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2.
Drug Des Devel Ther ; 15: 1561-1568, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33883879

RESUMO

Background: A method for the determination of selinexor by UPLC-MS/MS was established to study the effect of posaconazole on the pharmacokinetics of selinexor in rats. Methods: The experiment rats were divided into group A (0.5% CMC-Na) and group B (posaconazole, 20 mg/kg), 6 rats in each group. 30 minutes after administration of 0.5% CMC-Na or posaconazole, all the rats were given selinexor (8 mg/kg), and plasma samples were collected. The plasma samples underwent acetonitrile protein precipitation, and were separated by UPLC on an Acquity UPLC BEH C18 column with gradient elution. Acetonitrile and 0.1% formic acid were used as the mobile phases. The analyte detection was used a Xevo TQ-S triple quadrupole tandem mass spectrometer and multiple reaction monitoring (MRM) for analyte monitoring. We use acetonitrile for protein precipitation. Results: Selinexor had good linearity (1.0-1000 ng/mL, r2 =0.996 2), and the accuracy and precision, recovery rate and matrix effects(ME) were also met the FDA approval guidelines. Compared with group A, the Cmax, AUC(0-t) and AUC(0-∞) of selinexor in group B increased by 60.33%, 48.28% and 48.27%, and Tmax increased by 53.92%, CLz/F reduced by 32.08%. Conclusion: This bioanalysis method had been applied to the study of drug interactions in rats. It was found that posaconazole significantly increased the concentration of selinexor in rats. Therefore, when selinexor and posaconazole are combined, we should pay attention to the possible drug-drug interactions to reduce adverse reactions.

3.
World J Pediatr ; 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914258

RESUMO

BACKGROUND: Infantile hydrocephalus (IHC) is commonly related to other central nervous system diseases, which may have adverse effects on prognosis. The causes of IHC are heterogeneous, and the genetic etiologies are not fully understood. This study aimed to analyze the genetic etiologies of an IHC cohort. METHODS: The data for 110 IHC patients who had received exome sequencing at the Clinical Genetic Center of the Children's Hospital of Fudan University between 2016 and 2019 were reviewed and analyzed retrospectively. An exome-wide association analysis (EWAS) was performed within this cohort using IHC as the study phenotype. RESULTS: Of the 110 IHC patients, a pathogenic or likely pathogenic variant was identified in 16 (15%) patients, spanning 13 genes. The genes were mainly associated with metabolic disorders, brain abnormalities, and genetic syndromes. IHC patients who had unclear clinical etiology were more likely to possess a genetic etiology. Based on previous studies and on our EWAS results, ZEB1, SBF2, and GNAI2 were over-represented among IHC patients and might affect the signaling pathways involved in IHC formation. CONCLUSIONS: Our study showed heterogeneous genetic etiologies in an IHC cohort. It is essential to perform genetic testing on IHC patients who have unclear clinical etiology, and genes associated with metabolic disorders, brain abnormalities, and genetic syndromes should be noted. In addition, when aiming to discover IHC susceptibility genes, genes that might influence the signaling pathways involved in IHC formation should be prioritized.

4.
Ying Yong Sheng Tai Xue Bao ; 32(3): 1069-1079, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33754574

RESUMO

Based on seasonal bottom trawl surveys in November 2015 (autumn), February (winter), May (spring) and August (summer) in 2016, the index of relative importance (IRI), Shannon index and Pianka index were used to analyze the breadth and overlap of spatio-temporal niche of major fish species in the Pishan waters off Zhejiang Province. Redundancy analysis and interspecific competition coefficient were used to examine the competition relationship and niche differentiation of those major fish species. The results showed that a total of 61 fish species were recorded throughout the year, which belonged to 13 orders, 29 families and 48 genera. A total of 19 species with IRI>100 were identified as major fish species. The temporal niche overlap value between Chelidonichthys kumu and Atule kalla was largest, indicating high temporal synchronization. Both the spatial niche overlap value and the spatio-temporal niche overlap value between Trpauchen vagina and Cynoglossus interruptus were largest, indicating that their spatial homology was high and that the use of spatial and temporal two-dimensional resource of both species were consistent. The percentage of species pairs with spatio-temporal niche overlap at the significant level (Qik>0.6) was only 5.8% in Pishan waters, indicating that the spatial and temporal distribution of those species were quite different. The overlap of spatio-temporal niche significantly varied across different seasons. The results of the interspecific competition coefficient were basically consistent with the niche overlap. Results of the redundancy analysis revealed the relationships between major fish species and environmental factors (temperature, salinity, dissolved oxygen), and further explained the niche diffe-rentiation among species.


Assuntos
Ecossistema , Peixes , Animais , China , Humanos , Salinidade , Estações do Ano
5.
J Clin Lipidol ; 15(1): 116-123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33414089

RESUMO

BACKGROUND: CYP27A1 is the disease-causing gene of cerebrotendinous xanthomatosis (CTX). As a treatable lipid storage disease, early treatment can improve the prognosis. However, CTX patients reported in the literature are mostly adult patients; the phenotype spectrum of CTX in the infantile population remains elusive. OBJECTIVE: We aimed to investigate the phenotype spectrum of infants who carried pathogenic or likely pathogenic variants in the CYP27A1 gene and were suspected of having CTX. METHODS: From June 2014 to May 2020, infants with pathogenic or likely pathogenic variants in CYP27A1 gene were enrolled, who underwent next-generation sequencing or Sanger sequencing in Children's Hospital of Fudan University. Patient characteristics, clinical treatments and outcomes were extracted from electronic medical records. RESULTS: A total of 17 patients with an average onset age of 8 (1-42) days were found. The average diagnosis age was ten months. Cholestasis was the dominant symptom of these infants. Thirteen variants were detected, of which c.379C > T was a hotspot variant (26.5% alleles, 9/34). Cholestatic CTX is usually underestimated, but it could be severe or even fatal in infancy. For outcomes, 5 suffered from liver failure (36%, 5/14), 1 still showed cholestasis (7%, 1/14), 7 were asymptomatic (50%, 7/14), and 1 presented seizure and developmental delay in later childhood (7%, 1/14). CONCLUSION: Based on this infantile cohort, we concluded that it is necessary to consider the possibility of CTX caused by CYP27A1 gene variants for infants with cholestasis.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33170459

RESUMO

We describe a case of a 32-year-old man who died due to bilateral re-expansion pulmonary edema (RPE) following the insertion a chest tube for unilateral spontaneous pneumothorax. Fifteen minutes after inserting the chest tube, the patient with right spontaneous pneumothorax was diagnosed with right re-expansion edema by chest radiograph. Although multiple treatments were administered, the patient died. However, the findings from autopsy showed bilateral RPE existed in the decedent but not unilateral RPE. Autopsy, microscopic examination, and clinical records concluded that the cause of death was acute cardiac and respiratory failure due to bilateral re-expansion pulmonary edema following unilateral spontaneous pneumothorax. Bilateral RPE due to a unilateral pneumothorax is quite rare in clinical and forensic practice. To the best of our knowledge, this is the first time that the pathological changes of RPE have been described by gross and microscopic examinations. This case is reported to provide histopathologic references for diagnosis of RPE and indicate that combining death investigation, pathological findings and clinical courses plays a vital role in diagnosis of RPE in forensic pathology.

7.
Transl Pediatr ; 9(5): 707-712, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209735

RESUMO

The RARS2 gene encodes mitochondrial arginine-tRNA synthetase. Patients with variants of the RARS2 gene have pontocerebellar hypoplasia type 6 (PCH6), which is characterized by early onset seizures, progressive microcephaly, and developmental delay. PCH6 is a rare mitochondrial encephalopathy. To the best of our knowledge, the onset seizure type which the ictal video-electroencephalogram (VEEG) was compatible with early myoclonic encephalopathy (EME) has not been reported. Here we reported a term female neonate with EME caused by heterozygous variants of the RARS2 gene [NM_020320: exon10: c.773G>A (p. R258H) Maternal, NM_020320: exon4: c.282_285delAGAG Paternal]. Groan was the first symptom manifested, followed by metabolic disorders, and early marked cerebral atrophy. Metabolic disorders were corrected after feeding with extensively hydrolyzed protein formula. Seizures started at the 19th day of life. Interictal VEEG showed a suppression-burst (SB) pattern and ictal VEEG revealed myoclonic seizures that were compatible with early myoclonic encephalopathy (EME). She had frequent myoclonic seizures resistant to multi-antiepileptic drugs including phenobarbital, levetiracetam and oxcarbazepine, and soon developed into convulsive status epilepticus. At 7 months of age, she had severe developmental delay, and developed infantile spasms. Our case report expands the phenotypic spectrum of the PCH6, meanwhile, RARS2 should be considered be a causative gene in patients with EME.

8.
Biomed Environ Sci ; 33(9): 660-669, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33106211

RESUMO

Objective: To estimate the association between three B-vitamin intakes and sociodemographic factors among adults in China. Methods: We derived our data from the China Health and Nutrition Survey (CHNS) among 12,241 individuals aged 18-64 years. Log binomial regression was used to estimate adjusted prevalence ratios for factors associated with the inadequate intake of B-vitamins. Results: Females with low incomes and living in the north had a higher prevalence of inadequate riboflavin intake than those with high incomes and living in the south. Both males and females living in a village had a higher prevalence of inadequate riboflavin intake than adults living in a city. Adults with low income, low education, and living in the north or in a village had a higher prevalence of inadequate niacin intake than adults with a high income, high education, and living in the south or in a city. Conclusion: We found that income, region, and area of residence were associated with riboflavin intake. Education, income, region, and area of residence were associated with niacin intake. Well-tailored strategies and policies are needed to improve nutritional status in China.


Assuntos
Niacina/análise , Riboflavina/análise , Tiamina/análise , Complexo Vitamínico B/análise , Adulto , China , Estudos de Coortes , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores Socioeconômicos , Adulto Jovem
9.
Int J Obes (Lond) ; 44(11): 2267-2278, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32963328

RESUMO

BACKGROUND: Overweight and obesity are rising among Chinese reproductive-age women, while some studies have focused on the relationship between sedentary behavior and obesity in certain populations, none has focused on Chinese reproductive-age women specifically. This study examined secular trends in leisure time sedentary behaviors (watching television time, computer time and reading time, and the total sedentary time) among Chinese reproductive-age women and the association of those behaviors with five weight indicators-body mass index (BMI), waist circumference (WC) and overweight, obesity, and abdominal obesity status. METHODS: A prospective cohort study was conducted with Chinese reproductive-age women aged 15-49 who had participated in two or more rounds of the China Health and Nutrition Survey (CHNS), and completed the questionnaire and anthropometric measurements. The exposure variables were the average weekly time spent on three leisure time sedentary behaviors (watching television, using computer, and reading) and the total sedentary time (the sum of the above three sedentary time and video game time). Mixed-effect linear models were produced to explore the secular trends of the mean hours of these sedentary behaviors and the total sedentary time after adjusting covariates. Models were also produced to study the effects of these types of sedentary behavior levels on BMI and WC. Mixed-effect logistic regression models were produced to study the effects of the sedentary behavior levels on overweight, obesity, and abdominal obesity status. RESULTS: The total sedentary time among the reproductive-age women increased over time across most of age, region, educational levels, and income groups from 2004 to 2015. Television hours fluctuated, it increased and then declined over time across most of age, region, and income groups. Computer hours continually increased over time across all age, region, educational level, and income groups. Reading hours gradually decreased over time across most of age, region, educational level, and income groups. Those with a moderate level of television time (14 to <35 h/week) had 1.08 cm larger WCs and were 1.31 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Those with a high level of television time (≥35 h/week) had 1.74 cm larger WCs, 0.66 kg/m2 larger BMIs, were 1.50 times more likely to be overweight and were 1.47 times more likely to have abdominal obesity than those with a low level of television time (<14 h/week). Greater computer, reading time, and total sedentary time were not associated with WC, BMI, overweight, obesity, or abdominal obesity. CONCLUSIONS: These findings showed that among Chinese reproductive-age women ages 15-49, secular trends of computer time increased rapidly, reading time decreased gradually and television time fluctuated but showed not much difference from 2004 to 2015. The sharp increase in computer time far outweighed the decline in reading time. As a result, the overall sedentary behavior time of Chinese reproductive-age women gradually increased. These findings provided strong evidence that greater television time was significantly associated with higher BMI, WC, and higher risks of overweight, abdominal obesity among Chinese reproductive-age women. Computer, reading, and the total sedentary time were not associated with those weight indicators.

10.
J Anal Methods Chem ; 2020: 8831938, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923002

RESUMO

Chaihu-shugan-san (CHSGS) has been widely used in China to treat depression and gastrointestinal diseases for thousands of years, but little is known about its pharmacokinetic properties. The purpose of our study is to develop a reliable and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to detect five components in beagle plasma and study their pharmacokinetic after oral administration of CHSGS in beagles. An Agilent C18 column (2.1 × 150 mm, 3.5 µm) was used to separate the analytes, and the column temperature was maintained at 40°C. A gradient elution procedure was used with solvent A (acetonitrile) and solvent B (0.1% formic acid, aqueous) as mobile phases. The elution procedure was 60% B-10% B (0-3 min) and 10% B-60% B (3.1-4 min). The flow rate was 0.3 mL/min, and the total measurement time was 4 min. Within the determined range, the standard calibration curves of the five analytes had a satisfactory linear relationship (r 2 ≥ 0.9923). The recovery rate (n = 6) of the five analytes was between 85.42% and 90.85%, and the matrix effects (n = 6) were between 94.52% and 103.91%. These results show that the validated method could be successfully applied to study the pharmacokinetic in beagles after a single dose of CHSGS.

11.
Mol Cytogenet ; 13: 34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831907

RESUMO

Progression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution. Additional genetic abnormalities are seen in 10-20% of CML cases at the time of diagnosis, and in 60-80% of cases of advanced disease. Unbalanced chromosomal changes such as an extra copy of the Philadelphia chromosome (Ph), trisomy 8, and i(17)(q10) are common. Balanced chromosomal translocations, such as t(3;3), t(8;21), t(15;17), and inv(16) are typically found in acute myeloid leukemia, but rarely occur in CML. Translocations involving 11q23, t(8;21), and inv(16) are relatively common genetic abnormalities in acute leukemia, but are extremely rare in CML. In the literature to date, there are at least 76 Ph+ cases with t(3;21), 47 Ph+ cases with inv(16), 16 Ph+ cases with t(8;21), and 9 Ph+ cases with t(9;11). But most of what has been published is now over 30 years old, without the benefit of modern immunophenotyping to confirm diagnosis, and before the introduction of treatment regimes such as TKI. In this study, we explored the rare concomitant occurrence of coexistence current chromosomal translocation and t(9;22) in CML or acute myeloid leukemia (AML).

12.
Br J Nutr ; 124(7): 715-728, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32378502

RESUMO

The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(5): 482-487, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32434645

RESUMO

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.


Assuntos
Mutação , Proteínas do Tecido Nervoso/genética , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/genética , Criança , Pré-Escolar , Creatina , Epilepsia , Testes Genéticos , Humanos , Masculino , Síndrome
14.
J Epidemiol ; 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32224596

RESUMO

BACKGROUND: The diagnosis of hypertension should be based on the mean of two or more properly measured BP readings on each of two visits for clinical practice, but one-visit strategy was applied in most epidemiological surveys. The impact of hypertension definition based on two visits on estimates of hypertension burden is unknown. This study aims to assess the impact of hypertension diagnosis based on a two-visit strategy for estimating hypertension burden in China. METHODS: The one-visit and two-visit strategies were applied to investigate the incidence of hypertension in a cohort study based on the China Health and Nutrition Survey (CHNS) 1989-2011. Additionally the prevalence of hypertension was investigated in a cross-sectional study based on the CHNS 2006-2009/2011 and the hypertension burden in China was estimated with data from the 2012-2015 China hypertension survey. RESULTS: Overall, the age-adjusted incidence of hypertension based on the two-visit strategy (1.82%; 95% confidence interval [Cl] = 1.74%, 1.90%) was 62.1% lower than estimation based on the one-visit strategy (4.80%; 95% Cl = 4.68%, 4.93%). Similar results were found in the prevalence of hypertension (the one-visit: 18.13% [17.34, 18.92]; the two-visit: 9.47% [8.87, 10.07]). When the two-visit strategy was applied to the 2012-2015 China hypertension survey, the hypertension burden was predicted to be overestimated by 25.5%-47.8% (based on JNC 7) and 23.5%-48.2% (based on the 2017 ACC/AHA). CONCLUSION: The hypertension burden would decrease from 244.5 million persons to 127.5-182.3 million persons in China if the two-visit strategy was applied.

15.
Biomed Environ Sci ; 33(2): 133-137, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32131960

RESUMO

This study aimed to examine the association between famine exposure in different stages of life and the risk of overweight/obesity and abdominal obesity in laterlife. A total of 12,458 participants were categorized into non-exposure and four direct exposures, including fetal, childhood, adolescence, and adult exposure. Only risk of being overweight or obesity in adolescence exposure [odds ratio ( OR), 1.45; 95% confidence interval ( CI), 1.08-1.94] was significantly higher than in non-exposure. Childhood ( OR, 1.27; 95% CI, 1.05-1.54) and adolescence ( OR, 1.53; 95% CI, 1.15-2.05) exposures had significantly an increased risk of abdominal obesity compared with non-exposure. Additionally, different famine severity exposures had different influences on the development of overweight/obesity and abdominal obesity. Famine exposure in adolescence, which was a behavior formative period, can increase the risk of overweight/obesity and abdominal obesity in adulthood, specifically in famine severely affect area.


Assuntos
Fome Epidêmica , Sobrepeso/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , China , Estudos Transversais , Feminino , Feto/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Obesidade/etiologia , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/etiologia , Sobrepeso/etiologia , Fatores de Risco , Adulto Jovem
16.
Biomed Environ Sci ; 33(1): 19-29, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32029055

RESUMO

Objective: The present study aimed to investigate the association of red meat usual intake with metabolic syndrome (MetS), and explore the contribution of red meat usual intake to serum ferritin. Methods: Based on the data from the longitudinal China Health and Nutrition Survey (CHNS), 2,797 healthy adults aged 18-75 years without hypertension, diabetes, and MetS were selected in 2009 as subjects and follow-up studies were carried out till 2015. We used the National Cancer Institute (NCI) method to estimate the usual intake of foods. Multivariable logistic regressions were performed to evaluate the association between red meat usual intake and the risk of MetS. Quantile regression analysis was used to study the relationship between red meat consumption and serum ferritin levels. Results: After adjusting for potential confounders, red meat, and fresh red meat were positively associated with the risk of MetS ( RR = 1.41, 95% CI: 1.05-1.90 and RR = 1.37, 95% CI: 1.02-1.85, respectively). These relationships showed increasing trend ( P < 0.05). The level of serum ferritin increased significantly with the number of MetS components ( P < 0.05). The quantile regression analysis showed that red meat and fresh red meat usual intake had a significant positive association with serum ferritin levels across the entire conditional serum ferritin distribution ( P < 0.05). Processed red meat did not exhibit a similar association. Conclusion: Higher red meat usual intake was associated with an increased risk of MetS and elevated serum ferritin levels.


Assuntos
Ingestão de Alimentos , Ferritinas/sangue , Síndrome Metabólica/epidemiologia , Carne Vermelha/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
17.
Food Chem Toxicol ; 137: 111179, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035215

RESUMO

Methamphetamine (METH) is a highly addictive stimulant that results in serious and persistent neurotoxic effects. Studies have indicated that luteolin, a flavonoid, may confer neuroprotection against neurotoxicity. Nevertheless, the effects of luteolin on METH-induced neurotoxicity have not been sufficiently verified. In the present study, Sprague Dawley rats were pretreated with luteolin (100 mg/kg) or sodium dodecyl sulfate water, followed by administration of METH (15 mg/kg) or saline. Rat striata were then collected for RNA-sequencing and subsequent analyses. A total of 347 differentially expressed genes (DEGs) were identified in the METH group with 20 pathways, including the phosphoinositol 3 kinase (PI3K)/protein kinase B (Akt), found to be enriched by the KEGG analysis. Seventy-five of the 347 DEGs were modulated in luteolin-pretreated rats, which were enriched into 12 pathways, containing the PI3K/Akt. Results further showed that luteolin pretreatment significantly repressed the METH-induced increases of PI3K, Akt, p-Akt, p53, Bax, caspase 3, normalized the ratio of p-Akt/Akt, and autophagy-related proteins (Beclin1, Atg5 and LC3-II) expression. Taken together, these findings indicate that luteolin attenuates METH-induced apoptosis and autophagy by suppressing the PI3K/Akt pathway. In this case, it exerts protection against METH-induced neurotoxicity. This provides a platform for development of potential therapies for METH treatment.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Luteolina/uso terapêutico , Metanfetamina/toxicidade , Síndromes Neurotóxicas/prevenção & controle , Substâncias Protetoras/uso terapêutico , Animais , Expressão Gênica/efeitos dos fármacos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Análise de Componente Principal , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
18.
J Epidemiol ; 30(3): 128-135, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30880306

RESUMO

BACKGROUND: The prevalence of overweight is increasing dramatically worldwide. The aim of our study was to investigate the association of plain water intake (PWI) with the risk of new-onset overweight risk among Chinese adults. METHODS: A total of 3,200 adults aged 18-65 who were free of overweight at baseline were enrolled from China Health and Nutrition Survey (CHNS) cohort study in 2006-2011. The risk of new-onset overweight with different amounts of PWI per day was analyzed in this 5-year cohort. A multiple logistic regression model was used to assess the association of PWI and the risk of new-onset overweight and adjust for potential confounders. Moreover, dose-response models were developed to estimate the linear relationship. RESULTS: During 5 years of follow-up, 1,018 incident cases were identified. Our analysis indicated an inverse association of more than 4 cups of PWI per day and the risk of new-onset overweight among normal weight individuals. Compared with participants who drank 2 to 3 cups PWI, the adjusted odds ratios (OR) of overweight were 0.741 (95% confidence interval [CI], 0.599-0.916) in participants who drank 4 to 5 cups PWI, and 0.547 (95% CI, 0.435-0.687) in participants who drank more than 6 cups PWI. The dose-response analysis showed that every cup of PWI was associated with a 6.5% and 8.4% decrease in the risk of new-onset overweight among men and women, respectively. The interactions of PWI and covariates on the risk of overweight were not found. CONCLUSION: Drinking more than 4 cups (≈1 liter) per day of plain water is associated with decrease in the risk of new-onset overweight among normal-weight individuals.


Assuntos
Ingestão de Líquidos , Sobrepeso/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Medição de Risco , Adulto Jovem
19.
J Ethnopharmacol ; 249: 112301, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622746

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: BabaoDan (BBD) is a famous traditional Chinese formula frequently used in TCM clinics to eliminate jaundice and treat infectious viral hepatitis. This paper assesses BBD's preventive and therapeutic effects on hepatic encephalopathy after liver cirrhosis (CHE) and acute liver failure (AHE) in rats and explains its possible mechanism of action. METHODS: CHE rat model was established by injection of carbon tetrachloride (CCl4) twice a week for a total of 9 weeks and then by injection of thioacetamide (TAA) to induce hepatic encephalopathy. AHE rat model was established by injection of TAA once a day for a total of 3 days. In CHE rat model, BBD was gavaged once a day at the end of the 6th week until the experiment ended. In AHE rat model,BBD was gavaged once a day 3 days before TAA injection until the experiment ended. The preventive and therapeutic effects of BBD on brain dysfunction, as well as liver injury, pathology and fibrosis were evaluated in vivo. The role of BBD in the regulation of inflammatory factors and myeloid differentiation factor 88/Toll-like receptor 4/nuclear factor kappa-B (TLR4/MyD88/NK-κ B) pathway was detected in both liver and brain in vivo. The rat bone marrow derived macrophages (BMDMs) were activated by Lipopolysaccharide (LPS), and the role of BBD in the regulation of inflammatory factors and NK-κ B pathway were detected in vitro. RESULTS: In CHE rat model: BBD significantly improved the total distance as well as the activity rate of rats. BBD also improved the learning and memory abilities of rats compared with the control group. In addition, BBD effectively decreased ammonia levels and significantly decreased the levels of alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil) and total bile acid (TBA), as well as improved the levels of total protein (TP) and albumin (Alb). In the liver, BBD not only inhibited the gene expressions of tumor necrosis factor alpha (TNF-α), interleukini-6 (IL-6), TLR4, MyD88, and NF-κ B but also inhibited the protein expressions of TLR4, MyD88, NK-κ B and TNF-α. In the brain, BBD inhibited the gene expressions of iNOS, IL-6, TNF-α, TLR-4, MyD88, and NF-κ B, as well as inhibited the protein expressions of TLR4, MyD88, P65 TNF-α and ionized calcium binding adapter molecule 1 (Iba-1). BBD also decreased NO and TNF-α in the blood. IN AHE RAT MODEL: BBD improved neurological scores, blood ammonia levels and the brain inflammatory gene expressions of iNOS, TNF-α and IL-1ß. BBD also improved liver function biomarkers such as ALT, TBil, TBA, TP, ALB and inflammatory and apoptotic gene expressions of TNF-α, IL-1ß, IL-6, Bax, Bcl-2, caspase-9, caspase-3 and NF-κ B. In LPS-activated rat BMDMs, BBD decreased NO and TNF-α production in BMDM culture supernatant. In addition, BBD inhibited the gene expressions of TNF-α, IL-1 ß and IL-6 as well as the phosphorylation of P65. CONCLUSION: BBD can prevent and cure hepatic encephalopathy (HE) derived from both chronic and acute liver diseases. BBD can reduce hyperammonemia as well as the systematic and neurological inflammation. Inflammation is likely an important target of BBD to treat HE. The anti-inflammatory role of BBD may lie in its regulation of the TLR4/MyD88/NF-κ B pathways.


Assuntos
Amônia/metabolismo , Anti-Inflamatórios/farmacologia , Encefalopatia Hepática/tratamento farmacológico , Inflamação/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Encefalopatia Hepática/metabolismo , Inflamação/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/tratamento farmacológico , Falência Hepática Aguda/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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