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1.
J Food Biochem ; : e13033, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31486092

RESUMO

This work aimed to investigate the effects of p-synephrine on the differentiation of adipocyte and explore the underlying mechanism. We found that p-synephrine suppressed the 3T3-L1 cell adipogenesis by reducing the expression level of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which subsequently led to a reduction in the fatty acid-binding protein 4 (aP2) expression. p-Synephrine treatment markedly activated the protein kinase B (PKB/Akt) pathway and sequentially inhibited glycogen synthase kinase 3ß (GSK3ß) activity. Inhibition of GSK3ß activity by LiCl was found to partially ameliorate the above-mentioned effects. All these data suggested that p-synephrine exhibited the anti-adipogenic effects via the regulation of Akt signaling pathway and the suppression of adipogenesis-related proteins. PRACTICAL APPLICATIONS: Citrus aurantium often uses as herbal or dietary supplement in various countries around the world, including in Seville, Spain and South Africa. In traditional Chinese herbs, it is referred to as "Fructus aurantii immaturus," "Zhi shi," or "Zhi ke," and has been used for hundreds of years for various digestive problems. Its primary protoalkaloid, p-synephrine, exhibited lipolytic effects and energy expenditure, which has rapidly replaced ephedrine as an "ephedra-free" alternative dietary supplement. The current study firstly demonstrated the anti-adipogenic effects of p-synephrine in 3T3-L1 preadipocytes, which was due to the regulation of Akt signaling pathway and the subsequent suppression of adipogenesis-related proteins. The present study may offer invaluable opinions into the mechanisms of body weight/fat-losing activities of p-synephrine in theory, and scientific experimental evidence on dietary supplement in practice. p-Synephrine could be utilized for the preventive and therapeutic uses against metabolic syndrome.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31480145

RESUMO

In the present study, an LC/MS metabolomics approach was performed to investigate potential biomarkers of milk production in high- and low-milk-yield dairy cows and to establish correlations among rumen fluid metabolites; the results of this study provide insights into the mechanisms underlying the milk production-related characteristics of rumen fluid in dairy cows. Sixteen lactating dairy cows with similar parity and days in milk were divided into high-yield (HY) and low-yield (LY) groups based on milk yield. On day 21, rumen fluid metabolites were quantified applying LC/MS. The principal component analysis (PCA) and orthogonal partial least-squares (OPLS-DA) showed significantly separated clusters of the ruminal metabolite profiles of HY and LY groups. Compared with HY group, a total of 24 ruminal metabolites were significantly greater in LY group, such as 3-hydroxyanthranilic acid, carboxylic acids, carboxylic acid derivatives (L-isoleucine, L-valine, L-tyrosine, etc.), diazines (uracil, thymine, cytosine), and palmitic acid, while the concentrations of 30 metabolites were dramatically decreased in LY group compared to HY group, included gentisic acid, caprylic acid, and myristic acid. The metabolite enrichment analysis indicated that protein digestion and absorption, ABC transporters and unsaturated fatty acid biosynthesis were significantly different between the two groups. Correlation analysis between the ruminal microbiome and metabolites revealed that certain typical metabolites were exceedingly associated with definite ruminal bacteria; Firmicutes, Actinobacteria and Synergistetes phyla were highly correlated with most metabolites. These findings revealed that the ruminal metabolite profiles were significantly different between HY and LY groups, and these results may provide novel insights to evaluate biomarkers for a better feed digestion and may reveal the potential mechanism underlying the difference in milk yield in dairy cows.

3.
Cerebrovasc Dis ; : 1-8, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31514186

RESUMO

BACKGROUND: Whether the renal function influences the association between antiphosphatidylserine antibodies (aPS) and prognosis of ischemic stroke remains unclear. We aimed to investigate the prognostic value of aPS after ischemic stroke stratified by renal function status. METHODS: This prospective study was based on China Antihypertensive Trial in Acute Ischemic Stroke, a randomized clinical trial in 26 hospitals across China from August 2009 to May 2013. A total of 2,874 ischemic stroke patients with blood samples or baseline records of estimated glomerular filtration rate (eGFR) were included in this study. Serum aPS levels were quantitatively measured at baseline, and abnormal renal function in this study was defined as eGFR <90 mL/min per 1.73 m2. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were death and major disability separately. RESULTS: The association between aPS and primary outcome was significantly modified by renal function status (p for interaction = 0.02). After adjustment for covariates, increased aPS were significantly associated with the primary outcome in the patients with abnormal renal function (OR 2.09; 95% CI 1.24-3.53; p for trend = 0.006), but not in those with normal renal function (OR 0.92; 95% CI 0.69-1.23; p for trend = 0.59), when 2 extreme tertiles were compared. Furthermore, multiple-adjusted spline regression model showed a linear association between aPS and risk of primary outcome in the patients with abnormal renal function (p for linearity = 0.02) but not in those with normal renal function (p for linearity = 0.71). CONCLUSIONS: Increased aPS were positively and independently associated with death or major disability after acute ischemic stroke in the patients with abnormal renal function.

4.
Ann Vasc Surg ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394225

RESUMO

Diabetic foot ulcer and its complications are becoming more and more serious problems threatening people's health. In the last decade, multiple growth factors and their combined applications have shown potentials in promoting the healing process of diabetic foot ulcers. The purpose of this study is to perform a meta-analysis of the efficacy and safety of topical recombinant human epidermal growth factor (rhEGF) on the treatment of diabetic foot ulcers. As of November 30, 2018, we had conducted a comprehensive review of PubMed, EMBASE, Cochrane Library databases, and Web of Science. Seven randomized controlled trials (RCTs) that involved 610 participants were included in this review. The pooled results showed that topical rhEGF could significantly promote the healing of diabetic foot ulcers (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.30 to 1.83; I2 = 18%). Topical application of rhEGF could promote ulceration healing of diabetic feet of Wagner grade 1 or 2 significantly (RR, 1.61; 95% CI, 1.32 to 1.97; I2 = 0%), and intralesional injection of rhEGF appeared to promote the healing of more severe ulcers (RR, 2.06, 95%, CI 0.35 to 12.22; I2 = 50%). However, patients developed more shivering (RR, 4.67; 95% CI, 1.39 to 15.71; I2 = 0%), nauseas/vomiting (RR, 2.18; 95% CI, 0.72 to 6.55; I2 = 0%) in the group of intralesional injection of rhEGF compared with the control group, although these symptoms were not found with the topical application of rhEGF. No serious complications were found associated with topical rhEGF. Topical rhEGF treatment of diabetic foot ulcers has showed a broad application prospect, yet more relevant well-designed RCTs are needed in the future.

5.
J Cancer Res Ther ; 15(4): 784-792, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31436232

RESUMO

Purposes: This study aimed to investigate the efficacy of ultrasound (US)-, computed tomography (CT)-, and magnetic resonance imaging (MRI)-guided radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC). Materials and Methods: This retrospective study included 141 patients with HCC who were treated with US-guided (n = 29), CT-guided (n = 50), or MRI-guided RFA (n = 62). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), technique success (TS), and technique efficacy (TE). Cox model and logistic regression were used to determine the risk factors for tumor recurrence and TE. Results: The US, CT, and MRI groups did not show a significant difference in terms of baseline variables. The three groups did not differ significantly in PFS rate (P = 0.072) and OS rate (P = 0.231). The PFS rates at 3 years for the US, CT, and MRI groups were 40.90%, not reached, and 14.80%, respectively. The OS rates at 3 years were 94.70%, 97.50%, and 85.50% for US, CT, and MRI groups, respectively. No significant differences were observed between the three groups in terms of TS rate (P = 0.113) and TE rate (P = 0.682). In multivariate analysis, liver cirrhosis (P = 0.001), level of alpha-fetoprotein (AFP, P = 0.004), and number of tumors (P = 0.012) were independent risk factors for PFS. For TE, the level of AFP (P = 0.018) was an independent factor. Conclusion: US-, CT-, and MRI-guided RFA was effective for treating HCC patients. Liver cirrhosis, AFP level, and tumor number were associated with tumor recurrence, and the level of AFP was an independent risk factor affecting TE.

6.
Nat Commun ; 10(1): 3578, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395880

RESUMO

How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1071-1076, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418359

RESUMO

OBJECTIVE: To explore the relationship between the expression levels of JARID1B,Hes1 and MMP-9 genes and the stages of chronic myelogenous leukemia(CML) and the curative effect of imatinib mesylate (IM). METHODS: Peripheral blood samples of 15 cases of CML in chronic phase and 10 cases of CML in progressive phase were collected from the Hematology Department of Taihe Hospital affiliated to Hubei University of Medicine and 15 cases of healthy people in the Physical Examination Center. CML patients were divided into effective group and ineffective group based on the efficacy after treatment with IM, then real-time PCR was used to detect the expression levels of JARID1B, Hes1 and MMP-9 mRNA, finally, the differences in the level of gene expression and their correlations with CML stages and IM curative efficacy were analysed. RESULTS: The expression levels of Hes1 and MMP-9 in initially diagnosed patients in chronic and progressive phase without IM treatment were significantly higher than those of health people(P<0.05). There was no significant difference in the expression level of JARID1B between chronic phase patients and health people(P>0.05), but the expression level of JARID1B in the progressive phase patients was higher than that of health people (P<0.05). The expression levels of JARID1B and Hes1 in the IM-effective group were not significantly different from those in the IM-ineffective group (P=0.85,P=0.82), while the expression level of MMP-9 in the IM-effective group [JP2]was significantly lower than that in the IM-ineffective group(P<0.05). CONCLUSION: The expression levels of JARID1B Hes1 and MMP-9 relate with the different phase of CML; The expression levels of JARID1B and Hes1 have not significant relationship with IM curative efficacy, the MMP-9 gene expression level relates with IM curative efficacy.


Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Histona Desmetilases com o Domínio Jumonji , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Metaloproteinase 9 da Matriz , Proteínas Nucleares , Proteínas Repressoras , Fatores de Transcrição HES-1
8.
Curr Mol Med ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31456518

RESUMO

PURPOSES: Phosphorylation-related SNP (phosSNP) is a non-synonymous SNP that might influence protein phosphorylation status. The aim of this study was to assess the effect of phosSNPs on blood pressure (BP), coronary artery disease (CAD) and ischemic stroke (IS). METHODS: We examined the association of phosSNPs with BP, CAD and IS in large scale genome-wide association studies (GWAS) and tested if the disease loci were enriched with phosSNPs. Furthermore, we performed quantitative trait locus analysis to find out if the identified phosSNPs have impacts on gene expression, protein and metabolite levels. RESULTS: We found numerous phosSNPs in the GWAS loci for SBP (n = 148), DBP (n = 206), CAD (n = 20) and IS (n = 4). The most significant phosSNPs for SBP, DBP, CAD and IS were rs1801131 in MTHFR, rs3184504 in SH2B3, rs35212307 in WDR12 and rs3184504 in SH2B3, respectively. The GWAS identified loci were significantly enriched with phosSNPs and many well-known genes predisposing to cardiovascular diseases contain significant phosSNPs. We found that BP, CAD and IS shared for phosSNPs in loci which contain functional genes involve in cardiovascular diseases, e.g., rs11556924 (ZC3HC1), rs1971819 (ICA1L), rs3184504 (SH2B3), rs3739998 (JCAD), rs903160 (SMG6). Four phosSNPs in ADAMTS7 were significantly associated with CAD, including the known functional SNP rs3825807. Moreover, the identified phosSNPs seemed to have potential to affect transcription regulation and serum levels of numerous cardiovascular diseases-related proteins and metabolites. CONCLUSION: The findings suggested that phosSNPs may play important roles in the pathological mechanisms of cardiovascular diseases.

9.
JAMA Netw Open ; 2(7): e198103, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31365109

RESUMO

Importance: Clinical trials have generally shown a neutral effect of early blood pressure (BP) decreases on clinical outcomes after acute ischemic stroke. Whether the effect of early antihypertensive therapy differs for patients with ischemic stroke with or without prior hypertension is unclear. Objective: To investigate the association between immediate antihypertensive treatment and patient outcomes according to the presence or absence of hypertension before stroke onset. Design, Setting, and Participants: This study was a prespecified subgroup analysis of the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS), a multicenter, single-blind, blinded end-points randomized clinical trial of 4071 patients with acute ischemic stroke and elevated systolic BP. Patients were recruited from August 2009 to May 2013, and this statistical analysis was performed using the intention-to-treat population from January to October 2018. Interventions: Participants were randomly assigned to receive antihypertensive treatment (aimed at decreasing systolic BP by 10%-25% within the first 24 hours after randomization, achieving systolic BP <140 mm Hg and diastolic BP <90 mm Hg within 7 days, and maintaining this level during hospitalization) or to the control arm (discontinued all antihypertensive medications). Main Outcomes and Measures: Primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3; range 0-6, with higher values indicating greater disability) at 14 days or hospital discharge. Results: In total, 2038 patients were randomized to receive antihypertensive treatment, and 2033 patients were randomized to the control group. The mean (SD) age was 62.0 (10.9) years, and 2604 participants (64.0%) were men. At day 14 or hospital discharge, the primary outcome was not different between the treatment and control groups among patients with or without prior hypertension (P = .97 for homogeneity): odds ratios (ORs) associated with treatment were 1.00 (95% CI, 0.87-1.16) for patients with prior hypertension and 1.00 (95% CI, 0.75-1.32) for patients without. Early antihypertensive treatment was associated with different rates of 3-month recurrent stroke (patients with hypertension: OR, 0.44; 95% CI, 0.25-0.77 vs without hypertension: OR, 3.43; 95% CI, 0.94-12.55; P = .005 for homogeneity) and vascular events (patients with hypertension: OR, 0.66; 95% CI, 0.43-1.02 vs those without hypertension: OR, 1.91; 95% CI, 0.75-4.83; P = .04 for homogeneity) by hypertension history. Conclusions and Relevance: Among patients with acute ischemic stroke, early antihypertensive treatment was not associated with different death and major disability outcomes by hypertension history. However, early antihypertension therapy was associated with a decreased rate of recurrent stroke among patients with a history of hypertension and may inform future studies in the optimal approach to hypertension management in the setting of acute ischemic stroke. Trial Registration: ClinicalTrials.gov identifier: NCT01840072.

10.
J Neurol ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31321514

RESUMO

OBJECTIVE: Many genomic loci have been identified for multiple sclerosis (MS) by genome-wide association studies (GWAS). Discrimination of the most functionally relevant genes in these loci remains challenging. The aim of this study was to highlight potential causal genes for MS. METHODS: We detected potential causal DNA methylations and gene expressions for MS by integrating data from large scale GWAS and quantitative trait locus (QTL) studies using the summary data-based Mendelian randomization method. Potential functional SNPs in the identified genes were searched. RESULTS: We found 178 DNA methylation sites and mRNA expressions of 29 genes that were causally associated with MS. The identified genes enriched in 21 specific KEGG pathways and 80 GO terms (e.g., antigen processing and presentation, interferon gamma mediated signaling pathway). Among the identified non-MHC genes, METTL21B, METTL1 and TSFM were strongly connected. MS-associated SNPs in DDR1 were strongly associated with plasma MHC class I polypeptide-related sequence B (MICB) and Granzyme A levels. And plasma MICB and Granzyme A levels were causally associated with MS. Many SNPs in the causal genes showed QTL effects. The association between m6A-SNPs rs923829 and METTL21B expression level was validated in 40 unrelated Chinese Han individuals. CONCLUSIONS: This study identified many DNA methylations and genes as important risk factors for MS and provided novel evidence on the association between circulating MICB and Granzyme A and MS. We also showed that the interaction among DDR1, MICB and GZMA and interaction among METTL21B, METTL1 and TSFM may participate in the pathogenesis of MS.

11.
J Hum Hypertens ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31341238

RESUMO

The natriuretic peptide system plays an important role in regulation of blood pressure. The purpose of this study was to comprehensively examine the associations among NPPA gene SNPs, serum atrial natriuretic peptide (ANP) levels, and hypertension. In 736 new-onset hypertensive cases and 736 age- and sex-matched controls, we measured concentrations of serum NT-proANP and genotyped 3 tag-SNPs in NPPA. Serum ANP levels were significantly lower in hypertensive patients than in controls (Wilcoxon two sample test P = 0.011). The difference was also significant in male (P = 0.0161) and female subgroups (P = 0.0011). Compared with the reference group, participants with the highest quartile of ANP levels had a significant decreased risk of hypertension (odds ratio = 0.56, P = 0.0006). The nonsynonymous SNP rs5063 (p.Val32Met) seemed to be associated with ANP levels (P = 0.0209). eQTL analysis found that rs198358 was associated with NPPA gene expression in testis (1.66 × 10-9) and whole blood (4.58 × 10-52). The findings suggested that a common NPPA SNPs rs5063 was associated with serum ANP levels and ANP was prospectively associated with hypertension in the Chinese Han population.

12.
Cancer Res Treat ; 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31352772

RESUMO

Purpose: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. Material and Methods: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed. Results: Five hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven (81%) patients had advanced diseases at diagnosis. The 5-year overall survival (OS) and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, LL and DLBCL were 88%, 88%, and 89%, and those of ALCL and peripheral T-cell lymphoma (PTCL) were 71% and 56% (P<0.001). CNS involvement, high lactate dehydrogenase level (>250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (P<0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (P<0.001). Conclusion: In East Asia, PTCL was more frequent than in Western countries, and BM involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

13.
J Affect Disord ; 257: 160-165, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301618

RESUMO

BACKGROUND: Antiphospholipid activity was reported to be increased in depressive patients, while the impact of antiphospholipid antibodies (aPLs) on post-stroke depression (PSD) is unclear. We aimed to investigate the associations of aPLs, including antiphosphatidylserine (aPS) and anticardiolipin (aCL) antibodies with depression after acute ischemic stroke. METHODS: aPS and aCL were measured in 497 ischemic stroke patients recruited from 7 of 26 participating hospitals of China Antihypertensive Trial in Acute Ischemic Stroke. 24-item Hamilton Depression Rating Scale was used to evaluate PSD status at 3 months after stroke. RESULTS: Compared with aPS-negative or aCL-negative, the adjusted odds ratios (ORs) [95% confidence intervals (CIs)] associated with aPS-positive or aCL-positive were 1.77 (1.07-2.92) or 2.06 (1.11-3.80) for risk of PSD. On continuous analyses, per 1-SD increment of aPS and aCL were associated with 29% (OR 1.29, 95% CI 1.06-1.58) and 30% (OR 1.30, 95% CI 1.06-1.60) increased risks for PSD, respectively. Adding aPLs to conventional risk factors models significantly improved risk reclassification for PSD (net reclassification improvement index = 21.87%, P = 0.016 for aPS; net reclassification improvement index = 32.24%, P = 0.0004 for aCL). LIMITATIONS: aPLs levels were tested only at baseline without serial measurements, and we were unable to detect the association between aPLs changes and PSD. CONCLUSIONS: Higher aPS and aCL levels in the acute phase of ischemic stroke were associated with increased risk of 3-month PSD, suggesting that aPLs may play an important role in post-stroke depression prediction.

14.
Hypertens Res ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175347

RESUMO

N6-methyladenosine (m6A) has been shown to play critical roles in many biological processes and a variety of diseases. The aim of this study was to investigate the association between m6A-associated single-nucleotide polymorphisms (m6A-SNPs) and blood pressure (BP) in large-scale genome-wide association studies and to test whether m6A-SNPs are enriched among the SNPs that were associated with BP. Furthermore, gene expression analysis was performed to obtain additional evidence for the identified m6A-SNPs. We found 1236 m6A-SNPs that were nominally associated with BP, and 33 of them were significant genome wide. The proportion of m6A-SNPs with a P < 0.05 was significantly higher than that of non-m6A-SNPs. Using fgwas, we found that SNPs associated with diastolic BP (P < 5 × 10-8) were significantly enriched with m6A-SNPs (log 2 enrichment of 2.67, 95% confidence interval: [0.42, 3.68]). Approximately 10% of the BP-associated m6A SNPs were associated with coronary artery disease or stroke. Most of these m6A-SNPs were strongly associated with gene expression. We showed that rs56001051, rs9847953, rs197922, and rs740406 were associated with C1orf167 (P = 0.019), ZNF589 (P = 0.013), GOSR2 (P = 0.001), and DOT1L (P = 0.032) expression levels in peripheral blood mononuclear cells of 40 Chinese individuals, respectively. The present study identified many BP-associated m6A-SNPs and demonstrated their potential functionality. The results suggested that m6A might play important roles in BP regulation.

15.
Atherosclerosis ; 287: 30-37, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31185379

RESUMO

BACKGROUND AND AIMS: We aimed to evaluate the ability of multiple novel biomarkers representing several pathophysiological pathways to improve risk prediction of post-stroke cognitive impairment. METHODS: We conducted a prospective multicenter study in 638 ischemic stroke patients with elevated blood pressure based on a random subsample from China Antihypertensive Trial in Acute Ischemic Stroke and measured 12 circulating biomarkers in these participants. Cognitive impairment was assessed at 3 months after stroke with definitions of Mini-Mental State Examination (MMSE) score <27 or Montreal Cognitive Assessment (MoCA) score <25. RESULTS: According to MMSE score, 1 SD increase of rheumatoid factor (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.02-1.46), matrix metalloproteinase-9 (OR 1.47, 95% CI 1.22-1.77) and total homocysteine (OR 1.22, 95% CI 1.01-1.49) after log transformation was significantly associated with the risk of post-stroke cognitive impairment. The ORs associated with their simultaneously high levels were 4.89 (95% CI, 2.31-10.35; ptrend<0.001) and 3.09 (95% CI, 1.60-5.98; ptrend<0.001) for cognitive impairment and the severity of cognitive impairment, respectively. Adding these 3 biomarkers to conventional model significantly improved the risk prediction of cognitive impairment (C statistic 0.729 vs. 0.688, p = 0.004; net reclassification improvement = 33.67%, p < 0.001; integrated discrimination index = 4.61%; p < 0.001). Similar significant findings were observed when cognitive impairment was defined by MoCA score. CONCLUSIONS: Combination of rheumatoid factor, matrix metalloproteinase-9 and total homocysteine can improve the risk prediction of cognitive impairment among ischemic stroke patients with elevated blood pressure. Further studies are warranted to validate our findings and explore their roles as potential therapeutic targets.

16.
Hypertens Res ; 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31253944

RESUMO

The cardiovascular protective role of furin has been suggested by some animal-based studies but has not been well studied in humans. Therefore, the objective of this study was to examine the prospective association between serum furin and high blood pressure in a longitudinal cohort of Chinese adults. Leveraging a longitudinal prospective cohort with blood pressure examined twice on average 4 years apart, we systemically examined the cross-sectional, longitudinal, and prospective associations of baseline serum furin with blood pressure and incident hypertension. Conventional risk factors, including age, sex, education level, cigarette smoking, alcohol consumption, BMI, fasting glucose, and lipids, were controlled. All participants included were free of cardiovascular and kidney disease at baseline. The cross-sectional analysis of 2312 participants (mean age 53 years) revealed that individuals with the lowest quartile of serum furin had average systolic, diastolic, and mean arterial blood pressures that were 2.58, 1.38, and 1.61 mmHg higher, respectively, than the corresponding pressures in individuals with the highest quartile (all P < 0.001). These negative associations remained significant after controlling for the dynamic risk profiles during follow-up in the longitudinal analysis. The prospective analysis of 1088 participants free of prevalent hypertension at baseline revealed that compared with participants with the highest quartile of serum furin, those with the lowest quartile had a 46% increased risk of incident hypertension (HR = 1.46, P = 0.003). These results indicate that lower serum furin is significantly associated with higher blood pressure and predicts an increased future risk of developing hypertension in Chinese adults. Furin may be a protective factor or marker of hypertension.

17.
Plant Sci ; 285: 1-13, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203874

RESUMO

Bioactive gibberellins (GAs) play multiple roles in plant development and stress responses. GA2-oxidases (GA2oxs) are a class of 2-oxoglutarate-dependent dioxygenases that regulate the deactivation of bioactive GAs. In this study, we investigated the phylogeny and domain structures of the seven GA2ox genes present in the Arabidopsis thaliana genome. Comprehensive expression analysis using translational reporter lines showed that the seven GA2ox genes are differentially expressed during Arabidopsis growth and development: GA2ox1 is specifically expressed in the hypocotyl and lateral root primordium; GA2ox2 is highly expressed in aboveground tissues; GA2ox3 is expressed in the chalazal endosperm of the early embryo sac and inflorescences; GA2ox4 is expressed in the shoot apical meristem and during lateral root initiation; GA2ox6 is expressed in the maturation zone, but not in the meristem or elongating zone of the root; GA2ox7 is constitutively expressed during almost all developmental stages; and GA2ox8 is exclusively expressed in stomatal cells. Overexpression of each of these GA2ox genes inhibited high temperature-induced hypocotyl elongation in both wild-type and elongated hypocotyl 5 plants, which have an elongated hypocotyl phenotype, suggesting that these genes negatively regulate hypocotyl elongation by reducing bioactive GA levels. This study provides a valuable resource for further elucidating the roles of GA2ox genes during different stages of development.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Genes de Plantas/fisiologia , Giberelinas/metabolismo , Oxirredutases/genética , Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas/genética , Giberelinas/fisiologia , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Oxirredutases/metabolismo , Oxirredutases/fisiologia , Filogenia , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Transcriptoma
18.
Atherosclerosis ; 285: 163-169, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31071503

RESUMO

BACKGROUND AND AIMS: The association between homocysteine and prognosis of ischemic stroke remains controversial, and the role of platelet count on the effects of homocysteine in the prognosis of ischemic stroke is still not elucidated. METHODS: A total of 3229 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) with homocysteine and platelet measurements were included in this analysis. They were prospectively followed up for death, recurrent stroke and vascular events within 1 year after acute ischemic stroke. RESULTS: There was a significant interaction effect between platelet count and homocysteine level on death (p for interaction < 0.05) within 1 year after ischemic stroke. After multivariate adjustment, high homocysteine level was associated with increased risk of 1-year mortality in patients with low platelet level (hazard ratio, 1.70; 95% confidence interval, 1.01-2.88) but not in those with high platelet level (hazard ratio, 1.08; 95% confidence interval, 0.65-1.75). The addition of homocysteine to a model containing conventional risk factors improved risk prediction of 1-year death (net reclassification index 0.53%, p < 0.001; integrated discrimination improvement 0.07%, p < 0.001). CONCLUSIONS: High homocysteine may be merely an independent risk factor of death in ischemic stroke patients with low platelet levels. Further prospective studies from other populations and randomized clinical trials are needed to verify our findings and clarify the potential mechanisms.

19.
J Orthop Surg Res ; 14(1): 147, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118052

RESUMO

OBJECTIVES: This study aims to explore the clinical efficacy of applying a new reduction brace in the closed reduction of femoral shaft fracture. METHODS: A total of 18 patients with femoral shaft fracture, who were admitted to the Bone Trauma Surgery, Second Hospital of Shanxi Medical University, from September 2015 to January 2017, were chosen. A novel reduction brace combined with closed reduction intramedullary nail insertion on the traction table adopted for the orthopedic surgery was taken for the fixation. Then, surgical time, bleeding amount, and postoperational fracture healing time were recorded. RESULTS: All 18 patients with femoral shaft fracture successfully received closed reduction femoral nail with the application of the novel reduction brace. The follow-up period was 3-18 months, with an average of 12 months, and the femoral shaft fracture was well healed with good recovery of function. CONCLUSIONS: The design of the closed reduction brace of the femoral shaft fracture was reasonable, simple, and convenient to use and has a short learning curve. Furthermore, it led to little trauma to these patients and fully played the advantages of minimally invasive therapy for femoral fractures.

20.
Interdiscip Sci ; 11(2): 273-281, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31106388

RESUMO

In nearly 50% of patients with drug-induced liver injury, the bile flow is impaired known as cholestasis. Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease that happens in pregnancy. Some of the clinical symptoms include pruritus, dark urine, and abnormal liver function tests. A rise of serum bile acids is the most accurate diagnostic evidence. ICP may lead to premature birth, fetal distress, and even postpartum hemorrhage or stillbirth in some severe cases. Higher bile acid levels (> 40 µmol/L) are associated with higher rates of adverse fetal outcomes. Due to the multifactorial nature of ICP, its etiology is still not fully understood. Therefore, the current treatments of ICP are limited to control symptoms and protect fetuses. Among various causing factors, drug exposure during pregnancy is one common factor, and it can be prevented if we know drugs with increasing risk of cholestasis. Here we analyzed over 9.5 million FDA adverse effect reports to identify drugs with increasing risks of cholestasis as an adverse effect. Patients treated for cholestasis or liver diseases were removed. The odds ratio analysis reveals that lansoprazole (LSPZ), omeprazole (OMPZ) and amoxicillin (AMXC) are associated with an increased risk of cholestasis. LSPZ is associated with increased reported cholestasis by a factor of 2.32 (OR with 95% confidence interval [2.21, 2.43]). OMPZ is associated with increased reported cholestasis by a factor of 2.61 [2.54, 2.69]. AMXC is associated with increased reported cholestasis adverse effect by a factor of 6.79 [6.49, 7.11]. The risk of cholestasis associated with these three drugs is further increased in pregnant women. These findings justify careful reassessment of the safety of the three identified drugs.

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