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1.
J Pharm Biomed Anal ; 177: 112848, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479998

RESUMO

Metabolic syndrome (MetS) is an important risk factor for type 2 diabetes, cardiovascular diseases and all-cause morbidity and mortality. Biomarkers can provide insight into the mechanism, facilitate early detection, and monitor progression of MetS and its response to therapeutic interventions. To identify potential biomarkers, we applied a non-targeted and targeted lipidomics method to characterize plasma metabolic profile in MetS patients. Metabolic profiling was performed on a non-target set (40 cases and 40 controls) on UHPLC-Q-TOF/MS and target set (80 MetS patients and 80 healthy controls) on UHPLC-Q-orbitrap MS. Using comprehensive screening and validation workflow, we identified a panel of three metabolites including PC(18:1/P-16:0), PC(o-22:3/22:3), PC(P-18:1/16:1). Our results indicated that the identified biomarkers may improve the risk prediction and provide a novel tool for monitoring of the progression of disease and response to treatment in MetS patients.

2.
Toxicol In Vitro ; 62: 104660, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629066

RESUMO

Herba Epimedii is a famous Chinese edible herb, and due to its potential hepatotoxic effects, the safety associated with this herb has attracted a great deal of attention. In this study, the components of four types of the Herba Epimedii extracts were identified by HPLC-MS/MS. Among these components, 11 components that were present in all four extracts and could be obtained as reference substances were evaluated for their ability of cytotoxicity in HL-7702 and HepG2 cells, resulting in the identification of icarisid I and sagittatoside A as the most relevant with respect to the toxicity of the extracts. The targeted toxicological effects were further investigated using a series of correlated biological indicators to elucidate potentially hepatotoxic mechanisms. The results showed that the extracts and the selected compounds had varying degrees of influence on the leakage of ALT, AST and LDH; the activity of SOD, GSH and MDA; the increase in intercellular ROS; and the decrease in MMP. Among the tested substances, the ethanol extracts exhibited stronger hepatotoxicity, with icarisid I and sagittatoside A correlating with this toxic effect, and the hepatoxic mechanisms of which may be associated with damaged cell structure, increased oxidative stress and induction of apoptosis.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31677400

RESUMO

Water temperature can affect the metabolism of fish. Common carp (Cyprinus carpio) is a representative eurythermic fish that can survive at a wide range of ambient temperatures, allowing it to live in an extensive geographical range. The goal of this work was to study the glucose metabolism of common carp at different temperatures and determine the miRNAs involved in the regulation of glucose metabolism. We determined the indicators related to glucose metabolism after long-term temperature stress and constructed nine small RNA libraries of livers under different temperature stress (5 °C, 17 °C, and 30 °C, with three biological replicates for each temperature), and subjected these samples to high-throughput sequencing. A positive relationship was observed between weight gain rate (WGR) and temperature increase after 18 days of temperature stress. However, the glucose level in the plasma maintained a gentle decrease. Unexpectedly, liver lactic acid levels were elevated in HTG (high temperature group) and LTG (low temperature group). Six down-regulated miRNAs (miR-122, miR-30b, miR-15b-5p, miR-20a-5p, miR-1, and miR-7b) were identified as involved in the regulation of glycolysis. Twelve genes were predicted as targets of these miRNAs, and these genes are in pathways related to pyruvate metabolism, glycolysis/gluconeogenesis, and the citrate cycle (TCA cycle). The results allowed prediction of a potential regulatory network of miRNAs involved in the regulation of glycolysis. The target genes of six down-regulated miRNAs were up-regulated under temperature stress, including Aldolase C, fructose-bisphosphate, b (ALDOCB), multiple inositol-polyphosphate phosphatase 1 (MINPP1), phosphoenolpyruvate carboxykinase 1 (PCK1), pyruvate dehydrogenase E1 alpha 1 (PDHA1), aldehyde dehydrogenase 9 family member A1a (ALDH9A1A), Acetyl-coenzyme A synthetase (ACSS), lactate dehydrogenase b (LDH-b), and glyoxylate reductase/hydroxypyruvate reductase (GRHPR). Other key genes of glycolysis, glucose transporter 1 (GLUT-1), pyruvate kinase PKM (PKM), and mitochondrial pyruvate carrier (MPC) were significantly up-regulated in LTG and HTG. Overall, the results suggest that miRNAs maintain their energy requirements by regulating glycolysis and play an important role in the molecular response to cold and heat stress of common carp. These data provide the foundation for further studies of the role of miRNAs in environmental adaptation in fish.

4.
Inflammation ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701354

RESUMO

Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 µg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.

5.
Exp Cell Res ; : 111737, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759058

RESUMO

The presence of elevated T lymphocytic microparticles (TLMPs) during respiratory illness is associated with airway and lung inflammation and epithelial injuries. Although inflammasome and IL-1ß signaling are crucial in airway inflammation, little was known about their regulatory mechanism. We hypothesized that TLMPs trigger inflammasome activation and IL-1ß production in bronchial and alveolar epithelial cells to induce airway and lung inflammation. In this study, TLMPs induced IL-1ß and IL-18 secretion through NLRP3 inflammasome activation and upregulated TLR4 mRNA and protein expression in alveolar (A549) and human airway epithelial (16HBE) cells. Pretreatment with CLI-095, a specific inhibitor of TLR4 signaling, dramatically diminished the TLMP-induced release of IL-1ß and IL-18 by inhibiting the formation of NLRP3/ASC/pro-caspase-1 inflammasome in a dose-dependent manner. The TLMP-induced autophagy inhibition in epithelial cells was dependent on the PI3K/Akt signaling pathway, which significantly increased NLRP3 expression and enhanced TLMP-induced inflammation. TLR4, IL-1ß, and IL-18 proteins harbored in TLMPs were nonessential for the pro-inflammatory effect. In conclusion, TLMPs induce bronchial and alveolar epithelial cell secretion of IL-1ß and IL-18 cytokines by activating the TLR4 and PI3K/Akt signaling pathways and inhibiting autophagy. These effects lead to NLRP3 inflammasome formation and accumulation. TLMPs may be regarded as deleterious markers of airway and lung damage in respiratory diseases.

6.
BMC Med Genet ; 20(1): 170, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694563

RESUMO

OBJECTIVES: Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis. METHODS: A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis. RESULTS: During a median follow-up time of 5.01 years, 98 CHD incidence was identified (47.03/104 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08 mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ≥1.08 mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with < 1.08 mg/L, the adjusted HR (95% CI) was 1.69 (1.11-2.60) with a P value of 0.016. No significant casual association was observed between hs-CRP and CHD with a P value of 0.777. CONCLUSIONS: The association between hs-CRP and CHD is unlikely to be causal, hs-CRP might be a predictor for incidence of CHD in general population.

7.
Croat Med J ; 60(5): 439-448, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31686458

RESUMO

AIM: To explore the mechanism underlying the protective effect of adipose-derived mesenchymal stem cells (ADMSCs) against ischemic stroke by focusing on miR-21-3p/MAT2B axis. METHODS: Ischemic brain injury was induced in 126 rats by middle cerebral artery occlusion (MCAO). The effect of ADMSC administration on blood-brain barrier (BBB) condition, apoptosis, inflammation, and the activity of miR-21-3p/MAT2B axis was assessed. The role of miR-21-3p inhibition in the function of ADMSCs was further validated in in vitro neural cells. RESULTS: ADMSCs administration improved BBB condition, inhibited apoptosis, and suppressed inflammation. It also reduced the abnormally high level of miR-21-3p in MCAO rats. Dual luciferase assays showed that miR-21-3p directly inhibited the MAT2B expression in neural cells, and miR-21-3p inhibition by inhibitor or ADMSC-derived exosomes in neurons attenuated hypoxia/reoxygenation-induced impairments similarly to that of ADMSCs in vivo. CONCLUSION: This study confirmed the protective effect of ADMSCs against ischemic brain injury exerted by suppressing miR-21-3p level and up-regulating MAT2B level.

8.
Genomics ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765823

RESUMO

The small brown planthopper (SBPH), Laodelphax striatellus is one of the major insect pests of rice, but little is known about the molecular-level means by which it locates its hosts. SBPH host-seeking behavior heavily relies on chemosensory receptors (CRs). In this study, we utilized genome analysis of the SBPH to identify 169 CRs, including: 133 odorant receptors (ORs), 13 gustatory receptors (GRs) and 23 ionotropic receptors (IRs). The phylogenetic relationships of OR genes from three rice planthoppers and other insect species revealed that the odorant co-receptor (Orco) clade is the most conserved group. Among the candidate GRs, two sugar receptors and five fructose receptors have been identified but no carbon dioxide receptors investigated. Furthermore, we identified homologs of the three highly conserved IR co-receptors. The obtained results will provide us with precious information needed to better understand the interaction between insect pests and crop plants required for effective crop protection.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31746449

RESUMO

OBJECTIVE: Intracranial aneurysms treated with endovascular coil embolization may recur. We investigated the factors affecting aneurysmal recurrence after embolization and effects of endovascular retreatment within 1 year. METHODS: In 3 years, 1335 patients with 1385 intracranial aneurysms were treated with coil embolization. Factors affecting aneurysm recurrence and the effects of endovascular retreatment were analyzed. RESULTS: Angiography immediately following embolization showed total occlusion in 1030 aneurysms (74.4%), neck remnant in 207 (14.9%), and partial occlusion in 148 (10.7%), with a total peri-procedure complication rate of 4.2%. Overall, 145 patients with 151 aneurysms recurred within 1 year and the other 1234 aneurysms remained occluded (89.1%). A significant (p < 0.05) difference existed in aneurysm size, rupture status, use of stent and immediate occlusion outcome between the two groups, with significantly (p < 0.05) lower recurrence rates in aneurysms with smaller sizes, no rupture and stent-assistance coiling. Neck remnant, partial occlusion, coiling without stent assistance, large and giant aneurysms were significant (p < 0.05) risk factors for aneurysm recurrence during the first year. The rate of recurrence was 4.7% (11/232) in aneurysms with total occlusion and 35.9% (23/64) in aneurysms with neck remnant and partial occlusion. Of the 34 recurrent aneurysms, 6 were re-embolized with detachable coils alone, 12 with stent-assisted coiling, 8 with balloon-assisted embolization, and the remaining 8 aneurysms with covered stents, resulting in total occlusion in 28 aneurysms and neck remnant in 6. CONCLUSION: Recurrence of previously-coiled cerebral aneurysms is significantly affected by aneurysm size, use of stent and degree of immediate occlusion. Endovascular retreatment with balloon-or stent-assisted techniques or with covered stents can be safe and effective for recurrent cerebral aneurysms.

10.
Pediatr Pulmonol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31746563

RESUMO

OBJECTIVES: To investigate the association between particulate matter with an aerodynamic diameter of less than 2.5 µm (PM2.5 ) exposure during each trimester of pregnancy and development of lower respiratory tract infections (LRTIs) during the first 3 years of life and whether GSTM1 gene polymorphisms modify these effects. METHODS: This study included 1,180 mother-child pairs from the Cohort for Childhood Origin of Asthma and allergic diseases. The PM2.5 levels during pregnancy were estimated by residential address using land-use regression models based on a national monitoring system. A diagnosis of LRTIs was based on a parental report of a physician's diagnosis. Real-time polymerase chain reaction was used for GSTM1 genotyping. RESULTS: Higher PM2.5 exposure during the third trimester was associated with LRTIs at 1 year of age (aRR, 1.06; 95% CI, 1.00-1.13). This result did not change after adjusting for PM2.5 exposures during the first and second trimesters (aRR, 1.06; 95% CI, 0.99-1.13). This association was significant after adjusting for PM2.5 exposures during first year of age (aRR, 1.08; 95% CI, 1.02-1.15) and exposures to NO2 and ozone at the third trimester (aRR, 1.07; 95% CI, 1.00-1.16). In addition, PM2.5 exposure during the third trimester increased the risk of LRTIs at 1 year of age in cases with the GSTM1 null genotype (aRR, 1.26; 95% CI, 1.01-1.57; P for interaction .20). CONCLUSION: Higher PM2.5 exposure during the third trimester of pregnancy may increase the susceptibility to LRTIs at 1 year of age. This effect is modified by GSTM1 gene polymorphisms.

11.
Biomed Res Int ; 2019: 5907361, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31737670

RESUMO

Objectives: Obstructive sleep apnea (OSA) is a common disorder influenced by genetic and environmental factors. Mutations of AT-hook DNA-binding motif containing 1 (AHDC1) gene have been implicated which could cause rare syndromes presenting OSA. This study aims to investigate some rare mutations of AHDC1 in Chinese Han individuals with OSA. Patients and Methods: Three hundred and seventy-five patients with OSA and one hundred and nine control individuals underwent polysomnography. A targeted sequencing experiment was taken in 100 patients with moderate-to-severe OSA, and genotyping was taken in 157 moderate-to-severe OSA and 100 control individuals. The effect of mutations was validated by the luciferase reporter assay. Results: One rare missense mutation (AHDC1: p.G1484D) and two mutations (c.-88C>T; c.-781C>G) in 5'-untranslated region (UTR) of AHDC1 were identified. The rare mutation (c.-781C>G) in 5'-UTR that was identified in several patients presenting more severe clinical manifestations affects expression of AHDC1. Conclusions. Our results revealed three rare mutations of AHDC1 in patients with OSA in Chinese Hanindividuals.

12.
Inflamm Bowel Dis ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750918

RESUMO

The effect of treatment regimens on fungal microbiota is unclear in ulcerative colitis (UC) patients. Here, we aimed to clarify the effect of 5-aminosalicylic acid (5-ASA) treatment on gut fungal microbiota in UC patients. Fifty-seven UC patients, including 20 treatment-naïve and 37 5-ASA-treated, were recruited into an exploration study. We compared the gut fungal profiles of these 2 groups of patients using ITS1-2 rDNA sequencing. Ten out of 20 treatment-naïve UC patients were followed up and enrolled for a validation study and underwent a 5-ASA treatment. We assessed the longitudinal differences of fungal microbiota in these patients before and after 5-ASA treatment. Results acquired from the validation study were accordant to those from the exploration study. Ascomycota was the dominant phylum in both noninflamed and inflamed mucosae. At the phylum level, Ascomycota decreased in inflamed mucosae before 5-ASA treatment. At the genus level, pathogens such as Scytalidium, Morchella, and Paecilomyces increased, and Humicola and Wickerhamomyces decreased in inflamed mucosae. After 5-ASA treatment, Ascomycota and Wickerhamomyces increased and Scytalidium, Fusarium, Morchella, and Paecilomyces decreased in both noninflamed and inflamed mucosae. Additionally, the balanced bacteria-fungi correlation was interrupted in inflamed mucosae, and 5-ASA treatment altered group-specific fungal microbiota and restored bacteria-fungi correlation in UC patients. Our results demonstrated that fungal diversity and composition were altered and the bacteria-fungi correlation was restored in inflamed mucosae after 5-ASA treatment.

13.
J Agric Food Chem ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31702905

RESUMO

Because only a handful of agrochemicals can manage bacterial infections, the discovery and development of innovative, inexpensive, and high-efficiency antibacterial agents targeting these infections are challenging. Herein, a series of novel epimeric and chiral 18ß-glycyrrhetinic acid (GA) ester derivatives with various tertiary amine pendants were designed, synthesized, and screened for pharmacological activity. Results showed that some of the title compounds were conferred with significantly enhanced antibacterial activity toward phytopathogens Xanthomonas oryzae pv oryzae (A2, B1-B3, and C1, EC50 values within 3.81-4.82 µg/mL) and Xanthomonas axonopodis pv citri (B1, EC50 = 3.18 µg/mL; B2, EC50 = 2.76 µg/mL). These activities are superior to those of GA (EC50 > 400 µg/mL), thiodiazole copper, and bismerthiazol. Pharmacophore studies revealed that the synergistic combination of GA skeleton and tertiary amine scaffolds contributed to the biological actions. In vivo experiments displayed their promising applications in controlling bacterial infections. Antibacterial mechanism studies revealed that the title compounds could trigger apoptosis in the tested pathogens, evident by bacteria morphological changes observed in scanning electron microscopy images. This outcome should motivate the development of various apoptosis inducers against plant bacterial diseases by a novel mode of action compared to that of existing agricultural chemicals.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31770642

RESUMO

High temperatures and low oxygen in aquatic environments, such as intensive aquaculture or in natural watersheds, inevitably cause stress in fish. Fish are exposed to high temperatures during the summer, which exacerbates hypoxia. Hypoxia (1.2 ±â€¯0.2 mg/L) under 20 °C (20HG) and 26 °C (26HG) was simulated to induce stress in largemouth bass (Micropterus salmoides). Related enzymes and genes involved in antioxidant, immune, and apoptotic responses were selected to explore the interactive effects of temperature and hypoxia on largemouth bass. The results showed that malondialdehyde (MDA) levels in plasma, gill, and liver increased in the 26 HG (p < 0.05). Liver superoxide dismutase (SOD) activity increased in the 26 HG. Peak SOD (SOD1, SOD2, SOD3a, and SOD3b), CAT, and GSH-Px mRNA levels in the gill and liver were observed at 12-24 h of stress. The levels of gill and liver total antioxidant capacity, catalase (CAT), glutathione peroxidase (GSH-Px) activities and other enzyme activities and genes in the 26 HG were higher than those in the 20 HG (p < 0.05). The gill and liver acid phosphatase and alkaline phosphatase activities increased with time in the 26 HG (p < 0.05), while gill and liver lysozyme activities in the 26 HG were lower than those in the 20 HG (p < 0.05). Tumor necrosis factor-α mRNA level was upregulated in the gill and downregulated in the liver at 24 h in the 26 HG. Interleukin (IL)-1ß and IL-8 mRNA levels were upregulated in the gill and liver in the 26 HG at 24 h, whereas IL-15 mRNA level was downregulated in the 26 HG at 12 h. Transforming growth factor-ß1 mRNA level was upregulated in the gill in the 20 HG at 24 h, but downregulated in gill and liver in the 26 HG at 24 h. Similarly, IL-10, Hepcidin-1, and Hepcidin-2 showed lower expression levels in the 26 HG. Gill and liver caspase-3 activities were higher in the 26 HG (p < 0.05), and gill caspase-3 activity was higher than that in the liver. The mRNA levels of proapoptotic genes (caspase-3, caspase-8, and caspase-9) were higher in the 26 HG. The present study demonstrates the interactive effects of temperature and hypoxia on stress in largemouth bass gill and liver. These results will be helpful to understand the mechanisms of stress induced by temperature and hypoxia in fish and provide a theoretical basis for aquaculture management.

15.
J Agric Food Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774673

RESUMO

A novel simple 1,3,4-oxadiazole-2-carbohydrazides was reported to discover low-cost and versatile antifungal agents. Bioassay results suggested that a majority of the designed compounds were extremely bioactive against four types of fungi and two kinds of oomycetes. This extreme bioactivity was highlighted by the applausive inhibitory effects of compounds 4b, 4h, 5c, 5g, 5h, 5i, 5m, 5p, 5t, and 5v against Gibberella zeae, affording EC50 values ranging from 0.486 µg/mL to 0.799 µg/mL, which were superior to that of fluopyram (2.96 µg/mL) and comparable to those of carbendazim (0.947 µg/mL) and prochloraz (0.570 µg/mL). Meanwhile, compounds 4g, 5f, 5i, and 5t showed significant actions against Fusarium oxysporum with EC50 values of 0.652, 0.706, 0.813, and 0.925 µg/mL, respectively. Pharmacophore exploration suggested that the N'-phenyl-1,3,4-oxadiazole-2-carbohydrazide pattern is necessary for the bioactivity. Molecular docking of 5h with succinate dehydrogenase (SDH) indicated that it can completely locate the inside of the binding pocket via hydrogen-bonding and hydrophobic interactions, revealing that this novel framework might target SDH. This result was further verified by the significant inhibitory effect on SDH activity. In addition, SEM patterns were performed to elucidate the anti-G. zeae mechanism. Given these features, this type of frameworks is a suitable template for future exploration of alternative SDH inhibitors against plant microbial infections.

16.
Sci Total Environ ; 699: 134160, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31639548

RESUMO

The widespread use of antibiotics has accelerated the development of antibiotic resistance genes (ARGs), which are now recognized as emerging environmental contaminants that pose a high risk to public health. In this study, simultaneous antibiotic and ARGs removal and bioelectricity generation was explored in a microbial electro-Fenton system using erythromycin (ERY) as a model antibiotic compound. The results showed that ERY could be degraded, with an average removal efficiency of 88.73% in 48 h, and the average removal efficiency of chemical oxygen demand in the microbial electro-Fenton with 50 µg L-1 ERY reached 86.84% in 48 h, which was lower than that in the control group (89.11%). The produced ARGs were analyzed and degraded in a cathode chamber. The quantity of ermB was significantly reduced, with log removal reaching a value of 1.96. More importantly, all erm genes (ermB, ermC, ermG) showed a tendency to be degraded. Furthermore, the maximum power density obtained with respect to the electrode area was 0.193 W m-2 when ERY was added, corresponding to a current density of 0.583 A m-2 (external resistor = 1000 Ω), which was 14% larger than that of the control group (0.169 W m-2). The results of this study demonstrate the potential of microbial electro-Fenton for ERY and ARGs removal.

17.
Free Radic Biol Med ; 145: 357-373, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614179

RESUMO

Clusterin (CLU) is a stress-responding protein associated with cytoprotection in a broad range of pathological processes. However, clusterin's function in diabetes-induced endothelial dysfunction has not been defined. Herein, using two diabetes models, we investigated the role of clusterin in endothelial dysfunction triggered by diabetes and the molecular mechanisms involved. The results revealed that clusterin overexpression inhibited ICAM-1/VCAM-1 expression in aortas and improved endothelium-dependent vasodilatation in db/db diabetic mice and streptozotocin (STZ)-induced diabetes models. Consistently, in vitro, adenoviral clusterin overexpression reduced the expression of a range of pro-inflammatory cytokines and suppressed monocyte adhesion to endothelial cells subjected to high glucose and high palmitate. Further study indicated that clusterin overexpression mitigated mitochondrial excessive fission and reduced mitochondrial ROS production. Conversely, silencing clusterin aggravated mitochondrial fission and endothelial inflammatory activation in high glucose-exposed endothelial cells. Accumulating evidence indicates that impaired mitochondrial dynamics plays a considerable role in promoting endothelial dysfunction in diabetic subjects. Therefore, treatments targeting mitochondrial undue fission may be promising measures to prevent vascular complications of diabetes. Furthermore, AMP-activated protein kinase (AMPK) activation contributed to the modulation of mitochondrial dynamics executed by clusterin. Mechanistically, clusterin promoted the phosphorylation of AMPKα and its downstream target acetyl-CoA carboxylase (ACC), while the inhibition of AMPKα negated the improvement in mitochondrial dynamics provided by clusterin overexpression. Over all, these findings suggest that clusterin exerts beneficial effects in endothelial cells under diabetic conditions via inhibiting mitochondrial fragmentation mediated by AMPK.

18.
Medicine (Baltimore) ; 98(43): e17394, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651841

RESUMO

Child-Pugh (CP) grade A patients with early stage hepatocellular carcinoma (HCC) are candidates for curative surgery, while some patients still have a poor outcome. The aim of this study was to investigate the prognostic values of 2 new evaluation models for liver function, named albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (PALBI) grades, in CP grade A patients with HCC.In this retrospective cohort study, we reviewed 134 cases of CP grade A patients with hepatitis B-associated HCC who underwent radical surgery. ALBI and PALBI grades were calculated based on preoperative serologic examinations. Overall survival (OS) and recurrence-free survival (RFS) were estimated by Kaplan-Meier curve and Cox regression. The prognostic performances of the models were estimated by using the concordance index (C-index).During a median follow-up time of 27 months, 27.6% (37/134) of patients died and 26.1% (35/134) experienced recurrence. Kaplan-Meier analyses showed that ALBI and PALBI grades were significantly associated with OS and RFS. Multivariate analyses further revealed that both ALBI and PALBI grades were independent predictors for survival. Furthermore, the prognostic values of the combination of tumor size with ALBI (C-index = 0.754, 95% confidence interval [CI]: 0.675-0.849) or with PALBI (C-index = 0.762, 95% CI: 0.664-0.844) may be comparable with both Barcelona Clinic Liver Cancer and Cancer of Liver Italian Program staging systems.The ALBI and PALBI grades, in particular the combination with tumor size, are effective models for discriminating survival in CP grade A patients with HCC.


Assuntos
Bilirrubina/sangue , Plaquetas/metabolismo , Carcinoma Hepatocelular/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Albumina Sérica/análise , Adulto , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Feminino , Hepatite B/complicações , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Agric Food Chem ; 67(46): 12696-12708, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657554

RESUMO

In this study, a type of thiazolium-labeled 1,3,4-oxadiazole thioether bridged by diverse alkyl chain lengths was constructed. The antimicrobial activity of the fabricated thioether toward plant pathogenic bacteria and fungi was then screened. Antibacterial evaluation indicated that title compounds possess specific characteristics that enable them to severely attack three phytopathogens, namely, Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri with minimal EC50 values of 0.10, 3.27, and 3.50 µg/mL, respectively. Three-dimensional quantitative structure-activity relationship models were established to direct the following excogitation for exploring higher active drugs. The in vivo study against plant bacterial diseases further identified the prospective application of title compounds as alternative antibacterial agents. The proteomic technique, scanning electron microscopy patterns, and fluorescence spectrometry were exploited to investigate the antibacterial mechanism. Additionally, some target compounds performed superior inhibitory actions against three tested fungal strains. In view of their simple molecular architecture and highly efficient bioactivity, these substrates could be further explored as promising surrogates for fighting against plant microbial infections.

20.
J Clin Lab Anal ; : e23059, 2019 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-31587371

RESUMO

BACKGROUND: Fecal calprotectin (FC) is widely used to discriminate between patients with inflammatory diseases such as inflammatory bowel disease (IBD) and functional diseases such as irritable bowel syndrome (IBS). ELISA is a time-consuming method for the measurement of FC, whereas a fluorescent immunochromatography test can obtain results in around 30 minutes and thus enables a rapid response to clinical decision. METHODS: Two methods, the Proglead® calprotectin (FC Proglead) and the BÜHLMANN fCAL® ELISA (FC BÜHLMANN), were used to quantitatively examine FC in 111 stool samples. The comparison and bias estimation of both assays were assessed using CLSI EP09c protocol. RESULTS: The two methods were highly correlated (rho = .96). Deming regression was employed to calculate the regression equation, with a slope of 1.01 and an intercept of -4.98 µg/g. The estimated median bias (FC Proglead - FC BÜHLMANN) was -4.19 µg/g with the 95% limits of agreement (-55.59 to 47.21 µg/g), and the estimated median percent bias was -8.71% with the 95% limits of agreement (-50.31% to 32.90%). There was 4.50% (5/111) of values outside the 95% limits of agreement. Percent biases at the FC cutoff values of 50 and 200 µg/g between both methods evaluated by Deming regression were 8.96% and 1.49%, respectively. The biases were all less than the acceptable standard (10%). And, 99.10% of FC results were in agreement between both methods (kappa = .99, P < .001). CONCLUSIONS: FC Proglead may be used as a suitable alternative to FC BÜHLMANN for the disease activity assessment for patients with IBD, considering its convenience and shorter turnaround time.

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