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1.
Pancreas ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593014

RESUMO

OBJECTIVES: The aim of this study was to evaluate the role of parecoxib in patients with different severities of acute pancreatitis (AP). METHODS: A total of 772 eligible patients with AP were divided into 4 groups: mild and moderately AP (MAP) treated with parecoxib (group A, n = 236), MAP without parecoxib treatment (group B, n = 453), severe AP (SAP) treated with parecoxib (group C, n = 28), and SAP without parecoxib treatment (group D, n = 55). Patients in group A were exactly matched with patients in group B by propensity score matching, similar to the matching between group C and group D. RESULTS: The morbidity of abdominal infection in group A was significantly lower as compared with that in group B (P < 0.050). The progression of MAP to SAP significantly decreased in group A than group B (P < 0.050). No significant differences were observed between group C and group D. The risk factors independently related to the progression of MAP included alcoholic/high-fat dietary (P = 0.028) and parecoxib administration (P = 0.011). CONCLUSIONS: Early administration of parecoxib could reduce the morbidity of complications among patients with MAP. Parecoxib may prevent the progression of MAP to SAP and improve its outcomes.

2.
J Coll Physicians Surg Pak ; 29(10): 946-950, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31564267

RESUMO

OBJECTIVE: To compare the efficacies of unilateral and bilateral percutaneous kyphoplasty (PKP) in the treatment of thoracolumbar osteoporotic compression fractures. STUDY DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Department of Orthopedics, Hubei 672 Orthopedics Hospital of Integrated Chinese and Western Medicine, China, from November 2014 to January 2017. METHODOLOGY: One hundred and seventy-eight patients with single-level thoracolumbar osteoporotic compression fractures included in this study. These patients were randomly assigned to unilateral (n=83) and bilateral (n=95) PKP groups. The operation time, bone cement volume, number of X-ray views, preoperative and postoperative pain visual analogue scale scores (VAS), Oswestry Dysfunction Index (ODI), Cobb angle, and vertebral height in both groups were recorded. RESULTS: Operation time, bone cement volume and intraoperative number of X-ray views were significantly different between unilateral and bilateral PKP groups (29.8 ±2.7 vs. 31.5 ±3.9 minutes; 9.3 ±2.6 vs. 11.2 ±3.7 times; 3.1 ±0.7 vs. 3.5 ±1.2 ml, respectively, p <0.05). VAS scores and ODI in both groups were significantly different before and 24 hours, 3 months and 6 months after surgery. The heights of anterior and middle borders of vertebral body and Cobb angle in the two groups were significantly different before and after surgery (p <0.05). CONCLUSION: The short-term efficacy was identical between unilateral and bilateral PKP. The unilateral PKP is characterized by short operation time, low hospital cost, less number of X-ray views and less bone cement volume. The unilateral PKP shows a higher risk of re-fracture of adjacent vertebral body compared with the bilateral PKP.

3.
ACS Chem Neurosci ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566366

RESUMO

Many studies have focused on histidine behaviors in misfolding diseases. However, histidine behaviors on mature fibrils are still unknown. In the current study, we investigated mature fibrils with various histidine states to understand the structural properties of the histidine tautomeric effect on mature fibrils. Our results show that substituting chain 1 with different histidine states affects Aß structural properties in A2, D7-G9, H14-Q15, S26-N27, and G33-G37 regions. The binding free energies with substituted fibrils were influenced not only along the axial direction, but also between du-plex fibrils. Our results suggest that substituted (εδδ) preferentially disturbed the stability among the current mature fibrils. Further, H-bonded network differences indicate that twisted morphologies in mature fibrils are derived from the position and orientation of the imidazole ring in histidines. Our current study helps to elucidate histidine behaviors on mature fibrils, which will present opportunities to understand the misfolding mechanisms.

4.
Cancer Med ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566899

RESUMO

BACKGROUND: Portal vein tumor thrombus (PVTT) is a common complication in hepatocellular carcinoma (HCC), signaling dismal outcomes. This study was conducted to evaluate the survival benefit of postoperative portal vein perfusion chemotherapy (PVC) in patients with HCC and PVTT. METHODS: A retrospective review was conducted in 401 consecutive patients with HCC and PVTT who underwent hepatic resection between January 2009 and December 2015 and 67 patients received adjuvant postoperative PVC. A propensity score matching (PSM) was used to match patients with and without PVC at a ratio of 1:1. RESULTS: After PSM, the median time to recurrence (TTR) and overall survival (OS) were significantly longer in PVC group compared with control group (12.3 vs 5.8 months, P = .001; 19.0 vs 13.4 months, P = .037; respectively). At 1, 2, 3, and 5 years, the cumulative recurrence rates in PVC group were 48.1%, 86.5%, 92.3% ,96.2%, respectively, with OS rates of 63.8%, 37.9%, 24.4%, 18.3%, respectively; whereas cumulative recurrence rates of 76.6%, 91.5%, 94.3%, and 97.2%, respectively and OS rates of 55.4%, 23.0%, 12.4%, and 12.4%, respectively were recorded for the control group. In multivariate analysis, postoperative PVC emerged as a significant predictor for TTR (hazard ratio [HR], 0.523; P = .001) and OS (HR, 0.591; P = .010). PVC could reduce early recurrence (≤1 year) rate after surgical resection (40.3% vs 64.2%, P = .006) and clinical outcomes were further enhanced by adding sorafenib to postoperative PVC. CONCLUSIONS: Compared with surgical resection alone, postoperative adjuvant PVC treatment boosts survival and reduces early tumor recurrences in patients surgically treated for HCC and PVTT.

5.
Cancer Commun (Lond) ; 39(1): 54, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578148

RESUMO

BACKGROUND: Cancer cells reprogram metabolism for proliferation. Phosphoglycerate kinase 1 (PGK1), as a glycolytic enzyme and newly identified protein kinase, coordinates glycolysis and mitochondrial metabolism. However, the clinical significance of PGK1 expression and function in cancer progression is unclear. Here, we investigated the relationship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation. METHODS: We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets. Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation, we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types. RESULTS: The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types, respectively. In breast carcinoma, elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis. Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival (OS) in cancers of the breast, liver, lung, stomach, and esophagus and with advanced TNM stage in breast and esophageal cancers. PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver, lung, and stomach cancer. CONCLUSIONS: The elevated expression, promoter hypomethylation, and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer. PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.

6.
Sci Rep ; 9(1): 14384, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591431

RESUMO

Static magnetic field (SMF) plays important roles in biological processes of many living organisms. In plants, however, biological significance of SMF and molecular mechanisms underlying SMF action remain largely unknown. To address these questions, we treated Arabidopsis young seedlings with different SMF intensities and directions. Magnetic direction from the north to south pole was adjusted in parallel (N0) with, opposite (N180) and perpendicular to the gravity vector. We discovered that root growth is significantly inhanced by 600 mT treatments except for N180, but not by any 300 mT treatments. N0 treatments lead to more active cell division of the meristem, and higher auxin content that is regulated by coordinated expression of PIN3 and AUX1 in root tips. Consistently, N0-promoted root growth disappears in pin3 and aux1 mutants. Transcriptomic and gene ontology analyses revealed that in roots 85% of the total genes significantly down-regulated by N0 compared to untreatment are enriched in plastid biological processes, such as metabolism and chloroplast development. Lastly, no difference in root length is observed between N0-treated and untreated roots of the double cryptochrome mutant cry1 cry2. Taken together, our data suggest that SMF-regulated root growth is mediated by CRY and auxin signaling pathways in Arabidopsis.

7.
PLoS Biol ; 17(10): e3000461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31600191

RESUMO

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

8.
BMC Infect Dis ; 19(1): 835, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601192

RESUMO

BACKGROUND: Increasing number of hospitalized children with community acquired pneumonia (CAP) is co-detected with Mycoplasma pneumoniae (Mp). The clinical characteristics and impact of Mp co-detected with other bacterial and/or viral pathogens remain poorly understood. The purpose of this study was to evaluate the demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection. METHODS: A total of 4148 hospitalized children with CAP were recruited from January to December 2017 at the Children's Hospital of Hebei Province, affiliated to Hebei Medical University. A variety of respiratory viruses, bacteria and Mp were detected using multiple modalities. The demographic and clinical features of CAP children with Mp mono-detection and Mp co-detection were recorded and analyzed. RESULTS: Among the 110 CAP children with Mp positive, 42 (38.18%) of them were co-detected with at least one other pathogen. Co-detection was more common among children aged ≤3 years. No significant differences were found in most clinical symptoms, complications, underlying conditions and disease severity parameters among various etiological groups, with the following exceptions. First, prolonged duration of fever, lack of appetite and runny nose were more prevalent among CAP children with Mp-virus co-detection. Second, Mp-virus (excluding HRV) co-detected patients were more likely to present with prolonged duration of fever. Third, patients co-detected with Mp-bacteria were more likely to have abnormal blood gases. Additionally, CAP children with Mp-HRV co-detection were significantly more likely to report severe runny nose compared to those with Mp mono-detection. CONCLUSION: Mp co-detection with viral and/or bacterial pathogens is common in clinical practice. However, there are no apparent differences between Mp mono-detection and Mp co-detections in terms of clinical features and disease severity.

9.
J Gerontol Soc Work ; : 1-14, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31594489

RESUMO

There is a deficiency in empirical knowledge on the physical and mental health of lower-income older people with weak family support in western rural China. To address this research gap, this article uses the data from the 2014 China Longitudinal Aging Social Survey to analyze the disadvantaged situation of older people in western rural China through a regional comparative analysis. Our sample consisted of 7,138 older adults aged 60 or older in eastern and western, rural and urban China. We find that lower personal income is significantly associated with poor physical and mental health. Economic support from families means more for older people when they have a disability related to activities of daily living in western rural China. Fostering stronger family support networks might improve the mental health status of older people in western rural China. Our study suggests a broader scope for the state to play a greater role in economic empowerment and in the development of policies to effectively meet the present and future needs of older people in western rural China or other countries with an imbalance in the distribution of the aging population and welfare resources.

10.
Exp Cell Res ; : 111650, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31563695

RESUMO

Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4+Foxp3+T regulatory cell (CD4+Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8+Foxp3+T regulatory cells (CD8+Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8+Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8+Treg expansion. Moreover, we found that CD8+Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8+Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8+Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8+Treg expansion.

11.
Orthop Surg ; 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489784

RESUMO

OBJECTIVE: Limb salvage in pediatric patients remains a challenge. We describe a staged strategy. The procedure includes: (i) tumor removal and non-hinged static endoprosthesis reconstruction; (ii) leg length discrepancy (LLD) correction by shoe lift or distraction osteogenesis; and (iii) maturity reconstruction by regular endoprosthesis. The aim of the study was to investigate the results of non-hinged static megaprosthesis reconstruction and staged LLD correction in the treatment of malignant tumors in the distal femur in children. METHODS: Non-hinged megaprostheses were implanted in 12 pediatric patients with osteosarcoma in the distal femur. The prosthesis consists of a femoral component with constrained condylar knee (CCK) design, and a tibial component with a small-diameter press-fit stem and derotation fins. A posterior stabilizing polyethylene component is fixed on the tibial component. The cases were prospectively followed up with focus on the growth rate of adjacent uninvolved bone in the salvaged limb, joint stability, knee stability, function outcome, length discrepancy, and surgery-related complications. RESULTS: There were five girls and seven boys included in the study, with an average age at the time of primary surgery of 10.0 years (range, 8-12 years). All the tumors were located in the distal femur. The average follow up was 76.3 months (range, 24-139 months). The Ligament Augmentation and Reconstruction System (LARS) ligament was used in two patients to enhance the soft tissue reattachment and reconstruct medial collateral ligament (MCL). Ten patients were alive at the final follow-up and two had died of lung metastases. Expected LLD was 6.7 cm (range, 3.0-13.2 cm) at initial surgery. At the final follow-up, nine patients reached skeletal maturity and the actual LLD at the femur was 5.3 cm (range, 3.0-10.1 cm), excluding 1 cm correction at initial surgery by endoprosthesis. The proximal tibia physis showed an average of 86.7% (range, 56.5%-100%) growth of the contralateral side. The mean reduction in tibial length was 1.2 cm (range, 0.5-4.7 cm). Six patients received distraction osteogenesis at a mean length of 5.4 cm (range, 3.0-9.1 cm). Range of knee movement was between 85° and 125°, with an average of 102.5°. The Musculoskeletal Tumor Society 93 score of patients alive was 80.6 (range, 60-90). CONCLUSION: Non-hinged static megaprosthesis followed by LLD correction with shoe lift or staged distraction osteogenesis appears to be an alternative option to treat children with malignant bone tumors around the knee.

12.
Cell Death Dis ; 10(9): 662, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506423

RESUMO

Chronic pancreatitis (CP) is a progressive, recurrent inflammatory disorder of the pancreas. Initiation and progression of CP can result from serine protease 1 (PRSS1) overaccumulation and the ensuing endoplasmic reticulum (ER) stress. However, how ER stress pathways regulate the development and progression of CP remains poorly understood. In the present study we aimed to elucidate the ER stress pathway involved in CP. We found high expression of the ER stress marker genes ATF6, XBP1, and CHOP in human clinical specimens. A humanized PRSS1 transgenic mouse was established and treated with caerulein to mimic the development of CP, as evidenced by pathogenic alterations, collagen deposition, and increased expression of the inflammatory factors IL-6, IL-1ß, and TNF-α. ATF6, XBP1, and CHOP expression levels were also increased during CP development in this model. Acinar cell apoptosis was also significantly increased, accompanied by upregulated p53 expression. Inhibition of ATF6 or p53 suppressed the expression of inflammatory factors and progression of CP in the mouse model. Finally, we showed that p53 expression could be regulated by the ATF6/XBP1/CHOP axis to promote the development of CP. We therefore conclude that ATF6 signalling regulates CP progression by modulating pancreatic acinar cell apoptosis, which provides a target for ER stress-based diagnosis and treatment of CP.

13.
Math Biosci Eng ; 16(5): 4399-4414, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31499668

RESUMO

Releasing mosquitoes with Wolbachia into the wild mosquito population is becoming the very promising strategy to control mosquito-borne infections. To investigate the effects of wind and critical patch size on the Wolbachia establishment in the wild mosquito population, in this paper, we propose a diffusion-reaction-advection system in a heterogeneous environment. By studying the related eigenvalue problems, we derive various conditions under which Wolbachia can fully establish in the entire wild mosquito population. Our findings may provide some useful insights on designing practical releasing strategies to control the mosquito population.

14.
Sci Total Environ ; 692: 701-712, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31539978

RESUMO

Most trace metals exhibit a dual role in marine waters, acting as nutrients at low concentration and being toxic at high concentration. But besides concentration range, speciation is also an important factor. They both show both seasonal and spatial variations. A thorough comparison between total dissolved and particulate concentrations estimated from manual sampling and an assessment of the bioavailability using Diffusive Gradients in Thin Films (DGT) has been performed in this work for Cd, Co, Cu, Ni and Pb, at several sampling points of the Belgian Coastal Zone (BCZ). Additional information to trace back the origin and identify the anthropogenic fingerprint of Suspended Particulate Matter (SPM) was measured using stable carbon isotope measurements in particulate organic matter. Our results show that: (i) particulate and total dissolved metal concentrations are higher at two stations, one in the harbor of Oostende and one offshore; (ii) dissolved and particulate trace metal concentrations do not correlate with the dissolved labile fractions; and (iii) SPM in the harbor zone is likely from allochthonous sources, while in the offshore station marine origin has been evidenced. Our results indicate that, even though contamination is higher in the harbor zones, the trace metal toxicity, which is linked to the metal bioavailability, is most likely not higher than in the open sea. However, with increasing acidification of the ocean, a shift from particulate to dissolved phase might lead to increasing adverse effects on the coastal environment.

15.
Hepatology ; 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31520476

RESUMO

Microbial dysbiosis is associated with alcoholic hepatitis (AH) with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides - α-defensins, and to define the link between PC dysfunction and AH. Translocation of pathogen-associated molecular patterns (PAMPs) was determined in patients with severe AH and in a mouse model of alcoholic liver disease. Microbial composition and PC function were examined in mice. The link between α-defensin dysfunction and AH was investigated in α-defensin deficient mice. Synthetic human α-defensin 5 (HD5) was orally given to the alcohol-fed mice to test the therapeutic potential. The role of zinc deficiency in α-defensin was evaluated in acute and chronic mouse models of zinc deprivation. Hepatic inflammation was associated with PAMP translocation, and lipocalin-2 (LCN2) and CXCL1 elevation in AH patients. Antibiotic treatment, lipopolysaccharide injection to mice, and in vitro experiments showed that PAMPs, but not alcohol, directly induced LCN2 and CXCL1. Chronic alcohol feeding caused systemic dysbiosis and PC α-defensin reduction in mice. Knockout of functional α-defensins synergistically affected alcohol-perturbed bacterial composition and gut barrier, and exaggerated PAMP translocation and liver damage. Administration of HD5 effectively altered cecal microbial composition, especially increased Akkermansia muciniphila, and reversed alcohol-induced deleterious effects. Zinc regulated PC homeostasis and α-defensins function at multiple levels, and dietary zinc deficiency exaggerated the deleterious effect of alcohol on PC bactericidal activity CONCLUSIONS: Taken together, the study suggests that alcohol-induced PC α-defensin dysfunction is mediated by zinc deficiency and involved in the pathogenesis of AH. HD5 administration may represent a novel and promising therapeutic approach for treating AH.

16.
Theranostics ; 9(21): 6063-6079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534537

RESUMO

Background: The reciprocal repressive loop between ZEB1 and miRNAs has been extensively reported to play an important role in tumor progression and metastasis of various human tumor types. The aim of this study was to elucidate the role and the underlying mechanism of the double-negative feedback loop between ZEB1and miR-33a-5p in bone metastasis of prostate cancer (PCa). Methods: miR-33a-5p expression was examined in 40 bone metastatic and 165 non-bone metastatic PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-33a-5p expression and clinicopathological characteristics, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-33a-5p in bone metastasis of PCa were investigated both by EMT and the Transwell assay in vitro, and by a mouse model of left cardiac ventricle inoculation in vivo. siRNA library, real-time PCR and chromatin immunoprecipitation (ChIP) were used to identify the underlying mechanism responsible for the decreased expression of miR-33a-5p in PCa. Bioinformatics analysis, Western blotting and luciferase reporter analysis were employed to examine the relationship between miR-33a-5p and its potential targets. Clinical correlation of miR-33a-5p with its targets was examined in human PCa tissues and primary PCa cells. Results: miR-33a-5p expression was downregulated in PCa tissues with bone metastasis and bone-derived cells, and low expression of miR-33a-5p strongly and positively correlated with advanced clinicopathological characteristics, and shorter overall and bone metastasis-free survival in PCa patients. Upregulating miR-33a-5p inhibited, while silencing miR-33a-5p promoted EMT, invasion and migration of PCa cells. Importantly, upregulating miR-33a-5p significantly repressed bone metastasis of PC-3 cells in vivo. Our results further revealed that recurrent ZEB1 upregulation induced by copy number gains transcriptionally inhibited miR-33a-5p expression, contributing to the reduced expression of miR-33a-5p in bone metastatic PCa tissues. In turn, miR-33a-5p formed a double negative feedback loop with ZEB1 in target-independent manner, which was dependent on TGF-ß signaling. Finally, the clinical negative correlations of miR-33a-5p with ZEB1 expression and TGF-ß signaling activity were demonstrated in PCa tissues and primary PCa cells. Conclusion: Our findings elucidated that copy number gains of ZEB1-triggered a TGF-ß signaling-dependent miR-33a-5p-mediated negative feedback loop was highly relevant to the bone metastasis of PCa.

17.
Hum Mutat ; 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489982

RESUMO

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

18.
Chin J Nat Med ; 17(8): 591-599, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472896

RESUMO

Whitmania pigra has been used as a traditional Chinese medicine (TCM) for promoting blood circulation, alleviating blood coagulation, activating meridians and relieving stasis for several hundred years. However, the therapeutic components of this species, especially proteins and peptides were poorly exploited. Until now only a few of them were obtained by using chromatographic isolation and purification. In recent decade, transcriptome techniques were rapidly developed, and have been used to fully reveal the functional components of many animal venoms. In the present study, the cDNA of the salivary gland of Whitmania pigra was sequenced by illumina and the transcriptome was assembled by using Trinity. The proteome were analysed by LC-MS/MS. Based on the data of the transcriptome and the proteome, a potential antiplatelet protein named pigrin was found. Pigrin was cloned and expressed using P. pastoris GS115. The antiplatelet andantithrombotic bioactivities of pigrin were tested by using aggregometer and the rat arterio-venous shunt thrombosis model, respectively. Thebleeding time of pigrin was measured by a mice tail cutting method. The docking of pigrin and protease-activated receptor 1 (PAR1) or collagen were conducted using the ZDOCK Server. Pigrin was able to selectively inhibit platelet aggregation stimulated by PAR1 agonist and collagen. Pigrin attenuated thrombotic formation in vivo in rat, while did not prolong bleeding time at its effective dosage. There are significant differences in the key residues participating in binding of Pigrin-Collagen complex from Pigrin-PAR1 complex. In conclusion,a novel PAR1 inhibitor pigrin was found from the leech Whitmania pigra. This study helped to elucidate the mechanism of the leech for the treatment of cardiovascular disorder.

19.
Biochem Genet ; 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31552564

RESUMO

The common variants of the methylenetetrahydrofolate reductase (MTHFR) gene are related to the activity of the MTHFR enzyme and the concentrations of blood homocysteine (Hcy). This study was designed to investigate the associations of MTHFR in Chinese populations with early-onset coronary artery disease (EOCAD). The two common variants of the MTHFR gene were genotyped in 875 EOCAD patients and 956 controls using PCR, followed by direct sequencing of the PCR product. Serum levels of Hcy were measured using an automatic biochemistry analyzer. A significant association between the MTHFR-677C/T variant and the risk of EOCAD was detected in CC versus TT (odds ratio (OR) 1.456, 95% confidence interval (CI) 1.120-1.892), dominant genetic model (OR 1.266, 95% CI 1.027-1.546), and recessive genetic model (OR 1.306, 95% CI 1.040-1.639). Hcy was most abundant in TT genotype (18.31 ± 7.22 µmol/L), least abundant in CC genotype (11.37 ± 5.23 µmol/L), and detectable at intermediate levels in heterozygotes (15.25 ± 6.58 µmol/L). Elevated serum Hcy levels were an independent risk factor for EOCAD (ORadjust 1.431, 95% CI 1.135-1.763). Our findings indicated that the T allele of -677C/T MTHFR variant predisposes to high levels of Hcy, and that the T allele is an important risk factor for EOCAD in the Chinese population.

20.
J Enzyme Inhib Med Chem ; 34(1): 1678-1689, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31530032

RESUMO

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.

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