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1.
Infect Genet Evol ; : 104363, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32413573

RESUMO

Mycobacterium tuberculosis (M. tuberculosis) Lineage 4 (L4) is frequently prevailing in Western regions of China, where the tuberculosis incidence rate is high. However, the epidemiology characteristics of M. tuberculosis L4 in China remain poorly understood. Here, the 15-loci Variable number of tandem repeats (VNTR) patterns of 975 L4 isolates from a National Survey of Tuberculosis in China were used to construct a Minimum Spanning Tree (MST), which divided the 975 isolates into 5 major clonal complexes (CC; named CC1 to CC5). We found that the CCs of M. tuberculosis L4 were nationally distributed, geographically restricted, and different in epidemiology characteristics. For example, CC1 was mainly concentrated in East and Central China and significantly related to the farmer occupation and income of an individual (>4200 yuan) (p < .05); CC5 was mainly distributed in Southwest China and was associated with ethnic minorities. Notably, using whole genome sequencing (WGS) data of 141 strains that matched our samples, we found that both CC1 and CC5 were mapped to the sublineage L4.5. Nevertheless, due to the difference of geographical distribution, the epidemiology characteristics of these CCs were largely different. We found that income and occupation significantly contributed to the odds of infection by CC1 to CC5. Consequently, our findings revealed the epidemiology characteristics of the CCs of M. tuberculosis L4, and will help in the formulation of more effective intervention measures in line with regional specifications and patient characteristics in China.

2.
Heart Fail Rev ; 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32405811

RESUMO

The objective of this study was to evaluate the pharmacoeconomic value of sacubitril-valsartan for the treatment of heart failure (HF). PubMed, Embase, Cochrane Library, ScienceDirect, Scopus, CNKI, Wanfang, and VIP databases were searched systematically and the retrieval time ended in August 2019. According to the criteria of inclusion and exclusion, the quality of studies included was evaluated as per the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) scale, and the results were extracted and analyzed systematically. The total of 11 cost-effectiveness studies was identified, 10 were performed in the developed countries and 1 in Thailand. All the patients in the studies had chronic heart failure with reduced ejection fraction (HFrEF). Totally, the quality of all the 11 studies was reported to be of an average score of 20.5. Study perspective and time horizons were described in the 11 studies. All included studies discounted the cost or effectiveness. Only 1 study estimated direct and indirect costs; 10 studies evaluated direct cost. The incremental cost-effectiveness ratio (ICER) of sacubitril-valsartan treating HFrEF was $13,150 per quality-adjusted life-years (QALY) in Thailand and $86,735 in Singapore. In European countries, the ICER was from $21,786 to $34,576 per QALY and mean value was $25,410.6 per QALY. In the USA, ICER values ranged from $47,099 to $143,891 per QALY, and mean value was $73,383.5 per QALY; ICER was $30,090 per QALY in Colombia. With the exception of Thailand and Singapore, the ICER of other countries in the included literature was below the implemented country-specific thresholds. Based on existing literatures, with the exception of Thailand and Singapore, sacubitril-valsartan for the treatment of HFrEF is a better cost-effective therapy with ICER basically below the implemented country-specific thresholds. Sacubitril-valsartan was not considered a cost-effective treatment for heart failure with reduced ejection fraction in Thailand and Singapore with the current economic evaluation evidences, but with the willingness-to-pay (WTP) of other counties, sacubitril-valsartan was found to be a cost-effective treatment compared with comparator. Drug cost, time horizon, and hospitalization were the most influential variables across studies. Four studies indicated that with the longer time horizon, the lower ICER value would gain. Further studies are warranted to better evaluate comprehensive utility value of sacubitril-valsartan on heart failure.

3.
J Med Virol ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396272

RESUMO

Clinical data has shown that pulmonary interstitial fibrosis is likely to occur in the later stages of viral pneumonia. While viral infections are thought to cause chronic pulmonary interstitial inflammation and pulmonary fibrosis, it remains unclear if they promote pulmonary fibrosis by EMT. In this study, human epithelial cell line A549 has been used to model the infection of the EBV and the RSV. Their differences were compared and the possible infection mechanisms analyzed by randomly assigning cells to one of five treatments. Exposure of the LMP1 is thought to be the key gene during EBV-induced EMT in the A549 cells. ELISA analysis revealed that the EBV infection was associated with the induction of a number of cytokines (IL-8, IL-13, TNF-α, and TGF-ß1) and DXM could significantly prevent the phenotypic changes, and partly the mechanisms related with the IL-13 pathway. Surprisingly, different results were seen with the RSV infection as the A549 cells still displayed an epithelial morphology but the levels of E-cadherin, α-SMA, vimentin, and fibronectin did not change. This is the first study demonstrating the different reactions induced by different viruses, and the protective effects of DXM on the EBV-induced EMT in the A549 cells by partially inhibiting the IL-13 pathway. These findings suggest a novel mechanism, by which DXM or anti-IL-13 may delay the progression of pulmonary fibrosis by preventing the progress of EBV induced EMT. This article is protected by copyright. All rights reserved.

4.
J Soc Work End Life Palliat Care ; : 1-17, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32396458

RESUMO

Traditional Chinese art practices such as brush painting and calligraphy are thought to promote self-development through holistically engaging both physical and mental health. This pilot study investigated the beneficial effects of a community-based self-help group incorporating Chinese art practices as a culturally adapted bereavement intervention. Twenty-six Chinese parents aged over 49 years and who had lost their only child participated in a 20-session Chinese brush painting group over a 6-month period. Ten bereaved parents from the same community who did not participate in the art course but received living support were recruited as a control group. Compared with the control group, the art practice group exhibited a pre-post intervention effect in terms of promoting positive affect and preventing deterioration of prolonged grief symptoms, particularly through the improvement of accessory grief symptoms (e.g., "emotional numbness due to the loss", and "feeling that life is unfulfilling, empty or meaningless after the loss"). No effect was found on negative affect. These findings indicate that a culturally adapted community-based art group may be an effective means of improving grief-related health.

6.
Acad Radiol ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32386949

RESUMO

RATIONALE AND OBJECTIVES: Signal intensity of the lumbar spine in magnetic resonance imaging (MRI) correlates to bone mineral density (BMD). This study aims to explore a lumbar spine magnetic resonance imaging based on the radiomics model for detecting osteoporosis. MATERIALS AND METHODS: A total of 109 patients, who underwent both dual-energy X-ray absorptiometry (DEXA) and MRI of the lumbar spine, were recruited. Among these patients, 38 patients were normal, 32 patients had osteopenia, and 39 patients had osteoporosis, according to the DEXA results. A total of 396 × 2 radiomic features were extracted from the T1WI and T2WI images of the segmentation images in the lumbar magnetic resonance imaging. The correlated radiomic features were selected to establish the radiomic classification model. Then, the classification models (based on T1WI, T2WI, and T1WI+T2WI) of normal vs. osteopenia, normal vs. osteoporosis, and osteopenia vs. osteoporosis were established. The performance of the classification models was evaluated through the estimated area under the receiver operating characteristic curve. RESULTS: The area under the receiver operating characteristic curves based on T1WI, T2WI, and T1WI+T2WI were 0.772, 0.772, and 0.810, respectively, for the models of normal vs. osteopenia, 0.724, 0.682, and 0.797, respectively, for the models of normal vs. osteoporosis, and 0.730, 0.734, and 0.769, respectively, for the models of osteopenia vs. osteoporosis. CONCLUSION: Radiomic models established based on lumbar spine MRI can be used to detect osteoporosis.

7.
Neuroscience ; 437: 54-63, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32353459

RESUMO

A hallmark of the aging process is increased connectivity between networks and decreased connectivity within networks, which to some extent reflects the reorganization of the brain networks during normal aging. Considering the brain as a complex dynamic system, emerging evidence suggests the time-varying connectivity patterns to be more informative of brain functions. However, the age effect on the dynamic reconfiguration of intrinsic resting state networks is still elusive. By tracking the ongoing formation and dissipation of putative functional modules across time and space, we explored the age-related changes of segregation and integration and further elucidated the underlying brain network dynamics mechanism during normal aging. Results showed that aging strongly weakened dynamic global segregation while enhanced dynamic global integration across the whole brain. Aging was associated with decreasing dynamic segregation of most networks (except the cerebellum) while increasing dynamic integration of only a few networks at the large-scale network level. Notably, the fronto-parietal network, the default mode network, the visual network, and a small group of nodes from these networks, whose dynamic segregation and integration, were both modulated by age. These findings provide direct evidence that there are remarkable changes of dynamic network architecture across the human adult lifespan and suggest the age-related modulations of dynamic segregation and integration intuitively reflect the adaptive changes of the functional dedifferentiation and compensation in older adults.

8.
Exp Eye Res ; 195: 108040, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32360553

RESUMO

Animal studies suggest that the retinal dysfunction in diabetic subjects that precedes overt clinical vasculopathy may be due to a retinal dopamine deficit. We analyzed levels of dopamine (DA) and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the vitreous of diabetic and non-diabetic human subjects. Adult patients undergoing pars plana vitrectomy for non-hemorrhagic indications were prospectively recruited from the Emory Eye Center in Atlanta, GA. Vitreous samples were analyzed using high performance liquid chromatography (HPLC) to measure levels of DOPAC and DA in the vitreous specimens. Vitreous samples from 9 diabetic patients and 20 from non-diabetic patients were analyzed. No eyes had apparent diabetic retinopathy. Mean normalized DA concentration in vitreous of diabetic subjects was 0.76 ± 0.12 pg/µL vs. 0.73 ± 0.08 pg/µL in non-diabetic vitreous (p = 0.849). DOPAC concentration was 8.84 ± 0.74 pg/µL in vitreous of diabetic subjects vs. 9.22 ± 0.56 pg/µL in vitreous of non-diabetic subjects (p = 0.691). No difference was observed in the concentrations of DA and DOPAC in the vitreous of people without diabetes compared to those with diabetes without retinopathy.

9.
Fitoterapia ; : 104629, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32428563

RESUMO

Based on a method combining the LC-MS/MS molecular networking strategy with the conventional means of phytochemical research, the chemical constituents and the availability of Paris tengchongensis, a new species found in 2017 from Yunnan Province, were investigated for the first time. The molecular networking showed that this species contained the characteristic steroidal glycosides of the genus Paris by comparison of those of Paris polyphylla var. yunnanensis. Furthermore, the detailed investigation on the 80% EtOH extract of its rhizomes resulted to the isolation of twenty steroidal glycosides including three new spirostane-type saponins, named paristengosides A-C (1-3). Their structures were confirmed by spectroscopic analyses (HRMS and NMR) and chemical methods. The new isolates were evaluated for their cytotoxicities against two human cancer cell lines (HEL and MDA-MB-231), anti-inflammatory effects on a lipopolysaccharide (LPS)-stimulated NO production model in RAW264.7 macrophages, anti-AChE, and antimicrobial activities. The results from the molecular networking and the investigation on the chemical constituents suggested that P. tengchongensis can be used as a potential resource of Rhizoma Paridis.

10.
Food Microbiol ; 90: 103466, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32336350

RESUMO

Shiga toxin producing E. coli are a problem for food producers. STEC's require a combination of virulence factors to cause disease, so ideally detection techniques should detect the presence of multiple virulence factors in a single cell directly from food. Droplet Digital PCR (ddPCR) is commonly used to quantify the number of copies of a gene in a sample, moreover it is able to link two genes to the same piece of DNA. Here stx and an O-antigen specific gene are detected simultaneously with taqman probes confirming that the cells are intact as well as distinguishing between strains based on their genotype. Using ddPCR E. coli O157:H7 and O104:H4 are quantified from apple juice, milk and spinach washings without an enrichment step, the detection limit of ddPCR in apple juice was 2 cfu/mL. Also, ddPCR was used to detect pathogenic bacterial cells in the presence of background strains which shared one or none of the target genes, including avirulent strains. Whole cell ddPCR is compared to several DNA extraction techniques demonstrating that whole cell ddPCR is more reliable for linking genes within an organism. Whole cell ddPCR is a promising technique for the rapid and specific detection of foodborne pathogens.

11.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(2): 199-203, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32275006

RESUMO

OBJECTIVE: To analyze multiple factors that may affect renal function in septic shock patients with acute kidney injury (AKI) in the intensive care unit (ICU), in order to find factors of predictive value for renal function change in those patients. METHODS: Septic patients with AKI admitted to department of critical care medicine of Wuhan University Zhongnan Hospital from January 2017 to June 2019 were enrolled, and the patients were divided into renal function improvement group and renal function non-improvement group according to their renal function change. Baseline, laboratory and clinical indicators of them were collected to conduct retrospective analysis. Comparing the difference of each index between the two groups, the statistically significant indexes in the univariate analysis were selected to perform ridge regression analysis. The receiver operating characteristic (ROC) curve and its 95% confidence interval (95%CI) were used to analyze the predictive value of each influencing factor on the recovery of renal function in patients. RESULTS: A total of 323 patients met the inclusion criteria, and 195 of them were divided into renal function improvement group while the other 128 of them into the renal function non-improvement group. Univariate analysis showed that, there was significantly difference in acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), Glasgow coma score (GCS), heart rate (HR), serum creatinine (SCr), blood urea nitrogen (BUN), potassium (K+), white blood cell count (WBC), maximum central venous pressure (CVPmax), maximum-minimum central venous pressure distance (ΔCVP), fluid balance, maximum lactic acid (LACmax), and maximum norepinephrine infusion speed (NEmax) between the renal function improvement group and the renal function non-improvement group. Ridge regression analysis of those indexes found that APACHE II, SOFA, SCr, BUN, HR, WBC, fluid balance, and NEmax were influential factors of non-improvement renal function (t values were 5.507, 3.690, 2.026, 4.815, 2.512, 2.114, 3.532, 3.735, all P < 0.05). ROC analysis found the predictive value combining the APACHE II, SOFA, BUN, NEmax was the highest [the area under ROC curve (AUC) and 95%CI: 0.863 (0.821-0.899)], which had a higher AUC than any of APACHE II, SOFA, BUN, SCr and NEmax [AUC and 95%CI: 0.863 (0.821-0.899) vs. 0.755 (0.705-0.801), 0.722 (0.670-0.770), 0.738 (0.686-0.785), 0.743 (0.692-0.790), 0.748 (0.697-0.794), all P < 0.01], and so did it when compared to APACHE II, SOFA, SCr and NEmax combination [AUC and 95%CI: 0.863 (0.821-0.899) vs. 0.825 (0.799-0.865), P < 0.01]. CONCLUSIONS: APACHE II, SOFA, SCr, BUN, HR, WBC, fluid balance, and NEmax are the positive influencing factors for patients without renal function improvement. The combination of APACHE II, SOFA, BUN, and NEmax had a relatively high predictive value for renal function recovery.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32344554

RESUMO

This study was aimed at assessing the spatial and temporal distribution of surface water quality variables of the Xin'anjiang River (Huangshan). For this purpose, 960 water samples were collected monthly along the Xin'anjiang River from 2008 to 2017. Twenty-four water quality indicators, according to the environmental quality standards for surface water (GB 3838-2002), were detected to evaluate the water quality of the Xin'anjiang River over the past 10 years. Principal component analysis (PCA) was used to comprehensively evaluate the water quality across eight monitoring stations and analyze the sources of water pollution. The results showed that all samples could be analyzed by three main components, which accounted for 87.24% of the total variance. PCA technology identified important water quality parameters and revealed that nutrient pollution and organic pollution are major latent factors which influence the water quality of Xin'anjiang River. It also showed that agricultural activities, erosion, domestic, and industrial discharges are fundamental causes of water pollution in the study area. It is of great significance for water quality safety management and pollution control of the Xin'anjiang River. Meanwhile, the inverse distance weighted (IDW) method was used to interpolate the PCA comprehensive score. Based on this, the temporal and spatial structure and changing characteristics of water quality in the Xin'anjiang River were analyzed. We found that the overall water quality of Xin'anjiang River (Huangshan) was stable from 2008 to 2017, but the pollution of the Pukou sampling point was of great concern. The results of IDW helped us to identify key areas requiring control in the Xin'anjiang River, which pointed the way for further delicacy management of the river. This study proved that the combination of PCA and IDW interpolation is an effective tool for determining surface water quality. It was of great significance for the control of water pollution in Xin'anjiang River and the reduction of eutrophication pressure in Thousand Island Lake.

13.
Medicine (Baltimore) ; 99(16): e19689, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311944

RESUMO

The greatest regional variation in stroke prevalence exists in China. However, whether there are differences in population attributable risk (PAR) and clustering of stroke risk factors among regions resulting in stroke geographic variation is unclear.We conducted face-to-face surveys of residents of 14 provinces from September 2016 to May 2017 who participated in the Chinese Stroke Screening and Prevention Project. We compared the specific PAR values of eight risk factors and the different cluster rates and patterns in China.A total of 84,751partipants were included. Eight factors accounted for 70% to 80% of the PAR of overall stroke in China. Not only did the PAR of the total risk factors differ among the 3 regions, but the PAR of the same risk factor also varied among different regions. The top 3 factors with the greatest PAR variations among the 3 regions were dyslipidemia, physical inactivity and family history of stroke. The clustering rates and patterns varied by regions. The overall proportion of participants with 0, 1, 2, 3, and ≥4 risk factors were 34.4%, 28.0%, 17.4%, 9.2%, and 10.3% in eastern China; 31.0%, 27.9%, 19.8%, 10.8%, and 9.9% in Central China and 28.2%, 29.5%, 19.9%, 10.8%, and 11.0% in western China, respectively. On basis of hypertension, the most common risk cluster patterns were overweight or smoking, dyslipidemia and physical inactivity, with other risk factors in the eastern, central and western regions, respectively.The rates and patterns of clustering and the potential importance of stroke risk factors in different regions may together contribute to the geographical variation in stroke prevalence in China.


Assuntos
Acidente Vascular Cerebral/epidemiologia , China/epidemiologia , Análise por Conglomerados , Estudos Transversais , Feminino , Seguimentos , Geografia Médica , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
14.
Biodegradation ; 31(1-2): 139-152, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32306137

RESUMO

Pesticides introduced inadvertently or deliberately into environment by anthropogenic activity have caused growing global public concern, therefore the search of approaches for elimination of such xenobiotics should be encouraged. A cypermethrin-degrading bacterial strain Bacillus licheniformis B-1 was found to efficiently degrade carbaryl in LB medium at concentrations of 50-300 mg L-1 within 48 h, during which temperature and pH played important roles as reflected by increase in pollutant depletion. A stimulatory effect of Fe3+ and Mn2+ on microbial growth was observed, whereas Cu2+ caused inhibition of degradation. Results showed that 1-naphthol was a major transformation product of carbaryl which was further metabolised. An approximately 29 kDa carbaryl-degrading enzyme was purified from B-1 with 15.93-fold purification and an overall yield of 6.02% was achieved using ammonium sulphate precipitation, DEAE-Sepharose CL-6B anion-exchange chromatography and Sephadex G-100 gel filtration. The enzyme was identified through nano reversed-phase liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry as a phosphodiesterase (PDE). This is the first report on the characterization of carbaryl-degrading by Bacillus spp. and the role of a PDE in carbaryl-detoxifying. Also, strain B-1 showed versatile in carbosulfan, isoprocarb and chlorpyrifos degradation, demonstrating as ideal candidate for environment bioremediation.

15.
Nano Lett ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32343586

RESUMO

A highly efficient photoenergy conversion is strongly dependent on the cumulative cascade efficiency of the photogenerated carriers. Spatial heterojunctions are critical to directed charge transfer and, thus, attractive but still a challenge. Here, a spatially ternary titanium-defected TiO2@carbon quantum dots@reduced graphene oxide (denoted as VTi@CQDs@rGO) in one system is shown to demonstrate a cascade effect of charges and significant performances regarding the photocurrent, the apparent quantum yield, and photocatalysis such as H2 production from water splitting and CO2 reduction. A key aspect in the construction is the technologically irrational junction of Ti-vacancies and nanocarbons for the spatially inside-out heterojunction. The new "spatial heterojunctions" concept, characteristics, mechanism, and extension are proposed at an atomic-/nanoscale to clarify the generation of rational heterojunctions as well as the cascade electron transfer.

16.
Medicine (Baltimore) ; 99(16): e19803, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32311996

RESUMO

BACKGROUND: Available evidence shows conflicting results with regard to a potential detrimental effect of hypertension on clinical outcomes in patients who undergo mechanical thrombectomy (MT). We performed a meta-analysis to evaluate the impact of hypertension on the prognosis of patients with acute ischaemic stroke (AIS) treated by MT. METHODS: We systematically reviewed previous studies in the PubMed, EMBASE, and Cochrane library databases that reported MT outcomes in AIS patients and their relationships with hypertension or blood pressure. We used a poor outcome (modified Rankin score >2 at 3 months) as the primary end point. Mortality and symptomatic intracranial hemorrhage were the secondary end points. We incorporated a random effect for trials in all models. RESULTS: Data from 6650 patients in 31 articles that evaluated the effect of hypertension or blood pressure on outcomes after MT were included. Compared with patients without hypertension, patients with hypertension had significantly higher odds of a poor outcome (odds ratio 0.70; 95% confidence interval 0.57-0.85; I = 43%) and higher mortality (odds ratio 1.70; 95% confidence interval 1.26-2.29; I = 33%). Symptomatic intracranial hemorrhage did not differ by patient hypertension status. CONCLUSIONS: The present study confirms that hypertension and high blood pressure are associated with a poor outcome at 3 months after MT in AIS patients. However, the causal relationship between hypertension and a poor outcome remains undetermined, and further investigations are required to ascertain whether AIS patients receiving MT could benefit from intensive blood pressure control.


Assuntos
Isquemia Encefálica/terapia , Hipertensão/complicações , Trombólise Mecânica , Acidente Vascular Cerebral/terapia , Humanos , Resultado do Tratamento
17.
Int J Infect Dis ; 95: 174-175, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32251796

RESUMO

Among 78 laboratory-confirmed cases, we found two asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his RT-PCR test was still positive on the 15th day. We found that there may be virus carriers in the asymptomatic population with an epidemiological contact history. After 14 days of isolation, those with asymptomatic infection may still carry the virus, which means a risk of transmission, presenting a new challenge for the management of home isolation.

18.
Virol J ; 17(1): 50, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32268919

RESUMO

Antibody neutralization of cytomegalovirus (CMV) entry into diverse cell types is a key consideration for development of vaccines and immunotherapeutics. CMV entry into fibroblasts differs significantly from entry into epithelial or endothelial cells: fibroblast entry is mediated by gB and gH/gL/gO, whereas both epithelial and endothelial cell entry require an additional pentameric complex (PC) comprised of gH/gL/UL128/UL130/UL131A. Because PC-specific antibodies in CMV-seropositive human sera do not affect fibroblast entry but potently block entry into epithelial or endothelial cells, substantially higher neutralizing potencies for CMV-positive sera are observed when assayed using epithelial cells as targets than when using fibroblasts. That certain sera exhibit similar discordances between neutralizing potencies measured using epithelial vs. endothelial cells (Gerna G. et al.J Gen Virol, 89:853-865, 2008) suggested that additional mechanistic differences may also exist between epithelial and endothelial cell entry. To further explore this issue, neutralizing potencies using epithelial and endothelial cells were simultaneously determined for eight CMV-positive human sera, CMV-hyperimmune globulin, and a panel of monoclonal or anti-peptide antibodies targeting specific epitopes in gB, gH, gH/gL, or the PC. No significant differences were observed between epithelial and endothelial neutralizing potencies of epitope-specific antibodies, CMV-hyperimmune globulin, or seven of the eight human sera. However, one human serum exhibited a six-fold higher potency for neutralizing entry into epithelial cells vs. endothelial cells. These results suggest that epitopes exist that are important for epithelial entry but are less critical, or perhaps dispensable, for endothelial cell entry. Their existence should be considered when developing monoclonal antibody therapies or subunit vaccines representing limited epitopes.

19.
Biosci Biotechnol Biochem ; : 1-9, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32290769

RESUMO

MiR-181a-5p's mechanism in hypoxia-reoxygenation (H/R)-induced cardiomyocytes apoptosis has not been clarified. This study verified that SIRT1 was the target of miR-181a-5p. MiR-181a-5p expression was up-regulated or down-regulated in H/R-induced cardiomyocytes, and SIRT1 was transfected into cells alone or in combination with miR-181a-5p. Cell viability, apoptosis, levels of released lactate dehydrogenase (LDH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the Bcl-2, Bax, and Caspase 3 levels in treated cells were tested. On the one hand, down-regulated miR-181a-5p promoted cell viability, reduced released LDH and MDA, and increased SOD level in H/R-induced cardiomyocytes. On the other hand, miR-181a-5p inhibited apoptosis and elevated Bcl-2 expression while decreasing the expressions of Bax and Caspase 3 in treated cells, but the effects of miR-181a-5p could be rescued by SIRT1. In conclusion, miR-181a-5p involved in H/R-induced cardiomyocytes apoptosis through regulating SIRT1, which might become a novel direction for related diseases.

20.
Parasit Vectors ; 13(1): 164, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32245505

RESUMO

BACKGROUND: Smad proteins are essential cellular mediators within the transforming growth factor-ß (TGF-ß) superfamily. They directly transmit incoming signals from the cell surface receptors to the nucleus. In spite of their functional importance, almost nothing is known about Smad proteins in parasitic nematodes including Haemonchus contortus, an important blood-sucking nematode of small ruminants. METHODS: Based on genomic and transcriptome data for H. contortus and using bioinformatics methods, a Smad homologue (called Hco-daf-8) was inferred from H. contortus and the structural characteristics of this gene and its encoded protein Hco-DAF-8 established. Using real-time PCR and immunofluorescence assays, temporal transcriptional and spatial expression profiles of Hco-daf-8 were studied. Gene rescue in Caenorhabditis elegans was then applied to assess the function of Hco-daf-8 and a specific inhibitor of human Smad3 (called SIS3) was employed to evaluate the roles of Hco-DAF-8 in H. contortus development. RESULTS: The features of Hco-DAF-8 (502 amino acids), including conserved R-Smad domains and residues of the L3-loop that determine pathway specificity, are consistent with a TGF-ß type I receptor-activated R-Smad. The Hco-daf-8 gene was transcribed in all developmental stages of H. contortus studied, with a higher level of transcription in the fourth-stage larval (L4) females and the highest level in adult males. Hco-DAF-8 was expressed in the platymyarian muscular cells, intestine and reproductive system of adult stages. Gene rescue experiments showed that Hco-daf-8 was able to partially rescue gene function in a daf-8 deficient mutant strain of C. elegans, leading to a resumption of normal development. In H. contortus, SIS3 was shown to affect H. contortus development from the exsheathed third-stage larvae (L3s) to L4s in vitro. CONCLUSIONS: These findings suggest that Hco-DAF-8, encoded by the gene Hco-daf-8, is an important cellular mediator of H. contortus development via the TGF-ß signalling pathway. They provide a basis for future explorations of Hco-DAF-8 and associated pathways in H. contortus and other important parasitic nematodes.

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