课程文献中心 更多>>

关键词： Plasmodium vivax   Asymptomatic malaria   Malaria   CD4 T cells   B cells  

摘要： The adaptive immunity against Plasmodium vivax is thought to be essential to limit parasite growth during asymptomatic malaria, preventing the occurrence of symptoms. However, the mechanisms governing clinical immunity during asymptomatic infections are not understood. Here, we investigated the adaptive cellular compartment in asymptomatic P. vivax-infected individuals (ASY) compared to symptomatic patients (SY) and healthy donors (CTL). Our integrative analysis revealed a TH1-biased immune signature with expanded populations of TH1 CD4+ T cells associated with the asymptomatic infection. In addition, there is an expanded population of proliferating atypical memory B cells that correlate with IgG levels against P. vivax antigens and parasitemia. The absence of systemic inflammation based on a comprehensive panel of soluble markers and the lower expression of some regulatory markers suggests a controlled inflammatory response that can be derived from an effective control of parasite growth. Our findings suggest that ASY maintain a pool of IFN-gamma-associated Th cell phenotypes that orchestrate the immune response, limiting parasitemia and preventing clinical malaria.

关键词： CAR-T cells   glioblastoma   IL-15   CCL19   cancer immunotherapy   EGFRv III  

摘要： Despite the remarkable success of CAR-T cell therapy in hematologic malignancies, its progress in solid tumors has been slow. Overcoming challenges such as the recruitment and infiltration of CAR-T cells into the tumor site and the survival issues in the harsh tumor microenvironment are crucial for successful application in solid tumors. In this study, CAR-T cells were engineered to secrete both IL-15 and CCL19, and their efficacy was evaluated in a human glioblastoma orthotopic xenograft model. The results reveal that 15 x 19 CAR-T cells exhibit superior proliferation, chemotaxis, and phenotypic characteristics compared to conventional CAR-T cells in vitro. In vivo, 15 x 19 CAR-T cells exhibit superior control over tumors compared to conventional counterparts. Mechanistically, the improved efficacy can be attributed, in part, to IL-15 and CCL19 enhancing T-cell infiltration at the tumor site and fortifying resistance to exhaustion within the tumor microenvironment. In conclusion, the incorporation of IL-15 and CCL19 into CAR-T cells emerges as a promising strategy to elevate the anti-tumor efficacy of CAR-T cell therapy, positioning 15 x 19 CAR-T cells as a potential breakthrough for enhancing the application of CAR-T therapy in solid tumors.

关键词： IL-34   sepsis   ALI   prognosis   risk stratification  

摘要： Objective: This study aimed to evaluate the potential of interleukin-34 (IL-34) as a novel biomarker for predicting mortality in sepsis patients, with a specific focus on those with sepsis-induced acute lung injury (ALI). Methods: This prospective cohort study enrolled 115 sepsis patients admitted to the intensive care unit (ICU). The patients were divided into survival and non-survival groups, as well as ALI and non-ALI subgroups. Serum levels of IL-34, in conjunction with other established biomarkers such as interleukin-6 (IL-6), C-reactive protein (CRP), and lactate, were measured and analyzed. Statistical analyses, including receiver operating characteristic (ROC) curves, Kaplan-Meier survival curves and Cox regression models, were used to determine the prognostic significance of IL-34. Results: Serum IL-34 levels were significantly elevated in sepsis patients compared to healthy controls, and they were also higher in non-survival group compared to survival group (p < 0.05). Additionally, IL-34 levels exhibited a positive correlation with sepsis severity, as indicated by APACHE II and SOFA scores. Kaplan-Meier survival curves and multivariate COX regression analysis revealed that IL-34 is an independent risk factor for death within 28 days of sepsis. The serum IL-34 level in the ALI group was significantly higher than that in the non-ALI group, particularly in severe cases (p < 0.05). However, the prognostic value of IL-34 in sepsis-induced ALI requires further investigation. Conclusion: IL-34 shows promise as an independent prognostic factor in sepsis patients and may enhance risk stratification, especially in those with sepsis-induced ALI.

关键词： COVID-19   liver cirrhosis   sepsis   mortality  

摘要： Background/Objectives: Interleukin-32 (IL-32) is a pro-inflammatory cytokine primarily produced by immune cells and involved in bacterial and viral infections. This study investigates whether plasma IL-32 is associated with sepsis severity and clinical outcomes. Methods: Plasma IL-32 levels were measured in 186 patients with systemic inflammatory response syndrome (SIRS), sepsis, or septic shock, as well as in 40 controls. The relationship between IL-32 levels and SARS-CoV-2 or bacterial infections, alongside underlying etiological conditions, was assessed. Results: Patients with liver cirrhosis exhibited elevated plasma IL-32 levels. After excluding these patients, IL-32 levels were lower in SIRS/sepsis patients compared to the controls. No significant differences in IL-32 levels were observed among SIRS, sepsis, and septic shock patients. Additionally, underlying conditions such as pancreatitis and cholangitis did not influence IL-32 levels. Patients with bloodstream bacterial infections, SARS-CoV-2 infections, or no documented infection had comparable IL-32 levels. Notably, higher IL-32 levels were associated with increased mortality. Conclusions: These findings suggest that a reduction in plasma IL-32 levels may be protective in SIRS/sepsis patients, as elevated levels are linked to poor survival outcomes.

摘要： Obesity arises from an imbalance between adipogenesis and adipocyte thermogenesis. Interleukin-27 (IL-27), a heterodimer cytokine, is known to promote thermogenesis in brown adipose tissue. However, its role in adipogenesis remains unclear. This study aims to investigate the effects of IL-27 on adipogenesis both in vitro and in vivo, and to elucidate the underlying mechanisms. In vitro, an adipogenic differentiation model of adipose-derived mesenchymal stem cells (ADSCs) demonstrate that IL-27 is non-cytotoxic to ADSCs and inhibits ADSCs adipogenic differentiation. In vivo, using a high-fat diet (HFD)-induced obese mouse model and a targeted adipose tissue-specific IL-27 overexpression adeno-associated viral (AAV) vector, we confirm that IL-27 suppresses adipogenesis, prevents weight gain, and improves glucose and lipid metabolic homeostasis in obese mice. Additionally, the inhibition of adipogenesis by IL-27 is mediated through HDAC6 activation of the TGF beta/Smad3 signaling pathway. Our study suggests that IL-27 is a potential therapeutic target for obesity and metabolic disorders.

关键词： HLA   IPF   ILDs   idiopathic pulmonary fibrosis   genetics   Sardinia  

摘要： Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease characterized by the disruption of the alveolar and interstitial architecture due to extracellular matrix deposition. Emerging evidence suggests that genetic susceptibility plays a crucial role in IPF development. This study explores the role of human leukocyte antigen (HLA) alleles and haplotypes in IPF susceptibility and progression within the genetically distinct Sardinian population. Genotypic data were analyzed for associations with disease onset and progression, focusing on allele and haplotype frequencies in patients exhibiting slow (S) or rapid (R) progression. While no significant differences in HLA allele frequencies were observed between IPF patients and controls, the HLA-DRB1*04:05 allele and the extended haplotype (HLA-A*30:02, B*18:01, C*05:01, DQA1*05:01, DQB1*02:01, DRB1*03:01) were associated with a slower disease progression and improved survival (log-rank = 0.032 and 0.01, respectively). At 36 months, carriers of these variants demonstrated significantly better pulmonary function, measured with single-breath carbon monoxide diffusing capacity (DLCO%p) (p = 0.005 and 0.02, respectively). Multivariate analysis confirmed these findings as being independent of confounding factors. These results highlight the impact of HLA alleles and haplotypes on IPF outcomes and underscore the potential of the Sardinian genetic landscape to illuminate immunological mechanisms, paving the way for predictive biomarkers and personalized therapies.

关键词： Chronic hepatitis B   Nucleos(t)ide analogs   Seroreversion   Functional cure  

摘要： Background/Aims It is unclear whether nucleos(t)ide analogs (NUCs) continuation provides clinical benefits following HBsAg seroclearance with pegylated interferon (PEG-IFN)-based therapy. This study aims to investigate the role of NUCs continuation in HBsAg seroreversion. Methods Patients who experienced serum HBsAg loss after PEG-IFN-based therapy were enrolled and followed up for 96 weeks. Propensity score matching (PSM) was performed using a 1:1 ratio to adjust for the associated factors. A multivariate logistic regression analysis was used to determine the factors associated with HBsAg seroreversion. Results In total, 220 patients with HBsAg seroclearance were divided into NUCs (n = 54) and non-NUCs (n = 166) consolidation therapy groups. At week 96, the HBsAg seroreversion (12/54 vs. 31/166, P = 0.709) and virological relapse (2/54 vs. 10/166, P = 0.759) rates were similar in the NUCs and non-NUCs groups. After PSM, HBsAg seroreversion (12/53 vs. 13/53;P = 1.000) and virological relapse (2/53 vs. 4/53;P = 0.674) rates were not significantly different between the two groups. Serum hepatitis B surface antibody titer (odds ratio, 0.388;95% confidence interval, 0.245-0.616;P < 0.001) was found to be associated with HBsAg seroreversion, while NUCs continuation was not related to HBsAg seroreversion. Conclusions NUCs continuation is not associated with a lower risk of HBsAg seroreversion in patients with serum HBsAg loss following PEG-IFN-based therapy.

关键词： 猪繁殖与呼吸综合征病毒   GP2蛋白   单克隆抗体   抗原表位  

摘要： 为制备猪繁殖与呼吸综合征病毒（PRRSV）GP2蛋白单克隆抗体，本研究使用大肠杆菌表达系统表达并纯化了GP2蛋白。用该蛋白免疫BALB/c小鼠，通过细胞融合技术筛选到了1株稳定分泌GP2蛋白单克隆抗体的杂交瘤细胞株（2G10C3）。IFA结果显示2G10C3能与表达GP2的Marc-145细胞系发生特异性反应。而且与NADC30、HuN4、CH-1a和VR2332等不同亚型的PRRS毒株也发生反应。通过表达重叠截短蛋白与单克隆抗体的反应性分析鉴定出2G10C3针对的表位为133EATLSRI139，是一个新发现的细胞表位。氨基酸比对分析发现，该表位在美洲型毒株中较为保守，蛋白质建模及可视化分析显示其以α螺旋的形式存在蛋白结构表面，可能是GP2蛋白的优势表位。本研究获得的单克隆抗体为PRRSV GP2蛋白的功能研究及诊断试剂盒的开发提供了良好的工具。

摘要： Patient stratification is crucial for improving immunotherapy effectiveness. Acha-Sagredo et al. identified an interferon (IFN)-high immunophenotype and CD74 overexpression as predictors for immunotherapy response in colorectal cancer (CRC). This signature, involving cytotoxic T cells and antigen-presenting macrophages, was found in both mismatch repair-deficient and-proficient CRCs. CD74 overexpression could serve as a biomarker, enabling personalized CRC treatment.

摘要： Patient stratification is crucial for improving immunotherapy effectiveness. Acha-Sagredo et al. identified an interferon (IFN)-high immunophenotype and CD74 overexpression as predictors for immunotherapy response in colorectal cancer (CRC). This signature, involving cytotoxic T cells and antigen-presenting macrophages, was found in both mismatch repair-deficient and -proficient CRCs. CD74 overexpression could serve as a biomarker, enabling personalized CRC treatment.