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1.
BMC Gastroenterol ; 23(1): 367, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884863

RESUMO

BACKGROUND: It is widely known that muscle mass influences the outcomes of many chronic diseases. Erector spine mass is a convenient parameter obtained from routine abdominal computed tomography (CT). The clinical application value of erector spine mass, and whether erector spine mass could predict the outcome of disease has not been studied. AIM: To evaluate the role of the erector spine index (ESI) calculated based on abdominal CT imaging in the progression of acute-on-chronic liver failure related to the hepatitis B virus (HBV-ACLF). METHODS: We performed a retrospective study of 118 HBV-ACLF patients and calculated the ESI (the total erector spine area normalized for height2 in meters) for each patient through abdominal CT. The findings were analyzed regarding the progression of HBV-ACLF and the ESI at baseline, including mortality and the development of complications. RESULTS: The ESI level was associated with mortality and the development of complications. During the 90-day follow-up period, patients with a low ESI (<12.05 cm2/m2) had higher mortality than those with a high ESI (≥ 12.05 cm2/m2) (51.7% vs. 26.7%), and the cumulative survival rates were 71.0%±4.6 and 85.8%±3.9, respectively (log-rank P = 0.003). The hazard ratios (HRs) calculated using univariable and multivariable analyses were 2.23(95% confidence interval (CI): 1.25-4.21, P = 0.005) and 2.52 (95% CI: 1.34-9.24, P = 0.011), respectively. Patients with a low ESI (<12.05 cm2/m2) had higher incidences of kidney dysfunction (43.5% vs. 23.2%, P = 0.029; log-rank P = 0.017) and hepatic encephalopathy (39.6% vs. 14.0%, P = 0.003; log-rank P = 0.010) than those with a high ESI. A low ESI was an independent risk factor for kidney dysfunction (adjusted HR = 1.36, 95% CI: 1.05-2.93, P = 0.043) and the development of hepatic encephalopathy (adjusted HR = 2.26; 95% CI: 2.05-3.13, P = 0.036). In addition, the presence of hepatic encephalopathy (the odds ratio (OR) = 2.26, 95% CI: 2.05-3.18, P = 0.006), spontaneous bacterial peritonitis (OR = 3.95, 95% CI: 1.01-5.46, P = 0.037), and kidney dysfunction (OR = 4.47, 95% CI: 1.02-9.64, P = 0.032) was independently associated with a low ESI in patients. CONCLUSION: A low ESI is an independent risk factor for mortality in patients with HBV-ACLF, as well as the development of kidney dysfunction and hepatic encephalopathy.


Assuntos
Insuficiência Hepática Crônica Agudizada , Encefalopatia Hepática , Hepatite B Crônica , Hepatite B , Humanos , Vírus da Hepatite B , Estudos Retrospectivos , Insuficiência Hepática Crônica Agudizada/diagnóstico por imagem , Insuficiência Hepática Crônica Agudizada/etiologia , Fatores de Risco , Prognóstico , Hepatite B Crônica/complicações , Hepatite B/complicações
2.
Acta Pharmacol Sin ; 44(5): 999-1013, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36347996

RESUMO

Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.


Assuntos
Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Fatores de Diferenciação de Crescimento , Cicatrização , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Quimiocina CXCL12/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fatores de Diferenciação de Crescimento/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
3.
BMC Gastroenterol ; 22(1): 280, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35658837

RESUMO

BACKGROUND: To develop a scoring system related to the lactate clearance (ΔLA) to predict the mortality risk (MELD-ΔLA) for critically ill cirrhotic patients. METHODS: In this retrospective cohort study, 881 critically ill cirrhotic patients from the Medical Information Mart for Intensive Care (MIMIC-III) database were included eventually. The outcomes of our study were defined as ICU death, 28-day, 90-day and 1-year mortality. Predictors were identified by multivariate Cox analysis to develop the predictive scoring system. The C-index and area under the curve (AUC) of receiver operator characteristic curve (ROC) were used to identify the predicting performance of the MELD-ΔLA, sequential organ failure assessment (SOFA), chronic liver failure-sequential organ failure assessment (CLIF-SOFA), the model for end-stage liver disease (MELD), Child-Pugh, chronic liver failure consortium acute-on-chronic liver failure (CLIF-C ACLF), chronic liver failure consortium-acute decompensation (CLIF-C AD) and MELD-Na scoring systems. Additionally, subgroup analysis was also performed based on whether critically ill cirrhotic patients underwent liver transplantation. RESULTS: Creatinine, bilirubin, international normalized ratio (INR), lactate first, ΔLA and vasopressors were closely associated with ICU death of liver critically ill cirrhotic patients. The C-index of the MELD-ΔLA in ICU death was 0.768 (95% CI 0.736-0.799) and the AUC for the MELD-ΔLA scoring system in predicting 28-day, 90-day, and 1-year mortality were 0.774 (95% CI 0.743-0.804), 0.765 (95% CI 0.735-0.796), and 0.757 (95% CI 0.726-0.788), suggested that MELD-ΔLA scoring system has a good predictive value than SOFA, CLIF-SOFA, MELD, Child-Pugh, CLIF-C ACLF, CLIF-C AD) and MELD-Na scoring systems. Additionally, the study also confirmed the good predictive value of MELD-ΔLA scoring system for critically ill cirrhotic patients regardless of undergoing liver transplantation. CONCLUSION: The developed MELD-ΔLA score is a simple scoring system in predicting the risk of ICU death, 28-day, 90-day and 1-year mortality for critically ill cirrhotic patients, which may have a good predictive performance.


Assuntos
Estado Terminal , Doença Hepática Terminal , Doença Hepática Terminal/complicações , Humanos , Ácido Láctico , Cirrose Hepática/complicações , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
4.
J Nat Prod ; 84(10): 2623-2629, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34610746

RESUMO

Penispidins A-C (1-3), new aromatic sesquiterpenoids with two classes of rare carbon skeletons, were isolated from the endophytic fungus Penicillium virgatum HL-110. 1 represents the first example of a dunniane-type aromatic sesquiterpenoid, possessing a novel 4/6/6 tricyclic system, while (±)-2 and 3 have a 7,12-cyclized bisabolene skeleton, featuring a 3,4-benzo-fused 2-oxabicyclo[3.3.1]nonane central framework. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and ECD calculations. 1 inhibited hepatic lipid accumulation in HepG2 cells.


Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Penicillium/química , Sesquiterpenos/farmacologia , China , Células Hep G2 , Humanos , Estrutura Molecular , Sesquiterpenos/isolamento & purificação , Triglicerídeos/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4061-4068, 2021 Aug.
Artigo em Zh | MEDLINE | ID: mdl-34467715

RESUMO

Reverse prediction and molecular docking techniques were employed to evaluate the feasibility of reniformin A(RA) as an anti-tumor leading compound. Based on the reverse prediction, network pharmacology was used to construct a "disease-compound-target-pathway" network. Thirty-nine tumor-related targets of RA were predicted, which participated in the regulation of multiple cellular activities such as apoptosis, cell cycle, and tumor metastasis, and regulated estrogen signal transduction and inflammatory response. Discovery Studio 2020 was adopted for molecular docking and toxicity prediction(TOPKAT). As revealed by the results, the binding affinity of RA with the tumor-related targets ABL1, ESR1, SRC and BCL-XL was stronger than that of oridonin(OD), while its mutagenicity, rodent carcinogenesis, and oral LD_(50) in rats were all inferior to that of OD. Furthermore, in vitro experiments were performed to confirm the anti-tumor activity of RA, and the mechanism was preliminarily discussed. The results demonstrated that RA was superior to OD in cytotoxicity, inhibition of cell colony formation, and induction of apoptosis. RA, possessing potent anti-tumor activity, is expected to be a new anti-tumor leading compound.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias , Animais , Medicamentos de Ervas Chinesas/farmacologia , Chumbo , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Ratos , Transdução de Sinais
6.
Molecules ; 24(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212585

RESUMO

AIM: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. METHODS: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. RESULTS: AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. CONCLUSIONS: AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes.


Assuntos
Biflavonoides/química , Biflavonoides/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Animais , Biomarcadores , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental , Jejum , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Glucagon/sangue , Glucose/metabolismo , Teste de Tolerância a Glucose , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Oxirredução/efeitos dos fármacos , Fosforilação
7.
Zhongguo Zhong Yao Za Zhi ; 42(1): 119-124, 2017 Jan.
Artigo em Zh | MEDLINE | ID: mdl-28945035

RESUMO

To explore the effect of the licorice-processed Tripterygium wilfordii on reducing the liver toxicity. In animal experiments, the liver toxicity of T. wilfordii was evaluated both before and after processing, and the differences in liver tissue biopsy, serum biochemical indexes and inflammatory cell factor among blank group, T. wilfordii group and licorice-processed T. wilfordii group were observed. Liver tissue biopsy results showed that liver tissue injury was obvious in T. wilfordii group, and no obvious injury was found in licorice-processed T. wilfordii group. As compared with the blank group, the levels of AST, ALT and CRE were significantly increased (P<0.01), UREA was increased (P<0.05), and ALB level was significantly decreased (P<0.01) in the T. wilfordii group. As compared with T. wilfordii group, the levels of AST, ALT, CRE, and UREA were decreased (P<0.01), while ALB was increased (P<0.01) in the licorice-processed T. wilfordii group. The results of inflammatory factors in rats showed that the levels of IL-1ß, IL-6, and TNF-α in T. wilfordii group were significantly higher than those in blank group (P<0.01); the levels of IL-1ß, IL-6, and TNF-α in licorice-processed T. wilfordii group were significantly lower than those in T. wilfordii group (P<0.01). Overall, licorice processing of T. wilfordii can effectively reduce the liver toxicity and reduce the liver injury caused by T. wilfordii. The experiment can provide reference for the clinical rational use of the T. wilfordii, and provide data support for the studies on reducing the liver toxicity of T. wilfordii by licorice processing.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Glycyrrhiza/química , Fígado/efeitos dos fármacos , Tripterygium/toxicidade , Animais , Interleucina-1beta/sangue , Interleucina-6/sangue , Ratos , Fator de Necrose Tumoral alfa/sangue
8.
Zhongguo Zhong Yao Za Zhi ; 42(24): 4893-4897, 2017 Dec.
Artigo em Zh | MEDLINE | ID: mdl-29493164

RESUMO

In recent years, the issues related to herb-induced liver injury (HILI) have received much concern. Its clinical diagnosis is much difficult than that of Western medicine-induced liver injury due to its complicated drug combination and multiple constituents. Moreover, it is also correlated with physiques, inheritance and basic diseases. China Association of Chinese Medicine has released the first standards for HILI diagnosis and treatment technology in 2016, namely Guidelines for clinical diagnosis of herb-induced liver injury (hereinafter referred to as the Guidelines). The diagnostic processes with different diagnostic results were explained in this paper to help clinicians, particularly liver specialists, in diagnosing liver diseases by applying the operation of the Guidelines.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Medicamentos de Ervas Chinesas/toxicidade , China , Humanos , Fígado , Guias de Prática Clínica como Assunto
9.
Zhongguo Zhong Yao Za Zhi ; 41(15): 2915-2921, 2016 Aug.
Artigo em Zh | MEDLINE | ID: mdl-28914037

RESUMO

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Tripterygium/toxicidade , Linhagem Celular , China , Humanos , Análise Espectral , Testes de Toxicidade , Tripterygium/química
10.
Zhongguo Zhong Yao Za Zhi ; 41(16): 3096-3099, 2016 Aug.
Artigo em Zh | MEDLINE | ID: mdl-28920355

RESUMO

To compare the consistency and difference of herb-induced liver injury between two methods in guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) and guidelines for the diagnosis and treatment of drug-induced liver injury in China(2015). This retrospective analysis included 390 patients with herb-induced liver injury who had a history of suspicious Chinese herbal medicines or patent medicines; the patients with integrative Chinese and western medicines were excluded from this study. The results indicated that there were 14(4%) extremely probable patients (>8 points), 185(47%) highly probable patients (6-8 points) and 191(49%) probable patients(3-5 points) in 390 cases with guidelines for diagnosis and treatment of drug-induced liver injury of China (2015). While when guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China (2016) was used for 390 patients, the results indicated that there were 5 (1%) cases with proven diagnosis, 163(42%) cases with clinical diagnosis, and 222(57%) cases with suspected diagnosis. Statistics showed that two methods had a consistency of 43% and difference of 14%. The research results showed that Guidelines for clinical diagnosis and treatment of liver injury related to Chinese herbal medicine in China(2016) was more suitable for the diagnosis of herb-induced liver injury. Due to the limitations of retrospective case study, further more prospective studies would be needed.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Medicamentos de Ervas Chinesas/toxicidade , China , Humanos , Estudos Retrospectivos
11.
Yao Xue Xue Bao ; 50(12): 1534-7, 2015 Dec.
Artigo em Zh | MEDLINE | ID: mdl-27169273

RESUMO

There has been thousands of years' history that traditional Chinese medicines were used in the prevention and treatment of infectious disease. In recent years, traditional Chinese medicine plays a unique role in the control of variety of new infectious diseases. This article provides a summary on our knowledge of the traditional Chinese medicine theory in the explanation of infectious disease, application of Chinese medicines and the pharmacological mechanism in the successful management on the Ebola virus disease.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença pelo Vírus Ebola/terapia , Medicina Tradicional Chinesa , Humanos
12.
J Proteome Res ; 13(8): 3792-3801, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24940827

RESUMO

Autoimmune hepatitis (AIH) is often confused with other liver diseases because of their shared nonspecific symptoms and serological and histological overlap. This study compared the plasma metabolomic profiles of patients with AIH, primary biliary cirrhosis (PBC), PBC/AIH overlap syndrome (OS), and drug-induced liver injury (DILI) with those of healthy subjects to identify potential biomarkers of AIH. Metabolomic profiling and biomarker screening were performed using proton nuclear magnetic resonance spectroscopy (1H NMR) coupled with a partial least-squares discriminant analysis. Compared with the levels in healthy volunteers and other liver disease patients, AIH patients exhibited relatively high levels of plasma pyruvate, lactate, acetate, acetoacetate, and glucose. Such metabolites are typically related to energy metabolism alterations and may be a sign of metabolic conversion to the aerobic glycolysis phenotype of excessive immune activation. Increased aromatic amino acids and decreased branched-chain amino acids were found in the plasma of AIH patients. The whole NMR profiles were stepwise-reduced, and nine metabolomic biomarkers having the greatest significance in the discriminant analysis were obtained. The diagnostic utility of the selected metabolites was assessed, and these biomarkers achieved good sensitivity, specificity, and accuracy (all above 93%) in distinguishing AIH from PBC, DILI, and OS. This report is the first to present the metabolic phenotype of AIH and the potential utility of 1H NMR metabolomics in the diagnosis of AIH.

13.
Tohoku J Exp Med ; 234(4): 255-61, 2014 12.
Artigo em Inglês | MEDLINE | ID: mdl-25400121

RESUMO

Primary biliary cirrhosis (PBC) is a progressive autoimmune liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Interleukin-33 (IL-33) is expressed in various non-hematopoietic cells and a certain population of immune cells, and exerts its biological effects by binding to the specific receptor, suppression of tumorigenicity 2 (ST2). A soluble form of ST2 (sST2) has been postulated to act as a decoy receptor for IL-33. In this study, we aimed to investigate the role of IL-33 in the pathogenesis of PBC. The study included 20 healthy controls and 68 patients with PBC. We thus found the increased serum IL-33 levels in PBC patients. Its elevated levels were positively correlated with serum alkaline phosphatase levels (a key parameter for the definition of PBC) and with Child-Pugh scores, which were used to determine the prognosis of liver cirrhosis. Moreover, the serum concentrations of sST2 were significantly higher in PBC patients compared with healthy subjects, irrespective of the disease severity. Importantly, the cells that express IL-33 and/or myeloperoxidase (a marker for neutrophils) were accumulated in the livers of PBC patients, and their number increased with the severity of liver lesions. Lastly, in vitro chemotaxis assays revealed that IL-33 enhanced the migration of neutrophils. These data suggest that IL-33 may affect the progress of PBC by recruiting neutrophils to the liver. This expanded knowledge of IL-33 in PBC patients is important for developing therapeutic strategies (e.g., neutralization of IL-33), selecting optimal clinical management, and predicting prognosis.


Assuntos
Progressão da Doença , Interleucinas/metabolismo , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/patologia , Quimiotaxia , Humanos , Interleucina-33 , Interleucinas/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Biliar/sangue , Pessoa de Meia-Idade , Neutrófilos/metabolismo
14.
Molecules ; 19(11): 18767-80, 2014 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-25407718

RESUMO

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Curcumina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Fígado/efeitos dos fármacos , Cirrose Hepática/metabolismo , Testes de Função Hepática/métodos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Phytomedicine ; 128: 155291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38518640

RESUMO

BACKGROUND: As a traditional Chinese medicinal herb, the lipid-lowing biological potential of Eucommia ulmoides leaves (EL) has been demonstrated. After fermentation, the EL have been made into various products with lipid-lowering effects and antioxidant activity. However, the anti-hyperlipidemic mechanism of fermented Eucommia ulmoides leaves (FEL) is unclear now. PURPOSE: To evaluate the effects of FEL on hyperlipidemia and investigate the mechanism based on regulating gut homeostasis and host metabolism. METHODS: Hyperlipidemia animal model in Wistar rats was established after 8 weeks high-fat diet (HFD) fed. The administered doses of aqueous extract of FEL (FELE) were 128, 256 and 512 mg/kg/d, respectively. Serum biochemical parameters detection, histopathological sections analysis, 16S rDNA sequencing of gut microbiota and untargeted fecal metabolomics analysis, were performed to determine the therapeutic effects and predict related pathways of FELE on hyperlipidemia. The changes of proteins and genes elated to lipid were detected by Immunofluorescence (IF) and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: 56 Components in FELE were identified by UPLC-MS, with organic acids, flavonoids and phenolic acids accounting for the majority. The intervention of FELE significantly reduced the body weight, lipid accumulation and the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) in hyperlipidemia rats, while increased the level of High-density lipoprotein-cholesterol (HDL-C). Meanwhile, FELE improved the inflammatory makers and oxidative stress factors, which is tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT). These results demonstrated that FETE can effectively reduce blood lipids and alleviate inflammation and oxidative damage caused by hyperlipidemia. Mechanistically, FELE restore the homeostasis of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of probiotics, especially Lactobacillus, Rombousia, Bacteroides, Roseburia, Clostridia_UCG-014_Unclassified, while modulated metabolism through amino acid, bile acid and lipid-related metabolism pathways. In addition, the Pearson correlation analysis found that the upregulated bilirubin, threonine, dopamine and downregulated lipocholic acid, d-sphingosine were key metabolites after FELE intervention. IF and qRT-PCR analysis showed that FELE upregulated the expression of fatty acid oxidation proteins and genes (PPARα, CPT1A), bile acid synthesis and excretion proteins and genes (LXRα, CYP7A1, FXR), and downregulated the expression of adipogenic gene (SREBP-1c) by regulating gut microbiota to improve metabolism and exert a lipid-lowering effect. CONCLUSION: This work filled the lipid-lowering mechanism gap of FEL. FELE can improve HFD-induced hyperlipidemia by regulating the gut microbiota homeostasis and metabolism. Thus, FEL has the potential to develop into the novel raw material of lipid-lowering drugs.


Assuntos
Dieta Hiperlipídica , Eucommiaceae , Microbioma Gastrointestinal , Homeostase , Hiperlipidemias , Extratos Vegetais , Folhas de Planta , Ratos Wistar , Animais , Hiperlipidemias/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Eucommiaceae/química , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Folhas de Planta/química , Homeostase/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Fermentação , Hipolipemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia
16.
RSC Adv ; 14(30): 21623-21634, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38979472

RESUMO

Carbon nanofiber membranes (CNMs) are expected to be used in many energy devices to improve the reaction rate. In this paper, CNMs embedded with palladium nanoparticles (Pd-CNMs) were prepared by electrospinning and carbonization using polyimide as the raw material. The effects of carbonization temperature, carbonization atmosphere, and heating rate on the physicochemical properties of the as-obtained Pd-CNMs were studied in detail. On this basis, the electrocatalytic performance of Pd-CNMs prepared under optimal conditions was characterized. The results showed that highly active zero-valent palladium nanoparticles with uniform particle size could be distributed on the surface of carbon nanofibers. Under vacuum conditions, at a carbonization temperature of 800 °C and a heating rate of 2 °C min-1, Pd-CNMs have lower H2O2 yield, lower Tafel slope (73.3 mV dec-1), higher electron transfer number (∼4), and superior durability, suggesting that Pd-CNMs exhibit excellent electrocatalytic activity for ORR in alkaline electrolyte. Therefore, polyimide-derived CNMs embedded with Pd nanoparticles are expected to become an excellent cathode catalyst layer for fuel cells.

17.
J Ethnopharmacol ; 325: 117768, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38253275

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Atherosclerosis (AS), a lipid-induced inflammatory condition of the arteries, is a primary contributor to atherosclerotic cardiovascular diseases including stroke. Arctium lappa L. leaf (ALL), an edible and medicinal herb in China, has been documented and commonly used for treating stroke since the ancient times. However, the elucidations on its anti-AS effects and molecular mechanism remain insufficient. AIM OF THE STUDY: To investigate the AS-ameliorating effects and the underlying mechanism of action of an ethanolic extract of leaves of Arctium lappa L. (ALLE). MATERIALS AND METHODS: ALLE was reflux extracted using with 70% ethanol. An HPLC method was established to monitor the quality of ALLE. High fat diet (HFD) and vitamin D3-induced experimental AS in rats were used to determine the in vivo effects; and oxidized low-density lipoprotein-induced RAW264.7 macrophage foam cells were used for in vitro assays. Simvatatin was used as positive control. Biochemical assays were implemented to ascertain the secretions of lipids and pro-inflammatory mediators. Haematoxylin-eosin (H&E) and Oil red O stains were employed to assess histopathological alterations and lipid accumulation conditions, respectively. CCK-8 assays were used to measure cytotoxicity. Immunoblotting assay was conducted to measure protein levels. RESULTS: ALLE treatment significantly ameliorated lipid deposition and histological abnormalities of aortas and livers in AS rats; improved the imbalances of serum lipids including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C); notably attenuated serum concentrations of inflammation-associated cytokines/molecules including TNF-α, IL-6, IL-1ß, VCAM-1, ICAM-1and MMP-9. Mechanistic studies demonstrated that ALLE suppressed the phosphorylation/activation of PI3K, Akt and NF-κB in AS rat aortas and in cultured foam cells. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of ALLE on lipid deposition, productions of TC, TNF-α and IL-6, and protein levels of molecules of PI3K/Akt and NF-κB singnaling pathways. CONCLUSIONS: ALLE ameliorates HFD- and vitamin D3-induced experimental AS by modulating lipid metabolism and inflammatory responses, and underlying mechanisms involves inhibition of the PI3K/Akt and NF-κB singnaling pathways. The findings of this study provide scientific justifications for the traditional application of ALL in managing atherosclerotic diseases.


Assuntos
Arctium , Aterosclerose , Fragmentos de Peptídeos , Receptores do Fator de Crescimento Derivado de Plaquetas , Acidente Vascular Cerebral , Ratos , Animais , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Metabolismo dos Lipídeos , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Aterosclerose/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Lipídeos , Colesterol/farmacologia , Etanol/farmacologia , Lipoproteínas LDL/metabolismo , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 45(6): 971-4, 2013 Dec 18.
Artigo em Zh | MEDLINE | ID: mdl-24343084

RESUMO

OBJECTIVE: To explore the risk and protective factors of kidney calculi in order to put forward theoretical basis for preventive and control measures. METHODS: A 1:1 matched case-control study was performed using data from a hospital in Beijing. The case group included 100 inpatients who were diagnosed kidney calculi using B ultrasonic, X-ray and intravenous pyelography during the survey while other 100 urolithiasis and endocrine disease excluded inpatients who shared the same sex, within five years gap to the case group inpatients were for the control group. A face-to-face survey was conducted with self-made questionnaires which covered demographic characteristics, water issues, dietary habits, genetic and medical history. Epidata 3.0 was used to build the database and SPSS 19.0 for the statistical analysis. RESULTS: In the univariate Logistic regression analysis, ten variables were found showing statistical significance. For the multivariate Logistic regression analysis, variables left in the model were labor intensity (OR=0.622, 95%CI: 0.435-0.889), preferring to drink after dinner (OR=0.316, 95%CI: 0.122-0.815), loving drinking (OR=0.232, 95%CI: 0.084-0.642), drinking tea regularly (OR=1.463, 95%CI: 1.033-2.071), eating more vegetables (OR=0.571, 95%CI: 0.328-0.993), the history of the urolithiasis (OR=2.127, 95%CI: 1.065-90.145). CONCLUSION: Drinking tea regularly, urolithiasis history and brain work are the risk factors of kidney calculi while loving drinking and eating more vegetables for the protection.


Assuntos
Comportamento Alimentar , Cálculos Renais/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Bebidas , Estudos de Casos e Controles , China/epidemiologia , Ingestão de Líquidos , Comportamento de Ingestão de Líquido , Feminino , Humanos , Cálculos Renais/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Chá , Urolitíase/complicações , Verduras , Adulto Jovem
19.
Molecules ; 17(12): 13844-55, 2012 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-23174900

RESUMO

A reverse phase ultra performance liquid chromatography and photodiode array (UPLC-PDA) detection method was established for the determination of six alkaloids in Zoagumhwan (ZGW), and further for investigating the influence of nonpolar substances on the extraction efficiency of these alkaloids. The method was based on a BEH C(18) (50 mm × 2.1 mm, 1.7 µm) column and mobile phase of aqueous phosphoric acid and acetonitrile including 0.05% buffer solution under gradient elution. ZGW samples of ZGW I, II, III and IV were obtained and prepared by pre-processing the crude materials of Coptidis rhizoma and Evodiae fructus using four technologies, namely direct water decoction, removal of nonpolar substances in Evodiae fructus by supercritical fluid extraction (SFE), removal of nonpolar substances in ZGW by SFE and removal of nonpolar substances in ZGW by steam distillation. The developed and validated UPLC-PDA method was precise, accurate and sensitive enough based on the facts that the six alkaloids showed good regression (r > 0.9998), the limit of detections and quantifications for six alkaloids were less than 28.8 and 94.5 ng/mL, respectively, and the recovery was in the range of 98.56%-103.24%. The sequence of the total contents of six alkaloids in these samples was ZGW II > ZGW IV > ZGW III > ZGW I. ZGW II, in which nonpolar substances, including essential oils, were firstly removed from Evodiae fructus by SFE, had the highest content of the total alkaloids, indicating that extraction efficiency of the total alkaloids could be remarkably increased after Evodiae fructus being extracted by SFE.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas/química , Evodia/química , Alcaloides/química , Alcaloides/isolamento & purificação , Cromatografia Líquida , Coptis chinensis , Óleos de Plantas/química
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(3): 448-53, 2012 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-22692320

RESUMO

OBJECTIVE: To investigate and analyze the occupational hazards of ultraviolet radiation, protective measures and related factors for typical symptoms among workers in electric welding, and to provide basic information for revision of the occupational standards of UV. METHODS: Questionnaires and physical examinations were used in this investigation. A total of 828 workers from four vehicle manufacturers in Beijing and Guangdong Province were selected. Corresponding analyses were conducted with SPSS 16.0 statistic software. RESULTS: The top three injuries of faces and hands were burning tingling (48.7% & 41.3%), itch of skin (39% & 34.9%) and pigmentation (31.9% & 24.5%).The major injuries of eyes were ophthalmodynia (61.5%) , photophobia and tearing (61.4%), and blurred vision (50.2%). The incidences of facial and hands burning tingling, hands flushing, hands macula and papula were significantly different between the welders and auxiliary workers (P<0.05). The differences of facial and hands burning tingling, flushing, facial disesthesia and anaesthesia, symptoms and signs of eyes were significant in different working years groups (P<0.05). The top three usages of protective measures were welding masks (87.2%), gloves (84.3%) and glasses (65.9%). Except for UV cut cream, the usages of other protective equipments in the auxiliary workers were significantly lower than those in the welders (P<0.05). The logistic regression analysis showed that prolonged exposure to arc welding, using argon arc welding and CO(2) gas shielded arc welding, not wearing welding masks, and not using UV cut cream was significantly associated with the increased risk of face burning tingling, and the ORs were 3.894 (6 h to 8 h), 2.665 (4 h to 6 h), 2.052, 1.765, 1.759, 1.833, respectively; working years might be a protective factor, and the OR was 0.440, respectively. CONCLUSION: The study suggested that the UV radiation produced during welding operations not only caused harm to welders, but also to the auxiliary workers. Protection should be strengthened,for example, wearing welding masks, glasses, etc. Meanwhile automatic welding machines should be adopted by the factories to reduce the exposure time for workers.


Assuntos
Exposição Ocupacional/efeitos adversos , Lesões por Radiação/prevenção & controle , Raios Ultravioleta/efeitos adversos , Soldagem , Adolescente , Adulto , Automóveis , China , Feminino , Humanos , Indústrias , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/etiologia , Proteção Radiológica/métodos , Inquéritos e Questionários , Adulto Jovem
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