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1.
Pharmacol Res ; 173: 105885, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34536551

RESUMO

Type 2 diabetes and atherosclerosis have gradually garnered great attention as inflammatory diseases. Previously, the fact that Interleukin-1ß (IL-1ß) accelerates the development of type 2 diabetes and atherosclerosis has been proved in animal experiments and clinical trials. However, the continued studies found that the effect of IL-1ß on type 2 diabetes and atherosclerosis is much more complicated than the negative impact. Nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome, whose activation and assembly significantly affect the release of IL-1ß, is a crucial effector activated by a variety of metabolites. The diversity of NLRP3 activation mode is one of the fundamental reasons for the intricate effects on the progression of type 2 diabetes and atherosclerosis, providing many new insights for us to intervene in metabolic diseases. This review focuses on how NLRP3 inflammasome affects the progression of type 2 diabetes and atherosclerosis and what opportunities and challenges it can bring us.

2.
Disabil Health J ; 14(4): 101167, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34247966

RESUMO

BACKGROUND: Research has found that participation in travel declines for people after spinal cord injury (SCI) because the traumatic injury usually results in impaired physical mobility and sensation, and barriers in the environment make travel more challenging. While travel participation can offer numerous physical, psychological, and emotional benefits, empirical evidence on positive outcomes of travel for people after SCI is scarce in the literature. OBJECTIVE: To empirically examine the effects of travel participation on social integration and life satisfaction for people with SCI, along with other personal characteristics including income, self-perceived health status, levels of physical independence, occupational activities, and travel barriers. METHODS: Cross sectional data are collected from 250 patients enrolled in a SCI Model System. Hierarchical regression analyses, followed by mediation analyses, are conducted to assess the effects of travel participation on social integration and life satisfaction. RESULTS: Travel participation along with occupational activities is shown to significantly impact social integration, with participation in occupational activities partially mediating the relation from travel participation to social integration. The significant effect of travel participation on life satisfaction is fully mediated by social integration. Income and self-perceived health status both significantly contribute to social integration and life satisfaction. CONCLUSIONS: Travel participation should be considered as an independent domain that directly impacts the social integration of people with SCI, which in turn enhances their life satisfaction. Systematic interventions with standard protocols for travel-related skill training and assessments procedures are needed for people after SCI.

3.
Biomed Pharmacother ; 138: 111532, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311531

RESUMO

Fufang Zhenzhu Tiaozhi formula (FTZ), a preparation of Chinese herbal medicine, has various pharmacological properties, such as hypoglycemic, hypolipidemic, anticoagulant, and anti-inflammatory activities. Hepatocyte apoptosis is a marker of nonalcoholic steatohepatitis (NASH) and contributes to liver injury, fibrosis, and inflammation. Given the multiple effects of FTZ, we investigated whether FTZ can be a therapeutic agent for NASH and its mechanism. In the present study, we observed that FTZ treatment had an obviously favorable influence on hepatic steatosis and fibrosis in the histopathologic features of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) with NASH minipigs. In addition, immunohistochemical analysis showed increased expression of the fibrotic marker α-smooth muscle actin (α-SMA), and a TUNEL assay revealed increased apoptotic positive hepatic cells in the liver tissues of the model group. Furthermore, FTZ administration reduced the increased expression of α-SMA, and FTZ inhibited apoptosis by affecting Bcl-2/Bax and cleaved caspase-3 expression. Mechanistically, our data suggested that FTZ treatment attenuated hepatic steatosis and fibrosis via the adenosine monophosphate-activated protein kinase (AMPK) pathway. In vitro studies showed that FTZ also attenuated intracellular lipid accumulation in HepG2 cells exposed to palmitic acid (PA) and oleic acid (OA). FTZ upregulated the expression levels of P-AMPK and BCL-2 and downregulated BAX. The changes induced by FTZ were reversed by Compound C, an inhibitor of AMPK. In conclusion, FTZ attenuated NASH by ameliorating steatosis and hepatocyte apoptosis, which is attributable to the regulation of the AMPK pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Doença das Coronárias/enzimologia , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/enzimologia , Células Hep G2 , Humanos , Lipídeos/sangue , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/enzimologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/enzimologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Suínos , Porco Miniatura
4.
Environ Toxicol ; 36(9): 1923-1931, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34156151

RESUMO

Lead (Pb) exposure can cause central nervous system (CNS) damage. The process of Pb neurotoxicity is accompanied by the microglia activation. In addition, microglia activation was observed under the intervention of high-fat diets (HFD). This study was designed to investigate the effect of Pb on the cognitive function of mice with HFD, with focus on the microglia activation in brain. Male C57BL/6J mice, 8 weeks of age, were randomly divided into control, HFD, Pb, and HFD + Pb groups. The results showed that HFD following Pb exposure could exacerbate the learning and memory impairment in mice. Pb exposure could promote microglia activation and increase the expression of M1 microglia marker and decrease the expression of M2 microglia marker in the hippocampus of mice with HFD. Our finding suggested that Pb exposure may aggravate CNS damage by promoting M1 polarization and inhibiting M2 polarization of hippocampal microglia in HFD mice.


Assuntos
Dieta Hiperlipídica , Microglia , Animais , Dieta Hiperlipídica/efeitos adversos , Hipocampo , Chumbo/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Bull Environ Contam Toxicol ; 107(3): 553-558, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33880601

RESUMO

As one of the most harmful environmental pollutants, cadmium (Cd) has arisen much interest, and many researches have been carried out to study the adsorption of heavy metals by biochar, but the mechanisms were poorly explored and the roles components in biochar played are still indistinct. In this study, we evaluated the adsorption capacities and mechanisms of soybean root biochar pyrolyzed at four different temperatures. The results indicate the biochar properties are significantly determined by pyrolysis temperature, which affects the removal mechanisms of Cd(II) consequently. Microstructure characteristics and mechanism analysis further suggest that Cd(II)-π interactions and sulfur-containing functional groups are the main mechanisms of Cd(II) adsorption. This work shows a new perspective to explain the adsorption mechanisms onto biochar adsorbents and has a benefit for the exploitation of economical and effective adsorbents for Cd(II) removal based on biochars.


Assuntos
Cádmio , Pirólise , Adsorção , Carvão Vegetal , Soja , Temperatura
6.
Int J Mol Med ; 47(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33907839

RESUMO

Nowadays, metabolic syndromes are emerging as global epidemics, whose incidence are increasing annually. However, the efficacy of therapy does not increase proportionately with the increased morbidity. Type 2 diabetes mellitus (T2DM) and non­alcoholic fatty liver disease (NAFLD) are two common metabolic syndromes that are closely associated. The pathogenic mechanisms of T2DM and NAFLD have been studied, and it was revealed that insulin resistance, hyperglycemia, hepatic lipid accumulation and inflammation markedly contribute to the development of these two diseases. The 2­series prostaglandins (PGs), a subgroup of eicosanoids, including PGD2, PGE2, PGF2α and PGI2, are converted from arachidonic acid catalyzed by the rate­limiting enzymes cyclooxygenases (COXs). Considering their wide distribution in almost every tissue, 2­series PG pathways exert complex and interlinked effects in mediating pancreatic ß­cell function and proliferation, insulin sensitivity, fat accumulation and lipolysis, as well as inflammatory processes. Previous studies have revealed that metabolic disturbances, such as hyperglycemia and hyperlipidemia, can be improved by treatment with COX inhibitors. At present, an accumulating number of studies have focused on the roles of 2­series PGs and their metabolites in the pathogenesis of metabolic syndromes, particularly T2DM and NAFLD. In the present review, the role of 2­series PGs in the highly intertwined pathogenic mechanisms of T2DM and NAFLD was discussed, and important therapeutic strategies based on targeting 2­series PG pathways in T2DM and NAFLD treatment were provided.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33647481

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a frequently occurring renal cancer. Von Hippel-Lindau disease tumor suppressor (VHL), a known tumor suppressor, is frequently mutated in about 50% of patients with ccRCC. However, it is unclear whether VHL influences the progression of ccRCC tumors expressing wild-type VHL. In the present study, we found that higher expression of VHL was correlated with the better disease-free survival (DFS) in ccRCC patients using The Cancer Genome Atlas (TCGA) datasets. We revealed that VHL overexpression in ccRCC cells inhibited epithelial-mesenchymal transition (EMT), sterol regulatory element-binding protein 1 (SREBP1) regulated triglyceride synthesis, and cell proliferation. Proteomic analysis provided us a global view that VHL regulated four biological processes including metabolism, immune regulation, apoptosis, and cell movement. Importantly, we found that VHL overexpression led to upregulation of proteins associated with antigen processing and interferon-responsive proteins, rendering ccRCC cells with high VHL expression more sensitive to interferon treatment. We defined an interferon-responsive signature (IRS) with ten proteins, whose expression levels were positively correlated with DFS in ccRCC patients. Taken together, our results propose that the subset of ccRCC patients with high VHL expression benefit from immunotherapy.

8.
J Ethnopharmacol ; 274: 114056, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33771638

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi formula (FTZ) of which a patented preparation of Chinese herbal medicine has been well documented with significant clinical curative effect for hyperglycemia and hyperlipidemia. Because of the complexity of the chemical constituents of Chinese herbal formulas, the holistic pharmacological mechanism of FTZ acting on type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) remains unclear. AIM OF THE STUDY: To investigate the pharmacological efficacy and mechanism of FTZ in the treatment of T2DM accompanied by NAFLD. MATERIALS AND METHODS: Network pharmacology and validation in minipigs were used in this study. First, potential bioactive compounds of FTZ were identified by the traditional Chinese medicine system pharmacology technology platform (TCMSP). Then, targets of compounds were gathered using DrugBank, SwissTargetPrediction and TCMSP, while targets for T2DM and NAFLD were collected from CTD (compounds-targets-diseases network) and GeneCards. Common targets were defined as direct therapeutic targets acting on T2DM with NAFLD. In addition, crucial targets were chosen by the protein-protein interaction (PPI) network and contribution to compound-therapeutic targets in T2DM with the NAFLD network. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by FTZ. Candidate patterns selected by network pharmacology were tested in the minipigs model of T2DM with NAFLD. Measurements of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and fasting blood glucose (FBG) in the blood and the expression levels of proteins, including PI3K-AKT and HIF-1α, in the livers of the minipigs were followed by the administration of FTZ. RESULTS: A total of 116 active compounds and 82 potential targets related to T2DM and NAFLD were found. Pathway and functional enrichment analysis showed that FTZ mainly regulates metabolism-related pathways, including PI3K-AKT, HIF-1α, TNFα and MAPK. Animal experiments showed that FTZ treatment significantly reduced the serum levels of TG, TC, LDL-C and FBG, increased serum levels of HDL-C, ameliorated systemic insulin resistance (IR), and attenuated liver damage in minipigs with T2DM and NAFLD. FTZ treatment has an obviously favorable influence on hepatic steatosis and liver lipid accumulation in the histopathologic features of HE, Oil red O staining, and electron microscopy. Mechanistically, FTZ improved liver metabolism by increasing the phosphorylation of PI3K-AKT and decreasing the expression of HIF-1α. CONCLUSION: Network pharmacology was supported by experimental studies, which indicated that FTZ has demonstrated therapeutic benefits in T2DM and NAFLD by regulating the PI3K-AKT and HIF-1α signaling pathways.

9.
Biomed Pharmacother ; 137: 111343, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761594

RESUMO

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is a major risk factor for coronary heart disease (CHD). Previous research has reported that the Fufang-Zhenzhu-Tiaozhi (FTZ) formula has obvious effects on the treatment of dyslipidemia and hyperglycemia. In the present study, we intended to establish a convenient DM-CHD model in minipigs and investigated the protective effect of FTZ against myocardial injury and its mechanism. METHODS: The DM-CHD model was established by a high-fat/high-sucrose/high-cholesterol diet (HFSCD) combined with balloon injury in the coronary artery. Subsequently, sixteen Wuzhishan minipigs were assigned to three groups: control group, model group, and FTZ group. The model group and FTZ group were given a HFSCD, while the control group was given a normal diet (ND). FTZ was given with meals in the FTZ group. During this time, biochemical parameters, such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein (HDL-C), and fasting blood glucose (FBG), were measured by using testing kits. Insulin (INS) was determined by ELISA, and the homeostasis model assessment index of insulin resistance (HOMA-IR) was calculated to evaluate insulin resistance levels. After FTZ administration, the plasma levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), and cardiac troponin I (cTnI) were measured by using ELISA kits to evaluate myocardial injury. Coronary artery stenosis was analyzed by angiographic and HE staining. Myocardial ischemia was assayed with electrocardiogram (ECG). Moreover, cytokines, including interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP), and tumor necrosis factor-alpha (TNF-α), were measured by ELISA kits to assess inflammation. The myocardial tissue was collected, and the pathological morphology was observed by transmission electron microscopy (TEM), HE staining, and Masson staining. Western blots were used to detect the expression of PI3K, AKT, p-AKT, p-NF-κB, and NF-κB. RESULTS: A DM-CHD model in minipigs with glucose-lipid metabolism disorder, coronary artery incrassation and myocardial damage was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ effectively inhibited coronary artery incrassation and protected the myocardium against injury in DM-CHD minipigs. FTZ decreased proinflammatory cytokine levels and upregulated the protein expression of the PI3K/Akt pathway in the myocardium. CONCLUSIONS: A novel DM-CHD model in minipigs was successfully established through balloon injury in the coronary artery combined with HFSCD. FTZ has a protective effect against myocardial injury in DM-CHD by inhibiting inflammation and activating the PI3K/AKT signaling pathway.


Assuntos
Cardiotônicos/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Miocárdio/patologia , Angiografia , Animais , Glicemia/análise , Doença das Coronárias/patologia , Cardiomiopatias Diabéticas/patologia , Eletrocardiografia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Medicina Tradicional Chinesa , Suínos , Porco Miniatura
10.
Hepatology ; 74(2): 686-703, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33576035

RESUMO

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease, especially nonalcoholic steatohepatitis (NASH), has become a major cause of liver transplantation and liver-associated death. NASH is the hepatic manifestation of metabolic syndrome and is characterized by hepatic steatosis, inflammation, hepatocellular injury, and different degrees of fibrosis. However, there is no US Food and Drug Administration-approved medication to treat this devastating disease. Therapeutic activators of the AMP-activated protein kinase (AMPK) have been proposed as a potential treatment for metabolic diseases such as NASH. Cordycepin, a natural product isolated from the traditional Chinese medicine Cordyceps militaris, has recently emerged as a promising drug candidate for metabolic diseases. APPROACH AND RESULTS: We evaluated the effects of cordycepin on lipid storage in hepatocytes, inflammation, and fibrosis development in mice with NASH. Cordycepin attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes subjected to metabolic stress. In addition, cordycepin treatment significantly and dose-dependently decreased the elevated levels of serum aminotransferases in mice with diet-induced NASH. Furthermore, cordycepin treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration, and hepatic fibrosis in mice. In vitro and in vivo mechanistic studies revealed that a key mechanism linking the protective effects of cordycepin were AMPK phosphorylation-dependent, as indicated by the finding that treatment with the AMPK inhibitor Compound C abrogated cordycepin-induced hepatoprotection in hepatocytes and mice with NASH. CONCLUSION: Cordycepin exerts significant protective effects against hepatic steatosis, inflammation, liver injury, and fibrosis in mice under metabolic stress through activation of the AMPK signaling pathway. Cordycepin might be an AMPK activator that can be used for the treatment of NASH.

11.
Arch Pathol Lab Med ; 145(1): 32-38, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33367664

RESUMO

CONTEXT.­: The use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic tests detects antibodies in the host, contributing to the identification of individuals who have been exposed to coronavirus disease 2019 (COVID-19). OBJECTIVE.­: To critically evaluate 2 commercially available SARS-CoV-2 serology tests. DESIGN.­: A total of 333 unique, nonduplicated serum samples obtained from COVID-19 patients (n = 170) and negative controls (n = 163) obtained before December 2019 were used in the study. Samples were tested on the Roche E411 and Abbott Architect i4000SR platforms, and results were correlated to reverse transcription polymerase chain reaction (PCR) results and clinical symptoms. RESULTS.­: There was a strong level of agreement in the qualitative results between both assays, with a Cohen κ value of .840, P < .001. The specificity for both Roche and Abbott were excellent at 100%. Roche exhibited marginally better performance in the 21 days or more group with a sensitivity of 90.6% (95% CI, 75.8%-96.8%) versus an Abbott sensitivity of 84.4% (95% CI, 68.3%-93.1%), as well as in the 14- to 20-day group with a sensitivity of 85.7% (95% CI, 65.4%-95.0%) versus an Abbott sensitivity of 81.0% (95% CI, 60.0%-92.3%). Less than 14 days of symptoms groups exhibited poor sensitivity at less than 50% for both assays. The areas under curve (± standard error) for Roche (0.894 ± 0.025, P < .001) and Abbott (0.884 ± 0.026, P < .001) were very similar. Potential confounders for negative serologic results include antiretroviral medication use and pauci-symptomatic patients. CONCLUSIONS.­: Specificities for high-throughput Roche and Abbott immunoassays are excellent, but users need to be cautious to interpret serologic test results after 14 days of symptoms to avoid false negatives.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Anticorpos Antivirais/análise , Reações Falso-Positivas , Humanos , Sensibilidade e Especificidade
12.
Pathology ; 52(7): 770-777, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33092816

RESUMO

In this study, we evaluated and compared six SARS-CoV-2 serology kits including the Abbott SARS-CoV-2 IgG assay, Beckman Access SARS-CoV-2 IgG assay, OCD Vitros OCD Anti-SARS-CoV-2 Total antibody assay, Roche Elecsys Anti SARS-CoV-2 assay, Siemens SARS-CoV-2 Total assay, and cPass surrogate viral neutralising antibody assay. A total of 336 non-duplicated residual serum samples that were obtained from COVID-19 confirmed patients (n=173) on PCR and negative controls (n=163) obtained pre-December 2019 before the COVID-19 pandemic were used for the study. These were concurrently analysed on the different immunoassay platforms and correlated with clinical characteristics. Our results showed all assays had specificity ranging from 99.3% to 100.0%. Overall sensitivity across all days of symptoms, in descending order were OCD (49.1%, 95% CI 41.8-56.5%), cPass (44.8%, 95% CI 37.5-52.3%), Roche (41.6%, 95% CI 34.5-49.0%), Siemens (39.9%, 95% CI 32.9-47.3%), Abbott (39.8%, 95% CI 32.9-47.3%) and Beckman (39.6%, 95% CI 32.5-47.3%). Testing after at least 14 days from symptom onset is required to achieve AUCs greater than 0.80. OCD and cPass performed the best in terms of sensitivity for >21 days symptoms with 93.3% (95% CI, 73.5-99.2%) and 96.7% (95% CI, 82.8-99.9%), respectively. Both also shared the greatest concordance, kappa 0.963 (95% CI 0.885-1.0), p<0.001, and had the lowest false negative rates. Serology results should be interpreted with caution in certain cases. False negatives were observed in a small number of individuals with COVID-19 on immunosuppressive therapy, pauci-symptomatic or who received antiretroviral therapy. In conclusion, all assays exhibited excellent specificity and total antibody assays with spike protein configurations generally outperformed nucleocapsid configurations and IgG assays in terms of diagnostic sensitivity.


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , COVID-19/sangue , Humanos , SARS-CoV-2 , Sensibilidade e Especificidade
13.
Arch Pathol Lab Med ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32906149

RESUMO

CONTEXT: The use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests detect antibodies in the host, contributing to the identification of individuals who have been exposed to Coronavirus Disease 2019 (COVID-19). OBJECTIVE: To critically evaluate two commercially available SARS-CoV-2 serology tests. DESIGN: A total of 333 unique, non-duplicated serum samples obtained from COVID-19 patients (n=170) and negative controls (n=163) obtained pre-December 2019 were used in the study. Samples were tested on the Roche E411 and Abbott Architect i4000SR platforms and results were correlated to reverse transcription polymerase chain reaction (PCR) results and clinical symptoms. RESULTS: There was a strong level of agreement in the qualitative results between both assays with a Cohen's kappa value of 0.840, P<.001. The specificity for both Roche and Abbott were excellent at 100%. Roche exhibited marginally better performance in the ≥21 days group with a sensitivity of 90.6% (95% CI 75.8-96.8%) versus Abbott's sensitivity 84.4% (95% CI 68.3 - 93.1%) as well as the 14-20 days group with a sensitivity of 85.7% (95% CI 65.4 - 95.0%) versus Abbott sensitivity 81.0% (95% CI 60.0 - 92.3%). Less than 14 days of symptoms groups exhibited poor sensitivity at <50% for both assays. The area under curve (AUC ± standard error) for Roche (0.894 ± 0.025, P< .001) and Abbott (0.884 ± 0.026, P <.001) were very similar. Potential confounders for negative serological results include antiretroviral medication use and pauci-symptomatic patients. CONCLUSIONS: Specificities for high throughput Roche and Abbott immunoassays are excellent but users need to be cautious to interpret serological test results after 14 days of symptoms to avoid false negatives.

14.
Disabil Rehabil ; : 1-12, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539556

RESUMO

Purpose: To help enhance participation, the study aims to identify and document a comprehensive list of environmental barriers for people with SCI in the broad travel setting.Methods: Semi-structured interviews were conducted among four stakeholder groups: people with SCI (n= 39), caregivers and family members of people with SCI (n= 24), therapists who work with people with SCI (n= 9), and travel professionals specializing in accessible travel (n= 11).Results: Five major categories of travel barrier emerged from the interviews: Partial Accessibility, Systemic Ignorance, Travel Hassles, Poor Service Performance, and Lack of Support. Detailed barriers in each category are described. The analysis of multi-stakeholder perspectives indicates while respondents with SCI offered the most specific information about the barriers, family members/caregivers were most concerned about the impact of systemic ignorance on their loved ones. Therapists focused on offering their clients tools to overcome barriers, and travel agents emphasized their limitations of serving customers with disabilities.Conclusion: Results of the study should help not only health and travel professionals better assist individuals to reintegrate into society after SCI, but also travel and hospitality businesses to better meet the accessibility needs of people with SCI.Implications for rehabilitationTravel is important to full participation in society for people after SCI.The study has identified five categories of barriers to travel participation after SCI: partial accessibility, systemic ignorance, travel hassles, poor service performance and lack of support.While traveling is important for participation in society for people with SCI, rehabilitation professionals should work together with policy makers, travel and hospitality businesses and agencies to lower the found barriers.

15.
Biochem Biophys Res Commun ; 526(4): 1077-1084, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32312522

RESUMO

Bilobalide, one of the key bioactive components of Ginkgo biloba leaves, exerts prominent neuroprotective properties in central nervous system (CNS) disease. However, the effect of bilobalide on blood-brain barrier (BBB) permeability remains unknown. In this study, we investigated the effect of bilobalide on BBB permeability and its potential mechanism involved. Both the in vitro and in vivo results showed that significant enhancement of BBB permeability was found following bilobalide treatment, evidenced by the reduced transendothelial electrical resistance (TEER), the increased fluorescein sodium (Na-F) penetration rate in vitro and the leakage of FITC-dextran in vivo. Transmission electron microscope (TEM) images demonstrated that bilobalide modulated BBB permeability by changing the ultrastructure of tight junctions (TJs). In addition, actin-binding proteins ezrin, radixin and moesin (ERM) and Myosin light chain (MLC) phosphorylation was observed following bilobalide treatment. Moreover, the effect of bilobalide on TEER reduction and ERM/MLC phosphorylation was counteracted by adenosine A1 receptor (A1R) siRNA. The current findings suggested that bilobalide might reversibly modulate BBB permeability by the alteration of TJs ultrastructure through A1R-mediated phosphorylation of actin-binding proteins.


Assuntos
Bilobalídeos/farmacologia , Barreira Hematoencefálica/metabolismo , Proteínas dos Microfilamentos/metabolismo , Receptor A1 de Adenosina/metabolismo , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Dextranos/metabolismo , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Humanos , Masculino , Camundongos , Peso Molecular , Permeabilidade/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas de Junções Íntimas/metabolismo
16.
J Ethnopharmacol ; 246: 112243, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31541722

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba leaves and Panax ginseng are Chinese medicine commonly used in combination for cerebral disease. AIM OF THE STUDY: To investigate the effect of standard extract of Ginkgo biloba leaves (EGb) on facilitating brain uptake of ginsenoside and its underlying mechanisms. MATERIALS AND METHODS: The increasing uptake of ginsenosides in the brain of rats by EGb were detected by LC-MS/MS analysis. Evans blue and FITC-dextran leakage were determined to evaluate blood-brain barrier (BBB) permeability in vivo. Transendothelial electrical resistance (TEER) and Na-F penetration rate were measured with a co-culture of the human cerebral microvascular endothelial cell line (hCMEC/D3) and human normal glial cell line (HEB) in vitro BBB model. WB were used to analyzed the expression of BBB tight junctions (TJs) related protein (ZO-1, Occludin, Claudin-3, p-ERM, and p-MLC), ultrastructure of TJs was determined by transmission electron microscope. RESULTS: LC-MS/MS analysis demonstrated that EGb could improve brain uptake of ginsenoside Rg1, Re, Rd and Rb1. In vivo study showed that, BBB permeability was significantly increased after EGb administration, evidenced by the markedly increased penetration of FITC-dextran and Evans Blue into the mice brain parenchyma. In the in vitro BBB model, reduced TEER and increased Na-F penetration rate was observed in EGb group, which was associated with alteration of TJs ultrastructure. Furthermore, the expression of p-ERM and p-MLC in hCMEC/D3 as well as mice brain microvessels were significantly upregulated, but no significant change on the expression of TJs proteins (ZO-1, Occludin and Claudin-3). Moreover, the effect of EGb on in vitro BBB permeability and ERM, MLC phosphorylation was counteracted by DPCPX, an A1 adenosine receptor (A1R) antagonist. CONCLUSIONS: EGb might induce ERM/MLC phosphorylation and increase the cell-cell junction gaps to cause a reversible increase of the BBB permeability via A1R signaling pathway. Our results may contribute to better use of EGb in the treatment of brain diseases.


Assuntos
Agonistas do Receptor A1 de Adenosina/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Ginsenosídeos/farmacocinética , Extratos Vegetais/farmacologia , Receptor A1 de Adenosina/metabolismo , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Ginsenosídeos/metabolismo , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
17.
J Proteomics ; 213: 103601, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31809900

RESUMO

Protein methylation has been proposed as an important post-translational modification, which occurs predominantly on lysine and arginine residues. Recent discoveries have revealed that protein methylation is also present on non-histones besides histones, and plays critical roles in regulating protein stability and function. However, proteome-wide identification of methylated proteins in plants remains unexplored. Here, we present the first global survey of monomethyl arginine, symmetric and asymmetric dimethyl arginine, and monomethyl, dimethyl, trimethyl lysine modifications in the proteomes of 10-day-old Arabidopsis seedlings through a combination of immunoaffinity purification and mass spectrometry analysis. In total, we identified 617 methylation sites which mapped to 412 proteins, with 263 proteins harboring 381 lysine methylation sites and 149 proteins harboring 236 arginine methylation sites. Among them, 607 methylation sites on 408 proteins were novel findings. Motif analysis revealed that glycine preferentially flanked methylated arginine residues, whereas aspartate and glutamate enriched around mono- and dimethylated lysine sites. Methylated proteins were involved in a variety of metabolic processes, showing significant enrichment in RNA-related metabolic pathways including spliceosome, RNA transport, and ribosome. Our data provide a global view of methylated non-histone proteins in Arabidopsis, laying foundations for elucidating the biological function of protein methylation in plants. SIGNIFICANCE: Protein methylation has emerged as a common and important modification both in eukaryotes and prokaryotes. The identification of methylated sites/peptides is fundamental for further functional analysis of protein methylation. This study was the first proteome-scale identification of lysine and arginine methylation in plants. We found that methylation occurred widely on non-histone proteins in Arabidopsis and was involved in diverse biological functions. The results provide foundations for the investigation of the protein methylome in Arabidopsis and provide powerful resources for the functional analysis of protein methylation in plants.


Assuntos
Arabidopsis , Epigenoma , RNA , Arabidopsis/genética , Arabidopsis/metabolismo , Lisina/metabolismo , Metilação , Processamento de Proteína Pós-Traducional
18.
Sensors (Basel) ; 20(1)2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31861515

RESUMO

The fault-tolerant robust non-fragile H∞ filtering problem for networked control systems with sensor failures is studied in this paper. The Takagi-Sugeno fuzzy model which can appropriate any nonlinear systems is employed. Based on the model, a filter which can maintain stability and H∞ performance level under the influence of gain perturbation of the filter and sensor failures is designed. Moreover, the gain matrix of sensor failures is converted into a dynamic interval to expand the range of allowed failures. And the sufficient condition for the existence of the desired filter is derived in terms of linear matrix inequalities (LMIs) solutions. Finally a simulation example is given to illustrate the effectiveness of the proposed method.

19.
Front Plant Sci ; 10: 1031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552061

RESUMO

Soybean is an important economic crop for human diet, animal feeds and biodiesel due to high protein and oil content. Its productivity is significantly hampered by salt stress, which impairs plant growth and development by affecting gene expression, in part, through epigenetic modification of chromatin status. However, little is known about epigenetic regulation of stress response in soybean roots. Here, we used RNA-seq and ChIP-seq technologies to study the dynamics of genome-wide transcription and histone methylation patterns in soybean roots under salt stress. Eight thousand seven hundred ninety eight soybean genes changed their expression under salt stress treatment. Whole-genome ChIP-seq study of an epigenetic repressive mark, histone H3 lysine 27 trimethylation (H3K27me3), revealed the changes in H3K27me3 deposition during the response to salt stress. Unexpectedly, we found that most of the inactivation of genes under salt stress is strongly correlated with the de novo establishment of H3K27me3 in various parts of the promoter or coding regions where there is no H3K27me3 in control plants. In addition, the soybean histone modifiers were identified which may contribute to de novo histone methylation and gene silencing under salt stress. Thus, dynamic chromatin regulation, switch between active and inactive modes, occur at target loci in order to respond to salt stress in soybean. Our analysis demonstrates histone methylation modifications are correlated with the activation or inactivation of salt-inducible genes in soybean roots.

20.
Molecules ; 24(13)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324047

RESUMO

Quinoa (Chenopodium quinoa Willd.) was known as the "golden grain" by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of bioactivities. At least 193 secondary metabolites from quinoa have been identified in the past 40 years. They mainly include phenolic acids, flavonoids, terpenoids, steroids, and nitrogen-containing compounds. These metabolites exhibit many physiological functions, such as insecticidal, molluscicidal and antimicrobial activities, as well as various kinds of biological activities such as antioxidant, cytotoxic, anti-diabetic and anti-inflammatory properties. This review focuses on our knowledge of the structures, biological activities and functions of quinoa secondary metabolites. Biosynthesis, development and utilization of the secondary metabolites especially from quinoa bran were prospected.


Assuntos
Chenopodium quinoa/química , Chenopodium quinoa/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Metabolismo Secundário , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/farmacologia , Compostos Fitoquímicos/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/metabolismo , Terpenos/farmacologia
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