Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nat Immunol ; 20(5): 534-545, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962593

RESUMO

Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (TH17 cells) promote inflammation through the induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of LN and splenic stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without signaling via the IL-17 receptor, activated FRCs underwent cell cycle arrest and apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for the development of TH17 cells, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. Induction of the transcriptional co-activator IκBζ via IL-17 signaling mediated increased glucose uptake and expression of the gene Cpt1a, encoding CPT1A, a rate-limiting enzyme of mitochondrial fatty acid oxidation. Hence, IL-17 produced by locally differentiating TH17 cells is an important driver of the activation of inflamed LN stromal cells, through metabolic reprogramming required to support proliferation and survival.


Assuntos
Proliferação de Células , Fibroblastos/imunologia , Interleucina-17/imunologia , Linfonodos/imunologia , Células Estromais/imunologia , Animais , Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Sobrevivência Celular/genética , Sobrevivência Celular/imunologia , Células Cultivadas , Colite/genética , Colite/imunologia , Colite/metabolismo , Encefalomielite Autoimune Experimental/genética , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Fibroblastos/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Linfonodos/citologia , Linfonodos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptores de Interleucina-17/genética , Receptores de Interleucina-17/imunologia , Receptores de Interleucina-17/metabolismo , Células Estromais/metabolismo , Células Th17/imunologia , Células Th17/metabolismo
2.
Sensors (Basel) ; 22(20)2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298433

RESUMO

The key to evaluating the health status of cable-stayed bridges lies in the accuracy of cable force measurement. When measuring the cable force using the conventional frequency method, the clearance between the bracing cable and the protective tube is typically disregarded. Moreover, due to their large size, existing vibration sensors are difficult to install into protective tubes for steel strand-type bracing cables to measure the cable force. To address the above difficulties, a type of thin rod vibration sensor only 5 mm in diameter was designed based on the high sensitivity of Fiber Bragg grating (FBG), and high-throughput data processing software for engineering calculation (EC) was self-developed. Then, the recognition principle of the thin rod vibration sensor was theoretically analyzed and a step-by-step tension test was carried out. The results demonstrated that the relative error of the cable force measured by the thin rod vibration sensor within 12.865 Hz was less than 5% and the sensitivity reached 28.7 pm/Hz, indicating its high measurement precision. Upon subsequent application of the thin rod vibration sensor to a monitoring test in the field, the relative error of the fundamental frequency between artificial and natural excitations was less than 4%. In addition, the error relative to both the theoretical frequency and the third-party sampling frequency was less than 5%, further verifying the accuracy and applicability for monitoring the cable force of bridges under natural excitation. Compared with the traditional cantilever FBG sensor, the improved sensor with supporting data processing software has the advantages of small cross-section, high reliability, and good sensitivity. The research results can provide a reference for the subsequent accurate measurement of cable force and the development of a supporting sensor data processing system.


Assuntos
Fibras Ópticas , Vibração , Reprodutibilidade dos Testes , Aço
3.
Cytokine ; 148: 155715, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34587561

RESUMO

The IL-17 family is structurally distinct from other cytokine subclasses. IL-17A and IL-17F, the most closely related of this family, form homodimers and an IL-17AF heterodimer. While IL-17A and IL-17F exhibit similar activities in many settings, in others their functions are divergent. To better understand the function of IL-17F in vivo, we created mice harboring a mutation in Il17f originally described in humans with unexplained chronic mucosal candidiasis (Ser-65-Leu). We evaluated Il17fS65L/S65L mice in DSS-colitis, as this is one of the few settings where IL-17A and IL-17F exhibit opposing activities. Specifically, IL-17A is protective of the gut epithelium, a finding that was revealed when trials of anti-IL-17A biologics in Crohn's disease failed and recapitulated in many mouse models of colitis. In contrast, mice lacking IL-17F are resistant to DSS-colitis, partly attributable to alterations in intestinal microbiota that mobilize Tregs. Here we report that Il17fS65L/S65L mice do not phenocopy Il17f-/- mice in DSS colitis, but rather exhibited a worsening disease phenotype much like Il17a-/- mice. Gut inflammation in Il17fS65L/S65L mice correlated with reduced Treg accumulation and lowered intestinal levels of Clostridium cluster XIV. Unexpectedly, the protective DSS-colitis phenotype in Il17f-/- mice could be reversed upon co-housing with Il17fS65L/S65L mice, also correlating with Clostridium cluster XIV levels in gut. Thus, the Il17fS65L/S65L phenotype resembles an IL-17A deficiency more closely than IL-17F deficiency in the setting of DSS colitis.


Assuntos
Colite/induzido quimicamente , Colite/genética , Interleucina-17/metabolismo , Mutação/genética , Animais , Colite/imunologia , Colo/imunologia , Colo/patologia , Sulfato de Dextrana , Suscetibilidade a Doenças , Microbioma Gastrointestinal , Humanos , Interleucina-17/genética , Camundongos Endogâmicos C57BL , Fenótipo , Receptores de Interleucina-17/metabolismo , Transdução de Sinais , Linfócitos T Reguladores/imunologia
4.
Cancer Sci ; 110(4): 1220-1231, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30719823

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The most important reason for the occurrence of HCC is hepatitis C or B infection. Moreover, genetic factors play an important role in the tumorigenesis of HCC. Here, we demonstrated that Krüppel-like factor 2 (KLF2) expression was downregulated in HCC samples compared with adjacent tissues. Additionally, KLF2 was shown to inhibit the growth, migration and colony-formation ability of liver cancer cells. Further mechanistic studies revealed that KLF2 can compete with Gli1 for interaction with HDAC1 and restrains Hedgehog signal activation. Together, our results suggest that KLF2 has potential as a diagnostic biomarker and therapeutic target for the treatment of HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Transformação Celular Neoplásica/metabolismo , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Neoplasias Hepáticas/metabolismo , Transdução de Sinais , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Genes Reporter , Humanos , Masculino , Camundongos , Camundongos Knockout , Proteína GLI1 em Dedos de Zinco/metabolismo
5.
PLoS One ; 19(2): e0299382, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394259

RESUMO

BACKGROUND: Endothelial cell injury is one of the important pathogenic mechanisms in thrombotic diseases, and also neutrophils are involved. MicroRNAs (miRNAs) have been demonstrated to act as essential players in endothelial cell injury, but the potential molecular processes are unknown. In this study, we used cellular tests to ascertain the protective effect of miR-328-3p on human umbilical vein endothelial cells (HUVECs) treated with oxygen-glucose deprivation (OGD). METHODS: In our study, an OGD-induced HUVECs model was established, and we constructed lentiviral vectors to establish stable HUVECs cell lines. miR-328-3p and Toll-like receptor 2 (TLR2) interacted, as demonstrated by the dual luciferase reporter assay. We used the CCK8, LDH release, and EdU assays to evaluate the proliferative capacity of each group of cells. To investigate the expression of TLR2, p-P65 NF-κB, P65 NF-κB, NLRP3, IL-1ß, and IL-18, we employed Western blot and ELISA. Following OGD, each group's cell supernatants were gathered and co-cultured with neutrophils. An immunofluorescence assay and Transwell assay have been performed to determine whether miR-328-3p/TLR2 interferes with neutrophil migration and neutrophil extracellular traps (NETs) formation. RESULTS: In OGD-treated HUVECs, the expression of miR-328-3p is downregulated. miR-328-3p directly targets TLR2, inhibits the NF-κB signaling pathway, and reverses the proliferative capacity of OGD-treated HUVECs, while inhibiting neutrophil migration and neutrophil extracellular trap formation. CONCLUSIONS: miR-328-3p inhibits the NF-κB signaling pathway in OGD-treated HUVECs while inhibiting neutrophil migration and NETs formation, and ameliorating endothelial cell injury, which provides new ideas for the pathogenesis of thrombotic diseases.


Assuntos
Armadilhas Extracelulares , MicroRNAs , Humanos , NF-kappa B/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Armadilhas Extracelulares/metabolismo , Oxigênio/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Glucose/farmacologia , Transdução de Sinais , MicroRNAs/metabolismo , Apoptose
6.
Mol Med Rep ; 29(6)2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38606496

RESUMO

Deep vein thrombosis (DVT) is a prevalent clinical venous thrombotic condition that often manifests independently or in conjunction with other ailments. Thrombi have the propensity to dislodge into the circulatory system, giving rise to complications such as pulmonary embolism, thereby posing a significant risk to the patient. Virchow proposed that blood stagnation, alterations in the vessel wall and hypercoagulation are primary factors contributing to the development of venous thrombosis. Vascular endothelial cells (VECs) constitute the initial barrier to the vascular wall and are a focal point of ongoing research. These cells exert diverse stimulatory effects on the bloodstream and secrete various regulatory factors that uphold the dynamic equilibrium between the coagulation and anticoagulation processes. MicroRNAs (miRNAs) represent a class of non­coding RNAs present in eukaryotes, characterized by significant genetic and evolutionary conservation and displaying high spatiotemporal expression specificity. Typically ranging from 20 to 25 bases in length, miRNAs can influence downstream gene transcription through RNA interference or by binding to specific mRNA sites. Consequently, advancements in understanding the molecular mechanisms of miRNAs, including their functionalities, involve modulation of vascular­associated processes such as cell proliferation, differentiation, secretion of inflammatory factors, migration, apoptosis and vascular remodeling regeneration. miRNAs play a substantial role in DVT formation via venous VECs. In the present review, the distinct functions of various miRNAs in endothelial cells are outlined and recent progress in comprehending their role in the pathogenesis and clinical application of DVT is elucidated.


Assuntos
MicroRNAs , Embolia Pulmonar , Trombose Venosa , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais/metabolismo , Trombose Venosa/metabolismo , Coagulação Sanguínea
7.
J Ethnopharmacol ; 331: 118231, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38718891

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Chimonanthi Pracecocis (RCP), also known as Tiekuaizi, widely used by the Miao community in Guizhou, exhibits diverse biological activities and holds promise for the treatment of osteoarthritis (OA). However, there is a lack of contemporary pharmacological research in this area. AIMS OF THE STUDY: This study aims to explore the potential of targets and mechanisms of RCP in the treatment of OA. MATERIALS AND METHODS: The chemical components of RCP were identified using UPLC-MS/MS, and active components were determined based on the Lipinski rule. RCP and OA-related targets were retrieved from public databases such as TCMSP and GeneCards. Network pharmacology approaches were employed to identify key genes. The limma package (version 3.40.2) in R 4.3.2 was used to screen for differentially expressed genes (DEGs) between OA and healthy individuals in GSE82107. DEGs were analyzed using an independent sample t-test and receiver operating characteristic analysis in GraphPad Prism 9.5.1. Additionally, molecular docking (SYBYL2.1.1) was used to analyze the binding interactions between the active components and target proteins. Finally, we established a papain-induced osteoarthritis (OA) rat model and treated it with RCP aqueous extract by gavage. We validated relevant indicators using real-time fluorescence quantitative polymerase chain reaction, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Seven active components and 53 targets were identified. The results of GO and KEGG enrichment analyses confirmed the significant role of RCP in the regulation of pyroptosis. Hypoxia-inducible factor-1α (HIF-1α) was identified as a key gene involved in the main biological functions. Molecular docking analysis revealed that Praecoxin, Isofraxidin, Esculin, and Naringenin can bind to the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) (T-Score >5). Additionally, Praecoxin can bind to HIF-1α (T-Score >5). In vivo experiments demonstrated that RCP significantly affects the NLRP3 inflammasome, which is regulated by the HIF-1α pathway. RCP inhibited pyroptosis and reduced synovial inflammation. CONCLUSIONS: This study confirmed the efficacy of RCP aqueous extract in the treatment of OA and identified seven active components (esculin, dihydrokaempferol, naringenin, praecoxin, carnosol, hydroxyvalerenic acid, isofraxidin) that may play an anti-pyroptosis role in the treatment of OA by downregulating the expression of HIF-1α and NLRP3 inflammasome.


Assuntos
Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Farmacologia em Rede , Osteoartrite , Ratos Sprague-Dawley , Animais , Osteoartrite/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Ratos , Masculino
8.
Materials (Basel) ; 16(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36676565

RESUMO

In this paper, the connection performance of extrusion sleeves and the strain rate effect on 500 MPa-grade hot-rolled ribbed bar(HRB500E) connected with extrusion sleeves under a range of testing strain rates from 1.079/sto1.395/s, similar to what would be caused by an impact, were explored. The test results showed that, under strain rates likely caused by aircraft impact, the specimens mostly failed due to breaking outside the joint length. Furthermore, there was no relative slip between the rebar and the extrusion sleeve, indicating that the connection was stable and reliable in the used experimental parameter field. The percentage total elongation at maximum force (Agt) of HRB500E spliced by the extrusion sleeve showed an exponential decline with the increase in the strain rate, indicating a clear strain-rate sensitivity. The average deviation between the dynamic increase factors (DIF) calculated using the modified Cowper-Symonds formulas and the experimental values was within 5.4%, which can better reflect the strain rate effect on the strength of the spliced connection. The DIFy of sleeve-spliced rebars was higher than that of unspliced rebars, and the ratio of the DIFy of sleeve-spliced rebars to the DIFy of unspliced rebars increased with the strain rate. The experimental results can provide a basis for an optimized design of the aircraft impact-resistant extrusion sleeve rebar connections.

9.
Materials (Basel) ; 16(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37241520

RESUMO

As major projects such as nuclear power plants continuously increase, it is inevitable that loopholes will arise in safety precautions. Airplane anchoring structures, comprising steel joints and acting as a key component of such a major project, directly affect the safety of the project due to their resistance to the instant impact of an airplane. Existing impact testing machines have the limitations of being unable to balance impact velocity and impact force, as well as having inadequate control of impact velocity; they cannot meet the requirements of impact testing for steel mechanical connections in nuclear power plants. This paper discusses the hydraulic-based principle of the impact test system, adopts the hydraulic control mode, and uses the accumulator as the power source to develop an instant loading test system suitable for the entire series of steel joints and small-scale cable impact tests. The system is equipped with a 2000 kN static-pressure-supported high-speed servo linear actuator, a 2 × 22 kW oil pump motor group, a 2.2 kW high-pressure oil pump motor group, and a 9000 L/min nitrogen-charging accumulator group, which can test the impact of large-tonnage instant tensile loading. The maximum impact force of the system is 2000 kN, and the maximum impact rate is 1.5 m/s. Through the impact testing of mechanical connecting components using the developed impact test system, it was found that the strain rate of the specimen before failure was not less than 1 s-1, meeting the requirements of the technical specifications for nuclear power plants. By adjusting the working pressure of the accumulator group, the impact rate could be controlled effectively, thus providing a strong experimental platform for research in the field of engineering for preventing emergencies.

10.
iScience ; 26(6): 106915, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37305694

RESUMO

Urbanization drives the popularity of western diet (WD), which increased burden in metabolic diseases but also in inflammatory diseases. Here, we show continuous WD disrupted the gut barrier, initiating low-grade inflammation and enhancing the colitis response. Nevertheless, transient WD consumption followed by ad libitum normal diet enhanced mucin production and tight junction protein expression in recovered mice. Furthermore, transient WD consumption surprisingly reduced the subsequent inflammatory response in DSS colitis and Citrobacter rodentium-infection induced colitis. The protective effect of WD training was not sex-dependent, and co-housing experiments suggested microbiota changes were not responsible. We identified important roles for cholesterol biosynthesis pathway and macrophages, pointing to innate myeloid training. Together, these data suggest detrimental effects of WD consumption can be reversed on return to a healthier diet. Furthermore, transient WD consumption leads to beneficial immune training, suggesting an evolutionary mechanism to benefit from feasting when abundant food is available.

11.
Front Immunol ; 14: 1198952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680629

RESUMO

Deep venous thrombosis (DVT) is a part of venous thromboembolism (VTE) that clinically manifests as swelling and pain in the lower limbs. The most serious clinical complication of DVT is pulmonary embolism (PE), which has a high mortality rate. To date, its underlying mechanisms are not fully understood, and patients usually present with clinical symptoms only after the formation of the thrombus. Thus, it is essential to understand the underlying mechanisms of deep vein thrombosis for an early diagnosis and treatment of DVT. In recent years, many studies have concluded that Neutrophil Extracellular Traps (NETs) are closely associated with DVT. These are released by neutrophils and, in addition to trapping pathogens, can mediate the formation of deep vein thrombi, thereby blocking blood vessels and leading to the development of disease. Therefore, this paper describes the occurrence and development of NETs and discusses the mechanism of action of NETs on deep vein thrombosis. It aims to provide a direction for improved diagnosis and treatment of deep vein thrombosis in the near future.


Assuntos
Armadilhas Extracelulares , Trombose Venosa , Humanos , Neutrófilos , Extremidade Inferior , Dor , Trombose Venosa/terapia
12.
Front Immunol ; 14: 1257988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841272

RESUMO

Venous thromboembolism is a very common and costly health problem. Deep-vein thrombosis (DVT) can cause permanent damage to the venous system and lead to swelling, ulceration, gangrene, and other symptoms in the affected limb. In addition, more than half of the embolus of pulmonary embolism comes from venous thrombosis, which is the most serious cause of death, second only to ischemic heart disease and stroke patients. It can be seen that deep-vein thrombosis has become a serious disease affecting human health. In recent years, with the deepening of research, inflammatory response is considered to be an important pathway to trigger venous thromboembolism, in which the transcription factor NF-κB is the central medium of inflammation, and the NF-κB signaling pathway can regulate the pro-inflammatory and coagulation response. Thus, to explore the mechanism and make use of it may provide new solutions for the prevention and treatment of thrombosis.


Assuntos
Trombose , Tromboembolia Venosa , Trombose Venosa , Humanos , NF-kappa B , Tromboembolia Venosa/prevenção & controle , Trombose/etiologia , Transdução de Sinais
13.
Front Oncol ; 13: 1077598, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36761963

RESUMO

Background: Esophageal cancer remains a public health problem in many countries, especially developing countries. The early lifestyle preventive measures mentioned in the treatment guidelines for esophageal cancer are very limited. We aimed to evaluate the risk factors for esophageal cancer in a high-incidence area in China and to provide evidence for clinical intervention in esophageal cancer prevention. Methods: Symptom and lifestyle/habit questionnaires including 19 items were designed. The correlation between the occurrence of esophageal cancer and living habits was analyzed retrospectively through questionnaire survey. A total of 708 subjects (365 esophageal cancer, 343 non-esophageal cancer) enrolled from two hospitals in central China (Linzhou Esophageal Cancer Hospital and The Third Xiangya Hospital of Central South University) completed symptom and lifestyle/habit questionnaires. We used conditional logistic regression to estimate the odds ratio (OR) with consideration of 95% confidence interval (CI). Results: The composition ratio analysis showed that the top five lifestyle factors related to esophageal cancer were eating too fast, drinking, hot drinks, smoking and overeating. Univariate analysis showed that 15 factors, including male sex, smoking, drinking, eating too fast, overeating, hot drinks, greasy food, acidic food, hard food, strong tea, coffee, bedtime immediately after meals, eating food before bedtime, difficult defecation, and an overtight belt, were associated with esophageal cancer (all P <0.05). Logistic multivariate regression analysis showed, drinking (OR 3.609, 95%CI 2.223-5.859; P=0.000); hot drinks (OR 2.672, 95%CI 1.786-3.997; P=0.000); overeating (OR 2.110, 95%CI 1.411-3.154; P=0.000); eating too fast (OR 1.879, 95%CI 1.274-2.772; P=0.001); strong tea (OR 1.882, 95%CI 1.171~3.023; P=0.009); hard food (OR 1.723, 95%CI 1.113-2.667; P=0.015); smoking (OR 1.686, 95%CI 1.045-2.720; P=0.032), which were significantly associated with the development of esophageal cancer. Conclusion: The unhealthy lifestyles of patients in high-incidence areas of esophageal cancer in central China are significantly associated with the incidence of esophageal cancer. Lifestyle changes that address these factors, especially overeating and eating too fast, which are rarely studied or discussed despite being common, may improve esophageal cancer management and treatment outcomes. The present results may be used as a reference for preventive education and treatment.

14.
Front Surg ; 9: 1065070, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684177

RESUMO

Objective: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) is an accurate technique for sampling the pancreas and mediastinum. The aim of this study was to determine the value of EUS-FNA/FNB in the diagnosis of mediastinal lesions. Methods: Data from 107 patients who underwent EUS-FNA/FNB for mediastinal lesions were evaluated. Results: The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA/FNB for mediastinal lesions were 92.00%, 100%, 100%, and 85%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA for malignant mediastinal lesions were 92.00%, 100%, 100%, and 86.00%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNB for malignant mediastinal lesions were 92.00%, 100%, 100%, and 82.00%, respectively. Except for the discomfort caused by conventional gastroscopy, none of the patients had any complications, such as damage to surrounding large blood vessels or nerves. Conclusion: EUS-FNA/FNB is an effective tool for diagnosing unknown mediastinal lesions, without any obvious complications.

15.
Sci Immunol ; 6(66): eaao3669, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34919443

RESUMO

Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in lymphoid organs that support lymphocyte localization and survival and modulate adaptive immune responses. IL-17 signaling is important for FRC metabolism and proliferation during inflammatory responses. Here, we show that FRC-intrinsic IL-17 signaling was required for protective antibody-mediated immunity to the gut bacterial pathogen Citrobacter rodentium. We asked whether prior activation of FRC through nonspecific inflammatory "training" of the gut would alter subsequent immune response to C. rodentium. Inflammatory training increased the number of activated FRC in mesenteric LN (MLN) and enhanced the antibody response to C. rodentium in an IL-17­dependent manner. FRC demonstrated cardinal features of innate immune training, including increased epigenetic markers of activation and increased metabolic response to infection. Enhanced responses were still evident 6 weeks after training. The kinetics of bacterial infection were not changed by inflammatory training, but colon inflammation was paradoxically reduced. Mechanistically, IL-10 production by activated B cells was required for colon protective effects of inflammatory training. Enhancing tissue protective B cell responses thus led to increased production of antibody and IL-10, allowing clearance of infection with reduced tissue inflammation. These data identify a new mode of immune training through FRC to modulate future adaptive responses and better preserve host health.


Assuntos
Linfócitos B/imunologia , Fibroblastos/imunologia , Imunidade nas Mucosas/imunologia , Interleucina-10/biossíntese , Interleucina-17/imunologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
16.
Virulence ; 12(1): 1199-1208, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33870852

RESUMO

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.


Assuntos
COVID-19/mortalidade , Cirrose Hepática/complicações , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto , Idoso , COVID-19/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
17.
J Exp Med ; 217(10)2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32697822

RESUMO

The STAT3 signaling pathway is required for early Th17 cell development, and therapies targeting this pathway are used for autoimmune disease. However, the role of STAT3 in maintaining inflammatory effector Th17 cell function has been unexplored. Th17ΔSTAT3 mice, which delete STAT3 in effector Th17 cells, were resistant to experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Th17 cell numbers declined after STAT3 deletion, corresponding to reduced cell cycle. Th17ΔSTAT3 cells had increased IL-6-mediated phosphorylation of STAT1, known to have antiproliferative functions. Th17ΔSTAT3 cells also had reduced mitochondrial membrane potential, which can regulate intracellular Ca2+. Accordingly, Th17ΔSTAT3 cells had reduced production of proinflammatory cytokines when stimulated with myelin antigen but normal production of cytokines when TCR-induced Ca2+ flux was bypassed with ionomycin. Thus, early transcriptional roles of STAT3 in developing Th17 cells are later complimented by noncanonical STAT3 functions that sustain pathogenic Th17 cell proliferation and cytokine production.


Assuntos
Citocinas/fisiologia , Ativação Linfocitária , Fator de Transcrição STAT3/metabolismo , Células Th17/metabolismo , Animais , Antígenos/imunologia , Apoptose , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Citometria de Fluxo , Interleucina-6/metabolismo , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT1/metabolismo
18.
Virulence ; 11(1): 1250-1256, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32921249

RESUMO

The cause of some patients with negative RT-PCR results experienced turn-positive after treatment remains unclear. In addition, understanding the correlation between changes in clinical data in the course of COVID-19 and treatment outcomes is of great importance in determining the prognosis of COVID-19. To perform cause analysis of RT-PCR turn-positive and the effective screening factors related to treatment outcome in COVID-19. Clinical data, including clinical manifestations, laboratory tests, radiography results, treatment methods and outcomes, were retrospectively collected and analyzed from January to March 2020 in Renmin Hospitals of Wuhan University. 116 COVID-19 patients (40 in recurrent group, 29 in recovered group and 47 in unrecovered group) were recruited. In the recurrent group, white blood cell, Neutrophils, prothrombin time, activated partial thromboplastin time, CD3, CD4, CD8, ratio of CD4/CD8, IgG and C4 complement were of significant difference among the baseline, negative and turn-positive time points. CD19 and CT scan results were found notable difference between recurrent group and recovered group. Odds from CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT scan results validated associations with clinical outcomes of COVID-19. The so-called recurrence in some COVID-19 patients may be due to the false-negative of nucleic acid test results from nasopharyngeal swabs. Levels of CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT results were significantly correlated with the outcome of COVID-19. The cellular immunity test could be beneficial to further screen the reliability of RT-PCR test on the basis of CT images.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Reações Falso-Negativas , Feminino , Humanos , Imunidade Celular , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Virulência
19.
EBioMedicine ; 24: 277-285, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28965875

RESUMO

OBJECTIVE: To assess the effect of storage time and temperature on complete blood count (CBC) and comprehensive metabolic panel (CMP) testing. METHODS: PubMed, EMBASE, the Cochrane Library of Systematic Reviews, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), WanFang databases and SinoMed databases were searched up to May 2017. Clinical trials with adult whole blood samples were identified. Paired reviewers independently screened, extracted data and evaluated the quality of evidence (MINORS tool). Analyses were conducted using Revman 5.3 and Stata 14.0. RESULTS: A total of 89 studies were confirmed. For CBC, except MPV, most parameters were stable at least for 24h. Some indices, such as WBC, PLt, HCT, HGB and MCH were stable up to 3 d. However, stable CMP test results could only be acquired within 12h. at 4°C, including GLU, AST, ALT, Na, ALB, Cl, DBIL, TC, TG and ALP. Values were less stable when stored at RT. CONCLUSIONS: Specimens stored >12h. for CMP may generate unreliable results. For CBC, samples could reliably be stored for 24h. For longer storage, refrigeration (at 4°C) would be a better choice.


Assuntos
Contagem de Células Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Adulto , Feminino , Humanos , Masculino , Temperatura
20.
Oncotarget ; 8(31): 51331-51344, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28881651

RESUMO

OBJECTIVE: To assess clinical significance of CD147 in renal cell carcinoma. METHODS: Collect case-control studies which focus on CD147's expression in renal cell carcinoma. Trails were retrieved from CBM, CNKI, Wan-fang database, PubMed, Cochrane Library and Embase. According to the inclusion and exclusion criteria, data extraction and quality assessment were done by two researchers independently, and outcomes were pooled with Revman5.3 and STATA14.0. RESULTS: A total of 11 studies were confirmed, among which renal cell carcinoma 887 cases, non-cancer 505cases. As for the positive rate of CD147, there are statistical differences among survival, renal cell carcinoma tissue vs. non-cancer tissues [OR= 8.19, P= 0.0002], with vs. without lymph node metastases [OR= 6.52, P= 0.001], clinical stage III~IV vs. II~I [OR= 4.07, P< 0.00001], histopathological stage III~IV vs. II [OR= 3.01, P= 0.002], histopathological stage III~IV vs. I [OR= 7.50, P< 0.00001], tumor size [OR= 5.01, P= 0.0007]. No significant difference was tested among different age, gender, histological types and Position of cancer. CONCLUSION: As shown in our results, CD 147 may participate the whole course of carcinogenesis of renal cell carcinoma, which might be valuable for the diagnosis, treatment and prognosis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA