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1.
Phytomedicine ; 128: 155557, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38547622

RESUMO

BACKGROUND: In this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5'-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PURPOSE: The aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. STUDY DESIGN: HUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. METHODS: In type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. RESULTS: We first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. CONCLUSIONS: The main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.


Assuntos
Proteínas Quinases Ativadas por AMP , Antraquinonas , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células Endoteliais da Veia Umbilical Humana , Óxido Nítrico Sintase Tipo III , Transdução de Sinais , Trombospondina 1 , Animais , Humanos , Antraquinonas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Trombospondina 1/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Masculino , Ratos , Camundongos , Ratos Sprague-Dawley , Endotélio Vascular/efeitos dos fármacos , Glucose/metabolismo , Camundongos Endogâmicos C57BL
2.
Biol Reprod ; 110(4): 672-683, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38263524

RESUMO

Chemically defined oocyte maturation media supplemented with FGF2, LIF, and IGF-1 (FLI medium) enabled significantly improved oocyte quality in multiple farm animals, yet the molecular mechanisms behind such benefits were poorly defined. Here, we first demonstrated that FLI medium enhanced mouse oocyte quality assessed by blastocyst formation after in vitro fertilization and implantation and fetal development after embryo transfer. We then analyzed the glucose concentrations in the spent media; reactive oxygen species concentrations; mitochondrial membrane potential; spindle morphology in oocytes; and the abundance of transcripts of endothelial growth factor-like factors, cumulus expansion factors, and glucose metabolism-related genes in cumulus cells. We found that FLI medium enabled increased glucose metabolism through glycolysis, pentose phosphate pathway, and hexosamine biosynthetic pathway, as well as more active endothelial growth factor-like factor expressions in cumulus cells, resulting in improved cumulus cell expansion, decreased spindle abnormality, and overall improvement in oocyte quality. In addition, the activities of MAPK1/3, PI3K/AKT, JAK/STAT3, and mTOR signaling pathways in cumulus cells were assessed by the phosphorylation of MAPK1/3, AKT, STAT3, and mTOR downstream target RPS6KB1. We demonstrated that FLI medium promoted activations of all these signaling pathways at multiple different time points during in vitro maturation.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Técnicas de Maturação in Vitro de Oócitos , Animais , Camundongos , Feminino , Técnicas de Maturação in Vitro de Oócitos/veterinária , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fatores de Crescimento Endotelial/análise , Fatores de Crescimento Endotelial/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Oócitos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Suplementos Nutricionais , Glucose/farmacologia , Glucose/metabolismo , Células do Cúmulo/metabolismo
3.
Reprod Fertil ; 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37971749

RESUMO

The refinement of embryo culture media is essential in improving embryo viability and in vitro production efficiency. Our previous work demonstrated that the nutrients (carbohydrates, amino acids, and vitamins) in traditional culture media far exceed the need for an embryo and producing developmentally competent embryos in a reduced nutrient environment is feasible. Here, we aim to evaluate the impact of exogenous lipid and L-carnitine supplementation on bovine blastocyst development and refine our RN condition further. Zygotes were cultured in the control medium (100% nutrients) and reduced nutrient media containing 6.25% of the standard nutrient concentrations supplemented with L-carnitine and lipid free or lipid rich BSA. Increased blastocyst development was observed in the reduced nutrient lipid rich medium compared to the other two groups. However, in both reduced nutrient conditions, blastocyst cell numbers were lower than those obtained in the control condition. We then examined the expression level of 18 transcripts correlated with lipid metabolism, glucose metabolism, redox balance, and embryo quality, along with mitochondrial DNA copy numbers, ATP productions, and lipid profile. The results indicated lipid metabolism, embryo quality, and redox enzyme related genes were upregulated while glucose related gene was downregulated in embryos derived from reduced nutrient lipid rich condition Finally, we identified that the lipid rich BSA has enriched linoleic, stearic, oleic, palmitic, and alpha-linoleic fatty acids, a lipid profile that may contribute to the increased lipid metabolism and improved blastocyst development of the bovine embryos under the reduced nutrient condition.

4.
Chemosphere ; 262: 127977, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182103

RESUMO

Coastal wetlands are ecologically and economically important; however, they are currently faced with fragmentation and loss. Plants are a fundamental element of wetlands and previous researches have focused on wetland plant connectivity; however, these researches have been conducted at the landscape but not species level. Here, given that tidal flats are important areas in coastal wetlands, we investigated the connectivity characteristics of typical plant species and environmental factors in different wetland regions influenced by various tidal conditions to reveal vegetation connectivity and its relationship with environmental factors on a small-patch scale. We found that tides negatively affect plant connectivity because both the Tamarix chinensis and Suaeda salsa have the highest connectivity on river banks, which are not influenced by tides. Of two tidal regions, different tides conditions have different influence on two plant species. T. chinensis had higher connectivity in the supratidal zone, whereas S. salsa had higher connectivity in the intertidal zone. Besides, the soil water content and soil salinity were significantly different in the three regions, but the soil total nitrogen and phosphorous were not. Soil water content and soil salinity were two factors that significantly affected plant connectivity. Specifically, soil water content positively affected the connectivity of T. chinensis and S. salsa, whereas soil salinity negatively affected the connectivity of T. chinensis. Taken together, these results indicate that tidal conditions affect plant connectivity on a small-patch scale. River banks and supratidal zone are beneficial for the recovery and growth of T. chinensis, intertidal zone and river banks are more conducive to the recovery and growth of S. salsa. Based on the above research, this study provides insights that could be applied to vegetation restoration in coastal wetlands.


Assuntos
Chenopodiaceae/crescimento & desenvolvimento , Rios/química , Solo/química , Tamaricaceae/crescimento & desenvolvimento , Ondas de Maré , Áreas Alagadas , China , Nitrogênio/análise , Fósforo/análise , Salinidade
5.
Hepatol Int ; 14(6): 985-996, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33128206

RESUMO

BACKGROUND AND AIM: Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. METHODS: 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. RESULTS: The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9-43.2%) in the experiment group and 27.21% (95% CI 22.0-32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4-12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. CONCLUSION: Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. CLINICAL TRIAL NUMBER: ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).


Assuntos
Guanina/análogos & derivados , Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/uso terapêutico , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Resultado do Tratamento
6.
Trials ; 21(1): 708, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787905

RESUMO

BACKGROUND: Nucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal. METHODS/DESIGN: The study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120 weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5 mg per day for consolidation therapy for 96 weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5 mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24 weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial. CONCLUSION: This study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population. TRIAL REGISTRATION: Chinese Clinical Trial Registry No. ChiCTR1900021232 . Registered on February 2, 2019.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , China , Quimioterapia Combinada , Guanina/uso terapêutico , Antígenos E da Hepatite B , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Resultado do Tratamento
7.
Chin J Integr Med ; 26(5): 330-338, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31919749

RESUMO

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).


Assuntos
Adenina/análogos & derivados , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Organofosfonatos/uso terapêutico , Adenina/uso terapêutico , Adulto , Antivirais/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Antígenos E da Hepatite B/imunologia , Hepatite B Crônica/imunologia , Humanos , Masculino , Medicina Tradicional Chinesa , Adulto Jovem
8.
Environ Sci Pollut Res Int ; 26(28): 29041-29051, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392615

RESUMO

As a transitional zone between aquatic and terrestrial ecosystems, the riparian buffer is an important control measure for non-point source pollution. The research presented here mainly discussed the interception efficiencies of different vegetation types for nitrogen and phosphorus pollution. The results showed that canopy, shrub, and grass interceptions basically accounted for about 80.0% of total interception, and therefore riparian buffer configurations should clearly distinguish three levels of vegetation types. (1) Canopy, shrub, grass, and litter interceptions of Pinus tabuliformis (YS) were the highest, up to about 71.1%. (2) Platycladus orientalis (CB) had the highest transportation and enrichment for the elements nitrogen (N) and phosphorus (P) throughout the process, which the value of TP decreased from 0.2 to 0.12 mg/L and the value of TN decreased from 5.0 to 2.5 mg/L. (3) The transportation of total phosphorus (TP) of the three tree species was higher than the transportation of total nitrogen (TN), showing that the enrichment of P was stronger than that of N. Thus, Pinus tabuliformis is the best configuration for rainfall interception, while Platycladus orientalis is the best configuration for N and P removals. Different forest configurations should also be considered to build a riparian buffer to remove nutrient in the future.


Assuntos
Monitoramento Ambiental , Poluição da Água/análise , Pequim , Ecossistema , Florestas , Nitrogênio/análise , Fósforo/análise , Pinus , Árvores , Água , Poluição da Água/estatística & dados numéricos
9.
Environ Sci Pollut Res Int ; 26(18): 18304-18315, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041710

RESUMO

Litter decomposition is a complex process that is influenced by many different physical, chemical, and biological processes. Environmental variables and leaf litter quality (e.g., nutrient content) are important factors that play a significant role in regulating litter decomposition. In this study, the effects of adding fungi and using different mesh size litter bags on litter (Populus tomentosa Carr. and Salix matsudana Koidz.) decomposition rates and water quality were investigated, and investigate the combination of these factors influences leaf litter decomposition. Dissolved oxygen (DO), chemical oxygen demand (COD), total phosphorus (TP), and ammonia-nitrogen (NH3-N) were measured during the 112-day experiment. The salix leaf litter (k = 0.045) displayed faster decomposition rates than those of populous leaf litter (k = 0.026). Litter decomposition was initially slow and then accelerated; and by the end of the experiment, the decomposition rate was significantly higher (p = 0.012, p < 0.05) when fungi were added to the treatment process compared to the blank, and litter bags with different mesh sizes did not influence the decomposition rate. The variations in the decomposition rates and nutrient content were influenced by litter quality and a number of environmental factors. The decomposition rate was most influenced by internal factors related to litter quality, including the N/P and C/P ratios of the litter. By quantifying the interact effect of environment and litter nutrient dynamic, to figure out the revetment plant litter decomposition process in a wetland system in biological physical and chemical aspects, which can help us in making the variables that determine decomposition rates important for assessing wetland function.


Assuntos
Biodegradação Ambiental , Fungos/fisiologia , Folhas de Planta , Populus , Salix , Qualidade da Água , Áreas Alagadas , China , Ecossistema , Vidro , Nitrogênio/análise , Tamanho da Partícula , Fósforo/análise , Folhas de Planta/química , Microbiologia do Solo
10.
Biomed Pharmacother ; 112: 108689, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802825

RESUMO

AIM: The aim of this study was to evaluate the antihypertensive effect of Xin Mai Jia (XMJ) and to explore the mechanism of its hypotensive effect. METHODS: A total of 50 spontaneously hypertensive rats (SHR) were randomised into five groups. A total of 30 Wistar-Kyoto rats were randomised into three groups, comprising the control group. All of the rats were administered medicine through a gastrogavage once a day for 8 weeks. The tail-cuff method was applied to their monitor blood pressure. After 8 weeks of treatment, serum NO, SOD activity, MDA level, ET, ALD, AngII, RE, and CGRP in the serum were detected in all of the rats. Pathological changes in the aorta were observed via haematoxylin-eosin (HE) and immunohistochemical staining. Vasodilation function was assessed by measuring acetylcholine-induced vessel relaxation in the rats' organ chambers. The function of the mesenteric arteries was measured using DMT wire myography. Human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) injury models were induced by hydrogen peroxide (H2O2). HASMCs and HUVECs were injured by H2O2 and then exposed to various drugs. HASMC and HUVEC migration was evaluated using the cell scratch test. The expression of the AT1 receptors (AT1R) in the HASMCs was detected via immunofluorescence (IFC) assay. RESULTS: After 8 weeks of treatment, XMJ reduced the systolic blood pressure of the SHR. XMJ significantly reduced the serum RE, AngII, ALD, and ET-1 levels and increased the content of CGRP and NO in the SHR, upregulated the SOD content, and downregulated MDA level of the SHR. XMJ improved pathological damage of the aorta to varying degrees, decreased the expression of AT1R in the SHR aortic vessels, and improved the mesenteric microvascular relaxation of the SHR. Cell experiments confirmed that XMJ inhibited the migration of the HUVECs and HASMCs induced by H2O2 and the expression of AT1R in the HASMCs. CONCLUSION: XMJ had satisfactory hypotensive action on the SHR in this study. Its mechanism may be associated with inhibiting RAAS activity and improving RAAS function, inhibiting hypertensive-induced vascular diastolic dysfunction, and improving vascular endothelial function.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Animais , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Hipertensão/fisiopatologia , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
11.
Chin J Integr Med ; 24(9): 653-660, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30209792

RESUMO

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).


Assuntos
Antivirais/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Guanina/análogos & derivados , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Duplo-Cego , Quimioterapia Combinada , Guanina/administração & dosagem , Hepatite B Crônica/imunologia , Humanos , Estudos Multicêntricos como Assunto , Estudos Prospectivos
12.
Br J Cancer ; 117(5): 695-703, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-28697175

RESUMO

BACKGROUND: Selective platelet release of pro- or anti-angiogenic factors distinctly regulated angiogenesis. We hypothesised that selective release of platelet angiogenic factors could differently regulate tumour growth. METHODS: Breast cancer cell proliferation, cancer cell-induced endothelial tube formation in vitro, and tumour growth in vivo were studied in the presence of protease-activated receptor 1-stimulated platelet releasate (PAR1-PR; rich in pro-angiogenic factors) or PAR4-PR (rich in anti-angiogenic factors). RESULTS: The PAR1-PR and PAR4-PR supplementation (10%) similarly enhanced cell proliferation of MCF-7 and MDA-MB-231 breast cancer cells. The cancer cells triggered capillary-like tube formation of endothelial cells that was further enhanced by pro-angiogenic factor-rich PAR1-PR. The VEGF, but not SDF-1α, receptor blockade abolished PAR1-PR/PAR4-PR-enhanced cancer cell proliferation. Integrin blockade by RGDS had identical effects as VEGF inhibition. The Src and ERK inhibition diminished, whereas PI3K and PKC blockade abolished platelet releasate-enhanced cancer cell proliferation. Using a model of subcutaneous implantation of MDA-MB-231 cells in nude mice, PAR1-PR enhanced tumour growth more markedly than PAR4-PR, and seemed to achieve the exaggeration by promoting more profound tumour angiogenesis. CONCLUSIONS: Platelet releasate increases breast cancer cell proliferation through VEGF-integrin cooperative signalling. Pro-angiogenic factor-rich platelet releasate enhances cancer cell-induced angiogenesis more markedly, and thus exaggerates tumour growth in vivo.


Assuntos
Plaquetas/metabolismo , Neoplasias da Mama/metabolismo , Integrinas/metabolismo , Neovascularização Patológica/metabolismo , Receptor PAR-1/metabolismo , Receptores de Trombina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Animais , Plaquetas/efeitos dos fármacos , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/patologia , Proliferação de Células , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Integrinas/antagonistas & inibidores , Células MCF-7 , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Oligopeptídeos/farmacologia , Compostos de Fenilureia/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteína Quinase C/metabolismo , Quinolinas/farmacologia , Receptores CXCR4/antagonistas & inibidores , Transdução de Sinais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores
13.
Oncotarget ; 7(38): 61703-61715, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27533252

RESUMO

Cardiac fibrosis is a common pathological process accompanying diabetes mellitus. In this report, we studied the effects of neferine (a major bisbenzylisoquinline alkaloid derived from lotus embryos) on cardiac fibrosis induced by diabetes mellitus, as well as the underlying molecular pathways. In vivo, type 1 diabetes mellitus was induced in mice by administering streptozotocin. Diabetic mice were treated with neferine through oral gavage, and cardiac function was assessed using echocardiography. Total collagen deposition was assessed by Masson's trichrome and Picrosirius staining. In vitro, cardiac fibroblasts were cultured in normal or high-glucose medium with or without neferine. Neferine attenuated left ventricular dysfunction and remodeling and reduced collagen deposition in diabetic mice. In vitro, neferine inhibited cardiac fibroblast proliferation, migration, and differentiation into myofibroblasts. In addition, neferine reduced high-glucose-induced collagen production and inhibited TGF-ß1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. These results suggest that neferine may have antifibrogenic effects in diabetes-related cardiac fibrosis.


Assuntos
Benzilisoquinolinas/farmacologia , Colágeno/biossíntese , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Fibroblastos/metabolismo , Miocárdio/patologia , Animais , Ciclo Celular , Diferenciação Celular , Movimento Celular , Proliferação de Células , Medicamentos de Ervas Chinesas/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose , Glucose/química , Frequência Cardíaca , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
15.
Nat Rev Cardiol ; 12(2): 115-22, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25384847

RESUMO

Traditional Chinese medication (TCM) is increasingly used to treat cardiovascular disease (CVD) in China and some other Asian countries. However, therapeutic efficacy and adverse effects of TCM are difficult to evaluate because few large-scale, randomized controlled trials (RCTs) enrolling patients with CVD have been performed. In this Review, we critically examine the current evidence on the cardiovascular effects of TCM. We reviewed 68 RCTs that included a total of 16,171 patients. The methodological quality of the trials was generally low. Only three reports described adverse cardiovascular events specifically, although in most studies TCM was associated with significant improvements in surrogate end points for hypertension, coronary heart disease, cardiac arrhythmias, and heart failure. The risk of adverse effects was not increased compared with no intervention, placebo, or Western medications. However, whether TCM is effective in reducing the all-cause or cardiovascular mortality in patients with CVD remains unknown and must be tested in large-scale RCTs with adverse cardiovascular events as primary end points.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
16.
Cardiovasc Drugs Ther ; 26(2): 121-30, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22382902

RESUMO

PURPOSE: Myocarditis is an acute inflammatory disease of the heart and is often a precursor of dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. The purpose of this study was to investigate the therapeutic role of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on the development of EAM. METHODS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with murine cardiac α-myosin heavy chain (MyHc-α(614-629) [Ac-SLKLMATLFSTYASAD-OH]). High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) rosuvastatin or vehicle was administered orally by gastric gavage to mice with EAM from day 0 to day 21 after immunization. On day 21 after immunization, echocardiography was carried out and the severity of myocarditis was detected by histopathological evaluation. Levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured by ELISA. Histopathology was performed using haematoxylin and eosin. With apoptosis examined by Tunel, the expression of active caspase-3 in myocardium was investigated by immunohistochemistry. RESULTS: Rosuvastatin attenuated the histopathological severity of myocarditis. Cardiac function was improved in the two rosuvastatin-treated groups compared to the non-treated EAM group (LVFS: high-dose rosuvastatin group [group H], 0.38 ± 0.10%; low-dose rosuvastatin group [group L], 0.34 ± 0.06%; non-treated EAM group [group N], 0.29 ± 0.07%. LVEF: group H, 0.80 ± 0.09%; group L, 0.71 ± 0.07%; group N, 0.68 ± 0.07%). Furthermore, treatment with rosuvastatin decreased the expression levels of TNF-α (group H, 65.19 ± 7.06 pg/ml; group L, 108.20 ± 5.28 pg/ml; group N, 239.34 ± 11.65 pg/ml) and IL-6 (group H, 14.33 ± 2.15 pg/ml; group L, 19.67 ± 3.04 pg/ml; group N, 40.39 ± 7.17 pg/ml). The rates of expression of active Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology. CONCLUSIONS: These results demonstrate that administration of rosuvastatin can ameliorate EAM progression, inhibit apoptosis of cardiomyocytes, and preserve cardiac output, and they also suggest rosuvastatin may be a promising novel therapeutic strategy for the clinical treatment of myocarditis.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Fluorbenzenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Miocardite/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doenças Autoimunes/enzimologia , Doenças Autoimunes/metabolismo , Caspase 3/metabolismo , Ecocardiografia/métodos , Feminino , Interleucina-6/metabolismo , Lipídeos/sangue , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/enzimologia , Miocardite/imunologia , Miocardite/metabolismo , Miócitos Cardíacos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Rosuvastatina Cálcica , Fator de Necrose Tumoral alfa/metabolismo , Miosinas Ventriculares/efeitos dos fármacos , Miosinas Ventriculares/metabolismo
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 24(1): 45-9, 2004 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15768973

RESUMO

Near-infrared diffusion reflectance spectroscopy is a fast technique that can provide component information about intact soybean samples. We have combined this technique with partial least-squares (PLS) regression to perform a quantitative determination of protein and fat contents in soybean samples. In calibration set, the NIR model determination coefficient R2 of protein and fat is 0.9930 and 0.9752 respectively, and the relative standard deviation (RSD) is 0.76% and 1.3% respectively. The correlation coefficient r of validation set is 0.9473 and 0.8695 respectively. This NIR model is used to predict the contents of protein and fat in 264 soybean samples, using R-error to assess the deviation of analysis results. The minimum RSD of prediction of protein and fat is 0.04% and 2.46% respectively, and the maximum RSD of prediction of protein and fat is 2.45% and 4.25% respectively. These results are of great importance in early screening of crop breeding.


Assuntos
Gorduras na Dieta/metabolismo , Proteínas Alimentares/metabolismo , Glycine max/química , Óleos de Plantas/análise , Proteínas de Plantas/análise , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Difusão , Modelos Estatísticos , Óleos de Plantas/química , Proteínas de Plantas/química
18.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 22(7): 518-21, 2002 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-12592687

RESUMO

OBJECTIVE: To investigate the effect of Naoyi'an granule (NYAG) on basic fibroblastic growth factor (bFGF) mRNA expression and tumor necrosis factor (TNF) protein expression following intracerebral hemorrhage and provide the theoretical evidence of NYAG in treating intracerebral hemorrhage and promoting the rehabilitation of neural function. METHODS: Model rats of intracerebral hemorrhage induced by infusion of collagenase VII into the caudate-putamen were used to determine the related parameters of behavior scores (BS), Northern blot, Western blot assay and optical density (OD) scanning in the model and the model treated with NYAG. And the data got from the two groups were compared. RESULTS: BS in the model group began to lower 24 hrs after modeling and a significant decrease was shown 7 days later, while in the NYAG group, it decreased significantly three days after modeling, the difference between the two groups was significant (P < 0.05). Levels of bFGF mRNA expression and TNF protein expression increased after modeling, it reached the peak in three days and began to decrease gradually in seven days in both groups. However, the level in the NYAG group was higher than that in the model group in various times of the experimental process. CONCLUSION: NYAG could enhance the bFGF expression and suppress the TNF expression so as to improve the behavior deficit in treating intracerebral hemorrhage, which may be one of the main mechanisms of NYAG for promoting the rehabilitation of neural function.


Assuntos
Hemorragia Cerebral/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fator 2 de Crescimento de Fibroblastos/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Animais , Encéfalo/metabolismo , Fator 2 de Crescimento de Fibroblastos/genética , Masculino , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/genética
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