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1.
JAMA Intern Med ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683310

RESUMO

Importance: Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown. Objective: To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease. Design, Setting, and Participants: This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies-147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020. Exposures: Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish. Main Outcomes and Measures: Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death). Results: Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]). Conclusions and Relevance: Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

2.
Andrologia ; 53(4): e13923, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33583046

RESUMO

This study established an oligoasthenospermic rat model using tripterygium glycosides (TGs) and investigated the mechanism by which Qilin pills (QLPs) ameliorate reproductive hypofunction. Thirty-two male Sprague Dawley rats were allocated to four equal-sized groups: (1) the control group received continuous physiological levels of saline; (2) the oligoasthenospermia model group was induced with TGs by daily intragastric administration for 28 days; (3 and 4) oligoasthenospermic rats were treated intragastrically with low dose (1.62 g kg-1  d-1 ) and high dose (3.24 g kg-1  d-1 ) of QLPs once daily for 60 days. The QLP-treated rats showed a marked increase (p < .05) in testicular mass, testicular index and semen parameters compared with the untreated rats. Histopathologically, the QLP-treated groups exhibited restored seminiferous tubules in contrast to the model group. Reactive oxygen species and malondialdehyde levels were dramatically decreased (p < .05) in the testes of the QLP-treated rats. QLP treatment partly reverted (p < .05) the circulatory levels of reproductive hormones (FSH, LH, testosterone, prolactin and SHBG) and hepatic and renal function (AST, Cr and urea). Our results showed that oral QLP treatment had a curative effect on the testicular mass, sperm quality, testicular pathomorphology, antioxidants, plasmatic hormones, and liver and renal function of rats.

3.
Cancer Cell Int ; 21(1): 71, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33482821

RESUMO

BACKGROUND: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. METHODS: Quantitative real-time PCR was used to evaluate miR-335-5p levels in GC cell lines and tissues. MTT and colony formation assays were used to detect cell proliferation, and Transwell and wound-healing assays were used to evaluate the invasion and migration of GC cells. The correlation between levels of miR-335-5p and the cell cycle-related target gene mitogen-activated protein kinase 10 (MAPK10) in GC was analyzed. In addition, the candidate target was evaluated by a luciferase reporter assay, qRT-PCR, and western blotting. RESULTS: The levels of miR-335-5p were downregulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited the proliferation and migration of GC cells and induced apoptosis. Additionally, miR-335-5p arrested the cell cycle at the G1/S phase in GC cells in vitro. Levels of miR-335-5p and the cell cycle-related target gene MAPK10 in GC were correlated, and MAPK10 was directly targeted by miR-335-5p. CONCLUSIONS: These data suggest that miR-335-5p is a tumor suppressor and acts via MAPK10 to inhibit GC progression.

4.
J Psychosom Obstet Gynaecol ; : 1-9, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32498640

RESUMO

Purpose: The applicability of the Zung self-rating depression scale (SDS) in pregnancy is unknown. We aimed to identify redundant items and evaluate the Zung SDS's structural validity.Method: Two samples of pregnant women were invited from two districts in Shanghai (Yangpu sample, n = 6468 and Huangpu sample, n = 402). The Yangpu sample was randomly split into YGroup1/2/3. Item's properties were evaluated via the item response theory in YGroup1. Exploratory and confirmatory factor analyses were correspondingly executed in YGroup2 and YGroup3. Those items with discrimination parameter (α) lower than 0.65 or factor loading smaller than 0.4 were deleted from the scale. The final structure was validated in the Huangpu sample.Results: Items 4 (sleep), 7 (weight loss), 8 (constipation) and 9 (tachyarrhythmia) exhibited low discrimination power. Items 2 (diurnal variation), 5 (appetite), 10 (fatigue) and 19 (suicide idea) made a low contribution to all factors. A three-factor model was eventually constructed as cognitive (Items 14, 16, 17, 18 and 20), psychomotor (Items 6, 11 and 12) and affective (Items 1, 3, 13 and 15).Conclusion: The Zung SDS needs modification before applied to pregnant women in China. The items describing the overlap symptoms of the physical change in pregnancy and mood disorder should be deleted.

5.
BMC Complement Med Ther ; 20(1): 42, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046715

RESUMO

BACKGROUND: Qilin pills (QLPs), a classic Traditional Chinese Medicine (TCM) formula for treating male infertility, effectively improve semen quality in clinical trials. This study was designed to evaluate the effects of QLPs on spermatogenesis, reproductive hormones, oxidative stress, and the testis-specific serinekinase-2 (TSSK2) gene in a rat model of oligoasthenospermia. METHODS: Forty adult male Sprague-Dawley (SD) rats were randomly divided into four groups. The rat model with oligoasthenospermia was generated by intragastric administration of tripterygium glycosides (TGs) once daily for 4 weeks. Then, two treatment groups were given different doses (1.62 g/kg and 3.24 g/kg) of QLPs once daily for 60 days. Sperm parameters, testicular histology and reproductive hormone measurements, oxidative stress tests, and TSSK2 expression tests were carried out. RESULTS: QLPs effectively improved semen parameters and testicular histology; restored the levels of FSH, LH, PRL, fT, and SHBG; reduced the levels of oxidative stress products (ROS and MDA); increased testicular SOD activity; and restored the expression of spermatogenesis-related gene TSSK2. CONCLUSION: QLPs have a therapeutic effect on a rat model of oligoasthenospermia, and this effect is manifested as improvement of semen quality and testis histology, gonadal axis stability, decreased oxidative stress, and the regulation of testis-specific spermatogenesis-related gene TSSK2.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hormônios/metabolismo , Oligospermia/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/genética , Espermatogênese/efeitos dos fármacos , Animais , China , Modelos Animais de Doenças , Gonadotropinas Hipofisárias/metabolismo , Masculino , Medicina Tradicional Chinesa , Prolactina/metabolismo , Ratos , Ratos Sprague-Dawley , Globulina de Ligação a Hormônio Sexual/metabolismo , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/metabolismo
6.
J Thromb Thrombolysis ; 49(4): 591-601, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31975323

RESUMO

F8 intron 22 inversion (Inv22) accounts for about 40% of severe hemophilia A (HA) cases and is mainly genotyped by long-distance PCR (LD-PCR) or inverse-PCR (I-PCR). These methods require long separation times or enzymatic digestion. We aimed to shorten the separation time of LD-PCR. Long-read sequencing was applied for LD-PCR products from 20 Inv22 patients and 4 controls to validate the differences between products generated using P-Q and P-B primer pairs in LD-PCR. We then confirmed two unique regions (chrX: 154879481-154880814, chrX: 155376388-155376505, GRCh38) in the PCR products from P-Q and P-B primer pairs, respectively. The nested PCR P1, Q1, and B1 primers were located near the homologous sequence and two unique regions, respectively. The P1-Q1 and P1-B1 primer pairs generated 1621 bp and 540 bp fragments, respectively, and the Inv22 carriers produced both fragments. In total, 228 previously diagnosed subjects including 39 Inv22 carriers, 52 Inv22 patients, 82 Inv22 negative males, and 55 Inv22 negative females were genotyped using nested PCR, and the results revealed excellent sensitivity and specificity (100 and 100%, respectively). The separation time was shortened from 5 to 0.5 h. Therefore, we present a rapid genotyping method for F8 Inv22 by nested PCR based on LD-PCR.

7.
Neurosci Lett ; 717: 134722, 2020 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-31877334

RESUMO

Epidemiological evidence of the relationship between vitamin D receptor (VDR) rs2228570 (FokI) polymorphism and the susceptibility of Parkinson's disease (PD) is inconsistent, partially due to between-study variations in sample size, age, male/female ratio, and 25-OH vitamin D3 levels. Here, we examined the association between VDR rs2228570 polymorphism and PD risk in a Chinese population. A total of 940 subjects were included in this study, which consisted of 470 patients with sporadic PD (mean age: 62.65 ±â€¯9.34 years) and 470 healthy control subjects (mean age: 62.70 ±â€¯9.42 years). A TaqMan genotyping assay was applied to identify VDR rs2228570 polymorphism. The Hardy-Weinberg Equilibrium (HWE) was calculated for both groups with a Chi-square (χ2) test. The sample power was calculated with Power V3.0. The crude odds ratios (ORs) and 95 % confidence intervals (CIs) for sporadic PD in relation to VDR rs2228570 polymorphism were calculated using a logistic regression analysis. The minor A allele frequency was 0.42 and 0.48 in the control and PD groups, respectively. A allele carriers of rs2228570 were associated with an increased overall risk of PD as well as early-onset PD (EOPD) in the allele and additive genetic models. Stratification analyses showed similar results in male subjects in the allele and additive genetic models, but only in the additive genetic model in female subjects. In conclusion, our study suggests that the VDR rs2228570 A allele is associated with an increased risk of PD in a Chinese population. Further investigations with larger sample sizes with consideration of gene-gene and gene-environment interaction are needed to further elucidate the role of vitamin D receptors in the development of PD.


Assuntos
Predisposição Genética para Doença/genética , Doença de Parkinson/genética , Receptores de Calcitriol/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Frequência do Gene/genética , Interação Gene-Ambiente , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
9.
Lancet Diabetes Endocrinol ; 6(10): 798-808, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170949

RESUMO

BACKGROUND: Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use. METHODS: In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys. FINDINGS: Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines. INTERPRETATION: Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes. FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).


Assuntos
Diabetes Mellitus/economia , Medicamentos Essenciais/economia , Status Econômico , Hipoglicemiantes/economia , Adulto , Idoso , Custos e Análise de Custo , Diabetes Mellitus/epidemiologia , Acesso aos Serviços de Saúde , Humanos , Insulina/economia , Metformina/economia , Pessoa de Meia-Idade , Estudos Prospectivos , População Rural , Compostos de Sulfonilureia/economia , População Urbana
10.
Lancet ; 390(10113): 2643-2654, 2017 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-28943267

RESUMO

BACKGROUND: Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. METHODS: In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering. FINDINGS: Between Jan 1, 2003, and Dec 31, 2010, 168 916 participants were enrolled, of whom 141 945 completed the IPAQ. Analyses were limited to the 130 843 participants without pre-existing CVD. Compared with low physical activity (<600 metabolic equivalents [MET] × minutes per week or <150 minutes per week of moderate intensity physical activity), moderate (600-3000 MET × minutes or 150-750 minutes per week) and high physical activity (>3000 MET × minutes or >750 minutes per week) were associated with graded reduction in mortality (hazard ratio 0·80, 95% CI 0·74-0·87 and 0·65, 0·60-0·71; p<0·0001 for trend), and major CVD (0·86, 0·78-0·93; p<0·001 for trend). Higher physical activity was associated with lower risk of CVD and mortality in high-income, middle-income, and low-income countries. The adjusted population attributable fraction for not meeting the physical activity guidelines was 8·0% for mortality and 4·6% for major CVD, and for not meeting high physical activity was 13·0% for mortality and 9·5% for major CVD. Both recreational and non-recreational physical activity were associated with benefits. INTERPRETATION: Higher recreational and non-recreational physical activity was associated with a lower risk of mortality and CVD events in individuals from low-income, middle-income, and high-income countries. Increasing physical activity is a simple, widely applicable, low cost global strategy that could reduce deaths and CVD in middle age. FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Ontario SPOR Support Unit, Ontario Ministry of Health and Long-Term Care, AstraZeneca, Sanofi-Aventis, Boehringer Ingelheim, Servier, GSK, Novartis, King Pharma, and national and local organisations in participating countries that are listed at the end of the Article.


Assuntos
Doenças Cardiovasculares/epidemiologia , Exercício Físico , Mortalidade , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Países Desenvolvidos/estatística & dados numéricos , Países em Desenvolvimento/estatística & dados numéricos , Feminino , Saúde Global/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos
11.
Sci China Life Sci ; 60(9): 968-979, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28840532

RESUMO

Genetic modification of large DNA fragments (gene clusters) is of great importance in synthetic biology and combinatorial biosynthesis as it facilitates rational design and modification of natural products to increase their value and productivity. In this study, we developed a method for scarless and precise modification of large gene clusters by using RecET/RED-mediated polymerase chain reaction (PCR) targeting combined with Gibson assembly. In this strategy, the biosynthetic genes for peptidyl moieties (HPHT) in the nikkomycin biosynthetic gene cluster were replaced with those for carbamoylpolyoxamic acid (CPOAA) from the polyoxin biosynthetic gene cluster to generate a ~40 kb hybrid gene cluster in Escherichia coli with a reusable targeting cassette. The reconstructed cluster was introduced into Streptomyces lividans TK23 for heterologous expression and the expected hybrid antibiotic, polynik A, was obtained and verified. This study provides an efficient strategy for gene cluster reconstruction and modification that could be applied in synthetic biology and combinatory biosynthesis to synthesize novel bioactive metabolites or to improve antibiotic production.


Assuntos
Aminoglicosídeos/genética , Engenharia Genética/métodos , Família Multigênica/genética , Streptomyces/genética , Antifúngicos/metabolismo , Vias Biossintéticas/genética , Ácido Oxâmico/análogos & derivados , Nucleosídeos de Pirimidina/genética , Streptomyces/metabolismo
12.
Pharm Biol ; 55(1): 299-305, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27937670

RESUMO

CONTEXT: Griflola frondosa (Fr) S.F. Gray (Meripilaceae) (GF) is a medical mushroom, and its regulation of the immune system is of interest for the treatment of mood disorders. α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors are the central mediator for the treatment of depression. OBJECTIVE: This study examines the antidepressant effects of GF and the role of AMPA in these antidepressant effects. MATERIALS AND METHODS: The CD-1 mice were fed with GF- or Pleurotus ostreatus [(Jacq.: Fr) Kumm (Pleurotaceae)] (PO)-containing food for 1 day or 5 days. The antidepressant effects was determined in the tail suspension test (TST), forced swim test (FST), and open field test (OFT). The involvement of AMPA receptors was determined by the application of the AMPA-specific blocker GYKI 52466. RESULTS: Treatments with 20%, 33% or 50% of GF-containing food significantly decreased the immobility time (63.6, 56.9, and 52.0% in TST; and 50.8, 43.2, and 38.2% in FST) after 1 day and (62.3, 51.8, and 52.8% in TST; and 49.5, 45.1, and 40.3% in FST) after 5 days. GF-containing food did not cause hyperactive effects in the OFT. The antidepressant effects of the 33% of GF-containing food (down-to 51.3% in 1-day TST and 46.8% in 5-day FST) were significantly stronger than that of the 33% of PO-containing food (down-to 85.5% in 1-day TST and 82.0% in 5-day FST). AMPA-specific blocker GYKI 52466 was able to block the antidepressant effects of the GF-containing food. CONCLUSION: GF demonstrated the potential as a safe medical food supplement for the patient with depression.


Assuntos
Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Agonistas de Aminoácidos Excitatórios/farmacologia , Grifola/química , Atividade Motora/efeitos dos fármacos , Receptores de AMPA/agonistas , Animais , Antidepressivos/isolamento & purificação , Benzodiazepinas/farmacologia , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Agonistas de Aminoácidos Excitatórios/isolamento & purificação , Antagonistas de Aminoácidos Excitatórios/farmacologia , Camundongos , Receptores de AMPA/metabolismo , Natação , Fatores de Tempo
13.
Behav Brain Res ; 317: 263-271, 2017 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-27693847

RESUMO

Lentinan (LNT) is an immune regulator and its potential and mechanism for the treatment of mood disorder is of our interest. Dectin-1 is a ß-glucan (including LNT) receptor that regulates immune functions in many immune cell types. Cumulative evidence has suggested that the glutamatergic system seems to play an important role in the treatment of depression. Here, we studied the antidepressant-like effects of LNT and its therapeutical target in regulating the functions of AMPA receptors. We found that 60min treatment with LNT leads to a significant antidepressant-like effect in the tail suspension test (TST) and the forced swim test (FST) in mice. The antidepressant-like effects of LNT in TST and FST remained after 1day or 5days of injections. Additionally, LNT did not show a hyperactive effect in the open field test. Dectin-1 receptor levels were increased after LNT treatment for 5days and the specific Dectin-1 inhibitor laminarin was able to block the antidepressant-like effects of LNT. After 5days of treatment, LNT enhanced p-GluR1 (S845) in the prefrontal cortex (PFC); however, the total GluR1, GluR2, and GluR3 expression levels remained unchanged. We also found that the AMPA-specific blocker GYKI 52466 was able to block the antidepressant-like effects of LNT. This study identified LNT as a novel antidepressant with clinical potential and a new antidepressant mechanism for regulating prefrontal Dectin-1/AMPA receptor signaling.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Depressão/tratamento farmacológico , Lectinas Tipo C/metabolismo , Lentinano/uso terapêutico , Córtex Pré-Frontal/efeitos dos fármacos , Receptores de AMPA/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Animais , Antidepressivos Tricíclicos , Benzodiazepinas/farmacologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Elevação dos Membros Posteriores , Imipramina/farmacologia , Lentinano/farmacologia , Masculino , Camundongos , Natação/psicologia , Fatores de Tempo , Receptor 2 Toll-Like/metabolismo
14.
Lancet ; 390(10113): 2643-2654, 2017. tab, graf
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1064601

RESUMO

Background Physical activity has a protective effect against cardiovascular disease (CVD) in high-income countries, where physical activity is mainly recreational, but it is not known if this is also observed in lower-income countries, where physical activity is mainly non-recreational. We examined whether different amounts and types of physical activity are associated with lower mortality and CVD in countries at different economic levels. Methods In this prospective cohort study, we recruited participants from 17 countries (Canada, Sweden, United Arab Emirates, Argentina, Brazil, Chile, Poland, Turkey, Malaysia, South Africa, China, Colombia, Iran, Bangladesh, India, Pakistan, and Zimbabwe). Within each country, urban and rural areas in and around selected cities and towns were identified to reflect the geographical diversity. Within these communities, we invited individuals aged between 35 and 70 years who intended to live at their current address for at least another 4 years. Total physical activity was assessed using the International Physical Activity Questionnaire (IPQA). Participants with pre-existing CVD were excluded from the analyses. Mortality and CVD were recorded during a mean of 6·9 years of follow-up. Primary clinical outcomes during follow-up were mortality plus major CVD (CVD mortality, incident myocardial infarction, stroke, or heart failure), either as a composite or separately. The effects of physical activity on mortality and CVD were adjusted for sociodemographic factors and other risk factors taking into account household, community, and country clustering.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle
15.
Wei Sheng Yan Jiu ; 45(2): 273-9, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27301229

RESUMO

OBJECTIVE: To grasp research status and the revolution of Journal of Hygiene Research since started publishing, and also track research hot spots and developing trends of this field. METHODS: Using the method of bibliometrics and information visualization software CiteSpace III, quantities of published literature, supported funds, institutions, authors and keywords from 6775 articles published in Journal of Hygiene Research from 1972 to 2014 were analyzed. RESULTS: Amount of literatures published on Journal of Hygiene Research increased wave upon wave, the peak appeared in 1995. Institutions of Chinese Center for Disease Control and Prevention, such as National Institute for Nutrition and Health, Institute of Environmental Health and Related Product Safety, National Institute of Occupational Health and Poison Control and some medical colleges were the most productive. The scholars with the most number of publications were YANG Xiaoguang, YIN Shian and PIAO Jianhua, the researcher of National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, with more than 75 articles were published. The research contents included influencing factors, related concepts, diseases, methods and objects. "mutagenicity", "apoptosis", "lead poisoning", "HPLC" and "rat" were research focuses in this field. CONCLUSION: There were lots of matter and cooperation in the articles published on Journal of Hygiene Research. The centers for disease control and prevention in different regions and universities pay attention to the coorperation, research teams with members of various ages collaborate and grow together, form a close, complex collaborative network among authors, which promote the development of the magazine and research fields together.


Assuntos
Bibliometria , Pesquisa Biomédica/tendências , Publicações Periódicas como Assunto , Higiene
16.
Gynecol Endocrinol ; 32(10): 848-851, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27227658

RESUMO

High-density lipoprotein (HDL) is an important factor associated with the increasing risk of future ischaemic heart disease. In this study, we analyzed serum HDL2b level in the patients with polycystic ovary syndrome (PCOS). Total of 60 female patients with PCOS was enrolled for assessment and another 60 non-PCOS females with matched age and weight were selected as control. A highly sensitive microfluidic chip was employed to analyze the serum HDL subfractions. Serum HDL2b and HDL2b/HDL ratio were decreased in PCOS group than those in the control group (p < 0.05). Pearson correlation analysis revealed that serum HDL2b level was negatively correlated with body mass index, waist circumference, waist-to-hip ratio, INS0, HOMA-IR, T, estradiol, triglyceride (TG) and low-density lipoprotein (LDL)-C; and the ratio of HDL2b/HDL was negatively correlated with T, TG and LDL-C. Stepwise multiple regression analyses showed a reverse correlation for HDL2b and its ratio to HDL with hyperandrogenism. The results suggested that a reduction of serum HDL2b and its ratio to total serum HDL in PCOS patients by using the microfluidic chip method assessment. Hyperandrogenism was the main factor to affect HDL2b and its ratio to total HDL in PCOS patients, and it might increase the incidence of atherosclerosis as well as the risk of coronary heart disease.


Assuntos
Lipoproteínas HDL2/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos
17.
Hum Reprod ; 31(4): 763-73, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26851603

RESUMO

STUDY QUESTION: What is the effect of human ovarian tissue cryopreservation on single follicular development in vitro? SUMMARY ANSWER: Vitrification had a greater negative effect on growth and gene expression of human ovarian follicles when compared with fresh follicles. WHAT IS KNOWN ALREADY: For human ovarian cortex cryopreservation, the conventional option is slow freezing while more recently vitrification has been demonstrated to maintain good quality and function of ovarian tissues. STUDY DESIGN, SIZE, DURATION: Ovarian tissues were collected from 11 patients. For every patient, the ovarian cortex was divided into three samples: Fresh, slow-rate freezing (Slow) and vitrification (Vit). Tissue histology was performed and follicles were isolated for single-cell mRNA analysis and in vitro culture (IVC) in 1% alginate for 8 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicle morphology was assessed with hematoxylin-eosin analysis. Follicles were individually embedded in alginate (1% w/v) and cultured in vitro for 8 days. Follicle survival and growth were assessed by microscopy. Follicle viability was observed after Calcein-AM and ethidium homodimer-I (Ca-AM/EthD-I) staining. Expression of genes, including GDF9 (growth differentiation factor 9), BMP15 (bone morphogenetic protein 15) and ZP3 (zona pellucida glycoprotein 3) in oocytes and AMH (anti-Mullerian hormone), FSHR (FSH receptor), CYP11A (cholesterol side-chain cleavage cytochrome P450) and STAR (steroidogenic acute regulatory protein) in GCs, was evaluated by single-cell mRNA analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 129 follicles were separated from ovarian cortex (Fresh n = 44; Slow n = 40; Vit n = 45). The percentage of damaged oocytes and granulosa cells was significantly higher in both the Slow and Vit groups, as compared with Fresh control (P< 0.05). The growth of follicles in vitro was significantly delayed in the Vit group compared with the Fresh group (P< 0.05). Both slow freezing (P< 0.05) and vitrification (P< 0.05) down-regulated the mRNA levels of ZP3 and CYP11A compared with Fresh group, while there was no significant difference between the Slow and Vit groups (P> 0.05). Vitrification also down-regulates AMH mRNA levels compared with Fresh group (P< 0.05). LIMITATIONS, REASONS FOR CAUTION: Only short-term IVC studies (8 days) are reported. Further study should be performed to examine and improve follicular development in a long-term culture system after cryopreservation. WIDER IMPLICATIONS OF THE FINDINGS: This is the first comparison of gene expression and growth of single human ovarian follicles in vitro after either slow freezing or vitrification. With the decreased gene expression and growth during IVC, damage by cryopreservation still exists and needs to be minimized during the long-term IVC of follicles in the future for eventual clinical application. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (31230047, 81571386, 81471508, 31429004 and 81501247), National Natural Science Foundation of Beijing (7142166) and Mega-projects of Science Research for the 12th five-year plan (2012ba132b05). There are no conflicts of interest to declare.


Assuntos
Criopreservação , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Maturação in Vitro de Oócitos , Folículo Ovariano/citologia , Adulto , Hormônio Antimülleriano/genética , Hormônio Antimülleriano/metabolismo , Biomarcadores/metabolismo , Sobrevivência Celular , China , Enzima de Clivagem da Cadeia Lateral do Colesterol , Feminino , Congelamento , Células da Granulosa/fisiologia , Humanos , Folículo Ovariano/enzimologia , Folículo Ovariano/metabolismo , RNA Mensageiro/metabolismo , Análise de Célula Única , Fatores de Tempo , Técnicas de Cultura de Tecidos , Vitrificação , Glicoproteínas da Zona Pelúcida/genética , Glicoproteínas da Zona Pelúcida/metabolismo
18.
EBioMedicine ; 3: 155-162, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870826

RESUMO

BACKGROUND: Brain glucose hypometabolism is an invariant feature and has significant diagnostic value for Alzheimer's disease. Thiamine diphosphate (TDP) is a critical coenzyme for glucose metabolism and significantly reduced in brain and blood samples of patients with Alzheimer's disease (AD). AIMS: To explore the diagnostic value of the measurement of blood thiamine metabolites for AD. METHODS: Blood TDP, thiamine monophosphate, and thiamine levels were detected using high performance liquid chromatography (HPLC). The study included the exploration and validation phases. In the exploration phase, the samples of 338 control subjects and 43 AD patients were utilized to establish the models for AD diagnosis assayed by receiver operating characteristic (ROC) curve, including the variable γ that represents the best combination of thiamine metabolites and age to predict the possibility of AD. In the validation phase, the values of models were further tested for AD diagnosis using samples of 861 control subjects, 81 AD patients, 70 vascular dementia patients, and 13 frontotemporal dementia patients. RESULTS: TDP and the γ exhibited significant and consistent values for AD diagnosis in both exploration and validation phases. TDP had 0.843 and 0.837 of the areas under ROC curve (AUCs), 77.4% and 81.5% of sensitivities, and 78.1% and 77.2% of specificities respectively in the exploration and validation phases. The γ had 0.938 and 0.910 of AUCs, 81.4% and 80.2% of sensitivities, and 90.5% and 87.2% of specificities respectively in the exploration and validation phases. TDP and the γ can effectively distinguish AD from vascular dementia (64.3% for TDP, 67.1% for γ) and frontotemporal dementia (84.6% for TDP, 100.0% for γ). Interpretation. The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Metaboloma , Metabolômica , Tiamina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/genética , Apolipoproteínas E/genética , Biomarcadores , Feminino , Genótipo , Humanos , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença , Tiamina/sangue , Tiamina Monofosfato , Tiamina Pirofosfato
19.
Hum Reprod ; 29(3): 568-76, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24408318

RESUMO

STUDY QUESTION: What is the effect of basic fibroblast growth factor (bFGF) on the growth of individual early human follicles in a three-dimensional (3D) culture system in vitro? SUMMARY ANSWER: The addition of 200 ng bFGF/ml improves human early follicle growth, survival and viability during growth in vitro. WHAT IS KNOWN ALREADY: It has been demonstrated that bFGF enhances primordial follicle development in human ovarian tissue culture. However, the growth and survival of individual early follicles in encapsulated 3D culture have not been reported. STUDY DESIGN, SIZE, DURATION: The maturation in vitro of human ovarian follicles was investigated. Ovarian tissue (n= 11) was obtained from 11 women during laparoscopic surgery for gynecological disease, after obtaining written informed consent. One hundred and fifty-four early follicles were isolated by enzymic digestion and mechanical disruption. They were individually encapsulated into alginate (1% w/v) and randomly assigned to be cultured with 0, 100, 200 or 300 ng bFGF/ml for 8 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Individual follicles were cultured in minimum essential medium α (αMEM) supplemented with bFGF. Follicle survival and growth were assessed by microscopy. Follicle viability was evaluated under confocal laser scanning microscope following Calcein-AM and Ethidium homodimer-I (Ca-AM/EthD-I) staining. MAIN RESULTS AND THE ROLE OF CHANCE: After 8 days in culture, all 154 follicles had increased in size. The diameter and survival rate of the follicles and the percentage with good viability were significantly higher in the group cultured with 200 ng bFGF/ml than in the group without bFGF (P < 0.05). The percentage of follicles in the pre-antral stage was significantly higher in the 200 ng bFGF/ml group than in the group without bFGF (P < 0.05), while the percentages of primordial and primary follicles were significantly lower (P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The study focuses on the effect of bFGF on the development of individual human early follicles in 3D culture in vitro and has limited ability to reveal the specific effect of bFGF at each different stage. The findings highlight the need to improve the acquisition and isolation of human ovarian follicles. WIDER IMPLICATIONS OF THE FINDINGS: The in vitro 3D culture of human follicles with appropriate dosage of bFGF offers an effective method to investigate their development. Moreover, it allows early follicles to be cultured to an advanced stage and therefore has the potential to become an important source of mature oocytes for assisted reproductive technology; particularly as an option for fertility preservation in women, including patients with cancer. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Basic Research Program of China (2011|CB944504, 2011CB944503) and the National Natural Science Foundation of China (81200470, 81000275, 31230047, 8110197). There are no conflicts of interest to declare.


Assuntos
Fator 2 de Crescimento de Fibroblastos/farmacologia , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Adulto , Feminino , Humanos , Técnicas de Cultura de Tecidos/métodos
20.
J Pain Symptom Manage ; 47(2): 231-44, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23870414

RESUMO

CONTEXT: North American studies have documented practice variations and deficiencies in end-of-life (EOL) cancer care, such as trends toward treating dying patients aggressively and disparities in access to palliative care or hospice services. OBJECTIVES: To assess the frequency of aggressive health care usage at the EOL and identify factors associated with receiving aggressive care among patients who died of colorectal cancer. METHODS: Data from the Alberta Cancer Registry, in/outpatient hospital records, and cancer electronic medical records were linked. Death in an acute care hospital, chemotherapy use in the last 14 days of life, more than one emergency room (ER) visit, more than one hospital admission, and any intensive care unit (ICU) admission in the last 30 days of life were used as indicators of aggressive care. Logistic regression was used to identify risk factors associated with each indicator. RESULTS: A total of 2074 patients were included: 50.1% died in an acute care hospital; 3.7% received chemotherapy in the last 14 days of life; and 12.5% had multiple ER visits, 9.5% had multiple hospitalizations, and 2.2% had an ICU admission during the last 30 days of life. Age had the strongest association with chemotherapy use. Geographical region of residence had the strongest association with multiple ER visits and hospitalizations and dying in an acute care hospital. Tumor stage and duration of disease were associated with the ICU admission. CONCLUSION: The percentage of patients who died in an acute care hospital is higher than the 17% U.S. benchmark. Other indicators of receiving aggressive EOL care are consistent with existing care quality benchmarks. The considerable regional variation, however, indicates potential for system improvements.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Assistência Terminal , Adulto , Idoso , Idoso de 80 Anos ou mais , Alberta , Antineoplásicos/administração & dosagem , Cuidados Críticos/tendências , Serviços Médicos de Emergência/tendências , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Estudos Retrospectivos , Assistência Terminal/tendências , Adulto Jovem
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