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1.
Int J Biol Macromol ; : 123411, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706880

RESUMO

Huanglongbing (HLB), also known as citrus greening disease, is caused by Candidatus Liberbacter asiaticus (CLas) and transmitted by Diaphorina citri. Previous studies reported that CLas infection significantly influences the structure of the D. citri cytoskeleton. However, the mechanisms through which CLas manipulates cytoskeleton-related proteins remain unclear. In this study, we performed quantitative ubiquitylome crosstalk with the proteome to reveal the roles of cytoskeleton-related proteins during the infection of D. citri by CLas. Western blotting revealed a significant difference in ubiquitination levels between the CLas-free and CLas-infected groups. According to ubiquitylome and 4D label-free proteome analysis, 343 quantified lysine ubiquitination (Kub) sites and 666 differentially expressed proteins (DEPs) were identified in CLas-infected groups compared with CLas-free groups. A total of 53 sites in 51 DEPs were upregulated, while 290 sites in 192 DEPs were downregulated. Furthermore, functional enrichment analysis indicated that 18 DEPs and 21 lysine ubiquitinated proteins were associated with the cytoskeleton, showing an obvious interaction. Ubiquitination of D. citri tropomyosin was confirmed by immunoprecipitation, Western blotting, and LC-MS/MS. RNAi-mediated knockdown of tropomyosin significantly increased CLas bacterial content in D. citri. In summary, we provided the most comprehensive lysine ubiquitinome analysis of the D. citri response to CLas infection, thus furthering our understanding of the role of the ubiquitination of cytoskeleton proteins in CLas infection.

2.
Pest Manag Sci ; 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36680499

RESUMO

BACKGROUND: A key challenge for the UAV (unmanned aerial vehicle) spray seldom used in tea plantations is the downwash flow structure there stronger than in crops. Besides this factor the UAV spray is actually affected by the matching relationship between nozzle and pesticide. However, few of the current research focus on this aspect. As a preliminary step this study focuses on the most appropriate pesticide for a designated nozzle of the six-rotor UAV through the nozzle-pesticide relationship using the 3D computational fluid dynamics (CFD) model. This model considers the downwash flow structure effects and the nozzle spray performances in hover. Nozzle FVP110-02, widely used in the six-rotor UAV, is designated as a representative, whilst Bifenthrin and tea saponin water, commonly used in the tea plantation, as sprayed pesticides. RESULTS: The downwash flow structure of the six-rotor UAV in hover could conveniently be controlled by the flight height and the rotational speed, thereby causing the turbulence to be more stable. For nozzle FVP110-02, Bifenthrin was more appropriate than tea saponin water at the same concentration, whilst Bifenthrin and tea saponin water with the concentration of 1:1000 showed the greatest performance at the identical working condition. CONCLUSION: The developed numerical model is demonstrated to be effective for investigating the matching relationship between nozzle and pesticide. Our findings could help to not only improve the UAV spray for tea cultivation but also provide guidelines for pesticide selection in crops. Further work will address rigorous quantification of the numerical simulations by the field test. This article is protected by copyright. All rights reserved.

3.
Int Immunopharmacol ; 114: 109547, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36527877

RESUMO

Prothrombotic and proinflammatory properties of neutrophil extracellular traps (NETs) contribute to brain damage after ischemic stroke. CD21 is a novel phthalide neuroprotectant against cerebral ischemia in rodents. This study investigated effects of CD21 on the platelet-NET-thrombin axis and ischemic brain injury and the underlying mechanism. CD21 exerteddose-dependent neuroprotectionin rats that were subjected to2 h middle cerebral artery occlusion,dose-dependentlyinhibited adenosine diphosphate-mediatedplatelet aggregationin rats, and dose-dependentlyexertedanti-thrombotic activityin rodents that received a collagen-epinephrine combination, ferric chloride, or an arteriovenous shunt. Equimolar CD21 doses exerted stronger efficacy than 3-N-butylphthalide (NBP, natural phthalide for the treatment of ischemic stroke). CD21 dose-dependently improved regional cerebral blood flow, neurobehavioral deficits, and infarct volume in mice that were subjected to photothrombotic stroke (PTS). CD21 (13.79 mg/kg, i.v.) significantly decreased NET components (plasma dsDNA concentrations; mRNA levels of elastase, myeloperoxidase, and neutrophil gelatinase-associated lipocalin and protein level of citrullinated histone H3 in ischemic brain tissues), mRNA and protein levels of peptidyl-arginine deiminase 4 (PDA4, NET formation enzyme), and mRNA levels of NET-related inflammatory mediators (interleukin-1ß, interleukin-17A, matrix metalloproteinase 8, and matrix metalloproteinase 9) in ischemic brain tissues, despite no effect on mRNA levels of deoxyribonuclease I (NET elimination enzyme). Pretreatment with compound C (inhibitor of adenosine monophosphate-activated protein kinase [AMPK]) significantly reversed the inhibitory effects of CD21 on NETs, PDA4, and inflammatory mediators in PTS mice. These results suggest that CD21 might regulate the platelet-NET-thrombin axis and protect against ischemic brain injury partly through the induction of AMPK activation.


Assuntos
Isquemia Encefálica , Armadilhas Extracelulares , AVC Isquêmico , Acidente Vascular Cerebral , Ratos , Camundongos , Animais , Trombina/metabolismo , Roedores , Armadilhas Extracelulares/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , AVC Isquêmico/metabolismo , Mediadores da Inflamação/metabolismo
4.
Glob Health Res Policy ; 7(1): 48, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36474302

RESUMO

BACKGROUND: Identifying factors associated with cardiovascular disease (CVD) is critical for its prevention, but this topic is scarcely investigated in Kashgar prefecture, Xinjiang, northwestern China. We thus explored the CVD epidemiology and identified prominent factors associated with CVD in this region. METHODS: A total of 1,887,710 adults at baseline (in 2017) of the Kashgar Prospective Cohort Study were included in the analysis. Sixteen candidate factors, including seven demographic factors, 4 lifestyle factors, and 5 clinical factors, were collected from a questionnaire and health examination records. CVD was defined according to International Clinical Diagnosis (ICD-10) codes. We first used logistic regression models to investigate the association between each of the candidate factors and CVD. Then, we employed 3 machine learning methods-Random Forest, Random Ferns, and Extreme Gradient Boosting-to rank and identify prominent factors associated with CVD. Stratification analyses by sex, ethnicity, education level, economic status, and residential setting were also performed to test the consistency of the ranking. RESULTS: The prevalence of CVD in Kashgar prefecture was 8.1%. All the 16 candidate factors were confirmed to be significantly associated with CVD (odds ratios ranged from 1.03 to 2.99, all p values < 0.05) in logistic regression models. Further machine learning-based analysis suggested that age, occupation, hypertension, exercise frequency, and dietary pattern were the five most prominent factors associated with CVD. The ranking of relative importance for prominent factors in stratification analyses showed that the factor importance generally followed the same pattern as that in the overall sample. CONCLUSIONS: CVD is a major public health concern in Kashgar prefecture. Age, occupation, hypertension, exercise frequency, and dietary pattern might be the prominent factors associated with CVD in this region.In the future, these factors should be given priority in preventing CVD in future.

5.
Molecules ; 27(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36557986

RESUMO

The changes in the gel and rheological properties and water-holding capacity of PSE meat myofibrillar proteins with different amounts of sodium bicarbonate (SC, 0-0.6/100 g) were studied. Compared to the PSE meat myofibrillar proteins with 0/100 g SC, the texture properties and cooking yield significantly increased (p < 0.05) with increasing SC; meanwhile, adding SC caused the gel color to darken. All samples had similar curves with three phases, and the storage modulus (G') values significantly increased with the increasing SC. The thermal stability of the PSE meat myofibrillar proteins was enhanced, and the G' value at 80 °C increased with the increasing SC. Because water was bound more tightly to the protein matrix, the initial relaxation times of T21 and T22 shortened, the peak ratio of P21 significantly increased (p < 0.05), and the P22 significantly decreased (p < 0.05), which implied that the mobility of the water was reduced. Overall, SC could improve the thermal stability of the PSE meat myofibrillar proteins and increase the water-holding capacity and textural properties of the cooked PSE meat myofibrillar protein gels.


Assuntos
Proteínas de Carne , Bicarbonato de Sódio , Água , Culinária , Reologia , Géis
6.
Int J Mol Sci ; 23(23)2022 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-36499179

RESUMO

Ornamental kale, as a burgeoning landscaping plant, is gaining popularity for its rich color patterns in leaf and cold tolerance. Leaf variegation endows ornamental kale with unique ornamental characters, and the mutants are ideal materials for exploring the formation mechanisms of variegated phenotype. Herein, we identified a novel variegated leaf kale mutant 'JC007-2B' with green margins and white centers. Morphological observations and physiological determinations of the green leaf stage (S1), albino stage (S2) and variegated leaf stage (S3) demonstrated that the chloroplast structure and photosynthetic pigment content in the white sectors (S3_C) of variegated leaves were abnormal. Genetic analysis revealed that a single dominant nuclear gene (BoVl) controlled the variegated leaf trait of 'JC007-2B', and three candidate genes for BoVl were fine-mapped to a 6.74 Kb interval on chromosome C03. Multiple sequence alignment among the green-leaf mapping parent 'BS', recombinant individuals, mutant parent 'JC007-2B' and its same originated DH line population established that the mutation sites in Bo3g002080 exhibited a complete consensus. Bo3g002080, homologous to Arabidopsis&nbsp;MED4, was identified as the candidate gene for BoVl. Expression analysis showed that Bo3g002080 displayed a 2158.85-fold higher expression at albino stage than that in green leaf stage. Transcriptome analysis showed that related pathways of photosynthesis and chloroplast development were significantly enriched in the white sectors, and relevant DEGs involved in these pathways were almost down-regulated. Overall, our study provides a new gene resource for cultivar breeding in ornamental kale and contributes to uncovering the molecular genetic mechanism underlying the variegated leaf formation.


Assuntos
Arabidopsis , Brassica , Brassica/genética , Melhoramento Vegetal , Folhas de Planta/metabolismo , Cloroplastos/genética , Cloroplastos/metabolismo , Perfilação da Expressão Gênica , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
8.
J Oncol ; 2022: 6334546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36385959

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most aggressive and deadly cancer of the urinary system and is regulated by multiple signaling pathways. However, the specific molecular mechanisms underlying ccRCC have not been fully studied or demonstrated. This study aimed to elucidate the function of lysosomal-associated transmembrane protein 5 (LAPTM5) in ccRCC cell lines and animal models and determine the potential underlying mechanisms. Our results demonstrated that LAPTM5 expression in patients with ccRCC was significantly higher in the tumor group than that in the adjacent nontumor group. Moreover, LAPTM5 promoted proliferation, migration, and invasion of ccRCC cells through the gain and loss of the function of LAPTM5 in 786-0 and Caki-1 cell lines. Similar results regarding LAPTM5 overexpression were obtained in BALB/c nude mice. In addition, LAPTM5 activated the Jun N-terminal kinase (JNK)/p38 signaling cascade by interacting with Ras-related C3 botulinum toxin substrate 1 (RAC1). Treatment with an RAC1 inhibitor eliminated the effects of LAPTM5 in ccRCC. In conclusion, these results indicate that LAPTM5 may be a new therapeutic target for ccRCC via activation of the RAC1-JNK/p38 axis.

9.
Curr Microbiol ; 79(12): 377, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329318

RESUMO

Hospital grassplot soil is an important repository of pathogenic fungi exposed to the hospital environment, and the diffusion of these fungi-containing soil particles in the air increases the risk of nosocomial fungal infections. In this study, from the perspective of soil microbes-plant holobiont, four medicinal plants Mirabilis jalapa, Artemisia argyi, Viola philippica, and Plantago depressa were used as materials, based on ITS high-throughput amplicon sequencing and simulated pot experiments to explore the effect of medicinal plants on the fungal community in hospital grassplot soil, in order to provide a new exploration for hospital grassplot soil remediation. The results showed that the fungal community ecological guilds in primary test soil was mainly pathogen, and the abundance of animal pathogen with potential threats to human reached 61.36%. After planting medicinal plants, the composition and function of soil fungal community changed significantly. Although this change varied with plant species and growth stages, all samples collected in the pot experiment showed that the pathogen abundance decreased and the saprotroph abundance increased. In addition, 45 of the 46 core fungal genera defined in all potted samples were present in primary test soil, and many of them were human potential pathogens. These findings imply that the idea of enhancing soil quality in hospital grassplot soil by planting specific plants is feasible. However, the initial fungal community of the hospital grassplot soil has a certain stability, and it is difficult to completely eliminate the threat of pathogenic fungi by planting medicinal plants.


Assuntos
Mirabilis , Micobioma , Plantas Medicinais , Animais , Humanos , Solo , Microbiologia do Solo , Fungos/genética , Hospitais
10.
Transl Pediatr ; 11(9): 1445-1457, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36247889

RESUMO

Background: In recent years, parent-mediated intervention for children with autism spectrum disorder (ASD) has increased. Therefore, implementing effective parent training programs for parents of children with autism is of paramount importance, particularly in low- and middle-income countries. However, little is known about the status of and gaps in parents' knowledge on ASD, which may hinder the development of valid parental training programs. Herein, we aimed at exploring the status of Chinese parents' knowledge, attitude and behavior toward ASD, and potential factors affecting the acquisition of correct knowledge. Methods: This study used a self-designed parental knowledge questionnaire of autism (PKQA) comprising 20 questions alongside another questionnaire comprising additional 17 questions covering the aspects of family demographics, attitudes, and behaviors of parents. In total, we included 394 parents who visited the outpatient department of the Child's Development and Behavior Center of the Third Affiliated Hospital of Sun Yat-Sen University between December 2018 and May 2019, with their children meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic criteria for ASD. Results: The median knowledge score in the PKQA was 15 [interquartile range (IQR), 13-17]. Advanced paternal age and longer time interval from diagnosis to enrolling into the parent training program were associated with a lower total knowledge score (all P<0.001). Higher maternal education attainment, higher family income, child being currently under intervention, and family members sharing a common perception of the diagnosis were associated with a higher total knowledge score (all P<0.01). Reading autism-related books (P<0.001) or attending professional lectures (P=0.019) were also associated with a higher total knowledge score. Conclusions: Taken together, this study revealed that family demographics and parents' attitudes and behaviors toward ASD may significantly influence their knowledge about autism, suggesting the need for promoting more targeted parental skills training programs.

11.
Cell Stress Chaperones ; 27(6): 645-657, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36242757

RESUMO

Esophageal cancer has always been associated with poor prognosis and a low five-year survival rate. Chalcone, a flavonoid family member, has shown anti-tumor property in several types of cancer. However, few studies reported the potency and mechanisms of action of synthetic Chalcone derivatives against esophageal squamous cell carcinoma. In this study, we designed and synthesized a series of novel chalcone analogs and Ch-19 was selected for its superior anti-tumor potency. Results indicated that Ch-19 shows a dose- and time-dependent anti-tumor activity in both KYSE-450 and Eca-109 esophageal cancer cells. Moreover, treatment of Ch-19 resulted in the regression of KYSE-450 tumor xenografts in nude mice. Furthermore, we investigated the potential mechanism involved in the effective anti-tumor effects of Ch-19. As a result, we observed that Ch-19 treatment promoted ROS accumulation and caused G2/M phase arrest in both Eca-109 and KYSE-450 cancer cell lines, thereby resulting in cell apoptosis. Taken together, our study provided a novel synthetic chalcone derivative as a potential anti-tumor therapeutic candidate for treating esophageal cancer.


Assuntos
Antineoplásicos , Chalcona , Chalconas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Camundongos , Animais , Humanos , Chalcona/farmacologia , Chalcona/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Chalconas/farmacologia , Chalconas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Camundongos Nus , Linhagem Celular Tumoral , Transdução de Sinais , Apoptose , Proliferação de Células , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
12.
Meat Sci ; 194: 108990, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36183626

RESUMO

In the study, changes in salt-soluble protein (SSP) content, gel properties, rheological characteristic, and microstructure attributes of pale, soft, and exudative (PSE) pork batters with different concentrations of added sodium bicarbonate (0-0.6%) were investigated. The pH, b⁎ value, SSP content, cooking yield, texture properties, emulsion stability, and G' values at 72 °C significantly increased with the increase in sodium bicarbonate, but the texture properties and G' values of the samples with 0.4% and 0.6% did not significantly different, while the a⁎ value significantly decreased. Moreover, a greater G' value at 72 °C was in agreement with a higher hardness value of meat batter. The microstructure of cooked PSE meat batters with 0% and 0.2% sodium bicarbonate had a dense structure, and samples with 0.4% and 0.6% had some large cavities. In conclusion, the use of sodium bicarbonate can enhance the water holding capacity, texture and rheological properties of PSE meat batters by increasing their pH, SSP content, and emulsifying stability.

13.
Front Physiol ; 13: 934413, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36117703

RESUMO

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

14.
Allergy Asthma Immunol Res ; 14(5): 505-527, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36174993

RESUMO

PURPOSE: Neutrophilic asthma is associated with asthma exacerbation, steroid insensitivity, and severe asthma. Interleukin (IL)-24 is overexpressed in asthma and is involved in the pathogenesis of several allergic inflammatory diseases. However, the role and specific mechanism of IL-24 in neutrophilic asthma are unclear. We aimed to elucidate the roles of IL-24 and IL-37 in neutrophilic asthma, the relationships with IL-17A and the mechanisms regulating neutrophilic asthma progression. METHODS: Purified human neutrophils were isolated from healthy volunteers, and a cell coculture system was used to evaluate the function of IL-24 in epithelium-derived IL-17A-dependent neutrophil migration. IL-37 or a small interfering RNA (siRNA) targeting IL-24 was delivered intranasally to verify the effect in a murine model of house dust mite (HDM)/lipopolysaccharide (LPS)-induced neutrophilic asthma. RESULTS: IL-24 enhanced IL-17A production in bronchial epithelial cells via the STAT3 and ERK1/2 signaling pathways; this effect was reversed by exogenous IL-37. Anti-IL-17A monoclonal antibodies reduced neutrophil chemotaxis induced by IL-24-treated epithelial cells in vitro. Increased IL-24 and IL-17A expression in the airway epithelium was observed in HDM/LPS-induced neutrophilic asthma. IL-37 administration or IL-24 silencing attenuated neutrophilic asthma, reducing IL-17A levels and decreasing neutrophil airway infiltration, airway hyperresponsiveness, and goblet cell metaplasia. Silencing IL-24 inhibited T-helper 17 (Th17) immune responses, but not Th1 or Th2 immune responses, in the lungs of a neutrophilic asthma model. CONCLUSIONS: IL-24 aggravated neutrophilic airway inflammation by increasing epithelium-derived IL-17A production, which could be suppressed by IL-37. Targeting the IL-24/IL-17A signaling axis is a potential strategy, and IL-37 is a potential candidate agent for alleviating neutrophilic airway inflammation in asthma.

15.
Respir Res ; 23(1): 244, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100847

RESUMO

BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , Interleucina-1/farmacologia , Animais , Asma/metabolismo , Asma/prevenção & controle , Brônquios/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Interleucinas/metabolismo , Interleucinas/farmacologia , Camundongos , Pyroglyphidae/metabolismo , Transdução de Sinais , Vimentina/metabolismo
16.
World J Gastroenterol ; 28(26): 3132-3149, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36051331

RESUMO

BACKGROUND: The development of venous thromboembolism (VTE) is associated with high mortality among gastric cancer (GC) patients. Neutrophil extracellular traps (NETs) have been reported to correlate with the prothrombotic state in some diseases, but are rarely reported in GC patients. AIM: To investigate the effect of NETs on the development of cancer-associated thrombosis in GC patients. METHODS: The levels of NETs in blood and tissue samples of patients were analyzed by ELISA, flow cytometry, and immunofluorescence staining. NET generation and hypercoagulation of platelets and endothelial cells (ECs) in vitro were observed by immunofluorescence staining. NET procoagulant activity (PCA) was determined by fibrin formation and thrombin-antithrombin complex (TAT) assays. Thrombosis in vivo was measured in a murine model induced by flow stenosis in the inferior vena cava (IVC). RESULTS: NETs were likely to form in blood and tissue samples of GC patients compared with healthy individuals. In vitro studies showed that GC cells and their conditioned medium, but not gastric mucosal epithelial cells, stimulated NET release from neutrophils. In addition, NETs induced a hypercoagulable state of platelets by upregulating the expression of phosphatidylserine and P-selectin on the cells. Furthermore, NETs stimulated the adhesion of normal platelets on glass surfaces. Similarly, NETs triggered the conversion of ECs to hypercoagulable phenotypes by downregulating the expression of their intercellular tight junctions but upregulating that of tissue factor. Treatment of normal platelets or ECs with NETs augmented the level of plasma fibrin formation and the TAT complex. In the models of IVC stenosis, tumor-bearing mice showed a stronger ability to form thrombi, and NETs abundantly accumulated in the thrombi of tumor-bearing mice compared with control mice. Notably, the combination of deoxyribonuclease I, activated protein C, and sivelestat markedly abolished the PCA of NETs. CONCLUSION: GC-induced NETs strongly increased the risk of VTE development both in vitro and in vivo. NETs are potential therapeutic targets in the prevention and treatment of VTE in GC patients.


Assuntos
Armadilhas Extracelulares , Neoplasias Gástricas , Trombofilia , Trombose , Tromboembolia Venosa , Animais , Constrição Patológica , Células Endoteliais/metabolismo , Armadilhas Extracelulares/metabolismo , Fibrina , Camundongos , Neutrófilos/metabolismo , Neoplasias Gástricas/complicações , Neoplasias Gástricas/metabolismo , Trombose/etiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/metabolismo
17.
Chin J Nat Med ; 20(8): 633-640, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36031235

RESUMO

The ribose and phosphorus contents in Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) are two important chemical indexes for the development and quality control of Hib conjugate vaccine. A quantitative 1H- and 31P-NMR method using a single internal standard was developed for simultaneous determination of ribose and phosphorus contents in Hib CPS. Hexamethylphosphoramide (HMPA) was successfully utilized as an internal standard in quantitative 1H-NMR method for ribose content determination. The ribose and phosphorus contents were found to be affected by the concentration of polysaccharide solution. Thus, 15-20 mg·L-1 was the optimal concentration range of Hib CPS in D2O solution for determination of ribose and phosphorus contents by this method. The ribose and phosphorus contents obtained by the quantitative NMR were consistent with those obtained by traditional chemical methods. In conclusion, this quantitative 1H- and 31P-NMR method using a single internal standard shows good specificity, accuracy and precision, providing a valuable approach for the quality control of Hib glycoconjugate vaccines.


Assuntos
Vacinas Anti-Haemophilus , Haemophilus influenzae tipo b , Fósforo , Polissacarídeos Bacterianos , Ribose
18.
Front Neurosci ; 16: 880105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937890

RESUMO

Alzheimer's disease (AD) is a life-threatening neurodegenerative disease of the elderly. In recent observations, exposure to heavy metals environmental may increase the risk of AD. However, there are few studies on the causal relationship between heavy metal exposure and AD. In this study, we integrated two large-scale summaries of AD genome-wide association study (GWAS) datasets and a blood lead level GWAS dataset and performed the two-sample Mendelian randomization analysis to assess the causality of blood lead level and AD risk. The results showed that there is a significantly positive causality between blood lead level and AD risk both in the inverse-variance weighted (IVW) model and the weighted median estimator (WME) model. An independent additional verification also reached a consistent conclusion. These findings further confirm the conclusions of previous studies and improve the understanding of the relationship between AD pathogenesis and the toxicity of lead in environmental pollution.

19.
Signal Transduct Target Ther ; 7(1): 263, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35927231

RESUMO

Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.


Assuntos
Células-Tronco Mesenquimais , Psoríase , Feminino , Humanos , Masculino , Prostaglandinas A/uso terapêutico , Psoríase/tratamento farmacológico , Resultado do Tratamento , Cordão Umbilical
20.
Phytomedicine ; 106: 154389, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36037771

RESUMO

BACKGROUND: Cardiac fibrosis is a major structural change observed in the heart of patients with type 2 diabetes mellitus (T2DM), ultimately resulting in heart failure (HF). Suppression of inflammation is an effective therapeutic strategy for treating cardiac fibrosis and HF. Gentiopicroside (GPS), the primary component of Gentiana manshurica Kitagawa, possess potent anti-inflammatory activity. However, its cardioprotective role remains elusive. PURPOSE: We explored the potential cardioprotective role of GPS in T2DM rats and its underlying mechanisms. METHODS: T2DM rats built by high-fat diet and streptozotocin were orally administered 25, 50, or 100 mg/kg GPS, daily for 8 weeks. The positive control drug was Metformin (200 mg/kg/day). Primary cardiac fibroblasts (CFs) were induced by high glucose (30 mM) and subsequently treated with GPS (100 µM). Cardiac function and pathological changes were analyzed using echocardiography and histological staining. Potential targets of GPS were predicted using Molecular docking. Real-time PCR as well as western blotting were applied to verify the expression of objective genes. RESULTS: All three doses reduced fasting blood glucose levels, but only 50 and 100 mg/kg GPS improved cardiac function and alleviated inflammation and fibrosis in T2DM rats. GPS (100 mg/kg) exhibited a better effect, similar to that of metformin. Mechanistically, binding between GPS and the MH2 domain of Smad3 blocked high glucose-induced Smad3 phosphorylation, thus attenuating inflammation, oxidative stress, and activation in CFs. CONCLUSION: We, for the first time, demonstrated that GPS improved cardiac function in T2DM rats and elucidated the underlying mechanism through which GPS targeted Smad3 phosphorylation to suppress inflammation and activation in CFs, thereby revealing the potential application of GPS in HF therapy.


Assuntos
Diabetes Mellitus Tipo 2 , Síndrome de Fadiga Crônica , Insuficiência Cardíaca , Metformina , Animais , Anti-Inflamatórios/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome de Fadiga Crônica/tratamento farmacológico , Fibrose , Insuficiência Cardíaca/metabolismo , Inflamação/metabolismo , Glucosídeos Iridoides , Metformina/uso terapêutico , Simulação de Acoplamento Molecular , Miocárdio/metabolismo , Fosforilação , Ratos , Proteína Smad3/metabolismo , Estreptozocina
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