Search

Our group have demonstrated that splenic B cells contributed to the CD4+CD25− naive T cells conversion into CD4+CD25+Foxp3− regulatory T cells without adding appended cytokines, named Treg‐of‐B cells which were potent suppressors of adaptive immunity. We like to investigate whether Treg‐of‐B cells could promote alternatively activated macrophage (M2 macrophages) polarization and alleviate inflammatory disease, psoriasis. In this study, we co‐cultured the bone marrow‐derived macrophages (BMDMs) with Treg‐of‐B cells under LPS/IFN‐γ stimulation and analyzed the M2‐associated gene and protein using qPCR, western blotting, and immunofluorescence staining. We also examined the therapeutic effect of Treg‐of‐B cell‐induced M2 macrophage for skin inflammation using imiquimod (IMQ)‐induced psoriatic mouse model. Our results showed that BMDMs co‐cultured with Treg‐of‐B cells upregulated typical M2‐associated molecules, including Arg‐1, IL‐10, Pdcd1lg2, MGL‐1, IL‐4, YM1/2 and CD206. In an inflammatory environment, TNF‐α and IL‐6 production by macrophages co‐cultured with Treg‐of‐B cells was decreased significantly. The molecular mechanism revealed that Treg‐of‐B cells promoted M2 macrophage polarization via STAT6 activation in a cell contact‐dependent manner. Moreover, the treatment with Treg‐of‐B cell‐induced M2 macrophages attenuated the clinical manifestations of psoriasis, such as scaling, erythema and thickening in the IMQ‐induced psoriatic mouse model. T cell activation in draining lymph nodes was decreased in the Treg‐of‐B cell‐induced M2 macrophage group after IMQ application. In conclusion, our findings suggested that Foxp3− Treg‐of‐B cells could induce alternatively activated M2 macrophages through STAT6 activation, providing a cell‐based therapeutic strategy for psoriasis. [ABSTRACT FROM AUTHOR]

A novel cardiovascular stress biomarker known as galectin-3 might be useful for anticipating adverse cardiovascular outcomes. The objective of the current investigation was to assess the association between serum galectin-3 levels and aortic stiffness (AS) in 196 patients on peritoneal dialysis. An enzyme-linked immunosorbent examination and a cuff-based volumetric displacement were employed to determine the levels of serum galectin-3 and the carotid-femoral pulse wave velocity (cfPWV), respectively. The AS group had 48 patients in total (24.5%) with cfPWV greater than 10 m/s. The AS group, when compared with the group without AS, had a significantly higher prevalence of diabetes mellitus and hypertension in addition to greater fasting glucose levels, waist circumference, systolic blood pressure, and serum galectin-3 levels. Multivariate logistic and linear regression analysis demonstrated that serum glactin-3 levels, in addition to gender and age, were significantly and independently associated with cfPWV and AS. Serum galectin-3 levels were linked with AS, according to a receiver operating characteristic curve analysis, with an area under the curve of 0.648 (95% confidence interval, 0.576–0.714; p = 0.0018). In summary, there was a significant correlation between serum galectin-3 levels and cfPWV in patients undergoing peritoneal dialysis therapy for end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Aims and objectives: To assess the concurrent validity between logbooks and a single‐item rehabilitation adherence measurement for patients with stroke. Agreement between caregivers and patients and between caregivers and physical therapists regarding a single‐item measurement was investigated, and its predictive validity was explored. Background: Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients. Design: Prospective longitudinal study. Methods: Seventy‐five patients with stroke were recruited, measured four times and followed for 6 months. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to ensure comprehensive reporting. Adherence was documented in logbooks, and single‐item measurements were compared. Predictive validity was explored by assessing associations between adherence levels, self‐care ability and health‐related quality of life. The Spearman's correlation coefficients, weighted kappa, and generalised estimating equations statistics were used to explore the concurrent validity, measurement agreement, and predictive validity, respectively. Results: Logbook records had a fair correlation (rs =.23, p =.04) with the single‐item rehabilitation adherence measurements. There was moderate agreement (kappa = 0.42, p <.001) between caregiver and patient assessments and fair agreement (kappa = 0.29, p =.017) between caregiver and physical therapist assessments of patients' rehabilitation adherence levels. Perfect rehabilitation adherence, based on the logbook and single‐item measurements, predicted better scores for self‐care ability and quality of life than imperfect rehabilitation adherence during 6 months after inclusion. Conclusions: There was fair concurrent validity between logbooks and single‐item rehabilitation adherence measurements and moderate and fair adherence measure agreement between caregivers and patients and caregivers and physical therapists, respectively. Logbooks and single‐item rehabilitation adherence measurements had adequate predictive validity. Relevance to clinical practice: Single‐item rehabilitation adherence measurement is a workable and straightforward method to assess stroke patients' rehabilitation adherence in busy clinical care settings. Caregivers can represent stroke patients regarding their reported rehabilitation adherence. Patient or public contribution: Patients were diagnosed with stroke in the study hospital. Rehabilitation physicians transferred patients to a research nurse who then screened them for the inclusion criteria and invited them and their family caregivers to participate in this study if they met the requirements. We also recruited seven physical therapists responsible for the physical therapy of the study participants. After participants signed informed consent, the research nurse encouraged participants to respond to research questions face to face, including rehabilitation adherence data, daily physical function, and quality of life. Each participant was measured four times at baseline and at 1, 3, and 6 months after inclusion in this study. Physical therapists had to score their patients' rehabilitation adherence levels before discharge. Trial registration details: Not applicable. [ABSTRACT FROM AUTHOR]

Vascular calcification, characterized by calcium deposition in the intimal and medial layers of the arterial wall, is frequently encountered in patients with chronic kidney disease (CKD) and leads to an enhanced risk of adverse cardiovascular (CV) outcomes. However, the underlying complex pathophysiology remains incompletely understood. Recently, Vitamin K supplementation aimed at correcting Vitamin K deficiency highly prevalent in CKD holds great promise to mitigate the progression of vascular calcification. This article discusses the functional Vitamin K status in CKD, the pathophysiology linking Vitamin K deficiency and vascular calcification, and reviews current literature from animal models, observational studies, and clinical trials across the different spectrum of CKD. While favorable effects of Vitamin K on vascular calcification and CV outcomes are suggested in animal and observational studies, most recently published clinical trials investigating the effects of Vitamin K on vascular health failed to support the beneficial role of Vitamin K supplementation, despite improving the functional status of Vitamin K. We address the potential reasons for these discrepancies and provide further perspective on Vitamin K research in CKD. [ABSTRACT FROM AUTHOR]

Introduction The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) was originally identified from Arabidopsis mutants that mimic light-induced seedling development when grown in the dark (1). The mammalian COP9 contains 8 [...], The mammalian constitutive photomorphogenesis 9 (COP9) signalosome (CSN), a protein complex involved in embryonic development, is implicated in cell cycle regulation and the DNA damage response. Its role in tumor development, however, remains unclear. Here, we have shown that the COP9 subunit 6 (CSN6) gene is amplified in human breast cancer specimens, and the CSN6 protein is upregulated in human breast and thyroid tumors. CSN6 expression positively correlated with expression of murine double minute 2 (MDM2), a potent negative regulator of the p53 tumor suppressor. Expression of CSN6 appeared to prevent MDM2 autoubiquitination at lysine 364, resulting in stabilization of MDM2 and degradation of p53. Mice in which Csn6 was deleted died early in embryogenesis (E7.5). Embryos lacking both Csn6 and p53 survived to later in embryonic development (E10.5), which suggests that loss of p53 could partially rescue the effect of loss of Csn6. Mice heterozygous for Csn6 were sensitized to γ-irradiation--induced, p53-dependent apoptosis in both the thymus and the developing CNS. These mice were also less susceptible than wild-type mice to γ-irradiation--induced tumorigenesis. These results suggest that loss of CSN6 enhances p53-mediated tumor suppression in vivo and that CSN6 plays an important role in regulating DNA damage--associated apoptosis and tumorigenesis through control of the MDM2-p53 signaling pathway.