RESUMO
Gastrointestinal bleeding (GIB) is the most common serious bleeding complication of antiplatelet therapy. The bleeding risk score (BRS) of GIB may help to determine the risk of bleeding, and provides a reference for the formulation of antiplatelet therapy regimen in clinical practice, but we found that no specific risk scores are available in East Asian patients. This study analyzed patients who were administered antiplatelet therapy from May 2015 to December 2018 in two medical centers. Patient's baseline data were obtained. We assessed four BRSs (New Score, RIETE Score, Cuschieri Score, de Groot Score) and compared them using the area under the receiver operating characteristic curve (AUC). The 4,052 patients enrolled in this study had an average age of 69.6 ± 10.8 years, and 65.9% of them were male. Among the 4,052 patients included, 171 patients experienced GIB within 6 months of follow-up. In the study population, the AUCs for the New, RIETE, Cuschieri, and de Groot scores were 0.673 (95% confidence interval (CI) 0.616-0.729, P < .001), 0.742 (95% CI 0.690-0.794, P < .001), 0.598 (95% CI 0.537-0.659, P = .002), and 0.875 (95% CI 0.839-0.912, P < .001), respectively. After validation, the de Groot Score has better performance. Among the four scores, the de Groot Score might be more suitable for helping Chinese clinicians to predict the risk of GIB in patients taking antiplatelet drugs, and reduce GIB events.
Assuntos
Hemorragia Gastrointestinal , Inibidores da Agregação Plaquetária , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Curva ROC , Medição de Risco , Fatores de RiscoRESUMO
Gastrointestinal bleeding is the most common bleeding complication during anticoagulant therapy. A reliable bleeding risk score can help the clinician assess risk of bleeding in individual patients and select the anticoagulant regimen. This study retrospectively analyzed the data of patients with atrial fibrillation who received anticoagulant therapy from July 2015 to December 2018 at two centers-the Fujian Medical University Union Hospital and Fuzhou Second Hospital Affiliated to Xiamen University. Demographic data, clinical findings, and laboratory results were collected from the hospital records. Patients were followed up for 6 months. The performance of four bleeding risk scores (New Score, RIETE Score, Cuschieri et al. Score, de Groot et al. Score) for prediction of gastrointestinal bleeding was assessed using the area under the curve. A total of 3462 patients (mean age, 66.3 ± 11.5 years; 59.6% males; 1055 direct oral anticoagulants users and 2407 warfarin users) were followed up for 6 months. While 99/3462 (2.9%) patients had gastrointestinal bleeding. The area under the curves for the New, RIETE, Cuschieri et al., de Groot et al. scores were 0.652 (95% CI 0.576-0.728), 0.862 (95% CI 0.809-0.914), 0.606 (95% CI 0.527-0.685), and 0.873 (95% CI 0.816-0.929), respectively. Among the four BRSs evaluated, the RIETE score and the de Groot et al. score appear to have the good predictive value, while the NEW score and the Cuschieri et al. score did not sufficiently predict gastrointestinal bleeding risk within the study Chinese population.
Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Hemorragia Gastrointestinal/induzido quimicamente , Idoso , Anticoagulantes/uso terapêutico , China/epidemiologia , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/uso terapêutico , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Varfarina/efeitos adversos , Varfarina/uso terapêuticoRESUMO
BACKGROUND: Doxorubicin is a first-line chemotherapy agent on human myelogenous leukemia clinical treatment, but the development of chemoresistance has largely limited curative effect. In this study, we aimed to evaluate the biological function and molecular mechanisms of CrkL to Doxorubicin resistance. METHODS: Quantitative reverse transcription-PCR (qRT-PCR) assay was performed to examine the expression of CrkL in K562 and K562/ADR cells. The expression of CrkL was silenced through RNA interference technology. MTT assay and flow cytometry were performed to detect the proliferation inhibition and apoptosis rate after CrkL siRNA transfection. The protein expression changes of PI3K/AKT/MRP1 pathway induced by CrkL siRNA were observed by Western Blot assay. Xenograft tumor model was carried out to observe tumor growth in vivo. RESULTS: We observed that silencing of CrkL could effectively increase apoptosis rate induced by doxorubicin and dramatically reversed doxorubicin resistance in K562/ADR cells. Further studies revealed knockdown CrkL expression suppressed PI3K/Akt/MRP1 signaling, which indicated CrkL siRNA reversed doxorubicin effect through regulating PI3K/Akt/MRP1 pathway. In addition, overexpression of MRP1 could evidently reduce apoptosis rate and reversed the inhibitory effects of doxorubicin resistance caused by CrkL siRNA on K562/ADR cells. Finally, in vivo experiments revealed that CrkL silencing acted a tumor-suppressing role in myelogenous leukemia via regulating PI3K/Akt/MRP1 signaling. CONCLUSION: Together, we indicated that CrkL is up-regulated in myelogenous leukemia cells and silencing of CrkL could reverse Doxorubicin resistance effectively. These results show a potential novel strategy for intervention chemoresistance in myelogenous leukemia during chemotherapy.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Humanos , Células K562 , Camundongos Nus , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Nuclear factor kappa B (NF-кB) inhibition represents a new therapeutic strategy for the treatment of neuroinflammatory diseases. In this study, a series of 3,4-dihydronaphthalen-1(2H)-one (DHN; 6a-n, 7a-c) derivatives were synthesised and characterised by NMR and HRMS. We assessed the toxicity and anti-neuroinflammatory properties of these compounds and found that 6m showed the greatest anti-neuroinflammatory properties, with relatively low toxicity. Specifically, 6m significantly reduced reactive oxygen species production, down-regulated the expression of NOD-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1 and prevented lipopolysaccharide-stimulated BV2 microglia cells polarisation towards an M1 phenotype. Furthermore, 6m significantly decreased IκBα and NF-кB p65 phosphorylation, thus inhibiting the NF-кB signalling pathway. This suggests that 6m may be explored as a functional anti-neuroinflammatory agent for the treatment of inflammatory diseases in the central nervous system, such as multiple sclerosis, traumatic brain injury, stroke and spinal cord injury.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , NF-kappa B/antagonistas & inibidores , Naftalenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Células Cultivadas , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estrutura Molecular , NF-kappa B/metabolismo , Naftalenos/síntese química , Naftalenos/química , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
Inhibition of NF-κB signalling has been demonstrated as a therapeutic option in treating inflammatory diseases and cancers. Herein, we synthesized novel dissymmetric 3,5-bis(arylidene)-4-piperidones (BAPs, 83-102) and characterized fully. MTT and ELISA assay were performed to screen the anti-hepatoma and anti-inflammation properties. 96 showed the most potential bioactivity. 96 could promote HepG2 apoptosis through up-regulating the expression of C-Caspase-3 and Bax, down-regulating the expression of Bcl-2, while markedly inhibit LPS or TNF-α-induced activation of NF-κB through both inhibiting the phosphorylation of IκBα and p65, and preventing the p65 nuclear translocation to exhibit both anti-hepatoma and anti-inflammatory activities. Molecular docking verified that simulated 96 can effectively bond to the active site of Bcl-2 and NF-κB/p65 proteins. 96 inhibited xenografts growth by reducing the expression of TNF-α and Bcl-2 in the tumour tissue. This study suggested that 96 could be developed as a potential multifunctional agent for treatment of inflammatory diseases and cancers.
Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/prevenção & controle , Inflamação/prevenção & controle , Neoplasias Hepáticas/prevenção & controle , NF-kappa B/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Simulação de Acoplamento MolecularRESUMO
OBJECTIVE: To study the association of peripheral blood pH early after birth with amplitude-integrated electroencephalography (aEEG) findings in neonates with intrauterine distress. METHODS: The clinical data of the neonates with intrauterine distress who were born from January 2017 to May 2018 were collected. According to peripheral blood pH within 30 minutes after birth, these neonates were divided into 3 groups: pH ≤7.15, 7.15
Assuntos
Eletroencefalografia , Humanos , Concentração de Íons de Hidrogênio , Recém-NascidoRESUMO
We investigate the effects of interferon (IFN)-γ on human placenta-derived mesenchymal stromal cells (hPMSCs), in particular, their adhesion, proliferation and migration and modulatory effects on the CD4+CXCR5+Foxp3+Treg subset. And we compared hPMSCs ability to induce the generation of different Treg subsets in response to treatment with IFN-γ. We found that IFN-γ suppressed the proliferation and migration for hPMSCs. The ability of hPMSCs to induce the generation of CD4+CXCR5+Foxp3+Treg subset was enhanced by IFN-γ. And maximal effectiveness of IFN-γ treated hPMSCs upon inducing the generation of Treg subsets was for CD4+CXCR5+Foxp3+Treg subset as compared with that of CD4+CD25+Foxp3+, CD8+CD25+Foxp3+, CD4+IL-10+ and CD8+IL-10+Treg subsets. These results have important implications for the development and application of hPMSCs in clinical use.
Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fatores de Transcrição Forkhead/metabolismo , Interferon gama/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Receptores CXCR5/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Células-Tronco Mesenquimais/metabolismo , Placenta/citologia , Gravidez , Linfócitos T Reguladores/metabolismoRESUMO
Objective: To prepare porosity osmotic pump tablets of total glucosides of paeony( TGP),and to study the behavior on synchronous release of its main components. Methods: Taking the accumulative release of TGP as indexes, through single-factor test and orthogonal design to investigate the optimal formulation porosity osmotic pump tablets of TGP. The main components, paeoniflorin, albiflorin and benzoylpaeoniflorin were employed to study synchronous release of the optimal formulation. Results: The membrane weight, and the content of PEG 400,and diethyl phthalate( DEP) were the main factors influencing the behavior of TGP release. The accumulated release of the prepared osmotic pump release tablets achieved about 90%. Three main components achieved the desired zero-order release profile and had a synchronized release behavior. Conclusion: The prepared porosity osmotic pump tablets of TGP can achieve the behavior of synchronized release of multi-components with good reproducibility.
Assuntos
Paeonia , Hidrocarbonetos Aromáticos com Pontes , Preparações de Ação Retardada , Glucosídeos , Monoterpenos , Osmose , Polietilenoglicóis , Porosidade , Reprodutibilidade dos Testes , Solubilidade , ComprimidosRESUMO
To improve the bioavailability of 10-hydroxycamptothecin, 10-hydroxycamptothecin solid dispersion(HCPT-SD) and 10-hydroxycamptothecin-phospholipid complex-solid dispersion(HCPT-PC-SD) were prepared, and their solubility and dissolution rate were evaluated in this study. SD rates were administered intragastrically with HCPT-SD or HCPT-PC-SD respectively, then their blood samples were collected at different time intervals. The concentration of HCPT in blood was detected by HPLC method with camptothecin as internal standard, and then its pharmacokinetic parameters were calculated and obtained. The results showed that the Cmax, AUC0-t and AUC0-∞ of both kinds of solid dispersion of HCPT were significantly increased than those of crude drug. The AUC0-t of HCPT-SD was increased by 176.87%, and AUC0-t of HCPT-PC-SD was increased by 254.31% as compared with crude drug. Therefore, the two kinds of solid dispersion of HCPT could significantly enhance the bioavailability of HCPT in SD rates, and the effect of HCPT-PC-SD was more obvious.
Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Camptotecina/análogos & derivados , Medicamentos de Ervas Chinesas/farmacocinética , Animais , Antineoplásicos Fitogênicos/química , Disponibilidade Biológica , Camptotecina/química , Camptotecina/farmacocinética , Portadores de Fármacos/química , Medicamentos de Ervas Chinesas/química , Masculino , Fosfolipídeos/química , Ratos , Ratos Sprague-DawleyRESUMO
Small cell lung cancer (SCLC) accounts for 12 to 16% of lung neoplasms and has a high rate of metastasis. The present study demonstrates the antiproliferative effect of retinoic acid amide in vitro and in vivo against human lung cancer cells. The results from MTT assay showed a significant growth inhibition of six tested lung cancer cell lines and inhibition of clonogenic growth at 30 µM. Retinoic acid amide also leads to G2/M-phase cell cycle arrest and apoptosis of lung cancer cells. It caused inhibition of JAK2, STAT3, and STAT5, increased the level of p21WAF1, and decreased cyclin A, cyclin B1, and Bcl-XL expression. Retinoic acid amide exhibited a synergistic effect on antiproliferative effects of methotrexate in lung cancer cells. In lung tumor xenografts, the tumor volume was decreased by 82.4% compared to controls. The retinoic acid amide-treated tumors showed inhibition of JAK2/STAT3 activation and Bcl-XL expression. There was also increase in expression of caspase-3 and caspase-9 in tumors on treatment with retinoic acid amide. Thus, retinoic acid amide exhibits promising antiproliferative effects against human lung cancer cells in vitro and in vivo and enhances the antiproliferative effect of methotrexate.
Assuntos
Amidas/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Tretinoína/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Camundongos , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Fatores de Transcrição STAT/biossíntese , Fatores de Transcrição STAT/genética , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To prepare monolithic osmotic pump tablet of resveratrol. METHODS: Inclusion technology was adopted to enhance its solubility. The optimal formulation of resveratrol inclusion complex osmotic pump tablets was selected by the single-factor method and orthogonal design. The release in vitro of the optimized formulation was also fitted to different models. RESULTS: The tablets with optimized formulation achieved the desired zero-order release profile in 12 h (r = 0.9963) with the cumulative release over 90%. CONCLUSION: Resveratrol can be prepared into monolithic osmotic pump tablets based on the intermediate of inclusion technology, which have obvious characteristic of zero release.
Assuntos
Estilbenos/química , Comprimidos , Química Farmacêutica , Osmose , Resveratrol , SolubilidadeRESUMO
OBJECTIVE: To explore the expressions and functions of the kisspeptin/kiss1r system and GnRH in the hypothalamic arcuate nucleus (HAN) and the influence of the kisspeptin/kiss1r system on the hypothalamic-pituitary-testis (HPT) axis in the rat models of diet-induced obesity. METHODS: Ninety newborn SD male rats were randomly assigned to receive normal diet (n = 30) and high-fat diet (n = 60) for the establishment of obesity models. The model rats were again equally divided into a control group and an experimental group, the latter injected with kisspeptin via the lateral ventricle. Then the body mass index (BMI) and endocrine hormone levels of the rats were recorded, the protein expressions of LepR, kisspeptin, kiss1r, and GnRH in the HAN determined by immunohistochemistry and Western blot, and the levels of GnRH mRNA in the HAN measured by qRT-PCR. RESULTS: Significantly increased BMI and hormone levels indicated the successful establishment of diet-induced obesity models. Compared with the normal rats, the protein expressions of LepR, kisspeptin, and GnRH in the HAN were markedly decreased in the controls, and that of GnRH and the levels of LH and T significantly increased, but the expressions of LepR and kiss1r showed no remarkable changes in the experimental rats. CONCLUSION: Lateral ventricular injection of kisspeptin can upregulate obesity-induced low expression of GnRH, correct the dysfunction of the HPT axis, and thus improve reproductive function in rats.
Assuntos
Núcleo Arqueado do Hipotálamo/metabolismo , Sistema Hipotálamo-Hipofisário , Kisspeptinas/metabolismo , Obesidade/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de Kisspeptina-1 , Receptores para Leptina/metabolismoRESUMO
In order to obtain new anti-hepatoma drugs with low toxicity, some 1,4,5,6,7,8-hexahydropyrido[4,3-d]pyrimidines (PPMs, 4a-t) were synthesized in this study. Many of them showed significant anti-hepatoma effects against HCC cells and low toxicity toward HHL-5 cells. Combined with their anti-hepatoma activity and toxicity, 4-CF3-substituted 4k was selected as an effective lead compound. Preliminary mechanistic studies revealed that 4k could up-regulate the expression levels of Bax and caspase-3 proteins, down-regulate the expression levels of Bcl-2 protein, promote significant apoptosis of HepG2, and block cells in G2-M phase to prevent cells from completing mitosis. Also, 4k could significantly inhibit the activation of PI3K/AKT/NF-κB pathway by blocking the phosphorylation of PI3K, AKT, NF-κB/p65 and IFN-γ-induced nuclear transport. Docking analysis showed that 4k could reasonably bind to the active sites of Bcl-2, NF-κB/p65, PI3K and AKT. This result suggested that 4k could be used as a new type of NF-κB inhibitor, which provides a scientific basis for further research into the treatment of hepatoma.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Descoberta de Drogas , Neoplasias Hepáticas/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Estrutura Molecular , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-AtividadeRESUMO
OBJECTIVES: The purpose of this study was to detect the protective effects of adiponectin on coagulation dysfunction and its mechanism in sepsis of rats. MATERIALS AND METHODS: The experimental samples were composed of sham group, model group that was underwent cecal ligation and puncture (CLP) and three adiponectin treatment groups that treated by adiponectin with different dose (72 µg/kg, 96 µg/kg and 120 µg/kg) after CLP. The prothrombin time (PT), activated partial thromboplastin time (APTT) was measured, respectively, the level of malondialdehyde (MDA), tissue factor (TF), activated coagulation factor VIIa and Xa, p-selectin were detected, the histology structure of vascular was observed, the expressions of Caspase 9, Caspase 3, Bax, Bcl-2 and vWF in vascular were measured. RESULTS: The results demonstrated that adiponectin treatment lengthened PT and APTT, reduced the expression of MDA, TF, activated coagulation factor VIIa, Xa and p-selectin in plasma of septic rats. Additionally, adiponectin treatment alleviated endothelial cell apoptosis and oxidative stress, down-regulated the levels of Caspase 3, Caspase 9, Bax, Bcl-2 and vWF in vascular. CONCLUSION: These findings suggest that adiponectin treatment might be a promising therapeutic strategy for relieving septic endothelial cell injury and coagulation dysfunction via inhibiting endothelial cell apoptosis in septic rats.
RESUMO
AIMS: Dihydroartemisinin has been shown to inhibit the development of pulmonary fibrosis in rats, but its mechanism has yet to be elucidated. This study aimed to determine the mechanisms of dihydroartemisinin in bleomycin-induced pulmonary fibrosis in a rat model. MAIN METHODS: Morphological changes and collagen deposition were analyzed via hematoxylin-eosin staining and Masson staining and the expression of biotic-factor-related oxidative stress in lung tissues was assayed with standard assay kits. The expressions of α-SMA, E-cadherin, and Nrf2/HO-1 were detected by Western blot and RT-PCR, and the cell morphology and proliferation of cultured type II alveolar epithelial cells (AECs) were assessed via microscopy and immunocytochemical assay. KEY FINDINGS: Dihydroartemisinin treatment significantly decreased the level of oxidative stress and collagen synthesis and inhibited AECs differentiation in bleomycin-induced pulmonary fibrosis compared to the control group (Pâ¯<â¯0.001). SIGNIFICANCE: Our results indicated that dihydroartemisinin might decrease oxidative damage to attenuate lung injury and fibrosis.
Assuntos
Antimetabólitos Antineoplásicos , Antioxidantes/farmacologia , Artemisininas/farmacologia , Bleomicina , Estresse Oxidativo/efeitos dos fármacos , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Actinas/biossíntese , Células Epiteliais Alveolares/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Caderinas/biossíntese , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Miofibroblastos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/biossíntese , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: The kisspeptin/kiss1r system, expressed in the hypothalamic arcuate nucleus, has been proclaimed as one of the most powerful factors of the reproduction axis, according to recent researches in the reproductive field. The aim of this study was to ascertain the expression of kisspeptin, its receptor (kiss1r), and gonadotropin-releasing hormone (GnRH), and to explore the role on the development and maintenance of the reproductive function of developing female rats. METHODS: Expressions of the kisspeptin/kiss1r system were examined by immunohistochemistry and Real time Quantitative PCR (qRT-PCR). Expressions of estradiol (E2), luteinizing hormone, and follicle-stimulating hormone were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Expression of the kisspeptin/kiss1r system increased time dependently with aging, and their peak expression was demonstrated in the adult stage. GnRH showed a similar expression pattern to that of the kisspeptin/kiss1r system. ELISA results demonstrated that the E2, luteinizing hormone, and follicle-stimulating hormone secretion increased time dependently from infancy to prepuberty to puberty. However, E2 level decreased significantly in adult rats. Morphological changes of ovaries showed that primordial follicles, primary follicles, and growing follicle inhabited the dominant status in infancy, prepuberty, and puberty stages, respectively. CONCLUSION: GnRH neurons may play an intermediate role in the activation and maintenance of the reproductive function regulated by the kisspeptin/kiss1r system, which may also indirectly regulate the serum level of luteinizing hormone, follicle-stimulating hormone, and E2.
Assuntos
Hipotálamo/crescimento & desenvolvimento , Kisspeptinas/fisiologia , Receptores Acoplados a Proteínas G/fisiologia , Reprodução/fisiologia , Animais , Estradiol/sangue , Estro/fisiologia , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/análise , Hormônio Liberador de Gonadotropina/fisiologia , Kisspeptinas/análise , Kisspeptinas/genética , Hormônio Luteinizante/sangue , Ratos , Ratos Wistar , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/genética , Receptores de Kisspeptina-1RESUMO
OBJECTIVE: To study genetic polymorphism of D7S2846, D19S400 and D18S535 in Han population in Wenzhou. METHODS: DNA was extracted with chelex-100 method from EDTA-blood samples of 194 unrelated individuals in Wenzhou and amplified with PCR technique. The PCR products were analyzed by PAG vertical electrophoresis and silver-stain. RESULTS: 6 alleles and 15 genotypes of D7S2846, 10 alleles and 36 genotypes of D19S400, 8 alleles and 26 genotypes of D18S535 was observed. The heterozygosities of the three loci are 0.644, 0.724 and 0.772; The power of discriminating are 0.854, 0.940 and 0.938. CONCLUSION: The heterozygosities of the three loci are high and the frequencies was in accordance with Hardy-Weinberg equilibrium (P>0.05), so the three loci can be used in forensic medicine and in other genetic researches.
Assuntos
Alelos , Polimorfismo Genético , Sequências de Repetição em Tandem , China/etnologia , DNA/isolamento & purificação , Frequência do Gene , Genótipo , Humanos , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To investigate the polymorphism and forensic efficiency values of STR loci D12S391/D18S865 METHODS: Population studies on D12S391 and D18S865 were carried out in a sample of 454 unrelated Wenzhou Han individuals using PCR followed by PAGE and silver stain detection. RESULTS: 11/7 alleles and 50/21 genotypes of D12S391/D18S865 were respectively observed among the 454 unrelated individuals. The genotype frequency matched the Hardy-Weinberg equilibrium, The heterozygotes (H) in D12S391/D18S865 were 0.7974/0.7379, Power of Exclusion were 0.9566/0.9077, polymorphism information content (PIC) were 0.8260/0.7279 respectively. CONCLUSION: D12S391 and D18S865 were high polymorphic loci and the frequencies were in accordance with Hardy-Weinberg equilibrium (P>0.5), so the two loci can be used in forensic medicine and in other genetic research areas.