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1.
J Immunol ; 208(12): 2652-2662, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35649629

RESUMO

The molecular mechanisms of primary Sjögren's syndrome (pSS) are poorly understood. In this study, we explored the role of the IL-33/ST2 axis in the development of pSS. In the mouse model of experimental Sjögren's syndrome, we found that the saliva flow rate at weeks 4 and 30 was preserved in IL-33-/- and ST2-/- mice, compared with that of wild-type mice. At week 30 of experimental Sjögren's syndrome induction, the histological score, anti-nuclear Ab levels, and numbers of Th1 and B cells in draining lymph nodes of the salivary gland were lower in the IL-33-/- and ST2-/- mice, whereas Th17 cells and regulatory T cells were not changed. Primary salivary gland epithelial cells expressed the IL-33 receptor ST2. After stimulation with rIL-33, salivary gland epithelial cells increased the transcriptional levels of CD86 and CCL2, accompanied by the activation of the NF-κB inflammatory pathway. There was a synergistic effect between rIL-33 and rIL-12 in augmenting the production of IFN-γ in CD4+ T cells. In the pSS patients, the expression of IL-33 was elevated in the labial salivary gland, with the number of IL-33+ cells positively correlated with the score of the EULAR (European Alliance of Associations for Rheumatology) Sjögren's syndrome disease activity index (ESSDAI). ST2 was highly expressed in the cytoplasm of ductal epithelial cells, with low levels of expression in lymphatic infiltration sites. Our data suggest that the IL-33/ST2 axis may promote the development of pSS by enhancing salivary epithelial cell activation and the type 1 immune response.


Assuntos
Síndrome de Sjogren , Animais , Células Epiteliais/metabolismo , Imunidade , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Interleucina-33 , Camundongos
2.
Mod Rheumatol ; 33(3): 557-565, 2023 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35438773

RESUMO

OBJECTIVES: This study aimed to preliminarily address the levels of decorin (DCN, a critical component of extracellular matrix) and its potential roles in primary Sjögren's syndrome (pSS). METHODS: DCN levels were determined in the salivary glands of experimental SS (ESS) mice and pSS patients by RNA sequencing, bioinformatics analysis, or immunohistochemical staining. Its correlation with interested genes and co-localization with a putative receptor was studied in pSS patients. In addition, its potential roles on salivary gland epithelium and macrophages were tested by exogenous administration to corresponding cell lines, followed by the evaluation of apoptosis using flow cytometry or cytokine expression using quantitative real-time polymerase chain reaction. RESULTS: Our data revealed a significant elevation of DCN in the salivary glands of the ESS mice model and pSS patients. In addition, the bioinformatics analysis of DCN in the GSE40611 (RNA-seq, parotid glands) dataset displayed an elevation of the DCN level in the parotid glands of pSS patients that positively correlated with several chemokines (CXCL13, CXCL9, and CCL20), Interleukin -1 ß (IL1 -ß), and caspase3 but negatively correlated with the proliferation relative gene MKI67. The stimulatory effects of DCN on the salivary gland epithelial cells (A253 cell line) and macrophages have been determined as they are considered active participants in the progression of SS. The data showed that DCN induced the apoptosis of A253 cells and polarization of macrophages towards the M1 phenotype, characterized by the expression of pro-inflammatory cytokines. CONCLUSIONS: Our study provided preliminary evidence to understand the clinical significance of DCN in pSS and broadened our horizons in understanding the mechanism of pSS.


Assuntos
Síndrome de Sjogren , Humanos , Animais , Camundongos , Síndrome de Sjogren/genética , Síndrome de Sjogren/metabolismo , Decorina/genética , Decorina/metabolismo , Glândulas Salivares , Células Epiteliais/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo
3.
J Autoimmun ; 133: 102944, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36401985

RESUMO

OBJECTIVES: To investigate the landscape of T-B cell interaction, immune receptor profiles and effects of different types of immune responses in the involved tissues of IgG4-RD. METHODS: Single cell RNA sequencing, bulk sample RNA sequencing, immune receptor repertoire analysis (both BCR and TCR), multi-color flow cytometry, and in-vitro assays with model cells (e.g. EBV-immortalized B cells from IgG4-RD patient) and histologic methods were applied to investigate the immunopathological features of IgG4-RD from multiple aspects. RESULTS: Ectopic germinal center formation was observed in IgG4-RD patients at advanced disease stage, and a large part of B cells in involved tissue were germinal center B cell-like. Germinal center reaction in IgG4-RD led to the irregularities of both TCR and BCR clones in the involved tissues, and limited clonal overlaps among different samples. Enhanced Th1- and Th2-type responses were observed in involved tissues of IgG4-RD and patients with both increased Th1- and Th2-type response related cell subsets possessed more severe inflammatory indices. Analyses to the origin of IGHG4 transcripts in IgG4-RD indicated that IgG4 could be switched from IgM directly, or from other IgG subclasses. In vitro assays with EBV-immortalized B cells, fibroblasts and epithelial cells revealed the effects of Th1-type and Th2-type responses on germinal center reaction, ectopic expression of MHC-II molecules, and formation of tertiary lymphoid structures. CONCLUSIONS: Synergistic effects of Th1- and Th2-type responses were involved in the pathogenesis of IgG4-RD via their influences on both acute inflammatory processes and the chronicity and complexity of IgG4-RD.


Assuntos
Linfócitos B , Análise da Expressão Gênica de Célula Única , Humanos
4.
Ann Gen Psychiatry ; 20(1): 47, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34583733

RESUMO

BACKGROUNDS: The Positive and Negative Suicide Ideation (PANSI) Inventory is a widely used self-report questionnaire which is designed to comprehensively evaluate the protective factors and negative risk factors associated with suicidal behaviors among adolescents. The present study aimed to evaluate the psychometric properties and measurement invariance of the Chinese version of the PANSI in a non-clinical sample of Chinese adolescents. METHODS: Participants (N = 1198) were Chinese middle school students aged 11-17 years (44.8% boys and 51.9% girls, 3.3% missing values) in Guizhou Province. All participants completed the Chinese version of the Positive and Negative Suicide Ideation Inventory (PANSI-C), the Rosenberg self-esteem scale (RSE), and the suicide probability scale (SPS). Cronbach's alpha coefficients, confirmatory factor analysis, Pearson's correlations, and multigroup confirmatory factor analysis tests were conducted thereafter. RESULTS: The results showed that the Cronbach's alpha coefficients for the two subscales of the PANSI-positive suicide ideation and the PANSI-negative suicide ideation were .696 and .915, respectively. The confirmatory factor analysis supported the fit of the two-factor model as the best fitting model [Chi-square goodness of fit = 703.859, p < .001, degrees of freedom = 76, comparative fit index = .919, Tucker-Lewis index = .903, standardized root mean square residual = .047, root mean square error of approximation (90% CI) = .083 (.077, .089)]. Positive suicide ideation had negative correlations with the SPS and positive correlations with the RSE, whereas the negative suicide ideation had positive correlations with the SPS and negative correlations with the RSE. All correlations were statistically significant (p < .001), demonstrating the criterion validity of the PANSI-C. Moreover, the strict measurement invariance of the PANSI-C was supported across gender, single-parent and non-single-parent households groups, and the strong measurement invariance was supported across age. LIMITATIONS: The feasibility of this study is limited to Chinese normal adolescents and lack of clinical samples. CONCLUSION: Empirical support for the reliability and validity of the PANSI-C was found. The PANSI-C instrument is found to be useful in assessing positive and negative suicide ideation in Chinese normal adolescents.

5.
Int J Med Sci ; 17(16): 2468-2476, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029089

RESUMO

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/mortalidade , Pneumonia Viral/etiologia , Pneumonia Viral/mortalidade , Pró-Calcitonina/sangue , Idoso , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , COVID-19 , China/epidemiologia , Comorbidade , Infecções por Coronavirus/diagnóstico por imagem , Infecções por Coronavirus/tratamento farmacológico , Progressão da Doença , Feminino , Hospitalização , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Tratamento Farmacológico da COVID-19
7.
FASEB J ; 31(9): 3816-3830, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28522594

RESUMO

Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2-/-) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2-/- colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation. After undergoing transplantation of wild-type bone marrow, SMS2-/- mice also exhibited inhibition of DSS-induced inflammation in the colon, which suggested that SMS2 deficiency in bone marrow-derived immune cells was not involved in the inhibition of colitis. Finally, in an azoxymethane/DSS-induced cancer model, SMS2 deficiency significantly decreased tumor incidence in the colon. Our results demonstrate that SMS2 deficiency inhibits DSS-induced colitis and subsequent colitis-associated colon cancer via inhibition of colon epithelial cell-mediated inflammation; therefore, inhibition of SMS2 may be a potential therapeutic target for human colitis and colorectal cancer.-Ohnishi, T., Hashizume, C., Taniguchi, M., Furumoto, H., Han, J., Gao, R., Kinami, S., Kosaka, T., Okazaki, T. Sphingomyelin synthase 2 deficiency inhibits the induction of murine colitis-associated colon cancer.


Assuntos
Colite/complicações , Neoplasias do Colo/etiologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Animais , Proliferação de Células , Ceramidas/genética , Ceramidas/metabolismo , Colite/enzimologia , Neoplasias do Colo/enzimologia , Inflamação/metabolismo , Lipopolissacarídeos , Camundongos , Camundongos Knockout , Transdução de Sinais , Transferases (Outros Grupos de Fosfato Substituídos)/deficiência , Transferases (Outros Grupos de Fosfato Substituídos)/genética
8.
J Adv Res ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906325

RESUMO

INTRODUCTION: Pulmonary fibrosis (PF) is a fatal fibrotic lung disease without any options to halt disease progression. Feasible evidence suggests that aberrant metabolism of amino acids may play a role in the pathoetiology of PF. However, the exact impact of kynurenine (Kyn), a metabolite derived from tryptophan (Trp) on PF is yet to be addressed. OBJECTIVES: This study aims to elucidate the role of kynurenine in both the onset and advancement of PF. METHODS: Liquid chromatography-tandem mass spectrometry was employed to assess Kyn levels in patients with idiopathic PF and PF associated with Sjögren's syndrome. Additionally, a mouse model of PF induced by bleomycin was utilized to study the impact of Kyn administration. Furthermore, cell models treated with TGF-ß1 were used to explore the mechanism by which Kyn inhibits fibroblast functions. RESULTS: We demonstrated that high levels of Kyn are a clinical feature in both idiopathic PF patients and primary Sjögren syndrome associated PF patients. Further studies illustrated that Kyn served as a braking molecule to suppress fibroblast functionality, thereby protecting mice from bleomycin-induced lung fibrosis. The protective effects depend on AHR, in which Kyn induces AHR nuclear translocation, where it upregulates PTEN expression to blunt TGF-ß mediated AKT/mTOR signaling in fibroblasts. However, in fibrotic microenviroment, the expression of AHR is repressed by methyl-CpG-binding domain 2 (MBD2), a reader interpreting the effect of DNA methylation, which results in a significantly reduced sensitivity of Kyn to fibroblasts. Therefore, exogenous administration of Kyn substantially reversed established PF. CONCLUSION: Our studies not only highlighted a critical role of Trp metabolism in PF pathogenesis, but also provided compelling evidence suggesting that Kyn could serve as a promising metabolite against PF.

9.
Rheumatology (Oxford) ; 52(10): 1739-47, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23584368

RESUMO

High mobility group box chromosomal protein 1 (HMGB1) is a ubiquitous highly conserved single polypeptide in all mammal eukaryotic cells. HMGB1 exists mainly within the nucleus and acts as a DNA chaperone. When passively released from necrotic cells or actively secreted into the extracellular milieu in response to appropriate signal stimulation, HMGB1 binds to related cell signal transduction receptors, such as RAGE, TLR2, TLR4 and TLR9, and becomes a proinflammatory cytokine that participates in the development and progression of many diseases, such as arthritis, acute lung injury, graft rejection immune response, ischaemia reperfusion injury and autoimmune liver damage. Only a small amount of HMGB1 release occurs during apoptosis, which undergoes oxidative modification on Cys106 and delivers tolerogenic signals to suppress immune activity. This review focuses on the important role of HMGB1 in the pathogenesis of RA, mainly manifested as the aberrant expression of HMGB1 in the serum, SF and synovial tissues; overexpression of signal transduction receptors; abnormal regulation of osteoclastogenesis and bone remodelling leading to the destruction of cartilage and bones. Intervention with HMGB1 may ameliorate the pathogenic conditions and attenuate disease progression of RA. Therefore administration of an HMGB1 inhibitor may represent a promising clinical approach for the treatment of RA.


Assuntos
Artrite Reumatoide/fisiopatologia , Proteína HMGB1/fisiologia , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/metabolismo , Humanos , Mediadores da Inflamação/metabolismo
10.
J Huazhong Univ Sci Technolog Med Sci ; 33(4): 611-614, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23904386

RESUMO

IgG4-related disease (IgG4-RD) is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 elevation commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay (ELISA) in a variety of autoimmune diseases including systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), polymyositis or dermatomyositis (PM/DM) and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric assay. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups (P>0.05). The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.


Assuntos
Doenças Autoimunes/sangue , Doenças Autoimunes/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina G/sangue , Doenças Autoimunes/imunologia , Humanos
11.
J Immunol Res ; 2023: 2689360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842289

RESUMO

Background: Macrophage activation syndrome (MAS) is a fatal inflammatory condition, which is often associated with the elevation of multiple proinflammatory cytokines and multiple organ dysfunction. Previous studies have shown that ST2 contributes to T cell overactivation and plays a detrimental role in mouse models of primary hemophagocytic lymphohistiocytosis. The purpose of this study was to investigate the role of the IL-33/ST2 axis in a mouse model of MAS induced by repeated injections of cytosine-phosphate-guanine (CpG). Methods: Serum cytokines were determined using the cytometric bead array by flow cytometry. IL-33 and ST2 were detected by immunohistochemistry and real-time quantitative PCR in the liver and spleen of mice. CD3 and F4/80 in the liver were detected by immunohistochemistry. Inflammatory macrophages and effector memory T lymphocytes were detected by flow cytometry. Result: The CpG-induced MAS model was successfully induced after repeated CpG injections, presenting with hypercytokinemia and hepatosplenomegaly. The numbers of IL-33 positive cells in the liver and spleen decreased significantly, while the expression of ST2 in the liver tended to increase in the mice with MAS. IL-33 and St2 knockout mice showed similar levels of hepatosplenomegaly, peripheral blood count, and cytokine storm when compared with wild-type (WT) mice after induction of MAS. There were also no significant differences in liver pathology (including inflammatory cell infiltration of CD3 and F4/80) and levels of splenic inflammatory macrophages and effector memory T cells between the WT and knockout mice. Conclusion: These results suggested that IL-33 decreased in the liver and spleen tissues of MAS mice. Further results suggest that IL-33 and St2 knockout mice have no treatment potential in CpG-induced MAS. Thus, the IL-33/ST2 axis has little effect on the prognosis of CpG-induced MAS.


Assuntos
Interleucina-33 , Síndrome de Ativação Macrofágica , Animais , Camundongos , Citocinas/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Interleucina-33/metabolismo , Síndrome de Ativação Macrofágica/genética , Camundongos Knockout , Fosfatos
12.
Oxid Med Cell Longev ; 2023: 5012474, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36785790

RESUMO

Both epithelial-to-mesenchymal (EMT) and endothelial-to-mesenchymal (EndMT) transitions have shown to contribute to the development and progression of kidney fibrosis. It has been reported that apelin, a regulatory peptide, alleviates EMT by inhibiting the transforming growth factor ß (TGFß) pathway in renal diseases. Additionally, fibroblast growth factor receptor 1 (FGFR1) has been shown to be a key inhibitor of EndMT through suppression of the TGFß/Smad pathway. In this study, we found that apelin and FGFR1 were spatially close to each other and that the apelin and FGFR1 complex displayed inhibitory effects on TGFß/Smad signaling as well as associated EndMT in diabetic kidney fibrosis. In cultured human dermal microvascular endothelial cells (HMVECs), we found that the anti-EndMT and anti-TGFß/Smad effects of apelin were dampened in FGFR1-deficient cells. Either siRNA- or an inhibitor-mediated deficiency of apelin induced the Smad3 phosphorylation and EndMT. Streptozotocin-induced CD-1 diabetic mice displayed EndMT and associated kidney fibrosis, which were restored by apelin treatment. The medium from apelin-deficient endothelial cells stimulated TGFß/Smad-dependent EMT in cultured HK2 cells. In addition, depletion of apelin and the FGFR1 complex impaired CEBPA expression, and TGFß-induced repression of CEBPA expression contributed to the initiation of EndMT in the endothelium. Collectively, these findings revealed that the interaction between apelin and FGFR1 displayed renoprotective potential through suppression of the TGFß/Smad/CEBPA-mediated EndMT/EMT pathways.


Assuntos
Diabetes Mellitus Experimental , Nefropatias , Camundongos , Humanos , Animais , Células Endoteliais/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Apelina/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Diabetes Mellitus Experimental/metabolismo , Endotélio/metabolismo , Nefropatias/metabolismo , Rim/metabolismo , Fibrose , Transição Epitelial-Mesenquimal
13.
Psychol Rep ; 125(4): 2274-2291, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34034570

RESUMO

The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a self-report instrument widely used to assess resilience in particular demographics. This study aimed to evaluate the validity and measurement invariance (MI) of the CD-RISC-10 in Chinese left-behind children. A total of 968 children from three middle schools in Guizhou Province participated in this study, with the CD-RISC-10 used twice, at the base line time point and again after six months. The Ego-resilience Scale (ERS), and General Self-efficiency Scale (GSES-10) were also used as criteria-related validity instruments. Confirmatory factor analysis (CFA) was carried out to examine the one-factor model and the MI with regards to gender and left-behind status, as well as the longitudinal measurement invariance (LMI). The study proved satisfactory reliability and validity of the CD-RISC-10, with good criterion validity with the ERS and GSES-10. CFA results showed that the satisfactory model fit for the one-factor structure was supported in all groups (e.g., CFI = .942, TLI = .925, RMSEA = .057). The strict MI was evident across genders, as well as both the left-behind and non-left-behind groups. Additionally, the LMI of the CD-RISC-10 was also adequately supported. Generally speaking, these findings demonstrate that the CD-RISC-10 can effectively measure the resilience level of left-behind children - boys as well as girls - in China.


Assuntos
Resiliência Psicológica , Criança , China , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
14.
J Dermatol Sci ; 107(2): 95-104, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35940987

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is a chronic immune-mediated rheumatic disease that is characterized by fibrosis of the skin and internal organs. Interleukin-33 (IL-33) has been recently implicated in several autoimmune diseases through its receptor ST2. OBJECTIVE: The aim of this study was to investigate the role and underlying mechanism of IL-33/ST2 axis in the fibrotic disorder of SSc. METHODS: The bleomycin (BLM)-induced fibrotic skin and skin biopsies of SSc patients were used to detect the expression of IL-33 and ST2. Human dermal fibroblasts were stimulated with recombinant IL-33(rIL-33) protein and their activation, proliferation and migration were assessed. The role of IL-33/ST2 axis was investigated in mouse fibrosis model via histologically assessing skin fibrosis after IL-33 gene knockout. ST2 neutralizing antibody treatment was also obtained to estimate the possible effect. RESULTS: The number IL-33+ cells and ST2+ cells were increased in the lesion skin of SSc patients and BLM-induced mouse. Human skin fibroblasts highly expressed ST2 protein, and the proliferation, migration, and collagen expression were significantly elevated after rIL-33 stimulation, accompanied by the activation of MAPKs and NF-kB pathways. The severity of skin fibrosis was significantly reduced in il33-/- mice compared with WT mice. Blockade of IL-33 receptor using an anti-ST2 neutralizing antibody effectively ameliorated the skin fibrosis. CONCLUSION: These data indicate that IL-33/ST2 axis contributes to the fibrotic skin injury of SSc via promoting fibroblasts activation, and IL-33/ST2 blockade might serve as a novel strategy to inhibit the fibrosis progression in patients of SSc.


Assuntos
Interleucina-33 , Escleroderma Sistêmico , Animais , Anticorpos Neutralizantes/metabolismo , Bleomicina/toxicidade , Colágeno/metabolismo , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibrose , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Interleucina-33/metabolismo , Camundongos , NF-kappa B/metabolismo , Pele/patologia
15.
Front Psychol ; 12: 687589, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899455

RESUMO

The level of meaning in life not only affects the physical health of individuals, but also is closely related to their mental health. At present, many self-reported questionnaires are being used to measure the meaning in life of Chinese adolescents. Using the multivariate generalizability theory, this study investigated the psychometric properties and the internal structure of the Meaning in Life Questionnaires (MLQs), the most widely used questionnaire for assessing the level of meaning in life of Chinese adolescents. The data were sample of 1,951 junior high school students from Guizhou, China. Multivariate random measurement mode p × i° is the primary analytic approach. Results showed that the generalizability coefficient and dependability index of the scale were 0.86 and 0.85, respectively. The generalizability coefficients of presence of meaning and search for meaning were 0.76 and 0.85, respectively, and the dependability indexes were 0.75 and 0.85 for MLQ-P and MLQ-S, respectively. The design of each factor for MLQ is reasonable in terms of score ratio and the number of projects. In brief, the reliability and factor structure of the scale are satisfactory.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34832000

RESUMO

After COVID-19 appeared in China in December 2019, the mental health of adolescents, as a vulnerable group in public health emergencies, was negatively affected by the epidemic and the unprecedented prevention and control measures. The purpose of this study was to investigate the factor structure and psychometric properties of the Posttraumatic Stress Disorder (PTSD) Checklist (PCL) among Chinese adolescents. A total of 915 participants completed the PTSD. Confirmatory factor analyses (CFAs) and multi-group CFAs were used to test the factor structure and psychometric properties of PTSD. The CFA results showed that five-factor PCL was the optimal fitting model with satisfactory reliability and validity; moreover, it was suggested that the properties of PCL were invariant across gender, PTSD and asymptomatic groups, early and late adolescents, as well as over time. In summary, PCL is applicable among Chinese adolescents and can be used for effective measurement of PTSD caused by epidemics and to conduct cross-group studies.


Assuntos
COVID-19 , Transtornos de Estresse Pós-Traumáticos , Adolescente , Lista de Checagem , Manual Diagnóstico e Estatístico de Transtornos Mentais , Surtos de Doenças , Humanos , Psicometria , Reprodutibilidade dos Testes , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos/epidemiologia
17.
Front Psychol ; 12: 678979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630200

RESUMO

The Fear of COVID-19 Scale (FCV-19S) is a new one-dimensional scale used to measure fear of an individual about the COVID-19. Given the seriousness of the COVID-19 situation in China when our study was taking place, our aim was to translate and examine the applicability of the FCV-19S in Chinese students. The sample used for validation comprised 2,445 Chinese students. The psychometrical characteristics of the Chinese FCV-19S (FCV-19S-C) were tested using Rasch analysis. Principal component analysis (PCA) proved the unidimensional structure of the model. Both infit and outfit mean square (MNSQ) values (0.69-1.31) and point-measure correlations (0.82-0.86) indicated a good model fit. Person-item separation and reliability values indicated good reliability of the scale. The person-item map revealed an acceptable level of match between the persons and the items. Differential item functioning of the FCV-19S-C showed no differences with respect to age or gender. FCV-19S-C scores were significantly associated with anxiety, stress, depression, ego-resilience, and general health. The FCV-19S-C was proven to be effective in measuring fear of Chinese students about the COVID-19.

18.
Int J Nanomedicine ; 16: 2803-2818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880025

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been identified as key factors in the development of hepatocellular carcinoma (HCC). However, the role and potential molecular mechanism of circRNAs in HCC remain largely unclear. In addition, exosomes are known as important messengers of the cross-talk between tumor cells and immune cells, while the role of extracellular circRNAs in the cell-to-cell communication of tumor cells and immune cells remains not unclear. METHODS: The level of hsa_circ_0074854 in HCC cell lines and HCC cell-derived exosomes was assessed using RT-qPCR assay. In addition, CCK-8 and transwell assays were used to determine the viability, migration and invasion of HCC cells. RESULTS: Hsa_circ_0074854 expression was upregulated in HCC tissues and HCC cell lines. Additionally, hsa_circ_0074854 knockdown was found to inhibit HCC growth in vitro and in vivo. Mechanistically, hsa_circ_0074854 knockdown inhibited the migration and invasion of HCC cells via interacting with human antigen R (HuR) to reduce its stability. Furthermore, hsa_circ_0074854 can be transferred from HCC cells to macrophages via exosomes. Exosomes with downregulated hsa_circ_0074854 suppressed macrophage M2 polarization, which in turn suppressing migration and invasion of HCC cells both in vitro and in vivo. CONCLUSION: Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Collectively, these findings may help to understand the diagnosis and treatment of HCC.


Assuntos
Carcinoma Hepatocelular/genética , Movimento Celular/genética , Polaridade Celular , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Exossomos/metabolismo , Macrófagos/patologia , RNA Circular/metabolismo , Animais , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Ligação Proteica , RNA Circular/genética
19.
ESC Heart Fail ; 8(1): 644-651, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33336560

RESUMO

AIMS: Many studies have explored the clinical characteristics of patients with coronavirus disease (COVID-19), especially patients with cardiovascular disease. However, associated mechanisms and markers remain to be further investigated. This study aimed to investigate the effect of α-hydroxybutyrate dehydrogenase (α-HBDH) levels on disease progression and prognosis of patients with COVID-19. METHODS AND RESULTS: One thousand seven hundred and fifty-one patients from the Leishenshan hospital in Wuhan were divided into elevated and normal groups by α-HBDH level, and the clinical information between the two groups was compared retrospectively. The main outcome evaluation criteria included in-hospital death and disease severity. Univariate and multivariate regression analyses, survival curves, logistic regression, and receiver operating characteristic curve models were performed to explore the relationship between elevated α-HBDH and the two outcomes. Besides, curve fitting analyses were conducted to analyse the relationship between computed tomography score and survival. Among 1751 patients with confirmed COVID-19, 15 patients (0.87%) died. The mean (SD) age of patients was 58 years in normal α-HBDH group and 66 years in elevated α-HBDH group (P < 0.001). The mortality during hospitalization was 0.26% (4 of 1559) for patients with normal α-HBDH levels and 5.73% (11 of 192) for those with elevated α-HBDH levels (P < 0.001). Multivariate Cox analysis confirmed an association between elevated α-HBDH levels and higher risk of in-hospital mortality [hazard ratio: 4.411, 95% confidence interval (95% CI), 1.127-17.260; P = 0.033]. Multivariate logistic regression for disease severity and α-HBDH levels showed significant difference between both groups (odds ratio = 3.759; 95% CI, 1.895-7.455; P < 0.001). Kaplan-Meier curves also illustrated the survival difference between normal and elevated α-HBDH patients (P < 0.001). CONCLUSIONS: Our study found that serum α-HBDH is an independent risk factor for in-hospital mortality and disease severity among COVID-19 patients. α-HBDH assessment may aid clinicians in identifying high-risk individuals among COVID-19 patients.


Assuntos
COVID-19/diagnóstico , Hidroxibutirato Desidrogenase/sangue , Idoso , COVID-19/sangue , COVID-19/enzimologia , COVID-19/mortalidade , China/epidemiologia , Progressão da Doença , Mortalidade Hospitalar , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
20.
Aging (Albany NY) ; 12(10): 9793-9806, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32464601

RESUMO

Circular RNAs (circRNAs) play an important role in the tumorigenesis of hepatocellular carcinoma (HCC), but their specific functions in HCC remain largely unknown. Using bioinformatics analysis, we have found that the expression of circRNA hsa_circ_0003141 is significantly increased in HCC tissues. Ubiquitin-associated protein 2 (UBAP2) is the parent gene for hsa_circ_0003141, and its high expression correlates with poor overall survival rates in HCC patients. In addition, our results show that miR-1827 is a binding target of hsa_circ_0003141, and indicate that hsa_circ_0003141 regulates UBAP2 expression by sponging miR-1827 in HCC cells. Downregulation of hsa_circ_0003141 suppresses UBAP2 expression, induces apoptosis, and inhibits proliferation and invasion by HCC Huh-7 cells. Importantly, downregulation of hsa_circ_0003141 inhibits tumorigenesis in a xenograft mouse model of HCC. Together, our results indicate that hsa_circ_0003141 functions as an oncogene in HCC cells, and suggest that the hsa_circ_0003141/miR-1827/UBAP2 axis might represent a novel therapeutic option for the treatment of HCC.


Assuntos
Carcinogênese/genética , Carcinoma Hepatocelular/genética , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Animais , Apoptose/genética , Biomarcadores Tumorais/genética , Proliferação de Células/genética , Biologia Computacional , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
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