, respectively. Tumor necrosis factor-α (TNF-α) level was measured by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of PARP-1, IL-1 receptor (IL-1R), inducible nitric oxide synthase (iNOS), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were determined by real-time reverse transcriptase-polymerase chain reaction and western blot analysis, respectively. The expression and phosphorylation of NF-кB p65 were measured by western blot analysis. Results showed that stimulation of chondrocytes with IL-1ß caused a significant up-regulation of PARP-1 and IL-1R, resulting in NF-кB p65 nuclear translocation and phosphorylation associated with an increase of TNF-α secretion and iNOS expression. PARP-1 was inhibited by siRNA transfection. Results showed that PARP-1 inhibition suppressed IL-1ß-induced reduction of cell viability and up-regulation of cell apoptosis, with a reduced IL-1R expression. PARP-1 inhibition also effectively reversed IL-1ß-induced inflammatory response through inhibiting the IL-1R/NF-кB pathway. These data suggested that PARP-1 inhibition prevents IL-1ß-induced inflammation response at least partly by inhibiting the IL-1R/NF-кB signaling pathway in human articular chondrocytes. Moreover, PARP-1 inhibition reduced MMPs expression and increased TIMP-1 expression, suggesting that PARP-1 inhibition could suppress cartilage destruction by modulating the balance between MMPs and TIMP-1. Inhibition of PARP-1 might be useful in the treatment of OA.


Assuntos
Condrócitos/patologia , Inflamação/prevenção & controle , Interleucina-1beta/fisiologia , Osteoartrite/fisiopatologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/efeitos dos fármacos , Células Cultivadas , Humanos , NF-kappa B/metabolismo , Osteoartrite/patologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Clin Exp Pharmacol Physiol ; 42(1): 27-32, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25311380

RESUMO

Repaglinide is a short-acting insulin secretagogue, which often results in considerable interindividual variability in therapeutic efficacy when widely used in a clinical setting. Among various reasons under discussion is genetic polymorphism, especially the genes related to insulin secretion and resistance. Recent studies have described the importance of PPARD in regulating the secretion and resistance of insulin. However, little is known about the impacts of PPARD genetic polymorphism on the efficacy of repaglinide. Therefore, the current study was designed to investigate the associations of PPARD rs2016520 polymorphism with type 2 diabetes mellitus (T2DM) susceptibility and repaglinide therapeutic efficacy in Chinese Han T2DM patients. A total of 338 T2DM patients and 200 healthy subjects were genotyped for PPARD rs2016520 polymorphism by polymerase chain reaction-restriction fragment length polymorphism assay. A total of 84 patients with the same genotypes of CYP2C8*3 139Arg and OATP1B1 521TT were randomized to orally take repaglinide for 8 weeks. Then the pharmacodynamic parameters of repaglinide and biochemical indicators were determined before and after repaglinide treatment. No significant difference was found in either allelic frequency (P = 0.298) or genotype distribution (P = 0.151) of PPARD rs2016520 between T2DM patients and healthy subjects. However, T2DM patients carrying genotype TC showed a significantly lower increase in postprandial serum insulin (mU/L) than those with wild-type TT (P < 0.05). These findings suggest that PPARD rs2016520 polymorphism might influence the therapeutic effect of repaglinide rather than T2DM susceptibility in Chinese Han T2DM patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Carbamatos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Hipoglicemiantes/uso terapêutico , PPAR delta/genética , Piperidinas/uso terapêutico , Adulto , Carbamatos/farmacologia , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Piperidinas/farmacologia , Polimorfismo Genético/genética , Período Pós-Prandial/efeitos dos fármacos , Período Pós-Prandial/fisiologia , Resultado do Tratamento
18.
Zhongguo Zhong Yao Za Zhi ; 39(17): 3413-5, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25522641

RESUMO

In order to increase the yield and quality of the medicinal plant and enhance the competitive power of industry of medicinal plant in our country, this paper analyzed the status, problem and countermeasure of the tissue culture of medicinal plant on large scale. Although the biotechnology is one of the most efficient and promising means in production of medicinal plant, it still has problems such as stability of the material, safety of the transgenic medicinal plant and optimization of cultured condition. Establishing perfect evaluation system according to the characteristic of the medicinal plant is the key measures to assure the sustainable development of the tissue culture of medicinal plant on large scale.


Assuntos
Medicina Tradicional Chinesa/métodos , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/genética , Técnicas de Cultura de Tecidos/métodos , Indústria Farmacêutica/métodos , Indústria Farmacêutica/normas , Medicina Tradicional Chinesa/normas , Plantas Geneticamente Modificadas , Controle de Qualidade , Técnicas de Cultura de Tecidos/normas
19.
Arch Psychiatr Nurs ; 28(6): 368-71, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25457685

RESUMO

The incidence of PSD patients is very high. To analyze the related factors and incidence of post-stroke depression (PSD). A total of 465 stroke patients were evaluated by a self-designed questionnaire, Self-Rating Depression Scale (SDS) and Hamilton Depression Rating Scale (HAMD). The neurologic deficit score was tested using the National Institute of Health stroke scale (NIHSS). A multiple factor analysis with the logistic regression method was carried out to analyze related factors of PSD. A total of 146 cases (31.4%) were identified as suffering from PSD. In addition the stepwise regression analysis showed that important risk factors of PSD included of sex, lesion location, the course of post-stroke and degree of neurological deficit score (all P<0.05). Above mentioned factors about the patients of PSD are very significant and may provide reference for further treating.


Assuntos
Transtorno Depressivo/epidemiologia , Transtorno Depressivo/enfermagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/enfermagem , Fatores Etários , Idoso , China , Estudos Transversais , Transtorno Depressivo/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários
20.
Pharmacotherapy ; 34(2): 131-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24338736

RESUMO

STUDY OBJECTIVE: To investigate the associations of NOS1AP rs12742393 polymorphism with the risk of type 2 diabetes mellitus (T2DM) and repaglinide therapeutic efficacy in Chinese patients with T2DM. DESIGN: Prospective case-control study. SETTING: Academic medical center. PATIENTS: A total of 300 patients with T2DM and 200 healthy volunteers were enrolled to identify NOS1AP rs12742393 genotypes using the polymerase chain reaction-restriction fragment length polymorphism assay. Eighty-four patients with various genotypes were randomly selected to receive oral repaglinide as a single-agent therapy (3 mg/day) for 8 weeks. MEASUREMENTS AND MAIN RESULTS: Anthropometric measurements and fasting plasma glucose (FPG), postprandial plasma glucose, hemoglobin A1c , fasting serum insulin (FINS), postprandial serum insulin, homeostasis model assessment for insulin resistance (HOMA-IR), triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol tests were obtained before and after repaglinide treatment. The risk C allelic frequency of NOS1AP rs12742393 was higher in patients with T2DM than in healthy volunteers (p<0.001). Patients with T2DM and genotypes AA and AC at NOS1AP rs12742393 had a significant reduction in FPG (mmol/l) compared with those with genotype CC (p<0.01). Patients with CC homozygotes and AC heterozygotes had a greater increase in FINS (mU/l) than those with wild-type AA (p<0.05). In addition, the carriers of genotype CC at NOS1AP rs12742393 had higher differential values of HOMA-IR compared with genotypes AC and AA carriers (p<0.001). The effects of repaglinide treatment on FPG (p<0.01), FINS (p<0.05) and HOMA-IR (p<0.001) were reduced in patients with T2DM carrying the NOS1AP rs12742393 risk C allele compared with the AA genotype carriers. CONCLUSION: The NOS1AP rs12742393 polymorphism is associated with therapeutic efficacy of repaglinide in Chinese T2DM patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Carbamatos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Piperidinas/uso terapêutico , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Glicemia/efeitos dos fármacos , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Estudos Prospectivos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA