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1.
Medicine (Baltimore) ; 99(11): e18831, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176027

RESUMO

This study aimed to investigate diabetes distress, happiness, and its associated factors of patients with type 2 diabetes mellitus (T2DM) treated by different therapies, and to analyze the related impact factors. A total of 1512 patients with T2DM were randomly selected from 18 tertiary hospitals in Hunan province from January 2016 to April 2016 who has been treated with oral antidiabetics monotherapy, insulin monotherapy, and combination therapy. Use the general information questionnaire, WHO-5 (the World Health Organization 5 well-being index) and PAID (the problem areas in diabetes scale) to collect the data. There are 846 (55.95%) patients that have serious emotional disorders, and the diabetes related distress in insulin treatment group was higher than that in combination treatment group (P < .05). Happiness of T2DM patients in combination therapy was higher than oral antidiabetic drug monotherapy and insulin monotherapy (P < .05). There was a negative correlation between diabetic suffering and happiness in patients with different treatments (R ranged from -0.335 to -0.436, P < .001). Age and happiness experience could explain 14.8% of the variance. Acute and chronic complications, controlled blood glucose level, lifestyle, therapies, and school education can explain 18.3% variance. Under different therapies, the suffering and happiness of T2DM patients differed from each other. The suffering and happiness of T2DM were related to different therapies, age, complications, glycaemic control, lifestyle, school education, and so on.


Assuntos
Diabetes Mellitus Tipo 2/psicologia , Felicidade , Estresse Psicológico/etiologia , Adulto , Idoso , China , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estresse Psicológico/terapia , Inquéritos e Questionários
2.
Environ Microbiol ; 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32114713

RESUMO

The antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) in human gut microbiota have significant impact on human health. While high throughput metagenomic sequencing reveals genotypes of microbial communities, the functionality, phenotype and heterogeneity of human gut microbiota are still elusive. In this study, we applied Raman microscopy and deuterium isotope probing (Raman-DIP) to detect metabolic active ARB (MA-ARB) in situ at the single-cell level in human gut microbiota from two healthy adults. We analysed the relative abundances of MA-ARB under different concentrations of amoxicillin, cephalexin, tetracycline, florfenicol and vancomycin. To establish the link between phenotypes and genotypes of the MA-ARB, Raman-activated cell sorting (RACS) was used to sort MA-ARB from human gut microbiota, and mini-metagenomic DNA of the sorted bacteria was amplified, sequenced and analysed. The sorted MA-ARB and their associated ARGs were identified. Our results suggest a strong relation between ARB in human gut microbiota and personal medical history. This study demonstrates that the toolkit of Raman-DIP, RACS and DNA sequencing can be useful to unravel both phenotypes and genotypes of ARB in human gut microbiota at the single-cell level.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32170020

RESUMO

Plants balance their competing requirements for growth and stress tolerance via a sophisticated regulatory circuitry that controls responses to the external environments. We have identified a plant-specific gene, COST1 (constitutively stressed 1), that is required for normal plant growth but negatively regulates drought resistance by influencing the autophagy pathway. An Arabidopsis thaliana cost1 mutant has decreased growth and increased drought tolerance, together with constitutive autophagy and increased expression of drought-response genes, while overexpression of COST1 confers drought hypersensitivity and reduced autophagy. The COST1 protein is degraded upon plant dehydration, and this degradation is reduced upon treatment with inhibitors of the 26S proteasome or autophagy pathways. The drought resistance of a cost1 mutant is dependent on an active autophagy pathway, but independent of other known drought signaling pathways, indicating that COST1 acts through regulation of autophagy. In addition, COST1 colocalizes to autophagosomes with the autophagosome marker ATG8e and the autophagy adaptor NBR1, and affects the level of ATG8e protein through physical interaction with ATG8e, indicating a pivotal role in direct regulation of autophagy. We propose a model in which COST1 represses autophagy under optimal conditions, thus allowing plant growth. Under drought, COST1 is degraded, enabling activation of autophagy and suppression of growth to enhance drought tolerance. Our research places COST1 as an important regulator controlling the balance between growth and stress responses via the direct regulation of autophagy.

5.
Medicine (Baltimore) ; 99(12): e19400, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195935

RESUMO

Although the platelet distribution width (PDW) has been reported as a reliable predictor of prognosis in several types of cancer, to our knowledge the prognostic value of PDW in hilar cholangiocarcinoma (HC) has not been studied. The aim of the study was to investigate the prognostic value of PDW in HC patients. A retrospective analysis of 292 consecutively recruited HC patients undergoing radical resection with at least a 5-year follow-up. The optimal cutoff value of PDW was determined by receiver operating characteristic (ROC) curve. Survival analysis by the Kaplan-Meier method and the difference between the clinico-pathologic variables and survival was evaluated by log-rank analysis. Multivariate analysis identified independent prognostic risk factors of overall survival (OS). ROC curve analysis suggested that the optimal cutoff value for the PDW was 16.55. There were significant associations of high PDW with high white blood cell (P < .001) and high neutril-to-lymph ratio (P < .001). In a multivariate analysis, the PDW was an independent prognostic factor for overall survival (HR = 2.521, 95% CI 1.832-3.470, P < .001). In conclusions, our findings indicate that PDW may have clinical significance in predicting OS after surgery in HC patients.

6.
Microbiologyopen ; : e1020, 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153142

RESUMO

The intestinal microbiota plays an important role in the health and metabolism of the host. Next-generation sequencing technology has enabled the characterization of the gut microbiota of several animal species. We analyzed the intestinal microbiota in six different parts of the gastrointestinal tracts (GITs) of five Mongolian horses by sequencing the 16S rRNA gene V3-V4 hypervariable region. All horses were kept in the natural habitat of the Inner Mongolia grassland. Significant differences were observed among the microbiota compositions of the distinct GIT regions. In addition, while the microbial community structures of the small and large intestine were significantly different, those of the cecum and colon were similar. In the foregut, Firmicutes (65%) and Proteobacteria (23%) were the most abundant, while Firmicutes (45%) and Bacteroidetes (42%) were the most common in the hindgut. At the level of family, Ruminococcaceae (p = .203), Lachnospiraceae (p = .157), Rikenellaceae (p = .122), and Prevotellaceae (p = .068) were predominant in the hindgut, while the relative abundance of the Akkermansia genus (5.7%, p = .039) was higher in the ventral colon. In terms of the putative functions, the ratio of microbial abundance in the different parts of the GIT was similar, the result can help characterize the gut microbial structure of different animals.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32006752

RESUMO

OBJECTIVES: Little attention has been paid to heavy metal resistance (HMR) to pathogenic bacteria with the wide use of heavy metals as feed additives in food animals. Therefore, present study was constructed to investigate the presence of HMR in Escherichia coli and Salmonella, and its correlation with disinfectant resistance genes (DRGs) and antibiotic resistance genes (ARGs). METHODS: The heavy metal resistance genes (HMRGs) of 178 E. coli and 294 Salmonella isolated from chicken farms and retail meats were detected by polymerase chain reaction (PCR). The minimal inhibitory concentrations (MICs) of heavy metals were determined by broth micro-dilution method. The complete-genome of E. coli E308 which had indications of multi-resistance was recovered and assembled using third-generation sequencing. RESULTS: Results showed that frequency of different HMRGs in E. coli and Salmonella ranged 0.60 - 77.0% and 0.30 - 87.1%, respectively. MICs of heavy metals for E. coli and Salmonella ranged widely from ≤ 12.5 mg/L to 1600 mg/L. Moreover, the HMRGs (zntA, arsB, merA, pcoR, pcoA, pcoC and chrA) were found to be significantly associated with one or more DRGs (sugE(c), emrE, mdfA, ydgE/ydgF, qacF, sugE(p) and qacEΔ1) and ARGs (sul1, sul2, sul3, tetA, tetB, tetC, blaTEM, blaSHV and blaCTX) (p < 0.05). CONCLUSIONS: The present study demonstrated that HMRGs were widely present in E. coli and Salmonella isolated from chicken farm and retail meats, and the association between HMRGs with DRGs and ARGs may lead to the co-resistance of heavy metals and other antimicrobials.

8.
J Leukoc Biol ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32057138

RESUMO

BACKGROUND: Neutropenia and impaired functions were common manifestation in antiretroviral therapy (ART) in both naïve and experienced PLWHA. Granulopoiesis can be divided into two phases: lineage determination and committed granulopoiesis. However, stage-specific impairment of granulopoiesis in PLWHA with neutropenia remains unclear. METHODS: A total of 48 ART-naïve and 49 ART-experienced PLWHA from 2016 to 2018 were recruited and divided into non-, mild-, and moderate-to-severe-neutropenia groups according to their neutrophil counts. The bone marrow aspirates and peripheral blood were collected and analyzed by multicolor flow cytometry for granulocyte subsets, hematopoietic stem/progenitor cells (HSPC), apoptosis, and emigration and retention of different subsets. RESULTS: Compared with healthy donors, the percentages of circulating segmented neutrophils were significantly decreased along with an increase of immature neutrophils in both groups. ART-naïve patients with moderate to severe neutropenia exhibited decreased proportion and accelerated apoptosis of relative mature segmented neutrophils. In contrast, ART-experienced patients with neutropenia displayed decreased proportion of granulocyte macrophage progenitors, indicating a defect at a stage of lineage determination. Meanwhile, ART-experienced patients with neutropenia also the expression of CXCR4 segmented neutrophils, suggesting an increased retention of segmented neutrophils inn the bone marrow. CONCLUSIONS: ART-naïve patients with neutropenia is caused by increased apoptosis of relatively differentiated neutrophils at committed granulopoiesis, whereas impaired lineage determination and enhanced retention of segmented neutrophils contribute to in ART-experienced patients.

9.
Nature ; 579(7798): 270-273, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32015507

RESUMO

Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.


Assuntos
Betacoronavirus/classificação , Betacoronavirus/genética , Quirópteros/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Surtos de Doenças , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Animais , Anticorpos Antivirais/sangue , Betacoronavirus/metabolismo , Betacoronavirus/ultraestrutura , Linhagem Celular , China/epidemiologia , Feminino , Genoma Viral/genética , Humanos , Masculino , Peptidil Dipeptidase A/metabolismo , Filogenia , Vírus da SARS/classificação , Vírus da SARS/genética , Homologia de Sequência do Ácido Nucleico , Síndrome Respiratória Aguda Grave , Células Vero
10.
Artigo em Inglês | MEDLINE | ID: mdl-32109631

RESUMO

BACKGROUND & AIMS: Portal vein thrombosis (PVT) is a common and serious complication in patients with cirrhosis. However, little is known about PVT in patients with cirrhosis and acute decompensation (AD). We investigated the prevalence and clinical significance of PVT in nonmalignant patients with cirrhosis and AD. METHODS: We performed a retrospective study of 2 cohorts of patients with acute exacerbation of chronic liver disease who participated in the CATCH-LIFE study, established by the Chinese Chronic Liver Failure Consortium, from January 2015 through December 2016 (n=2600 patients) and July 2018 through January 2019 (n=1370 patients). We analyzed data on the prevalence, clinical manifestations, and risk factors of PVT from 2826 patients with cirrhosis, with and without AD. RESULTS: The prevalence of PVT in patients with cirrhosis and AD was 9.36%, which was significantly higher than in patients with cirrhosis without AD (5.24%) (P=.04). Among patients with cirrhosis and AD, 63.37% developed PVT recently (the first detected PVT with no indication of chronic PVT). Compared to patients without PVT, a significantly higher proportion of patients with PVT had variceal bleeding (47.33% vs 19.63%; P<.001) and patients with PVT had a significantly higher median serum level of D-dimer (2.07 vs 1.25; P<.001). Splenectomy and endoscopic sclerotherapy were independent risk factors for PVT in patients with cirrhosis and AD. The 1-year mortality rate did not differ significantly between patients with vs without PVT. CONCLUSIONS: In an analysis of data from 2826 patients with cirrhosis, a significantly higher proportion of those with AD had PVT than those without AD. PVT was associated with increased variceal bleeding, which would increase the risk for AD. Strategies are needed to prevent PVT in patients with cirrhosis, through regular screening, to reduce portal hypertension.

11.
Emerg Microbes Infect ; 9(1): 386-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32065057

RESUMO

In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Fezes/virologia , Pneumonia Viral/transmissão , Eliminação de Partículas Virais , China , Humanos
12.
Sci Total Environ ; 715: 136975, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32018106

RESUMO

Dissemination of antibiotic resistance genes (ARGs) in the water environment has become an increasing concern. There have been many reports on ARGs in surface water, but little is known about ARGs in groundwater. In this study, we investigated the profiles and abundance of ARGs in groundwater in comparison with those in surface water of Maozhou River using high-throughput quantitative PCR (HT-qPCR). Totally 127 ARGs and 10 MGEs were detected by HT-qPCR, and among them the sulfonamides, multidrug and aminoglycosides resistance genes were the dominant ARG types. According to the results of HT-qPCR, 18 frequently detected ARGs conferring resistance to 6 classes of antibiotics and 3 MGEs were further quantified by qPCR in the wet season and dry season. The absolute abundance ranged from 1.23 × 105 to 8.89 × 106 copies/mL in wet season and from 8.50 × 102 to 2.65 × 106 copies/mL in the dry season, with sul1 and sul2 being the most abundant ARGs. The absolute abundance of ARGs and MGEs has no significant difference between the wet season and dry season while the diversity of ARGs in the dry season was higher than that in the wet season (p < 0.05). Totally 141 and 150 ARGs were detected in the water and sediments of Maozhou River, respectively. A total of 116 ARGs were shared among the groundwater, river water, and sediment, which accounted for 67.1% of all detected genes. Redundancy analysis further demonstrated that the environmental factors contributed 70.7% of the total ARG variations. The findings of large shared ARGs, abundant Total Coliforms and large wastewater burden in the groundwater provide a clear evidence that anthropogenic activities had a significant impact on groundwater.

13.
J Nurs Manag ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31954085

RESUMO

AIM: To analyse the structural associations among job characteristics, organizational justice, work engagement and nursing care quality in Chinese nurses. BACKGROUND: Nursing care quality helps ensure patient safety, which are core concerns. The explicit relationships among the study's variables from a management perspective can help hospital managers to implement effective strategies to improve nursing care quality. METHODS: This cross-sectional study was conducted to investigate the relationships among the variables in 1,615 nurses in eight Chinese tertiary hospitals. Structural equation modelling was used to test a proposed model of these relationships. RESULTS: The scores of job characteristics, organizational justice, work engagement and nursing care quality were 3.55 ± 0.41, 3.84 ± 0.77, 4.67 ± 1.30 and 3.42 ± 0.70. Job characteristics and organizational justice had direct effects on nursing care quality. Work engagement mediated the relationship of nursing care quality with job characteristics and organizational justice. The final model explained 24% of nursing care quality. CONCLUSION: The results provide a better understanding of the associations between the study's variables. Perceived job characteristics and organizational justice can improve nursing care quality through work engagement. IMPLICATIONS FOR NURSING MANAGEMENT: Reconfiguring work design to strengthen nurses' positive perceptions of job characteristics and organizational justice can enhance nursing care quality.

14.
Int J Pediatr Otorhinolaryngol ; 131: 109887, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31981918

RESUMO

OBJECTIVE: The primary aim of the current study was to examine the social maturity of infants and children with cochlear implants in China. A secondary aim was to document the associated information using a General Condition Questionnaire for further cohort study in this population. MATERIALS AND METHODS: This is a retrospective cross-sectional observational study and a pilot study. Between July and December 2017, data from all implantees between the ages of 6 months and 14 years who presented to the Hearing and Speech Center of Shanghai Ninth People's Hospital for mapping were collected. There were 119 non-overlapping cases in total. Data were collected via the Infants-Junior Middle School Students' Social-Life Abilities Scale (S-M scale) and a structured General Condition Questionnaire. The S-M scale was used for social adaptability measurement for children aged between 6 months to 14 yearsold. The General Condition Questionnaire, which was completed by the parents or primary caregivers of the implantees, gathered 3 aspects of personal information: the patient's history of hearing loss, personal history of rehabilitation and their past medical history. RESULTS: Results showed that in 119 cases, 89 implantees (74.8%) were at or above a normal social maturity level. Thirty implantees (25.2%) scored lower than normal on the S-M standard score. Spearman's rank correlation indicated that the age at which hearing loss was noticed, the age of initial rehabilitation and the age at implantation were significantly correlated with the patients' scores on the S-M scale. CONCLUSION: In summary, most of the cochlear implantees showed normal social maturity, with the exception of 25.2% of implantees who performed at a lower level than their normal hearing peers. These findings suggest potential targets to investigate in future cohort studies in cochlear implantees.

15.
mSphere ; 5(1)2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31996413

RESUMO

Coronaviruses (CoVs) of bat origin have caused two pandemics in this century. Severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV both originated from bats, and it is highly likely that bat coronaviruses will cause future outbreaks. Active surveillance is both urgent and essential to predict and mitigate the emergence of these viruses in humans. Next-generation sequencing (NGS) is currently the preferred methodology for virus discovery to ensure unbiased sequencing of bat CoVs, considering their high genetic diversity. However, unbiased NGS is an expensive methodology and is prone to missing low-abundance CoV sequences due to the high background level of nonviral sequences present in surveillance field samples. Here, we employ a capture-based NGS approach using baits targeting most of the CoV species. Using this technology, we effectively reduced sequencing costs by increasing the sensitivity of detection. We discovered nine full genomes of bat CoVs in this study and revealed great genetic diversity for eight of them.IMPORTANCE Active surveillance is both urgent and essential to predict and mitigate the emergence of bat-origin CoV in humans and livestock. However, great genetic diversity increases the chance of homologous recombination among CoVs. Performing targeted PCR, a common practice for many surveillance studies, would not reflect this diversity. NGS, on the other hand, is an expensive methodology and is prone to missing low-abundance CoV sequences. Here, we employ a capture-based NGS approach using baits targeting all CoVs. Our work demonstrates that targeted, cost-effective, large-scale, genome-level surveillance of bat CoVs is now highly feasible.


Assuntos
Quirópteros/virologia , Coronavirus/classificação , Coronavirus/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Animais , Variação Genética , Genoma Viral
16.
J Agric Food Chem ; 68(5): 1198-1206, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31928001

RESUMO

In this study, three types of pyraclostrobin formulations (including emulsifiable concentrate (EC), suspension concentrate (SC), and microcapsules (MCs)) were used to control cucumber anthracnose. Pyraclostrobin EC had the highest inhibitory activity against Colletotrichum orbiculare in vitro. Much different from the bioactivity in vitro, pyraclostrobin MCs exhibited the highest control efficacy on cucumber anthracnose both in pot and field experiments. The physicochemical properties (particle size, surface tension) of the spray dilution, their interaction with target leaves (contact angle, adhesional tension, work of adhesion, retention, crystallization) and dissipation dynamic of the active ingredient were found to be highly potential factors that would significantly influence the control efficacy of pesticide formulations. Results showed that the control efficacies of different formulations of pyraclostrobin were determined mainly by the final behavior of the pesticides at the target interface, namely, the retention, crystallization, and dissipation dynamics of active ingredients. This study had revealed crucial factors that would influence the efficacy of different formulations of pyraclostrobin and thus could guide the rational and efficient use of different formulations of pesticides on target crops.


Assuntos
Colletotrichum/efeitos dos fármacos , Cucumis sativus/microbiologia , Composição de Medicamentos/métodos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Doenças das Plantas/microbiologia , Estrobilurinas/química , Estrobilurinas/farmacologia , Colletotrichum/fisiologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/microbiologia
17.
Environ Pollut ; 260: 113996, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31991359

RESUMO

Per-and polyfluoroalkyl substances (PFASs) are a group of chemicals with a wide range of industrial and commercial applications, but little is known about the contamination of PFASs in groundwater and their linkage to surface water. Here we investigated the occurrence of PFASs in groundwater and surface water at the Maozhou River basin in order to understand their contamination profiles and potential health risks. The results showed that total PFASs concentrations ranged from 9.9 to 592.2 ng/L, 50.2-339.9 ng/L and 3.7-74.3 ng/g in groundwater, river water and sediment, respectively. The detection frequencies of C4-C8 chains (C4-C8) PFASs were higher than C9-C14 chains PFASs in the river and groundwater. Statistical analysis showed an obvious correlation between the major contaminants in the river and those in the groundwater, indicating the potential linkage of PFASs in the groundwater to the surface water. The wastewater indicator found in groundwater suggested domestic wastewater was only one of the source for the PFASs in the river and groundwater of Maozhou River basin. Moreover, human health risk assessment showed low risks from the PFASs to the residents by drinking groundwater.

18.
J Investig Med ; 68(3): 728-737, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31892638

RESUMO

Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based transgenic system was used to generate bone marrow stem cells (BMSC) which stably expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A heterotopic heart transplant model in rats was used to evaluate allograft rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated immunosuppression were investigated by evaluating levels of proinflammatory and anti-inflammatory cytokines, and production of Tregs. A significant decrease in DC marker-positive cells and a significant increase in Tregs were observed in IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated with significantly prolonged graft survival. Compared with the control groups, transplanted animals treated with IDO-BMSCs had a (1) significantly higher ejection fraction and fractional shortening, (2) significantly lower expression of CD86, CD80, and MHCII, and significantly higher expression in CD274, and Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), transforming growth factor beta-1 (TGF-ß1), TGF-ß2, and TGF-ß3, and significantly lower levels of IL-2 and interferon gamma. Our results expand our understanding of the molecular mechanisms underlying suppression of heart allograft rejection via IDO-expressing BMSCs.

19.
Toxicology ; 429: 152312, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31693917

RESUMO

LPS-induced neuronal apoptosis leads to neurodegenerative diseases (NDs). However, the mechanisms underlying NDs pathogenesis remains unclear. The apoptotic response to activation of the c-Myc/chloride intracellular channel (CLIC4) pathway is directed through a mitochondrial pathway. In this study, we aimed to explore the c-Myc/CLIC4 pathway in the progression of NDs induced by lipopolysaccharide (LPS). In an in vivo experiment, the results of HE staining, transmission electron microscopic, immunofluorescence microscopy of cleaved caspase-3 and Bax and the increasing expression of apoptotic pathway related proteins in mitochondria showed that LPS (10 mg/kg) administration damaged mitochondrial and induced hippocampal neuron apoptosis. The Western blot and RT-PCR indicated that LPS induced the activation of c-Myc/CLIC4 pathway. Furthermore, in an in vitro experiment, PC12 cells were exposed to LPS to induce cell injuries to mimic the model of NDs. To further confirm the role of the c-Myc/CLIC4 pathway in LPS-induced neuronal apoptosis, the gene knockout of c-Myc and CLIC4 were performed by CRISPR/Cas9. The results of the flow cytometry assay and Annexin V-FITC/PI showed that knocking out c-Myc and CLIC4 significantly reduced cell apoptosis. The results of Western blot and dual immunofluorescence with Cyt c and TOM20 showed that knocking out c-Myc and CLIC4 significantly reduced the expression of mitochondrial apoptosis-related proteins. Our data confirmed that LPS-induced apoptosis is regulated by the activation of c-Myc/CLIC4 pathway. These results support further research mechanisms underlying neurodegenerative diseases and can provide effective pharmacodynamic targets for the clinical development of therapeutic drugs for neurodegenerative diseases.

20.
New Phytol ; 225(6): 2526-2541, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31675430

RESUMO

Powdery mildew disease, elicited by the obligate fungal pathogen Blumeria graminis f.sp. tritici (Bgt), causes widespread yield losses in global wheat crop. However, the molecular mechanisms governing wheat defense to Bgt are still not well understood. Here we found that TuACO3, encoding the 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase functioning in ethylene (ET) biosynthesis, was induced by Bgt infection of the einkorn wheat Triticum urartu, which was accompanied by increased ET content. Silencing TuACO3 decreased ET production and compromised wheat defense to Bgt, whereas both processes were enhanced in the transgenic wheat overexpressing TuACO3. TuMYB46L, phylogenetically related to Arabidopsis MYB transcription factor AtMYB46, was found to bind to the TuACO3 promoter region in yeast-one-hybrid and EMSA experiments. TuMYB46L expression decreased rapidly following Bgt infection. Silencing TuMYB46L promoted ET content and Bgt defense, but the reverse was observed when TuMYB46L was overexpressed. Hence, decreased expression of TuMYB46L permits elevated function of TuACO3 in ET biosynthesis in Bgt-infected wheat. The TuMYB46L-TuACO3 module regulates ET biosynthesis to promote einkorn wheat defense against Bgt. Furthermore, we found four chitinase genes acting downstream of the TuMYB46L-TuACO3 module. Collectively, our data shed a new light on the molecular mechanisms underlying wheat defense to Bgt.

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