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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 43(2): 265-270, 2023 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-36946047

RESUMO

OBJECTIVE: To investigate the efficacy of Bushen Huoxue Fang (BSHXF, a traditional Chinese medicine formula) for improving recurrent spontaneous abortion (RSA) in mice and the role of tyrosine kinase (JAK2) and transcriptional activator (STAT3) signaling pathway in its therapeutic mechanism. METHODS: Female CBA/J mice were caged with male DBA/2 mice to establish RSA mouse models, which were randomly divided into model group, dydrogesterone group and BSHXF group, with the female mice caged with male BALB/c mice as the control group (n=6). From the first day of pregnancy, the mice were subjected to daily intragastric administration of BSHXF, dydrogesterone, or distilled water (in control and model groups) for 12 days. After the treatments, serum levels of antithrombin III (AT-III), activated protein C (APC), tissue plasminogen activator (t-PA), progesterone, human chorionic gonadotropin (HCG), and estradiol (E2) were detected in each group using ELISA. HE staining was used to observe the morphological changes of the endometrium of the mice. Western blotting was performed to determine the expressions of p-JAK2, p-Stat3 and Bcl-2 in the placenta of the mice. RESULTS: Compared with the control mice, the mouse models of RSA showed a significantly increased embryo loss rate with decreased serum levels of AT-III, T-PA, progesterone, APC and HCG, increased placental expressions of p-JAK2, p-STAT3 and Bax, and decreased expression of Bcl-2 (P < 0.05). Treatments with BSHXF and dydrogesterone both increased serum levels of AT-III, t-PA and HCG in the mouse models; Serum APC level was significantly reduced in BSHXF group and serum progesterone level was significantly increased in dydrogesterone group (P < 0.05). CONCLUSION: BSHXF can improve the prethrombotic state and inhibit cell apoptosis by downregulating the JAK2/STAT3 pathway to increase the pregnancy rate in mouse models of RSA.


Assuntos
Aborto Habitual , Animais , Camundongos , Aborto Habitual/prevenção & controle , Transdução de Sinais , Regulação para Baixo , Modelos Animais de Doenças
2.
J Frailty Aging ; 10(3): 241-246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105708

RESUMO

OBJECTIVES: To better understand the role of nutrition in older adults (aged 50 years or older) with bipolar disorders (OABD), we conducted a systematic review of the literature and appraise existing evidence. METHODS: Following PRISMA guidelines, we searched databases including Medline/PubMed, PsychINFO, EMBASE, CINAHL, Scopus, Web of Science, Cochrane Register, FDA website, and clinical trial registries through 2019 for eligible reports. The search string combined MeSH terms for bipolar disorder, nutrition and older adults. This was supplemented by snowball searching of references in relevant studies and authors were contacted to request their work where necessary. All included studies were rated with the National Institutes of Health Study Quality Assessment Tools based on study designs. RESULTS: Of 2280 papers screened, ten studies including eight observational and two interventional studies. The topic foci of the papers examined several nutrients, (including vitamin B12, vitamin D, coenzyme Q10, homocysteine, and folate), nutritional deficiencies and biochemical correlates. The prevalence rates of deficiencies varied with specific nutrients (3.7% to 71.6% for Vitamin B12 and 34.6% for Vitamin D), and between inpatient versus outpatient populations. While nutritional interventions appeared to be associated with improvement in both affective and cognitive outcomes, the sample sizes of OABD varied and were generally small. CONCLUSION: While there is evidence for the benefits of nutritional interventions on affective, cognitive and overall outcome in OABD, the quality of the evidence is limited. Our findings underscore the need for high quality studies to inform evidence-based guidelines for nutritional assessment and supplemention in OABD.


Assuntos
Transtorno Bipolar , Desnutrição , Idoso , Transtorno Bipolar/terapia , Suplementos Nutricionais , Humanos , Estado Nutricional , Estados Unidos
3.
Fish Shellfish Immunol ; 106: 421-430, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32798694

RESUMO

An 8-week growth trial was conducted to study enterohepatic recirculation of bile acid metabolism and the intestinal microbiota of Amur sturgeon (Acipenser schrenckii) fed with three diets, including 540 g/kg, 270 g/kg or 0 g/kg fishmeal, which was correspondingly replaced by a plant protein blend (named P0, P50 and P100, respectively). The diets were designed to be isonitrogenous, isoenergetic and essential nutrients balanced. With rising levels of dietary plant protein, disruption of the spiral valve intestinal microbiota and more morbidity with liver disease were observed in the P100 group, although there were no haematological abnormalities observed. An obvious bile acids enterohepatic circulation disorder was found with phenotypes of increased liver bile acids compensatory synthesis, and reduced expression of bile acid receptors (FXR and TGR5), which induced BA accumulative toxicity. Accompanied by increased oxidative stress, it further induced hepatic lesions and hypoimmunity, which were non-negligible reasons for the high mortality and low utilization ability of plant protein by Amur sturgeon.


Assuntos
Ácidos e Sais Biliares/metabolismo , Circulação Êntero-Hepática , Peixes/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Proteínas de Vegetais Comestíveis/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Intestinos/microbiologia , Proteínas de Vegetais Comestíveis/administração & dosagem , Distribuição Aleatória
4.
Eur Rev Med Pharmacol Sci ; 24(3): 1468-1480, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32096197

RESUMO

OBJECTIVE: This study aimed to investigate the efficacy and safety of transcatheter arterial chemoembolization (TACE) using CalliSpheres beads loading with arsenic trioxide (ATO) (CBATO) in unresectable hepatocellular carcinoma (HCC) patients. PATIENTS AND METHODS: Eighty-six unresectable HCC patients about to receive TACE with CBATO or conventional TACE (cTACE) with ATO were consecutively enrolled and divided into CBATO group (N=38) or cTACE group (N=48), respectively. Treatment response at 3 months (M3) and 6 months (M6) after the first treatment, and the progression-free survival (PFS) and overall survival (OS) were evaluated. Also, the biochemical indexes were documented before treatment, at 7 days, M3, and M6 after the first treatment. RESULTS: The 3-month complete response (CR), overall response rate (ORR), and the 6-month CR, ORR, as well as the disease control rate (DCR) were increased in CBATO group compared with the cTACE group. Also, the TACE with CBATO was an independent predicting factor for lower stable disease+ progressive disease (non-ORR). Besides, PFS and OS were longer in CBATO group compared with cTACE group. Referring to biochemical indexes (including liver function indexes, kidney function indexes, and blood routine indexes), no difference between the two groups was found. As for adverse events, the prevalence of nausea and vomiting was decreased, while the prevalence of other adverse events were similar in CBATO group compared to cTACE group. CONCLUSIONS: TACE with CBATO is more effective and equally tolerant compared with cTACE in treating unresectable HCC patients.


Assuntos
Trióxido de Arsênio/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Óleo Etiodado/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Microesferas , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Sistemas de Liberação de Medicamentos/métodos , Feminino , Seguimentos , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
5.
J Mycol Med ; 30(1): 100915, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32008963

RESUMO

Aspergillus infections are increasingly recognized as a global health problem because of limited antifungal drugs and occurrence of azole resistance worldwide. More cyp51-mediated and non-cyp51-mediated mechanisms of azole resistance have been identified in clinical and laboratory studies in recent years with applications of molecular biotechnology including next-generation sequencing, reverse genetics and so on. In this review, current research on the molecular mechanisms of azole resistance in A. fumigatus were presented and summarized and meanwhile the putative clinical relevance of these findings from bench work were discussed. Important aims are to gain more insight to mechanism of azole resistance and provide some efficient lead for prevention strategy.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/genética , Azóis/uso terapêutico , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Aspergilose/genética , Aspergilose/microbiologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/patogenicidade , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Testes de Sensibilidade Microbiana , Mutação , Esterol 14-Desmetilase/genética
6.
J Chiropr Educ ; 34(2): 132-139, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31062989

RESUMO

OBJECTIVE: To determine the relationship between admissions criteria and grade point average (GPA) at the conclusion of the first-term of study at a chiropractic institution. METHODS: Secondary data analysis was used on the Fall 2017 entering cohort of doctor of chiropractic students. Independent samples t-tests and ordinary least squares linear regression were used to explain the extent to which incoming undergraduate GPA, undergraduate chemistry grade, undergraduate anatomy and physiology grade, and age, respectfully, influenced the end-of-trimester GPA. RESULTS: Linear regression found each of the four independent variables (undergraduate GPA, undergraduate chemistry grade, undergraduate anatomy and physiology grade, and age) to be significant influencers of end-of-trimester-1 GPA with undergraduate GPA being the most statistically significant predictor (p < .001).The difference in mean end-of-trimester GPAs for male and female students was not statistically significant. There also was no difference in mean end-of-trimester GPAs by race/ethnicity. CONCLUSION: Current admissions requirements may need to emphasize incoming undergraduate GPA and target student support for older students. This study should be repeated for increased sample size, be performed at other chiropractic institutions, and consider additional cohorts to strengthen results.

7.
Fish Shellfish Immunol ; 90: 338-348, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075404

RESUMO

N-Carbamylglutamate (NCG), an analogue of N-acetylglutamate (NAG), can promote the synthesis of endogenous Arginine (Arg) in mammals, but not well studied in fish. This study was conducted to investigate the capacity of Arg endogenous synthesis by NCG, and the effects of various dietary NCG doses on growth performance, hepatic health and underlying nutrient regulation metabolism on ERK1/2-mTOR-S6K1 signaling pathway in Japanese seabass (Lateolabrax japonicus). Four experimental diets were prepared with NCG supplement levels of 0 (N0), 360 (N360), 720 (N720) and 3600 (N3600) mg/kg, in which N360 was at the maximum recommended level authorized by MOA, China in fish feed, and the N720 and N3600 levels were 2 and 10-fold of N360, respectively. Each diet was fed to 6 replicates with 30 Japanese seabass (initial body weight, IBW = 11.67 ±â€¯0.02 g) in each tank. The results showed that the dietary NCG supplementation had no significant effects on the SGR and morphometric parameters of Japanese seabass, but 360-720 mg/kg NCG inclusion promoted PPV, while the 10-fold (3600 mg/kg) overdose of NCG had remarkably negative effects with significantly reduced feed efficiency, PPV and LPV. We found that Japanese seabass can utilize 360-720 mg/kg NCG to synthesis Arg to improve the amino acid metabolism by increasing plasma Arg and up-regulating intestinal ASL gene expression. Increased plasma GST and decreased MDA indicated the improved antioxidant response. Dietary NCG inclusion decreased plasma IgM and down-regulated the mRNA levels of inflammation (TNF-α and IL8), apoptosis (caspase family) and fibrosis (TGF-ß1) related genes in the liver. The immunofluorescence examination revealed significantly decreased hepatic apoptosis and necrosis signals in the NCG groups. The ameliorated liver function and histological structure were closely related to the improved lipid metabolism parameters with decreased plasma VLDL and hepatic TG and NEFA accumulation, down-regulated fatty acid and cholesterol synthesis and simultaneously increased lipolysis gene mRNA levels, which regulated by inhibiting phosphorylation of ERK1/2-mTOR-S6K1 signaling pathway. Consuming 3600 mg/kg of dietary NCG is not safe for Japanese seabass culturing with the significantly increased FCR and decreased protein and lipid retention, and reduced plasma ALB. Accordingly, the observed efficacy and safety level of dietary NCG in the diet of Japanese seabass is 720 mg/kg.


Assuntos
Bass , Doenças dos Peixes/prevenção & controle , Glutamatos/metabolismo , Hepatopatias/veterinária , Doenças Metabólicas/veterinária , Ração Animal/análise , Animais , Apoptose/efeitos dos fármacos , Arginina/biossíntese , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Glutamatos/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatopatias/imunologia , Hepatopatias/prevenção & controle , Doenças Metabólicas/imunologia , Doenças Metabólicas/prevenção & controle , Nutrientes/metabolismo , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos
8.
Biol Res ; 51(1): 34, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30219096

RESUMO

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.


Assuntos
Antioxidantes/farmacologia , Apolipoproteína B-48/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Hiperlipidemias/prevenção & controle , Lipoproteínas HDL/efeitos dos fármacos , Isquemia Miocárdica/prevenção & controle , Vitamina E/farmacologia , Animais , Apolipoproteína B-48/sangue , Cardiotônicos/farmacologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/prevenção & controle , Citocinas/sangue , Dieta Aterogênica , Suplementos Nutricionais , Ensaio de Imunoadsorção Enzimática , Feminino , Hiperlipidemias/sangue , Immunoblotting , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/sangue , Masculino , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/sangue , Proteínas de Transferência de Fosfolipídeos/sangue , Valores de Referência , Reprodutibilidade dos Testes , Receptores Depuradores Classe B/sangue , Receptores Depuradores Classe B/efeitos dos fármacos , Resultado do Tratamento
9.
Osteoporos Int ; 29(5): 1023-1047, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29525971

RESUMO

Fracture liaison services (FLS) have been demonstrated to improve outcomes following osteoporotic fracture. The aim of this systematic literature review (SLR) was to determine the characteristics of an FLS that lead to improved patient outcomes. We conducted a SLR, including articles published between 2000 and February 2017, using global (Medline, EMBASE, PubMed and Cochrane Library) and local databases. Studies including patients aged ≥ 50 years with osteoporotic fractures enrolled in an FLS were assessed. Information extracted from each article included key person coordinating the FLS (physician, nurse or other healthcare professional), setting (hospital vs community), intensity (single vs multiple), duration (long vs short term), fracture type and gender. A meta-analysis of randomised controlled trials was conducted based on the key person coordinating the FLS. Out of 7236 articles, 57 were considered to be high quality and identified for further analysis. The SLR identified several components which contributed to FLS success, including multidisciplinary involvement, driven by a dedicated case manager, regular assessment and follow-up, multifaceted interventions and patient education. Meta-analytic data confirm the effectiveness of an FLS following an osteoporotic fracture: approximate 27% increase in the likelihood of BMD testing and up to 21% increase in the likelihood of treatment initiation compared with usual care. The balance of evidence indicates that the multifaceted FLS and dedicated coordination are important success factors that contribute to effective FLS interventions which reduce fracture-related morbidity and mortality.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária/organização & administração , Conservadores da Densidade Óssea/uso terapêutico , Humanos , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Indicadores de Qualidade em Assistência à Saúde
10.
Am J Ophthalmol Case Rep ; 10: 119-121, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29511746

RESUMO

PURPOSE: We present the first case in the literature of a patient with Kartagener syndrome and ocular findings of nonexudative age-related macular degeneration. OBSERVATIONS: A 55-year-old woman with Kartagener syndrome and chronic angle closure glaucoma presented for evaluation of the retina. Optos ultra-widefield imaging of the fundus showed glaucomatous cupping, drusen, and retinal pigment epithelium changes within the macular region. Humphrey visual field testing confirmed glaucomatous changes. Drusenoid pigment epithelial detachments were observed bilaterally with optical coherence tomography. CONCLUSIONS AND IMPORTANCE: We hypothesize that in addition to the lungs, spermatozoa and the Fallopian tubes, the retinal pigment epithelium may also be affected by ciliary dysfunction in individuals with Kartagener syndrome. Given recent advances in our knowledge of retinal ciliopathies, further studies are needed to understand how ciliary dysfunction affects the retina in Kartagener syndrome.

11.
Poult Sci ; 97(4): 1238-1244, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29452404

RESUMO

This study aimed to evaluate the effects of vitamin C and vitamin E on antioxidant capacity and immune function in oxidative-stressed breeder roosters. One hundred twenty 45-week-old Lveyang black-boned breeder roosters were randomly assigned to 5 dietary treatments, including negative control group (NC), positive control group (PC), and 3 trial groups, which were fed the diets containing 300 mg/kg VC, 200 mg/kg VE, or 300 mg/kg VC and 200 mg/kg VE (VC+VE). At 47 wk of age, the positive control and trial groups were subcutaneously injected 3 times every other d with dexamethasone (DEX) 4 mg/kg of body weight, the negative control group was injected with saline. The experiment lasted for 35 d. The results showed that at 50 wk of age, average daily feed intake of birds challenged with DEX significantly increased (P < 0.05). During post-stress recovery period (52 wk of age), dietary supplemental VE or VC+VE notably increased body weight under oxidative stress (P < 0.01). Oxidative stress induced by DEX could significantly decrease superoxide dismutase (SOD), IgM, antibody titer of ND and mRNA expression of SOD or glutathion peroxidase activity (GSH-Px), increase serous malondialdehyde (MDA) (P < 0.05). Supplementation of VC or VE significantly decreased serous MDA, and increased SOD under oxidative stress (P < 0.05). Supplementation of VC or VE, or their combination significantly increased the relative expression of GSH-Px mRNA when compared to the oxidative-stressed control treatment (P < 0.05), whereas did not alleviate the relative expression of SOD mRNA (P > 0.05). Therefore, the results suggest that addition of 300 mg/kg VC, 200 mg/kg VE or their combination could improve antioxidant ability and immune performance in oxidative-stressed breeder roosters through up-regulating the expression of GSH-Px gene.


Assuntos
Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Galinhas/fisiologia , Imunidade Inata , Estresse Oxidativo , Vitamina E/metabolismo , Ração Animal , Animais , Ácido Ascórbico/administração & dosagem , Proteínas Aviárias/genética , Proteínas Aviárias/metabolismo , Galinhas/genética , Galinhas/imunologia , Dieta/veterinária , Suplementos Nutricionais/análise , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Imunidade Inata/efeitos dos fármacos , Masculino , Distribuição Aleatória , Regulação para Cima , Vitamina E/administração & dosagem
12.
Biol. Res ; 51: 34, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-983938

RESUMO

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.


Assuntos
Animais , Masculino , Feminino , Ácido Ascórbico/farmacologia , Vitamina E/farmacologia , Isquemia Miocárdica/prevenção & controle , Apolipoproteína B-48/efeitos dos fármacos , Hiperlipidemias/prevenção & controle , Lipoproteínas HDL/efeitos dos fármacos , Antioxidantes/farmacologia , Valores de Referência , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/sangue , Ensaio de Imunoadsorção Enzimática , Cardiotônicos/farmacologia , Immunoblotting , Reprodutibilidade dos Testes , Citocinas/sangue , Resultado do Tratamento , Isquemia Miocárdica/sangue , Suplementos Nutricionais , Proteínas de Transferência de Fosfolipídeos/sangue , Dieta Aterogênica , Receptores Depuradores Classe B/efeitos dos fármacos , Receptores Depuradores Classe B/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Apolipoproteína B-48/sangue , Hiperlipidemias/sangue , Lipoproteínas HDL/sangue , Camundongos Endogâmicos C57BL
13.
J Viral Hepat ; 24 Suppl 2: 25-43, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29105283

RESUMO

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.


Assuntos
Saúde Global , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/mortalidade , Modelos Estatísticos , Viremia/epidemiologia , Viremia/mortalidade , Antivirais/uso terapêutico , Política de Saúde , Hepatite C Crônica/tratamento farmacológico , Humanos , Incidência , Prevalência , Viremia/tratamento farmacológico
14.
Genes Brain Behav ; 16(4): 439-448, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27862969

RESUMO

Phenylpropanolamine (PPA)-induced appetite control is associated with oxidative stress in the hypothalamus. This study explored whether hypothalamic antioxidants participated in hypothalamic ghrelin system-associated appetite control in PPA-treated rats. Rats were given PPA daily for 4 days, and changes in food intake and the expression of neuropeptide Y (NPY), the cocaine- and amphetamine-regulated transcript (CART), superoxide dismutase, catalase, ghrelin, acyl ghrelin (AG), ghrelin O-acyltransferase (GOAT) and the ghrelin receptor (GHSR1a) were examined and compared. Results showed that both food intake and the expression of NPY and ghrelin/AG/GOAT/GHSR1a decreased in response to PPA treatment with maximum decrease on Day 2 of the treatment. In contrast, the expression of antioxidants and CART increased, with the maximum increase on Day 2, with the expression opposite to that of NPY and ghrelin. A cerebral infusion of either a GHSR1a antagonist or reactive oxygen species scavenger modulated feeding behavior and NPY, CART, antioxidants and ghrelin system expression, showing the involvement of ghrelin signaling and oxidative stress in regulating PPA-mediated appetite control. We suggest that hypothalamic ghrelin signaling system, with the help of antioxidants, may participate in NPY/CART-mediated appetite control in PPA-treated rats.


Assuntos
Apetite/efeitos dos fármacos , Grelina/metabolismo , Hipotálamo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenilpropanolamina/farmacologia , Animais , Anorexia/induzido quimicamente , Apetite/fisiologia , Peso Corporal , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Hipotálamo/metabolismo , Masculino , Neuropeptídeo Y/metabolismo , Estresse Oxidativo/fisiologia , Hormônios Peptídicos/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Receptores de Grelina/antagonistas & inibidores , Receptores de Grelina/metabolismo
15.
Nanomedicine ; 12(6): 1479-88, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26949161

RESUMO

Ionic complementary peptides have shown potential in delivering hydrophobic anticancer drugs. In this study, a series of four ionic complementary peptides, EAR16-II, EAR8-II, EAR8-IIa and ELR8-IIa, is derived from the most studied ionic complementary peptide EAK16-II. The purpose is to investigate the impact of peptide sequence on nanostructure formation, delivery efficacy and cell specificity of the peptide-drug complex. We show that the peptide length has a pronounced impact on the morphology of peptide complex with the anticancer drug ellipticine (EPT), and the amino acid arrangement affects the complex size. Cytotoxicity studies show that the complexes are effective at inhibiting the growth of A549 lung cancer cells and EAR16-II-EPT is the most effective. Interestingly, the complexes formulated with EAR16-II and EAR8-II become less active against MCF-7 breast cancer cells, but more hemolytic than the other two complexes. This work provides essential information to optimize self-assembling peptide-based drug delivery for cancer therapy.


Assuntos
Arginina/química , Portadores de Fármacos , Sequência de Aminoácidos , Humanos , Oligopeptídeos/química , Peptídeos/química
16.
Genet Mol Res ; 14(2): 5793-803, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26125778

RESUMO

We observed the influence of different concentrations of Rhizoma paridis total saponins (RPTS) on the apoptosis of colorectal cancer cells and explored the internal mechanism involved. We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis. We also cultured SW480 colorectal cancer cells using different concentrations of RPTS (10, 20, 40, and 80 µg/ mL), and observed the effect of RPTS on SW480 cell morphology under a fluorescence inverted microscope. We detected serum IL-6 using the polymerase chain reaction and the expression of JAK-STAT3 protein by western blot. After treating SW480 with RPTS and Hoechst 33258 dyeing, we found that the typical apoptosis morphology had changed. Secretion of IL-6 in the serum decreased significantly (P < 0.05), and STAT3 levels were reduced. RPTS can significantly promote apoptosis in SW480 colorectal cancer cells. The mechanism may be that it suppresses the secretion of IL-6 and inhibits the IL-6/JAK-STAT3 protein signaling pathway.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Interleucina-6/biossíntese , Janus Quinases/biossíntese , Saponinas/administração & dosagem , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/genética , Janus Quinases/genética , Fosforilação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética , Saponinas/química , Transdução de Sinais/efeitos dos fármacos
18.
Diabetes Obes Metab ; 17(5): 495-504, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25656402

RESUMO

AIM: To investigate the in vivo metabolic effects of treatment with BPR0912, a novel and potent peripheral cannabinoid receptor 1 (CB1R) antagonist, on both normal mice and diet-induced obese (DIO) mice. METHODS: The acute peripheral effects of BPR0912 administration on gastrointestinal transit and energy metabolism in normal mice were investigated. The effects of chronic BPR0912 treatment were compared with those of rimonabant using DIO mice. Alterations to body weight and biochemical and metabolic variables were determined. RESULTS: Acute treatment with BPR0912 did not alter food intake or energy metabolism, but efficiently reversed CB1R-mediated gastrointestinal delay. Chronic treatment of DIO mice with BPR0912 showed that BPR0912 exerts a food intake-independent mechanism, which contributes to weight loss. Genes involved in ß-oxidation and thermogenesis were upregulated in white adipose tissue (WAT) in addition to increased lipolytic activity, whereas Ucp1 expression was induced in brown adipose tissue (BAT) and body temperature was elevated. Expression of the ß2-adrenoceptor was specifically elevated in both WAT and BAT in a manner dependent on the BPR0912 dose. Lastly, chronic BPR0912 treatment was more efficacious than rimonabant in reducing hepatic triglycerides in DIO mice. CONCLUSION: BPR0912 exhibits significant in vivo efficacy in inducing food intake-independent weight loss in DIO mice, while tending to reduce their hepatic steatosis. The thermogenic effects of BPR0912, as well as its modulation of protein and gene expression patterns in WAT and BAT, may enhance its efficacy as an anti-obesity agent. The results of the present study support the benefits of the use of peripheral CB1R antagonists to combat metabolic disorders.


Assuntos
Fármacos Antiobesidade/farmacologia , Antagonistas de Receptores de Canabinoides/farmacologia , Obesidade/tratamento farmacológico , Pirazóis/farmacologia , Receptor CB1 de Canabinoide/antagonistas & inibidores , Termogênese/efeitos dos fármacos , Tiofenos/farmacologia , Redução de Peso/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Canais Iônicos/genética , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/genética , Obesidade/complicações , Piperidinas/farmacologia , Rimonabanto , Proteína Desacopladora 1
19.
Pharmacopsychiatry ; 48(2): 58-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25626060

RESUMO

INTRODUCTION: Serotonin may play an important role in the pathology of major depressive disorder (MDD). However, the relationship between serotonin transporter (SERT) availability and the medical outcome of antidepressant treatment is uncertain. METHODS: In this naturalistic study, SERT availability (expressed as the specific uptake ratio, SUR) in the midbrain of 17 drug-free patients with MDD and 17 controls matched for age and gender was measured using SPECT with [(123)I]ADAM. The severity of MDD was measured by the Hamilton Depression Rating Scale before, and after 6 weeks of non-standardized antidepressant treatment. RESULTS: A total of 12 patients completed the study. The SUR of the patients with MDD was significantly lower than that of the healthy controls. The SUR of SERT was not found to have a linear relationship with the treatment outcome; however, supplemental analysis found a curvilinear relationship between treatment outcome and the SUR of SERT. DISCUSSION: The findings indicate that the SUR of SERT is lower in patients with MDD; however it did not predict treatment outcome in a linear fashion. Studies with larger sample sizes are required.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Mesencéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adulto , Estudos de Casos e Controles , Cinanserina/análogos & derivados , Cinanserina/metabolismo , Feminino , Neuroimagem Funcional , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Adulto Jovem
20.
Genet Mol Res ; 14(4): 18384-95, 2015 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-26782486

RESUMO

No information is available on segregation analysis of DNA markers involving both pollen and self-progeny. Therefore, we used capillary electrophoresis- and fluorescence-based DNA fingerprinting together with single pollen collection and polymerase chain reaction (PCR) to investigate simple sequence repeat (SSR) marker segregation among 964 single pollens and 288 self-progenies (S1) of sugarcane cultivar LCP 85-384. Twenty SSR DNA fragments (alleles) were amplified by five polymorphic SSR markers. Only one non-parental SSR allele was observed in 2392 PCRs. SSR allele inheritance was in accordance with Mendelian laws of segregation and independent assortment. Highly significant correlation coefficients were found between frequencies of observed and expected genotypes in pollen and S1 populations. Within the S1 population, the most frequent genotype of each SSR marker was the parental genotype of the same marker. The number of genotypes was higher in pollen than S1 population. PIC values of the five SSR markers were greater in pollen than S1 populations. Eleven of 20 SSR alleles (55%) were segregated in accordance with Mendelian segregation ratios expected from pollen and S1 populations of a 2n = 10x polyploid. Six of 20 SSR alleles were segregated in a 3:1 (presence:absence) ratio and were simplex markers. Four and one alleles were segregated in 77:4 and 143:1 ratios and considered duplex and triplex markers, respectively. Segregation ratios of remaining alleles were unexplainable. The results provide information about selection of crossing parents, estimation of seedling population optimal size, and promotion of efficient selection, which may be valuable for sugarcane breeders.


Assuntos
Segregação de Cromossomos , Repetições de Microssatélites , Poliploidia , Saccharum/genética , Alelos , Genótipo , Pólen/genética
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