Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 675
Filtrar
1.
J Orthop Res ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31736104

RESUMO

The purpose of this investigation was to determine the role of extracellular vesicles (EVs), released from articular chondrocytes in a physiological or pathological state, in cell-cell communication with other articular chondrocytes or chondrocyte precursor cells. The conditioned medium from interleukin-1ß (IL-1ß)-treated human articular chondrocytes stimulated catabolic events and inhibited type II collagen expression in articular chondrocytes to a much greater degree than medium from IL-1ß-treated chondrocytes after complete removal of EVs. The vehicle-treated and IL-1ß-treated human articular chondrocytes released EVs of similar size; however, the number of EVs released by IL-1ß-treated chondrocytes was markedly higher than the number of EVs released from the vehicle-treated cells. Furthermore, our findings demonstrate that similar to medium from IL-1ß-treated chondrocytes containing EVs, EVs isolated from medium of IL-1ß-treated chondrocytes stimulated catabolic events in articular chondrocytes, whereas EVs isolated from the medium of vehicle-treated chondrocytes inhibited catabolic events and increased messenger RNA levels of aggrecan and type II collagen in IL-1ß-treated chondrocytes. Furthermore, the medium containing EVs from vehicle-treated articular chondrocytes or EVs isolated from this medium stimulated chondrogenesis of C3H10T1/2 cells, whereas medium containing EVs from IL-1ß-treated chondrocytes or EVs isolated from this medium inhibited chondrogenesis. Our findings suggest that EVs released by articular chondrocytes play a key role in the communication between joint cells and ultimately in joint homeostasis, maintenance, pathology, and repair. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

2.
Atherosclerosis ; 291: 71-77, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31704553

RESUMO

BACKGROUND AND AIMS: Atherosclerosis is an important contributing factor to cardiovascular mortality. The role of Helicobacter pylori (H. pylori) infection in atherosclerosis is inconsistent and sometimes controversial. The present study aimed to determine if H. pylori infection is associated with carotid atherosclerosis. METHODS: 17,613 males and females with both carotid ultrasonic examination and 13C-urea breath test for H. pylori infection were screened by a major Chinese university hospital from March 2012 to March 2017 for the study. Baseline demographics, cardiac risk factors, and laboratory studies were obtained. After exclusion for pre-specified conditions, 12,836 individuals were included in the analysis, including 8157 men (63.5%) and 4679 women (36.5%). Analysis was also made for 5-year follow-up data of 1216 subjects (869 males and 347 females) with and without H. pylori infection for development and progression of carotid atherosclerosis. RESULTS: After adjusting for age, sex, body mass index, lipid profile, hypertension, renal function, diabetes mellitus, and smoking, H. pylori infection was found as an independent risk factor for carotid atherosclerosis in males under 50 years, but not in older males or females (odds ratio 1.229, 95% CI 1.054-1.434, p = 0.009). Follow-up data analysis showed that the incidence of carotid atherosclerosis from no atherosclerosis to detectable lesions was significantly higher in young males with persistent H. pylori infection than those without H. pylori infection (p = 0.028) after 3 years. CONCLUSIONS: These data suggest that H. pylori infection might be an important risk factor for carotid atherosclerosis in young Chinese males under 50.

3.
J Dairy Sci ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31677844

RESUMO

Previous research reported that fermented yak milk had a diverse microbial composition. For this study, raw yak milk, qula, and fermented yak milk samples were collected from the Aba Tibetan autonomous region of China. The genus and species microbial composition of these samples were analyzed by high-throughput sequencing of 16S rRNA and groEL gene amplicons, and the volatile profile of the samples was quantified by gas chromatography-mass spectrometry. The results indicated variation in abundance of microbiota at the genus level among the fermented yak milk samples, with Lactobacillus as the most abundant genus in the majority of samples, ranging from 41.6 to 98.26%. The volatile profile of the samples varied among those collected from different villages. Correlations between bacterial composition and volatile compounds of the samples were also observed. Lactobacillus displayed a significant correlation with volatile compounds such as benzaldehyde, 2,3-pentanedione, ethanol, and ethyl acetate, whereas the samples with relatively high abundance of Streptococcus and Lactococcus displayed relatively low contents of volatile compounds.

4.
J Dairy Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31704010

RESUMO

The ability to use lactose is critical for the application of Streptococcus thermophilus in fermented dairy products. Most studies have evaluated the use of lactose of S. thermophilus by measuring lactose utilization, but its correlation with ß-galactosidase and urease has rarely been investigated. In this study, 10 strains of S. thermophilus isolated from fermented yak milk exhibited a diversity of ß-galactosidase and urease activities, growth, and acid production in de Man, Rogosa, and Sharpe-lactose. Among the strains, 15G5 possessed the highest ß-galactosidase activity and showed the highest cell growth, lactic acid production, and titratable acidity during fermentation. In contrast, 7G10, with the weakest ß-galactosidase activity, produced the lowest lactic acid content and change in titratable acidity. Further investigation indicated that ß-galactosidase activity of S. thermophilus showed significant positive correlations with the growth of cell densities, the production of lactic acid, and titratable acidity, and urease activity of S. thermophilus showed a significant correlation with the use of lactose and the production of lactic acid and acetaldehyde. These findings suggest that the differences of ß-galactosidase and urease activities are essential for the performance in the lactose metabolism, growth, and acid production of S. thermophilus, providing new insights into strain selection and application.

5.
J Vis Exp ; (151)2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31609326

RESUMO

Detailed and comprehensive geometric data of vertebrae endplates is important and necessary to improve the fidelity of finite element models of the spine, design and ameliorate spinal implants, and understand degenerative changes and biomechanics. In this protocol, a high-speed and highly accurate scanner is employed to convert morphology data of endplate surfaces into a digital point cloud. In the software system, the point cloud is further processed and reconstructed into three dimensions. Then, a measurement protocol is performed, involving a 3D coordinate system defined to make each point a 3D coordinate, three sagittal and three frontal surface curves that are symmetrically fitted on the endplate surface, and 11 equidistant points that are selected in each curve. Measurement and spatial analyses are finally performed to obtain geometric data of the endplates. Parametric equations representing the morphology of curves and surfaces are fitted based on the characteristic points. The suggested protocol, which is modular, provides an accurate and reproducible method to obtain geometric data of vertebral endplates and may assist in more sophisticated morphological studies in the future. It will also contribute to designing personalized spinal implants, planning surgical acts, making clinical diagnoses, and developing accurate finite element models.

6.
Sci Adv ; 5(9): eaaw6499, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31579820

RESUMO

RNA interference (RNAi) technology can specifically silence the expression of a target gene and has emerged as a promising therapeutic method to treat cancer. In the present study, we showed that natural halloysite nanotube (HNT)-assisted delivery of an active small interfering RNA (siRNA) targeting receptor-interacting protein kinase 4 ( RIPK4 ) efficiently silenced its expression to treat bladder cancer. The HNTs/siRNA complex increased the serum stability of the siRNA, increased its circulation lifetime in blood, and promoted the cellular uptake and tumor accumulation of the siRNA. The siRNA markedly down-regulated RIPK4 expression in bladder cancer cells and bladder tumors, thus inhibiting tumorigenesis and progression in three bladder tumor models (a subcutaneous model, an in situ bladder tumor model, and a lung metastasis model), with no adverse effects. Thus, we revealed a simple but effective method to inhibit bladder cancer using RIPK4 silencing, indicating a promising therapeutic method for bladder cancer.

7.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 673-681, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638563

RESUMO

Objective To investigate the impact of the macrophage-derived exosomes on transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) of lung epithelial cells in an inflammatory environment. Methods The morphology of exosomes derived from THP-1 macrophages was evaluated by transmission electron microscopy, and the biochemistry properties of exosomes were identified by accessing exosome-specific markers including tumor susceptibility gene 101 (TSG101), accessory protein ALG-2 interacting protein X (ALIX), CD81 and CD9 protein, and the calnexin, a negative control marker absent in exosomes, using an immunoblotting assay. The EMT of alveolar epithelial A549 cells was induced by TGF-ß1, and the impacts of exosomes on the EMT of A549 cells was ascertained by comparing cells treated with exsomes derived from LPS-primed THP-1 macrophages and naive THP-1 cells. Results We successfully established an A549 cell EMT model by TGF-ß1 induction and isolated exosomes derived from THP-1 macrophages. In comparison with the exosomes derived from untreated naive THP-1 macrophages, exosomes derived from LPS-primed THP-1 cells exhibited an ability to significantly promote TGF-ß-induced EMT of A549 cells, as determined by a significantly down-regulated E-cadherin, and an dramatically increased expression of proteins in EMT-related signaling including vimentin, alpha smooth muscle actin (α-SMA), TGF-ß1/Smad2/3 signaling proteins Smad2/3 protein and phosphorylated Smad2/3 (p-Smad2/3) and type 1 collagen (Col1). Conclusion Exosomes derived from LPS-stimulated macrophages are able to activate TGF-ß/Smad2/3 signaling, which in turn increase the expression of EMT-related proteins vimentin, α-SMA and Col1 in A549 cells, and subsequently promote EMT in A549 cells.


Assuntos
Transição Epitelial-Mesenquimal , Exossomos , Macrófagos , Fator de Crescimento Transformador beta1 , Células A549 , Transição Epitelial-Mesenquimal/fisiologia , Exossomos/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 890-893, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506148

RESUMO

OBJECTIVE: To study the long-term clinical effect of the CCLG-ALL2008 regimen in the treatment of children newly diagnosed with acute lymphoblastic leukemia (ALL) with different molecular biological features. METHODS: A total of 940 children who were newly diagnosed with ALL were enrolled in this study. The children were treated with the CCLG-ALL2008 regimen. A retrospective analysis was performed for the long-term outcome of ALL children with different molecular biological features. RESULTS: Among the 940 children with ALL, there were 570 boys and 370 girls, with a median age of onset of 5 years (range 1-15 years) and a median follow-up time of 65 months (range 3-123 months). The complete response (CR) rate was 96.7%, the predicted 10-year overall survival (OS) rate was 76.5%±1.5%, and the event-free survival (EFS) rate was 62.6%±3.0%. After CR was achieved after treatment, the overall recurrence rate was 21.9%. The children with positive ETV6-RUNX1 had the lowest recurrence rate and were prone to late recurrence, and those with positive MLL rearrangement had the highest recurrence rate and were prone to early recurrence. The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year OS rate than those with positive TCF3-PBX1, BCR-ABL, or MLL rearrangement and those without molecular biological features (P<0.05). The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year EFS rate than those with positive BCR-ABL or MLL rearrangement (P<0.05). CONCLUSIONS: Molecular biological features may affect the long-term prognosis of children with ALL, and positive MLL rearrangement and BCR-ABL fusion gene are indicators of poor prognosis. Children with positive ETV6-RUNX1 fusion gene have the highest long-term survival rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
9.
Endocrine ; 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31542859

RESUMO

OBJECTIVE: Metabolic syndrome is a chronic-metabolic disease caused by a variety of factors, including high peripheral blood insulin levels and insulin resistance. It has been reported that GLP-1 could regulate insulin resistance. It is not known whether and how GLP-1 protects from fat-induced inflammation and immune changes. We investigated if GLP-1 alters the populations of fat-induced inflammation and immune cells and the related mechanism. METHODS: We obtained obese C57BL/6J mice by feeding them high-fat food, then treated the obese mice with GLP-1+ high-fat diet (G + Hi), normal chow diet (Nor), or high-fat diet (Hi) (n = 20 for each group) for 8 weeks. The GLP-1 receptor-/- B6 group were fed with HFD for 8 weeks (GLP-1R KO + Hi). In vivo and in vitro experiments were conducted on mice immune cells to investigate the effects of GLP-1 on the changes of the immune components and functions in obesity. RESULTS: We found that GLP-1 could efficiently change the CD4+ T subsets and level of cytokines in high-fat-induced mice by GLP-1 receptor. Further, these changes were correlated with a reduction in fat content and serum lipid level. Interestingly, GLP-1 could enhance the function of Tregs in vitro. CONCLUSION: Our data showed that GLP-1 has an important role in shaping the CD4+ T population in high-fat-diet-induced mice by GLP-1 receptor, possibly providing a new target for the treatment of metabolic syndrome.

11.
ACS Appl Mater Interfaces ; 11(41): 37578-37585, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31522491

RESUMO

Compared with traditional metal-based photosensitizers, heterogeneous and organic photocatalysts with visible-light activity are more environmentally friendly and sustainable. The simultaneous introduction of electron-rich and electron-deficient units in donor-acceptor typed conjugated microporous polymer (CMP) photocatalysts can significantly enhance their visible-light harvesting and separation efficiency of photogenerated carriers. Here, two carbazole-based CMPs (CzBSe-CMP and CzBQn-CMP) were successfully constructed through a cost-effective process. They show inherent porosity with large Brunauer-Emmett-Teller surface area and excellent thermal and chemical stability. Their photoelectric properties, energy levels, optical band gaps, transient photocurrent response, and photocatalytic activity could be conveniently tailored through tuning the electron-deficient moiety in polymer networks. More importantly, CzBSe-CMP was found to be a superior solid photocatalyst for selective photo-oxidation of mustard gas simulant 2-chloroethyl ethyl sulfide into a nontoxic product by using molecular oxygen as a sustainable oxygen source under visible-light illumination. In addition, the obtained CMP-based photocatalysts also showed excellent recyclability and could be reutilized through adding more simulants or a simple separation procedure. The current contribution provides great application prospects for CMPs as metal-free, solid photocatalysts in organic transformation and environmental protection.

12.
World J Gastroenterol ; 25(35): 5220-5232, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31558869

RESUMO

Helicobacter pylori (H. pylori) is a Gram-negative bacterium with a number of virulence factors, such as cytotoxin-associated gene A, vacuolating cytotoxin A, its pathogenicity island, and lipopolysaccharide, which cause gastrointestinal diseases. Connexins function in gap junctional homeostasis, and their downregulation is closely related to gastric carcinogenesis. Investigations into H. pylori infection and the fine-tuning of connexins in cells or tissues have been reported in previous studies. Therefore, in this review, the potential mechanisms of H. pylori-induced gastric cancer through connexins are summarized in detail.

13.
J Cell Biol ; 218(10): 3336-3354, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31519728

RESUMO

The process of phagophore closure requires the endosomal sorting complex required for transport III (ESCRT-III) subunit CHMP2A and the AAA ATPase VPS4, but their regulatory mechanisms remain unknown. Here, we establish a FACS-based HaloTag-LC3 autophagosome completion assay to screen a genome-wide CRISPR library and identify the ESCRT-I subunit VPS37A as a critical component for phagophore closure. VPS37A localizes on the phagophore through the N-terminal putative ubiquitin E2 variant domain, which is found to be required for autophagosome completion but dispensable for ESCRT-I complex formation and the degradation of epidermal growth factor receptor in the multivesicular body pathway. Notably, loss of VPS37A abrogates the phagophore recruitment of the ESCRT-I subunit VPS28 and CHMP2A, whereas inhibition of membrane closure by CHMP2A depletion or VPS4 inhibition accumulates VPS37A on the phagophore. These observations suggest that VPS37A coordinates the recruitment of a unique set of ESCRT machinery components for phagophore closure in mammalian cells.

14.
Dalton Trans ; 48(36): 13711-13718, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31469134

RESUMO

Three benzenedithiolate-bridged diiron hexacarbonyl complexes (2, 3 and 4) with different functional groups were designed and synthesized. In addition, a well-defined benzenedithiolate-bridged complex without any functional groups, 5, was employed for comparison. Electrochemical investigations using five different acids showed that the first reduction potential of the complexes shifted positively in acidic media. This potential shift is attributed to a PCET (Proton-Coupled Electron Transfer) reaction and depends on the acid strength. When an acid is too weak (pKa ≥ 24 in this case), no potential shift is observed. Moreover, increasing the acid strength does not lead always to a linear trend in the potential shift for all of the complexes due to kinetic resistance during proton transfer for some of the complexes. The presence of a pendant basic group (2) can ease such kinetic resistance, and the linear trend holds valid up to pKa 1.8, whereas for the rest of the complexes (3-5), which do not bear an internal basic group, the correlation between the potential shift and the acid strength levels off after a certain pKa value (12). Alternatively, when the acid is strong enough to provide sufficient proton, further increases in the acid strength do not improve the potential shift and the kinetic resistance for a proton to cross the solvated layer becomes dominant.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 766-771, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31416500

RESUMO

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×109/L; n=629). The thrombocytopenia group was further divided into (50- <100)×109/L (n=243), (20- <50)×109/L (n=263), and <20×109/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×109/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×109/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). CONCLUSIONS: ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×109/L have the worst prognosis.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Intervalo Livre de Doença , Humanos , Imunofenotipagem , Prognóstico , Recidiva
16.
J Hazard Mater ; 381: 120936, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31377577

RESUMO

As a by-product of nickel production, the ferronickel slag (FNS) puts a lot of pressure on the environment. It is becoming more and more urgent to deal with the increasing FNS. The aim of this study is to explore the durability of concrete with FNS fine aggregate. Two kinds of FNS with different storage time were selected. The radioactivity detection, XRD test and stability detection of FNS were conducted to ensure FNS can be used as construction materials. Then the durability of concrete with 13%, 27%, 40% and 50% FNS (by weight of fine aggregate) was investigated, respectively. It was found that the properties of concrete prepared from FNS with different storage time had little difference. The results indicated that 27% FNS replacement showed improvement in resistance to sulfate attack by 22% but the resistance to chloride ion penetration was not significantly influenced. Moreover, 40% FNS addition brought a 33% abrasion reduction than that of original concrete. SEM analysis showed that FNS produced more C-S-H gels and improved the microstructure of concrete. This study indicated that proper content of FNS can be used as fine aggregate and it was beneficial to the durability of concrete, especially to the abrasion resistance.

17.
Bioresour Technol ; 292: 122007, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31445963

RESUMO

The aim of this work was to study the molecular compositional changes of dissolved organic matter (DOM) during hyperthermophilic composting (HTC) using electrospray ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. Our results reveal that DOM in hyperthermophilic compost mainly consisted of lignins/carboxylic-rich alicyclic molecules (72%) with relatively lower H/C (1.24), and the higher double bound equivalent (5.98) and aromaticity index (0.22) when compared with the DOM in composting materials, suggesting that HTC led to an increase in carboxyl-rich, unsaturated, and aromatic compounds. Profiles of the DOM's transformation indicated that low O/C (O/C < 0.3) and high H/C (H/C < 1.5) compounds were preferentially decomposed in the hyperthermophilic phase of HTC. Abundant produced intermediates, such as lignin phenols and amino sugars, were further transformed to refractory humic substances. This investigation extends the current understanding of the molecular mechanisms on humification of HTC, and reveals further applications for hyperthermophilic compost.


Assuntos
Compostagem , Substâncias Húmicas , Espectrometria de Massas , Compostos Orgânicos
18.
Genes (Basel) ; 10(7)2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336987

RESUMO

Lactobacillus is a fairly diverse genus of bacteria with more than 260 species and subspecies. Many profiling methods have been developed to carry out phylogenetic analysis of this complex and diverse genus, but limitations remain since there is still a lack of comprehensive and accurate analytical method to profile this genus at species level. To overcome these limitations, a Lactobacillus-specific primer set was developed targeting a hypervariable region in the groEL gene-a single-copy gene that has undergone rapid mutation and evolution. The results showed that this methodology could accurately perform taxonomic identification of Lactobacillus down to the species level. Its detection limit was as low as 104 colony-forming units (cfu)/mL for Lactobacillus species. The assessment of detection specificity using the Lactobacillus groEL profiling method found that Lactobacillus, Pediococcus, Weissella, and Leuconostoc genus could be distinguished, but non-Lactobacillus Genus Complex could not be detected. The groEL gene sequencing and Miseq high-throughput approach were adopted to estimate the richness and diversity of Lactobacillus species in different ecosystems. The method was tested using kurut (fermented yak milk) samples and fecal samples of human, rat, and mouse. The results indicated that Lactobacillus mucosae was the predominant gut Lactobacillus species among Chinese, and L. johnsonii accounted for the majority of lactobacilli in rat and mouse gut. Meanwhile, L. delbrueckii subsp. bulgaricus had the highest relative abundance of Lactobacillus in kurut. Thus, this groEL gene profiling method is expected to promote the application of Lactobacillus for industrial production and therapeutic purpose.

19.
Med Sci Monit ; 25: 4837-4848, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31256192

RESUMO

BACKGROUND Helicobacter pylori infection is associated with various vascular diseases. However, its mechanism is yet to be defined. The present study aimed to investigate the effect of H. pylori on vascular endothelial cells as well as the GATA3-related mechanism of H. pylori infection-induced endothelial injuries. MATERIAL AND METHODS A co-culture of H. pylori with human umbilical endothelial cells (HUVECs) was produced. The proliferation of HUVECs that had been incubated with H. pylori were examined via CCK-8 (Cell Counting Kit-8) and EdU (5-ethynyl-2'-deoxyuridine) staining. Cell migration and microtubules formation were studied using Transwell and tube formation respectively. Construction of a mouse model of H. pylori infection as well as the expression of GATA3 and CHI3L1 in vessels were tested using western blot and immunohistochemistry. Small interfering RNA (siRNA) of GATA3 were transfected into HUVECs in order to establish cell lines with knocked-down GATA3. The production of the aforementioned molecules and p38 mitogen-activated protein kinase (MAPK) related molecules in HUVECs was measured using quantitative real-time polymerase chain reaction and western blot. RESULTS H. pylori significantly inhibited the proliferation, migration, and tube formation of HUVECs, as well as increased the production of the inflammatory factor CHI3L1 and phosphorylated p38 from endothelial cells along with an increased expression of GATA3. Elevated levels of the GATA3 and CHI3L1 were also found in the arteries of H. pylori-infected mice. Following GATA3 knockdown, the H. pylori-induced dysfunction of HUVECs was restored. CONCLUSIONS H. pylori impaired vascular endothelial function. This might be due to the H. pylori-induced increased expression of GATA3, as well as the GATA3 mediated upregulated CHI3L1 and activation of the p38 MAPK pathway.

20.
Genome Biol ; 20(1): 143, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345249

RESUMO

While genetic relatedness, usually manifested as segments identical by descent (IBD), is ubiquitous in modern large biobanks, current IBD detection methods are not efficient at such a scale. Here, we describe an efficient method, RaPID, for detecting IBD segments in a panel with phased haplotypes. RaPID achieves a time and space complexity linear to the input size and the number of reported IBDs. With simulation, we showed that RaPID is orders of magnitude faster than existing method while offering competitive power and accuracy. In UK Biobank, RaPID identified 3,335,807 IBDs with a lenght ≥ 10 cM among 223,507 male X chromosomes in 11 min.


Assuntos
Técnicas de Genotipagem/métodos , Linhagem , Bancos de Espécimes Biológicos , Cromossomos Humanos X , Estudos de Coortes , Simulação por Computador , Haplótipos , Humanos , Masculino
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA