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1.
Front Cardiovasc Med ; 11: 1290610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374999

RESUMO

Background: Postoperative atrial fibrillation (POAF) is a frequent complication that may increase morbidity and mortality risk following cardiac surgery. The systemic immune-inflammation index (SII) is an emerging biomarker that provides an integrated measure of inflammation by incorporating neutrophil, lymphocyte, and platelet counts. Recent studies have reported associations between elevated SII and increased POAF risk; however, significant heterogeneity exists regarding its predictive efficacy. This meta-analysis aimed to assess SII's diagnostic efficacy for predicting POAF risk. Methods: To synthesize existing evidence on the ability of perioperative SII for predicting POAF in patients undergoing cardiac surgery, a systematic review and meta-analysis was conducted. In August 2023, a comprehensive literature search was performed to identify relevant studies reporting SII cutoff values with corresponding sensitivity and specificity. The primary aim was to evaluate SII's diagnostic utility for predicting POAF, whereas secondary outcomes included the pooled incidence of POAF and the relationship between the SII and POAF. Results: Eight studies published between 2021 and 2023 with 3,245 patients were included. Six studies involved coronary artery bypass grafting (CABG) surgery; one encompassed various cardiac procedures, and another focused solely on mitral valve surgery. The pooled incidence of POAF was 23.6% [95% confidence interval (CI), 18.7%-29.2%]. Elevated SII significantly increased the odds of POAF by 3.24-fold (odds ratio, 3.24; 95% CI, 1.6-6.55; p = 0.001). SII's pooled sensitivity and specificity for predicting POAF were 0.80 (95% CI, 0.68-0.89) and 0.53 (95% CI, 0.23-0.8), respectively. The SII had moderate predictive accuracy based on a hierarchical summary receiver operating characteristic (HSROC) area under the curve of 0.78 (95% CI, 0.74-0.81). Subgroup analyses, whether focusing on CABG alone or CABG with cardiopulmonary bypass (CPB), both indicated an area under the HSROC curve of 0.78 (95% CI, 0.74-0.81). Conclusion: Elevated SII is significantly correlated with an increased POAF risk following cardiac surgery, highlighting its utility as a predictive biomarker. Considering its moderate diagnostic accuracy, further research is essential for clarifying SII's clinical effectiveness, either as an independent predictor or combined with other risk factors, for stratifying patients at high POAF risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023456128].

2.
Front Immunol ; 14: 1320683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149257

RESUMO

Background: Postoperative infectious complications (PICs) are major concerns. Early and accurate diagnosis is critical for timely treatment and improved outcomes. Presepsin is an emerging biomarker for bacterial infections. However, its diagnostic efficacy for PICs across surgical specialties remains unclear. Methods: In this study, a systematic search on MEDLINE, Embase, Google Scholar, and Cochrane Library was performed on September 30, 2023, to identify studies that evaluated presepsin for diagnosing PICs. PIC is defined as the development of surgical site infection or remote infection. Pooled sensitivity, specificity, and hierarchical summary receiver operating characteristic (HSROC) curves were calculated. The primary outcome was the assessment of the efficacy of presepsin for PIC diagnosis, and the secondary outcome was the investigation of the reliability of procalcitonin or C-reactive protein (CRP) in the diagnosis of PICs. Results: This meta-analysis included eight studies (n = 984) and revealed that the pooled sensitivity and specificity of presepsin for PIC diagnosis were 76% (95% confidence interval [CI] 68%-82%) and 83% (95% CI 75%-89%), respectively. The HSROC curve yielded an area under the curve (AUC) of 0.77 (95% CI 0.73-0.81). Analysis of six studies on procalcitonin showed a combined sensitivity of 78% and specificity of 77%, with an AUC of 0.83 derived from the HSROC. Meanwhile, data from five studies on CRP indicated pooled sensitivity of 84% and specificity of 79%, with the HSROC curve yielding an AUC of 0.89. Conclusion: Presepsin exhibits moderate diagnostic accuracy for PIC across surgical disciplines. Based on the HSROC-derived AUC, CRP has the highest diagnostic efficacy for PICs, followed by procalcitonin and presepsin. Nonetheless, presepsin demonstrated greater specificity than the other biomarkers. Further study is warranted to validate the utility of and optimize the cutoff values for presepsin. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023468358.


Assuntos
Receptores de Lipopolissacarídeos , Pró-Calcitonina , Reprodutibilidade dos Testes , Biomarcadores , Proteína C-Reativa/análise
3.
Clin Immunol ; 257: 109842, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37981105

RESUMO

Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-bet+CD11c+ IgD+ activated naive B cells (aNAV) was higher in females and was associated with increased T-bet+CD11c+ IgD- age-related B cells, Fas+GL7+ germinal center B cells, Cxcr5-Icos+ peripheral T-helper cells, and Cxcr5+Icos+ follicular T-helper cells. IFN-ß was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.


Assuntos
Linfócitos B , Lúpus Eritematoso Sistêmico , Animais , Feminino , Humanos , Masculino , Camundongos , Autoanticorpos , Cruzamentos Genéticos , Centro Germinativo , Lúpus Eritematoso Sistêmico/genética , Camundongos Endogâmicos C57BL , Linfócitos T Auxiliares-Indutores , Caracteres Sexuais
4.
Clin Immunol ; 247: 109239, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682593

RESUMO

T-helper cytokines interferon gamma (IFNÉ£), interleukin 17 (IL-17) and IL-10 impact systemic lupus erythematosus (SLE) directly and indirectly via modulation of autoAb production. We determined the separate and combined effects on clinical manifestations of SLE (N = 62). IFNÉ£, IL-17 but not IL-10 were significantly elevated in patients with SLE. IFNÉ£ positively correlated with anti-DNA and anti-SSA. IL-17 positively correlated with anti-SSA and was significantly higher in patients with discoid rash and class V LN. IL-10 did not correlate with circulating autoantibodies but was significantly elevated in patients with LN. Patients with LN had elevated plasma levels of anti-DNA and anti-Sm/ribonuclear protein (RNP). Anti-Sm/RNP levels were decreased in patients with acute mucocutaneous manifestations, including photosensitivity and/or malar rash. The study provides critical insights into pathological mechanisms of LN, which could help guide future diagnoses and therapies.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Citocinas , Interleucina-17 , Estudos Transversais , Autoanticorpos , Linfócitos T , Interferon gama , Anticorpos Antinucleares
5.
Animals (Basel) ; 12(24)2022 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-36552376

RESUMO

Inflammatory bowel disease (IBD) is a non-infectious disease characterized by chronic inflammation of the gastrointestinal tract. Currently, management of IBD is still a clinical challenge. The purpose of this study was to investigate the therapeutic potential of surfactin containing Bacillus licheniformis-fermented products (SBLF) and commercial surfactin (CS) on the treatment of dextran sulfate sodium (DSS)-induced colitis in a mouse model. We found that mice that received drinking water containing 3% DSS developed significant colitis symptoms, including increased disease activity index, body weight loss, shortening of the colon length, splenomegaly, colonic inflammation and colonic NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation. Notably, orally received SBLF, CS or clinical anti-inflammatory drug 5-aminosalicylic acid improved DSS-induced colitis symptoms in mice. These findings show that SBLF can improve IBD in mice by reducing colonic inflammation and inhibiting the NLRP3 inflammasome activation, suggesting that SBLF has the potential to be used as a nutraceutical in humans or a feed additive in economic and companion animals for preventing IBD.

6.
Clin Immunol ; 244: 109130, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36189576

RESUMO

Here, we report a case of atopic dermatitis (AD) in a patient who received biweekly doses of dupilumab, an antibody against the IL-4 receptor α chain (IL-4Rα). Single cell RNA-sequencing showed that naïve B cells expressed the highest levels of IL4R compared to other B cell subpopulations. Compared to controls, the dupilumab-treated patient exhibited diminished percentages of IL4R+IGHD+ naïve B cells and down-regulation of IL4R, FCER2 (CD23), and IGHD. Dupilumab treatment resulted in upregulation of genes associated with apoptosis and inhibition of B cell receptor signaling and down-regulation of class-switch and memory B cell development genes. The dupilumab-treated patient exhibited a rapid decline in COVID-19 anti-spike and anti-receptor binding domain antibodies between 4 and 8 and 11 months post COVID-19 vaccination. Our data suggest that intact and persistent IL-4 signaling is necessary for maintaining robust survival and development of naïve B cells, and maintaining a long term vaccine response.


Assuntos
Tratamento Farmacológico da COVID-19 , Receptores de Interleucina-4 , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Vacinas contra COVID-19 , Humanos , Interleucina-4 , RNA , Receptores de Antígenos de Linfócitos B
7.
J Immunol ; 209(8): 1513-1522, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36165181

RESUMO

Activated naive (aNAV) B cells have been shown to be the precursor of the CD11c+T-bet+ IgD-CD27- double-negative (DN)2 or atypical memory (aMEM) B cells in systemic lupus erythematosus (SLE). To determine factors that maintain resting naive (rNAV) B cells, the transcriptomic program in naive (IGHD+IGHM +) B cells in human healthy control subjects (HC) and subjects with SLE was analyzed by single-cell RNA-sequencing analysis. In HC, naive B cells expressed IL-4 pathway genes, whereas in SLE, naive B cells expressed type I IFN-stimulated genes (ISGs). In HC, aNAV B cells exhibited upregulation of the gene signature of germinal center and classical memory (cMEM) B cells. In contrast, in SLE, aNAV B cells expressed signature genes of aMEM. In vitro exposure of SLE B cells to IL-4 promoted B cell development into CD27+CD38+ plasmablasts/plasma and IgD-CD27+ cMEM B cells. The same treatment blocked the development of CD11c+Tbet+ aNAV and DN2 B cells and preserved DN B cells as CD11c-Tbet- DN1 B cells. Lower expression of IL-4R and increased intracellular IFN-ß in naive B cells was correlated with the accumulation of CD21-IgD- B cells and the development of anti-Smith and anti-DNA autoantibodies in patients with SLE (n = 47). Our results show that IL-4R and type I IFN signaling in naive B cells induce the development of distinct lineages of cMEM versus aMEM B cells, respectively. Furthermore, diminished IL-4R signaling shifted activated B cell development from the DN1 to the DN2 trajectory in patients with SLE. Therapies that enhance IL-4R signaling may be beneficial for ISGhi SLE patients.


Assuntos
Subpopulações de Linfócitos B , Lúpus Eritematoso Sistêmico , Autoanticorpos/metabolismo , Humanos , Imunoglobulina D/metabolismo , Interleucina-4/metabolismo , RNA/metabolismo
8.
Mar Drugs ; 20(8)2022 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-36005521

RESUMO

The extensive use of conventional antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. Evidence suggests that cationic antimicrobial peptides (AMPs) have the greatest potential to serve as traditional antibiotic substitutes. Recent studies have also reported that certain AMPs have selective toxicity toward various types of cancer cells. The electrostatic attraction between the negatively charged membrane components and AMPs is believed to play a crucial role in the disruption of bacterial and cancer cell membranes. In the current study, we used a potent AMP called Pleurocidin (Ple) derived from winter flounder Pleuronectes americanus and its C-terminal-amidated derivative Pleurocidin-amide (Ple-a), and evaluated their antibacterial and anticancer activities. Our results indicated that both Ple and Ple-a exhibited significant antibacterial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, especially marine pathogens, with MIC values ranging from 0.25 to 32 µg/mL. These peptides are also potent against several multidrug-resistant (MDR) bacterial strains, with MIC values ranging from 2 to 256 µg/mL. When used in combination with certain antibiotics, they exhibited a synergistic effect against MDR E. coli. Ple and Ple-a also showed notable cytotoxicity toward various cancer cell lines, with IC50 values ranging from 11 to 340 µM, while normal mouse fibroblast 3T3 cells were less susceptible to these peptides. Ple-a was then selected to study its anticancer mechanism toward A549 human lung adenocarcinoma cells. Western blot analysis and confocal microscopy showed that Ple-a could inhibit autophagy of A549 cells, and induce apoptosis 48 h after treatment. Our findings provided support for the future application of Ple-a as potential therapeutic agent for bacterial infections and cancer treatment.


Assuntos
Linguado , Amidas/farmacologia , Animais , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Bactérias , Escherichia coli , Proteínas de Peixes , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Humanos , Camundongos , Testes de Sensibilidade Microbiana
9.
Arthritis Res Ther ; 24(1): 87, 2022 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436902

RESUMO

BACKGROUND: In systemic lupus erythematosus (SLE), detection of interferon-ß (IFNß) in B cells was found to be most prominent in patients with high anti-Smith (Sm) and renal disease, but a mechanistic connection was not clear. The objective of the present study is to determine the association of IFNß in peripheral blood naïve B cells with the histopathological features of lupus nephritis (LN). METHODS: The percentage of IFNß+ cells in IgD+CD27- naïve CD19+ B cells (B cell IFNß) among peripheral blood mononuclear cells (PBMCs) from 80 SLE patients were analyzed using flow cytometry. Serological and clinical data were collected. The correlations of B cell IFNß with LN classification and with histopathological findings (light, electron, and immunofluorescence [IF] microscopic analyses for deposition of IgM, IgG, IgA, C1q, and C3) were determined in 23 available biopsy specimens. RESULTS: B cell IFNß is positively associated with anti-Sm (p = 0.001), anti-DNA (p = 0.013), and LN (p < 0.001) but was negatively associated with oral/nasal ulcer (p = 0.003) and photosensitivity (p = 0.045). B cell IFNß positively correlated with immune complex (IC) deposit in the glomerular basement membrane (GBM) (p = 0.002) but not in the mesangial (p = 0.107) or tubular region (p = 0.313). Patients with high B cell IFNß had statistically increased development of the proliferative LN (Classes III, IV and/or V), compared to patients with low B cell IFNß (p < 0.0001). Histopathological features positively associated with increased B cell IFNß included active glomerular lesions as determined by fibrocellular crescents (p = 0.023), chronic glomerular lesions indicated by segmental sclerosis (p = 0.033), and a membranous pattern of renal damage indicated by spike/holes (p = 0.015). CONCLUSION: B cell IFNß correlates with history of severe LN, glomerular basement membrane (GBM) IC deposition, and anatomical features of both active and chronic glomerular lesions.


Assuntos
Nefropatias , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Anticorpos Antinucleares , Feminino , Humanos , Interferon beta , Leucócitos Mononucleares/metabolismo , Nefrite Lúpica/patologia , Masculino , Estudos Retrospectivos
10.
Arthritis Rheumatol ; 74(4): 634-640, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34725967

RESUMO

OBJECTIVE: To determine the extent to which the gut microbiome influences systemic autoimmunity in a mouse model of lupus. METHODS: We generated germ-free (GF) lupus-prone BXD2 mice, which under normal conditions develop spontaneous germinal centers (GCs) and high titers of serum autoantibodies. GF status was confirmed by gut bacterial culture. The autoimmune phenotypes of 6- and 12-month-old gnotobiotic GF BXD2 mice and specific pathogen-free (SPF) BXD2 mice were compared. Serum levels of autoantibodies were measured by enzyme-linked immunosorbent assay. Histologic sections of the mouse kidney and joints were evaluated. Flow cytometry was used to analyze GCs and age-associated B cells. CD4+ T cells were analyzed for PD-1+ICOS+ activated T cells, T follicular regulatory (Tfr) cells (Foxp3+CD25+ PD-1+CXCR5+), and PD-1+ICOS+ T cells expressing interleukin-17A (IL-17A) or interferon-γ (IFNγ) after stimulation with phorbol myristate acetate (PMA)/ionomycin. RESULTS: In 6-month-old mice, GF status did not affect splenomegaly, GC B cells, age-associated B cells, or serum autoantibody levels, except for IgG antihistone. GF BXD2 mice exhibited a significantly higher percentage of Tfr cells compared to their SPF counterparts (P < 0.05). At 12 months of age, however, GF BXD2 mice had significantly diminished IgG autoantibody levels and a lower percentage of GC B cells and age-associated B cells (P < 0.05). Following stimulation with PMA/ionomycin, PD-1+ICOS+ CD4+ T cells expressed significantly lower IL-17A, but not IFNγ, levels in GF BXD2 mice compared to SPF BXD2 mice (P < 0.01). SPF BXD2 mice and GF BXD2 mice developed equivalent renal and joint disease with no significant differences in severity. CONCLUSION: Our results suggest a model in which genetics plays a dominant role in determining the initial development of autoimmunity. In contrast, gut microbiomes may regulate the persistence of certain aspects of systemic autoimmunity.


Assuntos
Doenças Autoimunes , Microbioma Gastrointestinal , Animais , Autoanticorpos , Doenças Autoimunes/genética , Imunoglobulina G , Interferon gama , Interleucina-17 , Ionomicina , Camundongos , Receptor de Morte Celular Programada 1
11.
Healthcare (Basel) ; 9(12)2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34946451

RESUMO

OBJECTIVE: To compare the differences between the work competencies self-reported by nurse aides' and those perceived by nurses. METHOD: A cross-sectional survey was employed. The settings were units implemented a skill mix model institution in Taiwan. The instruments consisted of the participants' demographic data and a nurse aide work competence scale. RESULTS: The results indicated that the nurse aides had room for improvement in terms of "problem solving" and "activity design". The nurse aides and nurses differed significantly in terms of the nurse aides' competence in "activity design", as the nurse aides reported themselves to be more competent in "activity design" than reported by the nurses. CONCLUSION: Nurse aides should be incorporated into cross-disciplinary teams. Activity design should be handled by other healthcare providers such as physical therapists or senior social workers.

13.
J Clin Med ; 9(8)2020 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-32751135

RESUMO

BACKGROUND: Benign immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD)-characterized as tumors mimicking malignant orbital lymphoma (OL)-responds well to steroids, instead of chemotherapy, radiotherapy and/or surgery of OL. The objective of this study was to report the differences in computed tomography (CT) features and- serum IgG4 levels of IgG4-ROD and OL. METHODS: This study retrieved records for patients with OL and IgG4-ROD from a pathology database during an eight-year-and-five-month period. We assessed the differences between 16 OL patients with 27 lesions and nine IgG4-ROD patients with 20 lesions according to prebiopsy CT features of lesions and prebiopsy serum IgG4 levels and immunoglobulin G (IgG) levels This study also established the receiver-operating curves (ROC) of precontrast and postcontrast CT Hounsfield unit scales (CTHU), serum IgG4 levels, serum IgG levels and their ratios. RESULTS: Significantly related to IgG4-ROD (all p < 0.05) were the presence of lesions with regular borders, presence of multiple lesions-involving both lacrimal glands on CT scans-higher median values of postcontrast CTHU, postcontrast CTHU/precontrast CTHU ratios, serum IgG4 levels and serum IgG4/IgG level ratios. Compared to postcontrast CTHU, serum IgG4 levels had a larger area under the ROC curve (0.847 [95% confidence interval (CI): 0.674-1.000, p = 0.005] vs. 0.766 [95% CI: 0.615-0.917, p = 0.002]), higher sensitivity (0.889 [95% CI: 0.518-0.997] vs. 0.75 [95% CI: 0.509-0.913]), higher specificity (0.813 [95% CI: 0.544-0.960] vs. 0.778 [95% CI: 0.578-0.914]) and a higher cutoff value (≥132.5 mg/dL [milligrams per deciliter] vs. ≥89.5). CONCLUSIONS: IgG4-ROD showed distinct CT features and elevated serum IgG4 (≥132.5 mg/dL), which could help distinguish IgG4-ROD from OL.

14.
Br J Cancer ; 123(4): 673-688, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32528118

RESUMO

BACKGROUND: Mammography is not effective in detecting breast cancer in dense breasts. METHODS: A search in Medline, Cochrane, EMBASE and Google Scholar databases was conducted from January 1, 1980 to April 10, 2019 to identify women with dense breasts screened by mammography (M) and/or ultrasound (US). Meta-analysis was performed using the random-effect model. RESULTS: A total of 21 studies were included. The pooled sensitivity values of M alone and M + US in patients were 74% and 96%, while specificity of the two methods were 93% and 87%, respectively. Screening sensitivity was significantly higher in M + US than M alone (risk ratio: M alone vs. M + US = 0.699, P < 0.001), but the slight difference in specificity was statistically significant (risk ratio = 1.060, P = 0.001). Pooled diagnostic performance of follow-up US after initial negative mammography demonstrated a high pooled sensitivity (96%) and specificity (88%). The findings were supported by subgroup analysis stratified by study country, US method and timing of US. CONCLUSIONS: Breast cancer screening by supplemental US among women with dense breasts shows added detection sensitivity compared with M alone. However, US slightly decreased the diagnostic specificity for breast cancer. The cost-effectiveness of supplemental US in detecting malignancy in dense breasts should be considered additionally.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Mamografia/métodos , Ultrassonografia Mamária/métodos , Densidade da Mama , Terapia Combinada , Detecção Precoce de Câncer , Feminino , Humanos , Sensibilidade e Especificidade
15.
J Immunol ; 205(2): 346-358, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32554431

RESUMO

IL-23 promotes autoimmune disease, including Th17 CD4 T cell development and autoantibody production. In this study, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19-/- ) mouse leads to a shift of the follicular T helper cell program from follicular T helper (Tfh)-IL-17 to Tfh-IFN-γ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19-/- mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that whereas Ifngr1, Il21r, and Il4r genes exhibited a synchronized expression pattern with Cxcr5 and plasma cell program genes, Il17ra exhibited a synchronized expression pattern with Cxcr4 and GC program genes. Downregulation of Ighg2b in BXD2-p19-/- GC B cells was associated with decreased expression of CSR-related novel base excision repair genes that were otherwise predominantly expressed by Il17ra + GC B cells in BXD2 mice. Together, these results suggest that although IL-23 is dispensable for GC formation, it is essential to promote a population of Tfh-IL-17 cells. IL-23 acts indirectly on Il17ra + GC B cells to facilitate CSR-related base excision repair genes during the dark zone phase of GC B cell development.


Assuntos
Doenças Autoimunes/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Imunoglobulina G/metabolismo , Interleucina-23/metabolismo , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia , Animais , Diferenciação Celular , Inibidor de Quinase Dependente de Ciclina p19/genética , Switching de Imunoglobulina , Imunoglobulina G/genética , Interferon gama/metabolismo , Interleucina-23/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
PLoS One ; 14(11): e0225043, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31710641

RESUMO

OBJECTIVE: Primary hepatic angiosarcoma (PHA) is extremely rare and most patients die within 12 months of diagnosis. The object of the study is to determine the association of initial clinical-radiological features and staging with outcomes in patients with PHA. METHODS: The medical records of adult patients with PHA were retrieved from an electronic medical record database and a pathology database and retrospectively reviewed. During 10 years, 22 eligible patients were included. Data extracted focused on the information before the first formal treatment with a pathological proof, including demographic characteristics, medical history, laboratory data, preliminary images, histopathological records, treatment, and follow-up survival period. Two radiologists blindly re-analyzed preliminary images of all 22 patients together and recorded tumor features and imaging stage based on the American Joint Committee on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) Staging System for hepatocellular carcinoma. A radiologist compiled the initial clinical data and preliminary image stage to analyze the association with patients' survival outcome. RESULTS: Higher aspartate aminotransferase (AST), higher total bilirubin (TB), lower albumin (ALB), longer prothrombin time (PT) and lower platelet count of serum relative to the normal reference range were more common in patients who survived ≤ 90 days (all P < 0.05). Overall survival was much better in patients with single PHA than in those with other tumor patterns of multiple PHA (all P < 0.05). Overall survival determined by preliminary imaging showed significant differences between stage I and stage III (P = 0.044), stage I and stage IV (P = 0.011), and stage III and IV (P = 0.047). No patients were at stage II. CONCLUSIONS: Initial serum levels of ALT, TB, ALB, and PT, platelet count, single mass in liver, and preliminary imaging staging could help predict survival outcomes of patients with PHA.


Assuntos
Carcinoma Hepatocelular/patologia , Hemangiossarcoma/patologia , Neoplasias Hepáticas/patologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Registros Eletrônicos de Saúde , Feminino , Hemangiossarcoma/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X
17.
Immunol Rev ; 292(1): 120-138, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31631359

RESUMO

The current concepts for development of autoreactive B cells in SLE (systemic lupus erythematosus) focus on extrinsic stimuli and factors that provoke B cells into tolerance loss. Traditionally, major tolerance loss pathways are thought to be regulated by factors outside the B cell including autoantigen engagement of the B-cell receptor (BCR) with simultaneous type I interferon (IFN) produced by dendritic cells, especially plasmacytoid dendritic cells (pDCs). Later, in autoreactive follicles, B-cells encounter T-follicular helper cells (Tfh) that produce interleukin (IL)-21, IL-4 and pathogenic cytokines, IL-17 and IFN gamma (IFNÉ£). This review discusses these mechanisms and also highlights recent advances pointing to the peripheral transitional B-cell stage as a major juncture where transient autocrine IFNß expression by developing B-cells imprints a heightened susceptibility to external factors favoring differentiation into autoantibody-producing plasmablasts. Recent studies highlight transitional B-cell heterogeneity as a determinant of intrinsic resistance or susceptibility to tolerance loss through the shaping of B-cell responsiveness to cytokines and other environment factors.


Assuntos
Autoanticorpos/imunologia , Autoimunidade/imunologia , Linfócitos B/imunologia , Tolerância Imunológica/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia
18.
J Clin Nurs ; 28(21-22): 3866-3878, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31294503

RESUMO

AIM AND OBJECTIVE: To explore the disability, emotional distress and well-being of patients with lumbar spondylolisthesis. BACKGROUND: Few studies have investigated the correlations between disability, emotional distress and well-being of patients with lumbar spondylolisthesis. DESIGN: This study used a cross-sectional research design. METHODS: Participants were 133 patients aged over 50 years who were experiencing lumbar spondylolisthesis. The research instruments included a demographic information questionnaire; the Numeric Rating Scale (NRS); the Charlson Comorbidity Index (CCI); the Chinese versions of the Oswestry Disability Index (ODI), State-Trait Anxiety Inventory-State (STAI-S) and Center for Epidemiological Study-Depression (CES-D); and the Psychological Well-being (PWB) Scale. Emotional distress was measured by the STAI-S and CES-D. Pearson's correlations coefficient, multiple linear regression and a mediating effect model were introduced to explore correlations between the variables and predictors of psychological well-being, and details of the methods are reported in coherence to STROBE criteria. RESULTS: Eighty-six participants (64.6%) had moderate and severe anxiety, and 42 (31.6%) experienced depression. Participants reported medium to high levels of well-being; "satisfaction with interpersonal relationships" was rated the highest and "physical and mental health" the lowest. Disability, depression and anxiety had significant negative correlations with well-being. Depression and anxiety mediated the relationship between disability and well-being. Moreover, depression, family support, educational background and anxiety were predictors of well-being, accounting for 39.1% of the total variance. CONCLUSIONS: Disability and emotional distress among patients with lumbar spondylolisthesis had a negative impact on well-being. Anxiety and depression were closely correlated with and substantially influenced well-being. RELEVANCE TO CLINICAL PRACTICE: Health professionals will enhance the understanding of important factors influencing well-being among patients with lumbar spondylolisthesis. This study suggests the conduct of depression and anxiety evaluations at outpatient clinics and prior to surgery, so that clinicians will be aware of the emotional distress status of patients with lumbar spondylolisthesis and, therefore, enhance their well-being.


Assuntos
Angústia Psicológica , Espondilolistese/psicologia , Idoso , Ansiedade/epidemiologia , Ansiedade/etiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/etiologia , Avaliação da Deficiência , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Espondilolistese/complicações , Inquéritos e Questionários
19.
J Immunol ; 202(6): 1649-1658, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30833421

RESUMO

Although multiple and overlapping mechanisms are ultimately responsible for the immunopathology observed in patients with systemic lupus erythematosus, autoreactive Abs secreted by autoreactive plasma cells (PCs) are considered to play a critical role in disease progression and immunopathology. Given that PCs derive from the germinal centers (GC), long-term dysregulated GC reactions are often associated with the development of spontaneous autoantibody responses and immunopathology in systemic lupus erythematosus patients. In this review, we summarize the emerging evidence concerning the roles of T follicular helper cells in regulating pathogenic GC and autoreactive PC responses in lupus.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Autoanticorpos/imunologia , Centro Germinativo/imunologia , Humanos , Plasmócitos/imunologia
20.
J Immunol ; 201(8): 2203-2208, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30201809

RESUMO

In systemic lupus erythematosus (SLE), type I IFNs promote induction of type I IFN-stimulated genes (ISG) and can drive B cells to produce autoantibodies. Little is known about the expression of distinct type I IFNs in lupus, particularly high-affinity IFN-ß. Single-cell analyses of transitional B cells isolated from SLE patients revealed distinct B cell subpopulations, including type I IFN producers, IFN responders, and mixed IFN producer/responder clusters. Anti-Ig plus TLR3 stimulation of SLE B cells induced release of bioactive type I IFNs that could stimulate HEK-Blue cells. Increased levels of IFN-ß were detected in circulating B cells from SLE patients compared with controls and were significantly higher in African American patients with renal disease and in patients with autoantibodies. Together, the results identify type I IFN-producing and -responding subpopulations within the SLE B cell compartment and suggest that some patients may benefit from specific targeting of IFN-ß.


Assuntos
Subpopulações de Linfócitos B/fisiologia , Linfócitos B/fisiologia , Negro ou Afro-Americano , Interferon Tipo I/metabolismo , Interferon beta/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Insuficiência Renal Crônica/imunologia , Autoanticorpos/sangue , Circulação Sanguínea , Células Cultivadas , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem , Interferon Tipo I/genética , Espaço Intracelular , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Análise de Célula Única , Transcriptoma , Estados Unidos/epidemiologia
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