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1.
J Pharm Biomed Anal ; 201: 114087, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33932858

RESUMO

BACKGROUND: The Bushen Huoxue prescription is a traditional Chinese medicine formula treating diabetic retinopathy, which was developed by our research group. Catalpol, puerarin, salvianolic acid B, ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rd are six of main effective components, which could be partly representative of this prescription. The corona charged aerosol detector (corona CAD) is one kind of universal detectors equipped with the high performance liquid chromatography (HPLC). The CAD has many advantages for the analysis of complex mixtures, but too few applications in traditional Chinese medicine compounds. OBJECTIVE: The aims of this study are to establish a method for the determination of six components in Bushen Huoxue prescription, and to increase the use of the CAD in traditional Chinese medicine compounds. METHODS: HPLC-CAD analysis was performed on an Inertsil ODS-SP (4.6 mm × 250 mm, 5 µm) with a mobile phase consisting of 0.5 % formic acid solution(A)-acetonitrile(B) at a flow rate of 1 mL/min (0-7 min, 1 % B; 7-12 min, 1 %-12 % B; 12-22 min, 12 %-19 % B; 22-40 min, 19 %-28 % B; 40-43 min, 28 %-33 % B; 43-50 min, 33 % B; 50-65 min, 33 %-42 % B). The column temperature maintained at 30 ℃, the injection volume was 20 µL, the atomization temperature mode was LOW, the filtration constant (filter) was 3.6 and data collection rate was 10 Hz. The methodology was examined and the linearity of regression of different functions was compared. Sixteen batches of samples were prepared and their contents were determined. RESULTS: The six compounds showed a better linearity (R2 > 0.9990) in their concentration ranges when using the linear function. The average recoveries were 99.18 %-101.30 %. Although the RSD value of puerarin and ginsenoside Rg1 was slightly out of 3 % during the average recovery investigation, all the other methodological investigations of the six components were within 3 %. The precision, stability and repeatability of the method were good. In sixteen batches of Bushen Huoxue prescription samples, the contents of six components were 0.3138 %-0.6042 % for catalpol, 0.8095 %-1.2917 % for puerarin, 0.7416 %-1.1189 % for salvianolic acid B, 0.0231 %-0.0418 % for ginsenoside Rg1, 0.0702 %-0.1724 % for ginsenoside Rb1, 0.0384 %-0.1196 % for ginsenoside Rd. CONCLUSION: In this experiment, a method for the determination of six components in Bushen Huoxue prescription based on HPLC-CAD was established with high accuracy, good repeatability and simple operation, and it can provide references for the improvement of quality standard of the Bushen Huoxue prescription. It is reasonable and accessible for the CAD application in the determination of traditional Chinese medicine compound prescriptions.

2.
J Nutr Sci Vitaminol (Tokyo) ; 67(2): 84-90, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33952739

RESUMO

Few studies have been performed to investigate the effect of vitamin D supplementation and T2DM in type 2 diabetic animal models. The present study aimed to explore the relationship between early 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the incidence of T2DM and determine whether early 1,25(OH)2D3 supplementation was associated with inflammation in KK-Ay mice. The KK-Ay mice were divided into 4 vitamin D treatment groups, the low-dose vitamin D supplementation group (VDS-L, 1.5 µg/kg 1,25(OH)2D3), moderate-dose vitamin D supplementation group (VDS-M, 3.0 µg/kg 1,25(OH)2D3), high-dose vitamin D supplementation group (VDS-H, 6.0 µg/kg 1,25(OH)2D3) and the model control group (MC). C57BL/6J mice were used as the controls. The treatment period lasted for 9 wk. During this treatment period, fasting blood glucose (FBG) level of the mice was measured on a weekly basis. The levels of lipid profile, insulin and inflammation biomarkers were determined after 9 wk of 1,25(OH)2D3 intragastric gavage. After 9 wk of 1,25(OH)2D3 intragastric gavage, FBG level was significantly decreased in the vitamin D treatment groups compared with the MC group. The number of T2DM incidence in the VDS-L group (n=7), VDS-M group (n=5) and VDS-H group (n=3) was lower than those in the MC group (n=10) on week 9. Moreover, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in the vitamin D treatment groups were significantly suppressed by 1,25(OH)2D3 administration compared with the MC group. Early 1,25(OH)2D3 supplementation could effectively lower the incidence of T2DM via ameliorating inflammation in KK-Ay mice.

3.
World J Gastroenterol ; 27(15): 1643-1654, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33958849

RESUMO

BACKGROUND: In the early stage of acute pancreatitis (AP), a large number of cytokines induced by local pancreatic inflammation seriously damage the intestinal barrier function, and intestinal bacteria and endotoxins enter the blood, causing inflammatory storm, resulting in multiple organ failure, infectious complications, and other disorders, eventually leading to death. Intestinal failure occurs early in the course of AP, accelerating its development. As an alternative method to detect small intestinal bacterial overgrowth, the hydrogen breath test is safe, noninvasive, and convenient, reflecting the number of intestinal bacteria in AP indirectly. This study aimed to investigate the changes in intestinal bacteria measured using the hydrogen breath test in the early stage of AP to clarify the relationship between intestinal bacteria and acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Early clinical intervention and maintenance of intestinal barrier function would be highly beneficial in controlling the development of severe acute pancreatitis (SAP). AIM: To analyze the relationship between intestinal bacteria change and ALI/ARDS in the early stage of SAP. METHODS: A total of 149 patients with AP admitted to the intensive care unit of the Digestive Department, Xuanwu Hospital, Capital Medical University from 2016 to 2019 were finally enrolled, following compliance with the inclusion and exclusion criteria. The results of the hydrogen breath test within 1 wk of admission were collected, and the hydrogen production rates at admission, 72 h, and 96 h were calculated. The higher the hydrogen production rates the more bacteria in the small intestine. First, according to the improved Marshall scoring system in the 2012 Atlanta Consensus on New Standards for Classification of Acute Pancreatitis, 66 patients with a PaO2/FiO2 score ≤ 1 were included in the mild AP (MAP) group, 18 patients with a PaO2/FiO2 score ≥ 2 and duration < 48 h were included in the moderately SAP (MSAP) group, and 65 patients with a PaO2/FiO2 score ≥ 2 and duration > 48 h were included in the SAP group, to analyze the correlation between intestinal bacterial overgrowth and organ failure in AP. Second, ALI (PaO2/FiO2 = 2) and ARDS (PaO2/FiO2 > 2) were defined according to the simplified diagnostic criteria proposed by the 1994 European Union Conference. The MSAP group was divided into two groups according to the PaO2/FiO2 score: 15 patients with PaO2/FiO2 score = 2 were included in group A, and three patients with score > 2 were included in group B. Similarly, the SAP group was divided into two groups: 28 patients with score = 2 were included in group C, and 37 patients with score > 2 were included in group D, to analyze the correlation between intestinal bacterial overgrowth and ALI/ARDS in AP. RESULTS: A total of 149 patients were included: 66 patients in the MAP group, of whom 53 patients were male (80.3%) and 13 patients were female (19.7%); 18 patients in the MSAP group, of whom 13 patients were male (72.2%) and 5 patients were female (27.8%); 65 patients in the SAP group, of whom 48 patients were male (73.8%) and 17 patients were female (26.2%). There was no significant difference in interleukin-6 and procalcitonin among the MAP, MSAP, and SAP groups (P = 0.445 and P = 0.399, respectively). There was no significant difference in the growth of intestinal bacteria among the MAP, MSAP, and SAP groups (P = 0.649). There was no significant difference in the growth of small intestinal bacteria between group A and group B (P = 0.353). There was a significant difference in the growth of small intestinal bacteria between group C and group D (P = 0.038). CONCLUSION: Intestinal bacterial overgrowth in the early stage of SAP is correlated with ARDS.

4.
Br J Clin Pharmacol ; 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963595

RESUMO

AIM: Oral flucloxacillin may be co-administered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic-pharmacodynamic (PK/PD) targets. The aims of this study were to develop a population PK model of free flucloxacillin when administered orally with probenecid, and to identify optimal dosing regimens for this combination. METHODS: We performed a prospective observational study of adults (45 participants) treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly for proven or probable staphylococcal infections. Steady-state mid-dose-interval flucloxacillin measurements (45 concentrations) were combined with existing data from a crossover study of healthy participants receiving flucloxacillin with and without probenecid (11 participants, 363 concentrations). We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, and used Monte Carlo simulation to explore optimal dosing regimens to attain PK/PD targets proposed in the literature (fT>MIC ). RESULTS: Flucloxacillin disposition was best described by a one-compartment model with a lag time and first order absorption. Free flucloxacillin clearance depended on probenecid, allometrically-scaled fat free mass (FFM), and eGFR. Predicted PK/PD target attainment was suboptimal with standard dosing regimens with flucloxacillin alone, but substantially improved in the presence of probenecid. CONCLUSION: The simulation results reported can be used to identify dose regimens which optimise flucloxacillin exposure according to eGFR and FFM. Patients with higher FFM and eGFR may require the addition of probenecid and 6-hourly dosing to achieve PK/PD targets. The regimen was well-tolerated, suggesting a potential for further evaluation in controlled clinical trials to establish efficacy.

5.
Endocr Connect ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33909592

RESUMO

OBJECTIVE: The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been little clinical reports based on large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves' disease (GD), Hashimoto's thyroiditis (HT) and T1DM patients with AITD. METHODS: Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by radioimmunoassay. RESULTS: The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P<0.05); but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P<0.0001). CONCLUSIONS: An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.

6.
Int J Mol Sci ; 22(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925342

RESUMO

Canavalia rosea (bay bean), distributing in coastal areas or islands in tropical and subtropical regions, is an extremophile halophyte with good adaptability to seawater and drought. Late embryogenesis abundant (LEA) proteins typically accumulate in response to various abiotic stresses, including dehydration, salinity, high temperature, and cold, or during the late stage of seed development. Abscisic acid-, stress-, and ripening-induced (ASR) genes are stress and developmentally regulated plant-specific genes. In this study, we reported the first comprehensive survey of the LEA and ASR gene superfamily in C. rosea. A total of 84 CrLEAs and three CrASRs were identified in C. rosea and classified into nine groups. All CrLEAs and CrASRs harbored the conserved motif for their family proteins. Our results revealed that the CrLEA genes were widely distributed in different chromosomes, and all of the CrLEA/CrASR genes showed wide expression features in different tissues in C. rosea plants. Additionally, we introduced 10 genes from different groups into yeast to assess the functions of the CrLEAs/CrASRs. These results contribute to our understanding of LEA/ASR genes from halophytes and provide robust candidate genes for functional investigations in plant species adapted to extreme environments.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33794039

RESUMO

The relationship between insulin-like growth factor-1 (IGF-1) and systolic blood pressure (SBP) is controversial in adults and children. The purpose of this study was to investigate the relationship between the IGF-1 standard deviation score (IGF-1 SDS) and SBP in children with short stature. A cross-sectional analysis including 1315 children with short stature was conducted from March 2013 to October 2020. We estimated IGF-1, blood pressure and other laboratory tests, and anthropometric indicators were also evaluated. Subgroup analyses of the pubertal stage, sex, growth hormone levels, thyroid hormone levels, fasting blood glucose levels, and triglyceride levels were performed. A positive association between the IGF-1 SDS and SBP was observed by univariate analysis (p < .001). We further found a nonlinear association between the IGF-1 SDS and SBP. The inflection point for the curve was found at an IGF-1 SDS level of -2.91. In multivariate piecewise linear regression, there was a positive association between the IGF-1 SDS and SBP when the IGF-1 SDS was greater than -2.91 (ß 1.56, 95% CI: 0.91, 2.22; p < .001). However, we did not observe a significant relationship between the IGF-1 SDS and SBP when the IGF-1 SDS level was less than -2.91 (ß -0.95, 95% CI -3.17, 1.28; p = .379). This association was consistent across subgroup analyses. The present study demonstrated that there is a nonlinear relationship between the IGF-1 SDS and SBP in children with short stature. Increased serum IGF-1 levels were associated with elevated SBP when the IGF-1 levels reached the inflection point.

8.
Environ Toxicol Pharmacol ; 85: 103653, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33812011

RESUMO

Ambient air fine particulate matter (PM2.5) may increase cardiovascular disease risks. In this study, we investigated the miR-208/GATA4/myosin heavy chain (MHC) regulation mechanisms on cardiac injury in rats after PM2.5 exposure via an animal inhalation device. The results showed that PM2.5 exposure for 2 months caused pathological heart injury, reduced nucleus-cytoplasm ratio, and increased the levels of CK-MB and cTnI, showing cardiac hypertrophy. Oxidative stress and inflammatory responses were also observed in rats' hearts exposed to PM2.5. Of note, PM2.5 exposure for 2-month significantly elevated GATA4 and ß-MHC mRNA and protein expression compared with the corresponding controls, along with the high-expression of miR-208b. The ratios of ß-MHC/α-MHC expression induced by PM2.5 were remarkably raised in comparison to their controls. It suggested that the up-regulation of miR-208b/ß-MHC and GATA4 and the conversion from α-MHC to ß-MHC may be the important causes of cardiac hypertrophy in rats incurred by PM2.5.

9.
Br J Nutr ; : 1-44, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33858522

RESUMO

Poor utilization efficiency of carbohydrate always leads to metabolic phenotypes in fish. The intestinal microbiota plays an important role in carbohydrate degradation. Whether the intestinal bacteria could alleviate high-carbohydrate diet (HCD) induced metabolic phenotypes in fish remains unknown. Here, a strain affiliated to Bacillus amyloliquefaciens was isolated from the intestine of Nile tilapia. A basal diet (CON), high carbohydrate diet (HCD), or HCD supplemented with B. amy SS1 (HCB) was used to feed fish for 10 weeks. The beneficial effects of B. amy SS1 on weight gain and protein accumulation were observed. Fasting glucose and lipid deposition were decreased in the HCB group compared with the HCD group. Highthroughput sequencing showed that the abundance of acetate-producing bacteria was increased in the HCB group relative to the HCD group. Gas chromatographic analysis indicated that the concentration of intestinal acetate was increased dramatically in the HCB group compared with that in the HCD group. Glucagon-like peptide-1 (GLP-1) was also increased in the intestine and serum of the HCB group. Thus, fish were fed with HCD, HCD supplemented with sodium acetate at 900 mg/kg (HLA), 1800 mg/kg (HMA) or 3600 mg/kg (HHA) diet for 8 weeks, and the HMA and HHA groups mirrored the effects of B. amy SS1. This study revealed that B. amy SS1 could alleviate the metabolic phenotypes caused by HCD by enriching acetate-producing bacteria in fish intestines. Regulating the intestinal microbiota and their metabolites might represent a powerful strategy for fish nutrition modulation and health maintenance in future.

10.
Br J Clin Pharmacol ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33855722

RESUMO

AIMS: To evaluate the effect of severe chronic obstructive pulmonary disease (COPD) on drug metabolism by comparing the pharmacokinetics of patients with severe COPD with healthy volunteers and using the modified Inje drug cocktail. METHODS: This was a single-centre pharmacokinetic study with 12 healthy participants and 7 participants with GOLD D COPD. Midazolam 1 mg, dextromethorphan 30 mg, losartan 25 mg, omeprazole 20 mg, caffeine 130 mg and paracetamol 1000 mg were simultaneously administered and intensive pharmacokinetic sampling was conducted over 8 hours. Drug metabolism by CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP1A2, UGT1A6 and UGT1A9 in participants with COPD were compared with phenotypes in healthy controls. RESULTS: The oral clearance (95% confidence interval) in participants with COPD relative to controls was: midazolam 63% (60-67%); dextromethorphan 72% (40-103%); losartan 53% (52-55%); omeprazole 35% (31-39%); caffeine 52% (50-53%); and paracetamol 73% (72-74%). There was a 5-fold increase in AUC for omeprazole and approximately 2-fold increases for caffeine, losartan, dextromethorphan, and midazolam. The AUC of paracetamol, which is mostly glucuronidated, was increased by about 60%. CONCLUSION: Severe COPD is associated with a clinically significant reduction in oral drug clearance. This may be greater for cytochrome P450 substrates than for glucuronidated drugs. This supports reduced starting doses when prescribing for patients with severe COPD.

11.
Expert Rev Vaccines ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33929930

RESUMO

BACKGROUND: Although the inactivated SARS-CoV-2 vaccine (CoronaVac) has undergone preclinical tests and clinical trials evaluating its efficacy and safety before being approved for authorization, few data have been reported in the post-licensure real-world setting. We aimed to assess the safety of the vaccine among healthcare workers. METHODS: A self-administered online survey on monitoring adverse reactions post vaccination was conducted among the staff who worked at and were vaccinated in a tertiary hospital in Taizhou, China, from February 24 to March 7, 2021. A total of 1526 subjects responded to the questionnaire when they received an email or an e-poster on WeChat. RESULTS: The incidences of overall adverse reactions after the first and second injections were 15.6% (238/1526) and 14.6% (204/1397), respectively. The most common adverse reaction was localized pain at the injection site, with an incidence of 9.6% and 10.7% after each dose, accounting for 61.8% and 73.0% of adverse reactions, respectively. Fatigue, muscle pain, and headache were the most common systemic adverse reactions. CONCLUSIONS: These findings implied that the inactivated CoronaVac vaccine has an acceptable safety profile among healthcare workers due to the low incidence of self-reported adverse reactions. This may boost public confidence in nationwide mass vaccination campaigns.

12.
Sci Rep ; 11(1): 8730, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33888749

RESUMO

This paper develops a two-dimensional (2D) radiomics approach with computed tomography (CT) to differentiate between benign and malignant ovarian neoplasms. A retrospective study was conducted from July 2017 to June 2019 for 134 patients with surgically-verified benign or malignant ovarian tumors. The patients were randomly divided in a ratio of 7:3 into two sets, namely a training set (of n = 95) and a test set (of n = 39). The ITK-SNAP software was used to delineate the regions of interest (ROI) associated with lesions of the largest diameters in plain CT image slices. Texture features were extracted by the Analysis Kit (AK) software. The training set was used to select the best features according to the maximum-relevance minimum-redundancy (mRMR) criterion, in addition to the algorithm of the least absolute shrinkage and selection operator (LASSO). Then, we employed a radiomics model for classification via multivariate logistic regression. Finally, we evaluated the overall performance of our method using the receiver operating characteristics (ROC), the DeLong test. and tested in an external validation test sample of patients of ovarian neoplasm. We created a radiomics prediction model from 14 selected features. The radiomic signature was found to be highly discriminative according to the area under the ROC curve (AUC) for both the training set (AUC = 0.88), and the test set (AUC = 0.87). The radiomics nomogram also demonstrated good calibration and differentiation for both the training (AUC = 0.95) and test (AUC = 0.96) samples. External validation tests gave a good performance in radiomic signature (AUC = 0.83) and radiomics nomogram (AUC = 0.95). The decision curve explicitly indicated the clinical usefulness of our nomogram method in the sense that it can influence major clinical events such as the ordering or abortion of other tests, treatments or invasive procedures. Our radiomics model based on plain CT images has a high diagnostic efficiency, which is helpful for the identification and prediction of benign and malignant ovarian neoplasms.

13.
Math Biosci Eng ; 18(3): 2675-2687, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33892566

RESUMO

OBJECTIVE: Insulin resistance is a major risk factor for coronary artery disease (CAD). The C-peptide-to-insulin ratio (C/I) is associated with hepatic insulin clearance and insulin resistance. The current study was designed to establish a novel C/I index (CPIRI) model and provide early risk assessment of CAD. METHODS: A total of 865 adults diagnosed with new-onset diabetes mellitus (DM) within one year and 54 healthy controls (HC) were recruited to develop a CPIRI model. The CPIRI model was established with fasting C/I as the independent variable and homeostasis model assessment of insulin resistance (HOMA-IR) as the dependent variable. Associations between the CPIRI model and the severity of CAD events were also assessed in 45 hyperglycemic patients with CAD documented via coronary arteriography (CAG) and whom underwent stress echocardiography (SE) and exercise electrocardiography test (EET). RESULTS: Fasting C-peptide/insulin and HOMA-IR were hyperbolically correlated in DM patients and HC, and log(C/I) and log(HOMA-IR) were linearly and negatively correlated. The respective correlational coefficients were -0.83 (p < 0.001) and -0.76 (p < 0.001). The equations CPIRI(DM) = 670/(C/I)2.24 + 0.25 and CPIRI(HC) = 670/(C/I)2.24 - 1 (F = 1904.39, p < 0.001) were obtained. Patients with insulin resistance exhibited severe coronary artery impairment and myocardial ischemia. In CAD patients there was no significant correlation between insulin resistance and the number of vessels involved. CONCLUSIONS: CPIRI can be used to effectively evaluate insulin resistance, and the combination of CPIRI and non-invasive cardiovascular examination is of great clinical value in the assessment of CAD.

14.
Org Lett ; 23(9): 3274-3277, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33881880

RESUMO

Two novel natural products, beetleane A (1) and epicoane A (2), were obtained from the metabolites of an endophytic Epicoccum nigrum. Compound 1 has a unique beetlelike structure that is constructed by the fusion and further fold of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring. Compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both 1 and 2 showed strong antiliver fibrosis activity in vitro.

15.
Aging (Albany NY) ; 13(7): 10240-10274, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33819195

RESUMO

A recent study showed that a gestational high fat diet protects 3xTg-AD offspring from memory impairments, synaptic dysfunction, and brain pathology. However, it is unknown whether this diet exerts the same effects on normal mice or on other functions, and if so, how. In the present study, mother mice were pre-fed a high sugar and high fat (HSHF) diet for 1 month and then fertilized; the HSHF diet was continued until birth and then mother mice were returned to a standard diet. The gut microbiota, and intestinal and brain functions of the offspring were dynamically monitored at 7, 14, 28, and 56 days old until 16 months of age. Results showed that the HSHF diet significantly affected the gut microbiota structure of the offspring, especially during the early life stage. In addition, in the HSHF diet offspring, there were influenced on various types of neurons, including cholinergic and GABAergic neurons, on autophagy levels in the brain, and on inflammation levels in the intestinal tract. When the offspring grew older (16 months), we found that some genes of benefit against nervous system disease were activated, such as Lhx8, GPR88, RGS9, CD4, DRD2, RXRG, and Syt6, and the expression of cholinergic and GABAergic neurons biomarker protein increased. Although the inflammation levels in the nervous and peripheral systems showed no obvious differences, the AFP level of individuals on the HSHF diet was much higher than those on the standard diet, suggesting that more accurate and/or personalized nutrition is needed. Taken together, the results show that a maternal HSHF diet benefits the offspring by reducing the risk of nervous diseases, which might depend on LHX8 activation to modulate cholinergic and GABAergic neurons via the gut-brain axis, but still need much more deep studies.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33864019

RESUMO

Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.

17.
Pediatr Blood Cancer ; : e29067, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33871892

RESUMO

BACKGROUND: Gemtuzumab ozogamicin (GO) administered before allogeneic hematopoietic cell transplantation (alloHCT) has been linked to an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). PROCEDURE: This retrospective analysis examined VOD/SOS risk and clinical outcomes in pediatric patients with acute myeloid leukemia who received myeloablative alloHCT in 2008-2011 with (n = 148) and without (n = 348; controls) prior GO exposure and were reported to the Center for International Blood and Marrow Transplant Research. RESULTS: Cumulative incidences (95% confidence interval [CI]) of VOD/SOS and severe VOD/SOS, respectively, at 100 days were 16% (11-23%) and 8% (4-13%) for GO-exposed patients and 10% (7-13%) and 3% (2-5%) for controls. With a median follow-up of approximately 7 years, the 5-year adjusted overall survival probability (95% CI) after alloHCT was 51% (43-58%) and 55% (50-60%) for GO-exposed patients and controls, respectively; three (4%) and one (<1%) deaths were attributed to VOD/SOS. In multivariate analyses, GO exposure was observed to be associated with an increased risk of VOD/SOS at 100 days, but was not associated with overall survival, disease-free survival, relapse, or nonrelapse mortality. CONCLUSIONS: Results suggest that GO treatment prior to alloHCT in pediatric patients may increase the risk of VOD/SOS but not death.

18.
Trials ; 22(1): 258, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827631

RESUMO

BACKGROUND: Hearing loss is quite prevalent and can be related to people's quality of life. To our knowledge, there are limited studies assessing the efficacy of hearing interventions on quality of life in adults. Therefore, we aim to conduct a randomized controlled trial (RCT) to determine the impact and cost-effectiveness of community-based hearing rehabilitation on quality of life among Chinese adults with hearing loss. METHODS/DESIGN: In this two-arm feasibility study, participants aged 16 and above with some degree of hearing loss (n = 464) will be recruited from Linyi City, Shandong Province. They are randomly assigned to the treatment group or the control group. Those in the treatment group are prescribed with hearing aids, while those in the control group receive no intervention. Reinstruction in use of devices is provided for the treatment group during booster visits held 12 months post-randomization or unscheduled interim visits when necessary. Data are collected at baseline and the follow-up 20 months later. The primary outcome is changes in quality of life over a 20-month study period. Secondary outcomes include sub-dimensions in quality of life, physical functioning, chronic diseases, cognitive function, depression, social support, hospitalizations, falls, and healthcare costs. Finally, we will evaluate whether hearing aids intervention is cost-effective to apply in a large scale. DISCUSSION: The trial is designed to evaluate the impact and cost-effectiveness of a community-based rehabilitation intervention on quality of life among Chinese adults with hearing loss. We hope that it would help improve the well-being for Chinese adults and provide references in policy and practice for China and other countries. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024739 . Registered on 26 July 2019.

19.
Int J Biol Sci ; 17(5): 1234-1249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33867842

RESUMO

Dickkopf-1 (DKK1) was recently shown to play an important role in cardiovascular disease. The aim of this work was to assess the role of DKK1 in the regulation of smooth muscle cell function by mechanical stretch and the mechanisms underlying this process. Methods: Wild-type C57BL/6J mice were subjected to sham or abdominal aortic constriction (AAC) surgery. The expression level of DKK1 was examined by immunohistochemical staining and Western blotting. Analyses of DKK1 function in vascular smooth muscle cell (VSMC) proliferation and migration were performed. Transcriptome sequencing analysis was performed to identify the differentially expressed genes and pathways regulated by DKK1. Smooth muscle-specific Dkk1 knockout mice were used to confirm the function of DKK1 in vivo. Chromatin immunoprecipitation (ChIP) was used to confirm DNA-protein interactions. Promoter luciferase analysis was used to detect transcription factor activity. Results: We found that AAC significantly increased DKK1 protein levels in the thoracic aorta and coronary artery in vivo. In vitro, high-level stretch (18%) induced the expression of DKK1 in VSMCs. Knocking down DKK1 inhibited VSMC proliferation and migration under high-level stretch (18%). We identified ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) as a target gene of DKK1. Knockdown of UHRF1 with small interfering RNAs partially reversed the regulatory effect of recombinant DKK1 on VSMCs. Specific deletion of DKK1 in VSMCs was sufficient to attenuate the AAC-induced upregulation of UHRF1, thickening of arterial media and increase in VSMC proliferation. Furthermore, we found that DKK1 regulated UHRF1 expression through the YAP-TEAD pathway. TEAD1 and TEAD4 bound directly to the promoter of UHRF1, and blocking the YAP-TEAD interaction inhibited UHRF1 upregulation due to DKK1. Conclusions: This study reveals that DKK1 mediates the mechanical stretch regulation of smooth muscle cell function by modulating UHRF1 expression through the YAP-TEAD pathway.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33921471

RESUMO

In order to describe the changes of soil temperature field, air flow field and remediation situation with time during the process of thermally enhanced SVE (soil vapor extraction), a remediation experiment of benzene contaminated soil with single extraction pipe was carried out in a box device. The results showed that the whole temperature of the system was raised to 80 °C in 4 h. 43% of benzene were removed in the first 2% of the extraction time. After 24 h, the repair efficiency was close to 100%. The device can efficiently remove benzene from soil. By continuously monitoring the parameters in the operation process of the system, the spatial distribution of temperature and soil gas pollutant concentration with time was plotted. It showed the benzene concentration distribution in the soil gas was more consistent with the temperature distribution before the start of ventilation, and the concentration of benzene in the soil gas dropped rapidly after ventilation, while the temperature distribution was almost unaffected. In the treatment of soil with a benzene content of 17.8 mg∙kg-1, when the soil gas benzene concentration is the highest at 180 min, the peak value is 11,200 mg∙m-3, and the average concentration is 7629.4 mg∙m-3.

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