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1.
Toxicol Appl Pharmacol ; 434: 115820, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896432

RESUMO

Arsenic is a well-known environmental pollutant due to its toxicity, which can do harm to animals and human. Curcumin is a polyphenolic compound derived from turmeric, commonly accepted to have antioxidant properties. However, whether curcumin can ameliorate the damage caused by arsenic trioxide (ATO) in duck skeletal muscle remains largely unknown. Therefore, the present study aims to investigate the potential molecular mechanism of curcumin against ATO-induced skeletal muscle injury. The results showed that treating with curcumin could attenuate body weight loss induced by ATO and reduced arsenic content accumulation in the skeletal muscle of duck. Curcumin was also able to alleviated the oxidative stress triggered by ATO, which was manifested by the increase of T-AOC and SOD, and MDA decrease. Moreover, we observed that curcumin could ease mitochondrial damage and vacuolate degeneration of nucleus. Our further investigation found that ATO disrupted normal mitochondrial fission/fusion (Drp1, OPA1, Mfn1/2) and restrained mitochondrial biogenesis (PGC-1α, Nrf1/2, TFAM), while curcumin could promote mitochondrial fusion and activated PGC-1α pathway. Furthermore, curcumin was found that it could not only reduce the mRNA and protein levels of mitophagy (PINK1, Parkin, LC3, p62) and pro-apoptotic genes (p53, Bax, Caspase-3, Cytc), but also increased the levels of anti-apoptotic genes (Bcl-2). In conclusion, curcumin was able to alleviate ATO-induced skeletal muscle damage by improving mitophagy and preserving mitochondrial function, which can serve as a novel strategy to take precautions against ATO toxicity.


Assuntos
Arsênio/toxicidade , Curcumina/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Doenças Musculares/induzido quimicamente , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biologia Computacional , Patos , Poluentes Ambientais/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitofagia/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ubiquitina-Proteína Ligases/genética
2.
BMC Infect Dis ; 20(1): 856, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203355

RESUMO

BACKGROUND: Disseminated Nocardia infection is a disease that is easily overlooked in patients with lesions occupying the intracranial space complicated with coma. Early diagnosis and treatment are crucial. CASE PRESENTATION: A 65-year-old man was admitted to the First Affiliated Hospital of Zhejiang University in October 2018 with weakness in the right limbs for 3 days and altered consciousness for 1 day. Five months earlier, he had been diagnosed with membranous kidney disease and had received cyclophosphamide and prednisone. At admission, the white blood cell count was 1.37 × 1010/L (with 86.4% neutrophils), and C-reactive protein was 115.60 mg/L. Imaging examinations revealed a lesion occupying the intracranial space, lung infection, and multiple abscesses in the rhomboid muscle. The abscesses were drained. Pus culture confirmed Nocardia cyriacigeorgica infection. With antibiotics and vacuum-sealed drainage of the back wound, the patient improved and was discharged from the hospital. CONCLUSIONS: This case report shows that infection should be considered during the differential diagnosis of lesions in the intracranial space, especially in patients receiving immunosuppressive treatment. In patients with disseminated N. cyriacigeorgica infection, combination antibiotic therapy and surgical drainage of localised abscesses can be effective.


Assuntos
Coma/complicações , Mesencéfalo/diagnóstico por imagem , Nocardiose/complicações , Nocardiose/diagnóstico , Nocardia/isolamento & purificação , Tálamo/diagnóstico por imagem , Idoso , Antibacterianos/uso terapêutico , Ciclofosfamida/efeitos adversos , Diagnóstico Diferencial , Drenagem , Seguimentos , Humanos , Imunossupressores/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Mesencéfalo/patologia , Nocardiose/tratamento farmacológico , Nocardiose/microbiologia , Tálamo/patologia , Tomógrafos Computadorizados , Resultado do Tratamento
3.
Clin Interv Aging ; 13: 2443-2452, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568435

RESUMO

Calcium is an important integrative component of the human body and critical for human health. It has been well established that calcium intake is helpful in the prevention and treatment of osteoporosis, which has become one of the most serious public health problems across the world. However, community-dwelling adults with and without osteoporosis are rarely concerned or even not aware of the potential side effects of high or inappropriate doses of calcium intake. Some recent studies have revealed that excessive calcium intake might increase the risks of cardiovascular diseases. The purpose of this article was to review the health benefits, costs, and consequences of calcium supplementation on osteoporosis/osteoporotic fractures, cardiovascular events, kidney stones, gastrointestinal diseases, and other important diseases. In the end, we suggest that calcium supplementation should be prescribed and taken cautiously, accounting for individual patients' risks and benefits. Clearly, further studies are needed to examine the health effects of calcium supplementation to make any solid recommendations for people of different genders, ages, and ethnicities.


Assuntos
Cálcio da Dieta/administração & dosagem , Cálcio/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Gastroenteropatias/epidemiologia , Cálculos Renais/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Cálcio/efeitos adversos , Cálcio da Dieta/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Humanos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia
4.
Sci Rep ; 7: 40593, 2017 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-28079136

RESUMO

The level of serum 25-Hydroxyvitamin D [25(OH)D] has high heritability, suggesting that genes may contribute to variations in serum 25(OH)D level and vitamin D dose-response. As vitamin D deficiency has been linked to numerous diseases, understanding how genetic variation contributes to vitamin D dose-response is important for personalized vitamin D treatment and cost-effective disease prevention. To identify genetic variants responsible for vitamin D status and dose-response, we performed two vitamin D3 and calcium clinical supplementation trials in 2,207 postmenopausal Caucasian women. We examined the association of 291 SNPs with baseline serum 25(OH)D levels and 25(OH)D dose-response. Five SNPs, rs10500804 (P = 4.93 × 10-7), rs2060793 (P = 6.63 × 10-7), rs10741657 (P = 1.49 × 10-6), rs10766197 (P = 1.05 × 10-5) and rs11023380 (P = 7.67 × 10-5) in the CYP2R1 gene, as well as 6 SNPs, rs4588 (P = 7.86 × 10-7), rs2298850 (P = 1.94 × 10-6), rs1155563 (P = 6.39 × 10-6), rs705119 (P = 2.80 × 10-5), rs705120 (P = 1.08 × 10-4) and rs222040 (P = 1.59 × 10-4) in the GC gene were associated with baseline serum 25(OH)D levels. SNP rs11185644 near the RXRA was significantly associated with 25(OH)D dose-response (P = 1.01 × 10-4). Our data suggest that polymorphisms in the CYP2R1 and GC gene may contribute to variation in baseline serum 25(OH)D concentration, and that polymorphism rs11185644 may contribute to variation in 25(OH)D dose-response in healthy postmenopausal Caucasian women.


Assuntos
Colecalciferol/uso terapêutico , Suplementos Nutricionais , Polimorfismo de Nucleotídeo Único/genética , Receptor X Retinoide alfa/genética , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/genética , Vitamina D/análogos & derivados , Vitamina D/sangue
5.
Hepatobiliary Pancreat Dis Int ; 15(4): 399-405, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27498580

RESUMO

BACKGROUND: Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS: Oral supplementation with Salmonella enterica serovar enteritidis (S. enteritidis) was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver injury. RESULTS: The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury (P<0.01); The peyer's patch CD3+ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group (P<0.05). S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial translocation. CONCLUSIONS: Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was severe. Major factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Fígado/microbiologia , Infecções por Salmonella/microbiologia , Salmonella enteritidis/patogenicidade , Doença Aguda , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Translocação Bacteriana , Bilirrubina/sangue , Biomarcadores/sangue , Complexo CD3/imunologia , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Endotoxinas/metabolismo , Galactosamina , Interações Hospedeiro-Patógeno , Fígado/metabolismo , Fígado/patologia , Masculino , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/microbiologia , Ratos Sprague-Dawley , Infecções por Salmonella/sangue , Infecções por Salmonella/imunologia , Infecções por Salmonella/patologia , Salmonella enteritidis/imunologia , Salmonella enteritidis/metabolismo , Linfócitos T/imunologia , Linfócitos T/microbiologia , Fatores de Tempo
6.
Cancer Prev Res (Phila) ; 9(4): 324-34, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26851235

RESUMO

Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA-binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR-23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-κB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI-induced hepatocarcinogenesis.


Assuntos
Ácidos Aristolóquicos/toxicidade , Carcinogênese/efeitos dos fármacos , Carcinógenos/toxicidade , Neoplasias Hepáticas/induzido quimicamente , Extratos Vegetais/toxicidade , Lesões Pré-Cancerosas/induzido quimicamente , Administração Oral , Animais , Aristolochia/química , Ácidos Aristolóquicos/administração & dosagem , Carcinogênese/metabolismo , Carcinógenos/administração & dosagem , Cães , Proteína Forkhead Box O1/metabolismo , Humanos , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Fosforilação , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas de Ligação a RNA/metabolismo , Receptores de Interleucina-6/metabolismo , Transdução de Sinais
7.
Zhongguo Zhong Yao Za Zhi ; 41(12): 2344-2349, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-28901083

RESUMO

To analyze the regularities of prescriptions in "a guide to clinical practice with medical record" (Ye Tianshi) for diarrhoea based on traditional Chinese medicine inheritance support system(V2.5), and provide a reference for further research and development of new traditional Chinese medicines in treating diarrhoea. Traditional Chinese medicine inheritance support system was used to build a prescription database of Chinese medicines for diarrhoea. The software integration data mining method was used to analyze the prescriptions according to "four natures", "five flavors" and "meridians" in the database and achieve frequency statistics, syndrome distribution, prescription regularity and new prescription analysis. An analysis on 94 prescriptions for diarrhoea was used to determine the frequencies of medicines in prescriptions, commonly used medicine pairs and combinations, and achieve 13 new prescriptions. This study indicated that the prescriptions for diarrhoea in "a guide to clinical practice with medical record" are mostly of eliminating dampness and tonifying deficienccy, with neutral drug property, sweet, bitter or hot in flavor, and reflecting the treatment principle of "activating spleen-energy and resolving dampness".


Assuntos
Diarreia/tratamento farmacológico , Prescrições de Medicamentos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Mineração de Dados , Bases de Dados de Produtos Farmacêuticos , Humanos , Prontuários Médicos , Meridianos
8.
Artigo em Chinês | WPRIM | ID: wpr-236088

RESUMO

To analyze the regularities of prescriptions in "a guide to clinical practice with medical record" (Ye Tianshi) for diarrhoea based on traditional Chinese medicine inheritance support system(V2.5), and provide a reference for further research and development of new traditional Chinese medicines in treating diarrhoea. Traditional Chinese medicine inheritance support system was used to build a prescription database of Chinese medicines for diarrhoea. The software integration data mining method was used to analyze the prescriptions according to "four natures", "five flavors" and "meridians" in the database and achieve frequency statistics, syndrome distribution, prescription regularity and new prescription analysis. An analysis on 94 prescriptions for diarrhoea was used to determine the frequencies of medicines in prescriptions, commonly used medicine pairs and combinations, and achieve 13 new prescriptions. This study indicated that the prescriptions for diarrhoea in "a guide to clinical practice with medical record" are mostly of eliminating dampness and tonifying deficienccy, with neutral drug property, sweet, bitter or hot in flavor, and reflecting the treatment principle of "activating spleen-energy and resolving dampness".

9.
World J Gastroenterol ; 21(36): 10409-17, 2015 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-26420967

RESUMO

AIM: To investigate the microbiological characteristics and drug resistance in liver cirrhosis patients with spontaneous peritonitis. METHODS: We analyzed the data of patients with liver cirrhosis and abdominal infection at the First Affiliated Hospital of Zhejiang University between January 2011 and December 2013. Pathogens present in the ascites were identified, and their sensitivity to various antibiotics was determined. RESULTS: We isolated 306 pathogenic bacteria from 288 cases: In 178 cases, the infection was caused by gram-negative strains (58.2%); in 85 cases, gram-positive strains (27.8%); in 9 cases, fungi (2.9%); and in 16 cases, more than one pathogen. The main pathogens were Escherichia coli (E. coli) (24.2%), Klebsiella pneumoniae (18.9%), Enterococcus spp. (11.1%), and Staphylococcus aureus (7.5%). Of the 306 isolated pathogens, 99 caused nosocomial infections and 207 caused community-acquired and other infections. The E. coli and K. pneumoniae strains produced more extended-spectrum ß-lactamases in cases of nosocomial infections than non-nosocomial infections (62.5% vs 38%, P < 0.013; 36.8% vs 12.8%, P < 0.034, respectively). The sensitivity to individual antibiotics differed between nosocomial and non-nosocomial infections: Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections (4% vs 20.8%, P < 0.021). Nitrofurantoin had stronger antibacterial activity against Enterococcus species causing non-nosocomial infections (36.4% vs 86.3%, P < 0.009). CONCLUSION: The majority of pathogens that cause abdominal infection in patients with liver cirrhosis are gram-negative, and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Cirrose Hepática/complicações , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/diagnóstico , China , Infecções Comunitárias Adquiridas/diagnóstico , Infecção Hospitalar/diagnóstico , Quimioterapia Combinada , Feminino , Hospitais Universitários , Humanos , Cirrose Hepática/diagnóstico , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Peritonite/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
10.
J Sep Sci ; 38(5): 804-12, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25546170

RESUMO

A simultaneous determination method based on liquid chromatography coupled with time-of-flight mass spectrometry was developed for the analysis of 11 bioactive constituents in tripterygium glycosides tablets, an immune and inflammatory prescription used in China. The analysis was fully optimized on a 1.8 µm particle size C18 column with linear gradient elution, permitting good separation of the 11 analytes and two internal standards in 21 min. The quantitation of each target constituent was carried out using the narrow window extracted ion chromatograms with a ±l0 ppm extraction window, yielding good linearity (r(2) > 0.996) with a linear range of 10-1000 ng/mL. The limits of quantitation were low ranging from 0.25 to 5.02 ng/mL for the 11 analytes, and the precisions and repeatability were better than 1.6 and 5.3%, respectively. The acceptable recoveries obtained were in the range of 93.4-107.4%. This proposed method was successfully applied to quantify the 11 bioactive constituents in commercial samples produced by nine pharmaceutical manufacturers to profile the quality of these preparations. The overall results demonstrate that the contents of the 11 bioactive constituents in different samples were in great diversity, therefore, the quality, clinical safety, and efficacy of this drug needs further research and evaluation.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Espectrometria de Massas/métodos , Tripterygium/química , Sensibilidade e Especificidade , Comprimidos/química
11.
Appl Microbiol Biotechnol ; 98(12): 5619-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24639205

RESUMO

This work investigated the effect of the intragastric administration of five lactic acid bacteria from healthy people on acute liver failure in rats. Sprague-Dawley rats were given intragastric supplements of Lactobacillus salivarius LI01, Lactobacillus salivarius LI02, Lactobacillus paracasei LI03, Lactobacillus plantarum LI04, or Pediococcus pentosaceus LI05 for 8 days. Acute liver injury was induced on the eighth day by intraperitoneal injection of 1.1 g/kg body weight D-galactosamine (D-GalN). After 24 h, samples were collected to determine the level of liver enzymes, liver function, histology of the terminal ileum and liver, serum levels of inflammatory cytokines, bacterial translocation, and composition of the gut microbiome. The results indicated that pretreatment with L. salivarius LI01 or P. pentosaceus LI05 significantly reduced elevated alanine aminotransferase and aspartate aminotransferase levels, prevented the increase in total bilirubin, reduced the histological abnormalities of both the liver and the terminal ileum, decreased bacterial translocation, increased the serum level of interleukin 10 and/or interferon-γ, and resulted in a cecal microbiome that differed from that of the liver injury control. Pretreatment with L. plantarum LI04 or L. salivarius LI02 demonstrated no significant effects during this process, and pretreatment with L. paracasei LI03 aggravated liver injury. To the best of our knowledge, the effects of the three species-L. paracasei, L. salivarius, and P. pentosaceus-on D-GalN-induced liver injury have not been previously studied. The excellent characteristics of L. salivarius LI01 and P. pentosaceus LI05 enable them to serve as potential probiotics in the prevention or treatment of acute liver failure.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Galactosamina/toxicidade , Lactobacillus/crescimento & desenvolvimento , Pediococcus/crescimento & desenvolvimento , Probióticos/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Citocinas/sangue , Histocitoquímica , Íleo/patologia , Fígado/patologia , Testes de Função Hepática , Ratos Sprague-Dawley , Resultado do Tratamento
12.
J Steroid Biochem Mol Biol ; 144 Pt A: 207-14, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24128439

RESUMO

Factors contributing to the variability of serum 25-hydroxyvitamin D [25(OH)D] in response to a given dose of vitamin D supplementation are largely unknown. We examined whether DNA methylation levels of Cytochrome P450 (CYP) enzymes (CYP2R1, CYP24A1, CYP27A1, and CYP27B1) are potential biomarkers predicting vitamin D response variation. We randomized 446 white postmenopausal women to a calcium and vitamin D (1100IU/day) intervention for at least 12 months. From these subjects, 18 with the highest 12-month increase in serum 25(OH)D were selected as "responders." Another 18 with the lowest 12-month increase in serum 25(OH)D were selected as "non-responders." DNA methylation levels between the groups were compared. To validate findings in the first study, association between DNA methylation levels and vitamin D response variation was studied in another 145 extended independent white postmenopausal women. In the first study, compared to non-responders, responders had significantly lower baseline DNA methylation levels in the promoter region of CYP2R1 (8% in the responders vs. 30% in the non-responders, P=0.004), and CYP24A1 (13% in the responders vs. 32% in the non-responders, P=0.001). In the validation study, for CYP2R1, baseline DNA methylation levels at eight CpG sites were negatively associated with 12-month increases in serum 25(OH)D (P<0.05). For CYP24A1, baseline DNA methylation levels at two CpG sites were also negatively associated with vitamin D response variation (r=-0.151, P=0.011; r=-0.131, P=0.025). These negative associations were consistent with the first study's results. Our findings indicate that baseline DNA methylation levels of CYP2R1 and CYP24A1 may predict vitamin D response variation. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.


Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Metilação de DNA , Variação Genética , Esteroide Hidroxilases/genética , Vitamina D/análogos & derivados , Vitaminas/sangue , Família 2 do Citocromo P450 , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D3 24-Hidroxilase , Vitaminas/administração & dosagem
13.
Artigo em Inglês | MEDLINE | ID: mdl-22701506

RESUMO

The anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid isolated from Laggera alata was studied using the D-galactosamine- (D-GalN-) induced hepatocyte damage model, HepG2.2.15 cells, and with HBV transgenic mice. In vitro results showed that 3,4-O-dicaffeoylquinic acid improved HL-7702 hepatocyte viability and markedly inhibited the production of HBsAg and HBeAg. At a concentration of 100 µg/mL, its inhibitory rates on the expression levels of HBsAg and HBeAg were 89.96% and 81.01%, respectively. The content of hepatitis B virus covalently closed circular DNA (HBV cccDNA) in HepG2.2.15 cells was significantly decreased after the cells were treated with the test compound. In addition, 3,4-O-dicaffeoylquinic acid significantly increased the expression of heme oxygenase-1 (HO-1) in HepG2.2.15 cells. In vivo results indicated that the test compound at concentrations of 100 µg/mL significantly inhibited HBsAg production and increased HO-1 expression in HBV transgenic mice. In conclusion, this study verifies the anti-hepatitis B activity of 3,4-O-dicaffeoylquinic acid. The upregulation of HO-1 may contribute to the anti-HBV effect of this compound by reducing the stability of the HBV core protein, which blocks the refill of nuclear HBV cccDNA. Furthermore, the hepatoprotective effect of this compound may be mediated through its antioxidative/anti-inflammatory properties and by the induction of HO-1 expression.

14.
J Clin Endocrinol Metab ; 97(8): 2699-705, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22585090

RESUMO

OBJECTIVE: It is well documented that there is wide variation in the response of serum 25-hydroxyvitamin D [25(OH)D] to a given dose of vitamin D supplementation. Understanding factors affecting the response variation is important for identifying subjects who are susceptible to vitamin D deficiency or toxicity. This study aimed to evaluate potential predictors for vitamin D response variation. DESIGN AND PARTICIPANTS: A total of 1179 non-Hispanic white postmenopausal women were enrolled into a 4-yr calcium and vitamin D (1100 IU/d) clinical trial. Among them, serum 25(OH)D level of 1063 subjects were measured at both baseline and after 12 months treatment. Vitamin D response was computed for these 1063 subjects as the difference in levels of serum 25(OH)D concentration at the end of a 12-month vitamin D treatment compared with baseline. Stepwise linear regression was used to identify predictors of vitamin D response variation. RESULTS: Increase in vitamin D intake, baseline serum 25(OH)D level, baseline blood collection season, baseline serum calcium level, and baseline body mass index were predictors of vitamin D response variation. These five factors explained 46.8% of the vitamin D response variation in the 1063 subjects. The first three factors [increase in vitamin D intake, baseline serum 25(OH)D level, baseline blood collection season] remained as predictors in the 392 subjects with trial vitamin D supplementation. For the first time, our study indicated that season is an important prediction factor for vitamin D response variation. Subjects who started vitamin D treatment in a cold season (autumn and winter) achieved a significantly higher serum 25(OH)D increase than those started in a hot season (summer) (P < 0.001). CONCLUSION: Our study suggests that the increase in vitamin D supplementation, baseline serum 25(OH)D level, and the season when initiating the vitamin D supplementation can partially predict vitamin D response variation in non-Hispanic postmenopausal women.


Assuntos
Pós-Menopausa/metabolismo , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Idoso , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Regressão , Estações do Ano , Vitamina D/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-23983374

RESUMO

This study explored the effects of a classical Chinese medicine formula- Xiao-Chai-Hu Tang(XCHT) on the model mice with D-galactosamine -induced liver injury. Sixty male imprinting control region (ICR) mice were used in the present study, and they were separated randomly into 6 groups: a normal control group (Group A, n=10), a model control (Group B, n=10), a positive control (Group C, n=10), a low dose of XCHT group (Group D, n=10), a medium dose of XCHT group (Group E, n=10), and a high dose of XCHT group (Group F, n=10). ELISA was used to detect the IL-6 and TNF-α levels in the serum. Real-time PCR was performed to assess the expression of FasmRNA, Fas-LmRNA, Bcl-2mRNA of the liver tissues. Western blotting was used to detect the Bax protein expression of the liver tissues. The serum IL-6 and TNF-α levels of Group B were significantly higher than the other groups (P<0.05). The expression of Fas mRNA, Fas-LmRNA, and Bax protein of the liver tissues of Group B were significantly higher than those of the other groups (P<0.05). The expression of Bcl-2 mRNA of the liver tissues of Group B was significantly lower than other groups (P<0.05). Both of XCHT and biphenyl dicarboxylate significantly decreased the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increased the Bcl-2 mRNA expression of the liver tissues of model mice (P<0.05). It may be through decreasing the serum IL-6 and TNF-α levels and FasmRNA, FasLmRNA, Bax protein expression and increasing the Bcl-2 mRNA expression of the liver tissues that XCHT significantly relieved the D-galactosamine -induced liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado/efeitos dos fármacos , Magnoliopsida , Fitoterapia , Animais , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Galactosamina , Interleucina-6/sangue , Fígado/metabolismo , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-23983378

RESUMO

Traditional medicines have become the most productive source of leads for drugs development, particularly as anti-cancer agents. Various screening approaches are being applied. Sorafenib, a multikinase inhibitor, is used to treat primary kidney cancer (advanced renal cell carcinoma) and advanced primary liver cancer. A small library of compounds analogous to sorafenib were designed and screened for the treatment of liver cancer. Multiple members of the family in an assay panel of tyrosine kinase family and serine/threonine-protein kinase family, including VEGFR, Abl, Aurora A, p 38, Lck, Src, PDGFR, Flt3, c-RAF, c-KIT, MEK(MAPKK) were selected to test these compounds. Analysis of the selectivity patterns for these compounds shows specificity for many kinase families. IC50 were measured for the selected compounds. Multiple compounds have very similar kinase inhibition profiles of VEGFR, Flt3, FGFR to that of sorafenib. The IC50 of c-RAF of BB1 is lower than sorafenib. The IC50 of c-RAF of BB3-12 is higher than that of sorafenib. For Flt3, IC50 of BB1-4 is less than sorafenib. The IC50 value of KDR of BB1-10 is less than sorafenib. especially against c-RAF, PDGFR, c-KIT, KDR compared to sorafenib. These compounds are potent Raf1 and Flt4 kinase inhibitors.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Neoplasias Hepáticas/enzimologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Medicina Tradicional , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe
17.
Drug Resist Updat ; 14(4-5): 236-50, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21807550

RESUMO

A comprehensive surveillance system for bacterial resistance in tertiary hospitals has been established in China that involves tertiary hospitals in distinct regions nationwide, enabling the collection of a large amount of antimicrobial surveillance data. Antimicrobial resistance in China has become a serious healthcare problem, with high resistance rates of most common bacteria to clinically important antimicrobial agents. Methicillin-resistant S. aureus, ESBL-producing Enterobacteriaceae and carbapenem-resistant Acinetobacter baumannii represent more than 50% of microbial isolates. Additionally, bacterial resistance to fluoroquinolones, macrolides and third-generation cephalosporins is of serious concern. The molecular epidemiology and resistance mechanisms of the antimicrobial strains in China exhibited regional specificity, as well as the influence of dissemination of international clonal complexes. The molecular characteristics of MRSA, ESBL- and carbapenemase-producing Enterobacteriaceae, and macrolide-resistant gram-positive Streptococci in China were significantly different from those in other countries and regions, while S. pneumoniae serotypes appear to have been affected by the global spread of prevalent clones in other parts of the world. Moreover, important antimicrobial resistant bacteria such as community-acquired-MRSA, multidrug-resistant P. aeruginosa and extensive-resistant A. baumannii, and the antimicrobial resistance in primary healthcare and outpatient setting should be intensely monitored and investigated in the future.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana/fisiologia , Farmacoepidemiologia , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , China/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Farmacorresistência Bacteriana Múltipla/fisiologia , Humanos , Testes de Sensibilidade Microbiana
18.
Nutr Metab (Lond) ; 7: 62, 2010 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-20650013

RESUMO

BACKGROUND: It is undetermined whether calcium supplementation has an effect on obesity or body composition in postmenopausal women. The purpose of the study is to detect the effect of calcium supplementation on indices of obesity and body composition. METHODS: This is a secondary analysis of data from a population-based, double-blind, placebo-controlled, randomized trial designed to determine the effects of calcium and vitamin D on osteoporotic fractures. The cohort included 1179 postmenopausal women who were randomly assigned into one of three groups: 1) supplemental calcium (1400 mg/d or 1500 mg/d) plus vitamin D placebo (Ca-only group); 2) supplemental calcium (1400 mg/d or 1500 mg/d) plus supplemental vitamin D3 (1100 IU/d) (Ca + D group); or, 3) two placebos (placebo group). After applying the exclusion criteria for this analysis, 870 subjects were included in this study. The primary outcomes for the present study were changes in body mass index, trunk fat, trunk lean, and percentage of trunk fat after calcium supplementation. RESULTS: Changes in trunk fat, trunk lean, and percentage of trunk fat were significantly different between the calcium intervention groups (Ca-only group or Ca + D group) and the placebo group during the trial (P < 0.05). The calcium intervention groups gained less trunk fat and maintained more trunk lean when compared to the placebo group. No significant difference was observed for body mass index between groups. CONCLUSION: Calcium supplementation over four years has a beneficial effect on body composition in postmenopausal women.

19.
Zhongguo Zhong Yao Za Zhi ; 33(3): 292-5, 2008 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-18536469

RESUMO

OBJECTIVE: To investigate the effects of Paecilomyces cicadae polysaccharide (PCPS) on the immunological function of aged rats in vivo. METHOD: The young and old rats were administered with normal saline as control groups, and the rats from test group were sc given 50, 100, 200 mg x kg(-1) x d(-1) dosage of PCPS for 3 weeks. The phagocytizing rate and index of PMphi, AMphi to S. aureas were observed, and the colorimetric MTI was used to analyze the proliferative activity of spleenocytes which had been stimulated with ConA or LPS. We also inspected the ability varing of ACP, LDH, ARG of spleen, and observed the ultramicro structure of spleen under the SEM. RESULT: The phagocytosis of Mphi was lower in aged group than that in young' s group, and the proliferative activity of spleenocytes was lower too. The activities of ACP, LDH, ARG of spleen were extremely decreased (P < 0.01) in aged rats as well. The proliferative activity and phagocytotic rate were both extremely increased in PCPS groups (P < 0.01), and the mitochondrion and endoplasmic reticulum of spleen were accrementition as well (P < 0.01). CONCLUSION: PCPS could enhance the phagocytizing function of PMphi, AMphi of aged rats in vivo, and strengthen the immune function of spleen and its proliferative activity as well. Then the immunity of aged rats could be improved. The PCPS may be an anti-aging agent.


Assuntos
Hypocreales/química , Imunidade/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Hypocreales/isolamento & purificação , Masculino , Microscopia Eletrônica de Transmissão , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/ultraestrutura
20.
J Gastroenterol Hepatol ; 21(4): 647-56, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16677148

RESUMO

BACKGROUND AND AIM: Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia-reperfusion (I/R) liver injury. METHODS: Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor-alpha (TNF-alpha), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied. RESULTS: All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF-alpha and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF-alpha, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD. CONCLUSION: Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.


Assuntos
Bifidobacterium , Lactobacillus , Fígado/irrigação sanguínea , Fígado/microbiologia , Probióticos/uso terapêutico , Traumatismo por Reperfusão/microbiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Técnicas de Cocultura , Suplementos Nutricionais , Modelos Animais de Doenças , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/patologia , Resultado do Tratamento
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