Potential roles of non-lymphocytic cells in the pathogenesis of IgG4-related disease

Studies have confirmed the involvement of a variety of lymphocyte subsets, including type 2 helper T lymphocytes (Th2) and IgG4+ B lymphocytes, in the pathogenesis of IgG4-related disease (IgG4-RD). Those lymphocytes contribute to the major pathogenetic features of IgG4-RD. However, they are not the only cellular components in the immunoinflammatory environment of this mysterious disease entity. Recent studies have suggested that various non-lymphocytic components, including macrophages and fibroblasts, may also play an important role in the pathogenetic process of IgG4-RD in terms of contributing to the chronic and complex progress of the disease. Therefore, the potential role of non-lymphocyte in the pathogenesis of IgG4-RD is worth discussing

Increased Expression of Ganglioside GM1 in Peripheral CD4+ T Cells Correlates Soluble Form of CD30 in Systemic Lupus Erythematosus Patients

Gangliosides GM1 is a good marker of membrane microdomains (lipid rafts) with important function in cellular activation processes. In this study we found that GM1 expression on CD4+ T cells and memory T cells (CD45RO/CD4) were dramatic increased after stimulation with phytohaemagglutinin in vitro. Next, we examined the GM1 expression on peripheral blood CD4+ T cells and CD8+ T cells from 44 patients with SLE and 28 healthy controls by flow cytometry. GM1 expression was further analyzed with serum soluble CD30 (sCD30), IL-10, TNF-alpha and clinical parameters. The mean fluorescence intensity of GM1 on CD4+ T cells from patients with SLE was significantly higher than those from healthy controls, but not on CD8+ T cells. Increased expression of GM1 was more marked on CD4+/CD45RO+ memory T cells from active SLE patients. Patients with SLE showed significantly elevated serum sCD30 and IL-10, but not TNF-alpha levels. In addition, we found that enhanced GM1 expression on CD4+ T cells from patients with SLE positively correlated with high serum levels of sCD30 and IgG as well as disease activity (SLEDAI scores). Our data suggested the potential role of aberrant lipid raft/GM1 on CD4+ T cells and sCD30 in the pathogenesis of SLE

The role of high mobility group box chromosomal protein 1 in rheumatoid arthritis

Abstract 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

Can Long-Term Regular Practice of Physical Exercises Including Taichi Improve Finger Tapping of Patients Presenting With Mild Cognitive Impairment?

Background: Mild cognitive impairment (MCI) is a brain disease with both anatomical and functional alterations. There is clear evidence that individuals that are diagnosed with MCI have a high risk to develop dementia in the next 2–5 years compared to an age-matched population with a non-MCI diagnosis. The present study aimed to investigate whether the finger tapping frequency of patients with MCI was different from that of healthy individuals without MCI, and whether Tai Chi, a traditional Chinese movement discipline, could improve the finger tapping frequency of MCI patients.Methods: The study population consisted of subjects of ≥50 years of age. Group one included 40 subjects without exercise habits from communities of Yangpu District in Shanghai, and group two included 60 subjects from a Tai Chi class in Shanghai Elderly University of Huangpu District. The Montreal Cognitive Assessment (MoCA) and a finger tapping test were conducted to assess the finger tapping frequency of all subjects.Results: The MoCA score of MCI subjects was significantly lower compared to subjects without MCI (P < 0.01), and was not influenced by age, weight, or height. The finger tapping frequency of MCI subjects’ left hands was significantly lower compared to that of healthy subjects without MCI (P < 0.01), and a similar trend was observed for the subjects’ right hand. The MoCA score of MCI subjects in the Tai Chi class was significantly lower than that of healthy subjects without MCI (P < 0.01), which was not influenced by age, weight or height. The finger tapping frequency of MCI subjects’ right hands was lower compared to that of healthy subjects in the Tai Chi class without MCI (P < 0.05), but no significant difference regarding the finger tapping frequency of the left hand was observed.Conclusion: These findings suggested that finger tapping frequency of MCI subjects was significantly lower compared to normal subjects without MCI, and long-term Tai Chi exercise could reduce this significant difference. Moreover, there was no significant difference between groups for the subjects’ non-dominant (left) hand

GLP-1 receptor agonist as a modulator of innate immunity

Glucagon-like peptide-1 (GLP-1) is a 30-amino acid hormone secreted by L cells in the distal ileum, colon, and pancreatic α cells, which participates in blood sugar regulation by promoting insulin release, reducing glucagon levels, delaying gastric emptying, increasing satiety, and reducing appetite. GLP-1 specifically binds to the glucagon-like peptide-1 receptor (GLP-1R) in the body, directly stimulating the secretion of insulin by pancreatic β-cells, promoting proliferation and differentiation, and inhibiting cell apoptosis, thereby exerting a glycemic lowering effect. The glycemic regulating effect of GLP-1 and its analogues has been well studied in human and murine models in the circumstance of many diseases. Recent studies found that GLP-1 is able to modulate innate immune response in a number of inflammatory diseases. In the present review, we summarize the research progression of GLP-1 and its analogues in immunomodulation and related signal pathways

Breast cancer survival analysis with molecular subtypes : an initial step

As a predominant threat to women's health world-wide, breast cancer has become increasingly important in on-cology research. The discovery of molecular subtypes of breast cancer has led to more subtype oriented treatment and prognosis prediction. Effective prognosis models help to estimate the recurrence as well as the quality and duration of survival, leading to more personalized treatments. However, most traditional prognostic models either ignore molecular subtypes or only make limited use of them. The roles of molecular subtypes in the development and treatment of breast cancer have not been fully revealed. With the over 1200 cases collected by Sir Run Run Shaw Hospital of Zhejiang University in the past two decades, we aim to improve understanding of molecular subtypes and their impacts on the prognosis via data analysis in the long run. As the initial stage, this short paper presents our preliminary work of logistic regression experiments with the data. Though molecular subtypes have not been included the tentative model, they are to be explored further in following stages

Toxicity Study of VOSO4 Using NMR-based Metabonomics

NMR-Based metabonomics combined with clinical biochemical analysis and histopathological examination was applied to investigate the toxicity effects of vanadyl sulfate with insulin-like activity in male Wistar rats. Male Wistar rats were administrated with VOSO4 at doses of 15 and 45 mg/kg body weight by intragastric administration for 16 d. Urine and serum samples were collected and analyzed by H-1 NMR experiment. Multivariate analyses were employed to identify the characteristic metabolites for the toxicity effects of vanadyl sulfate. Then the metabolic networks of these characteristic metabolites were built up using TICL (a web Tool for automatic Interpretation of Compound List). The relationship between the characteristic metabolites and the main matebolic pathways perturbed were analyzed and discussed. The differences of metabolic profiles were examined among high-dose (45 mg/kg), low-dose (15 mg/kg) of VOSO4 and control groups. Compared to the control group, increased levels of lactate, creatinine and taurine in serum and increased excretion of trymethylamine-N-2-oxide, creatinine, taurine and glycine in urine were found in both high- and low-dose groups which showed an obvious dose-dependent relationship. On the other hand, the concentration of acetate and succinate were decreased in both serum and urine samples of dosed groups. These results indicate that VOSO4 have disturbed the carbohydrate metabolism, lipid metabolism and gut microflora and the high-dosage of VOSO4 may cause liver and kidney injury

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List of 290 FLNC reads showing cross-contig mapping. (XLS 40 kb

Elevated plasma levels of pigment epithelium-derived factor correlated with inflammation and lung function in COPD patients

Rationale: Pigment epithelium-derived factor (PEDF) is a 50 kD small secreting glycoprotein that participates in multiple physiological and pathological processes. Recent studies have reported that PEDF plays an important role in inflammatory responses in several diseases. However, the role of PEDF in the pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear. Objective: The aim of the present study is to explore the potential relationship between PEDF and COPD. Methods: We used differential proteomics – stable isotope labeling with amino acids in cell culture – to investigate protein expression profile changes in cigarette smoke extract-treated pulmonary cells and found that the neurotrophic and antiangiogenic protein PEDF was abnormally expressed. Furthermore, Western blotting was used to detect the expression of PEDF in the lung tissue of rats that were exposed to cigarette smoke. Eighty subjects between the ages of 40–90 years, including 20 healthy nonsmokers, ten smoking volunteers, and 50 COPD patients, were recruited from September 2012 until August 2013 in Sichuan Province, People’s Republic of China. We measured the plasma PEDF concentration and classic proinflammatory cytokines by multiplex enzyme-linked immunosorbent assay. In addition, we performed a spirometry examination to diagnose COPD patients and we also analyzed the correlation between PEDF and lung function. Results: First, we found that the expression of PEDF in cigarette smoke extract-treated cells increased 16.2-fold when compared with the control group. Next, we confirmed that 4 weeks’ exposure to cigarette smoke can upregulate PEDF levels in rat lung tissues. We also discovered that plasma PEDF in COPD patients was significantly increased when compared with either healthy nonsmoking or smoking subjects. Furthermore, circulating PEDF was correlated with inflammatory cytokine and blood neutrophil numbers, but it was reversely associated with a decline in forced expiratory volume in 1 second percent predicted. Conclusion: Our findings provide a novel link between PEDF and COPD. Elevated PEDF levels may be involved in promoting the development of COPD by performing proinflamma-tory functions

IL-2 Inhibition of Th17 Generation Rather Than Induction of Treg Cells Is Impaired in Primary Sjögren’s Syndrome Patients

ObjectiveTo investigate the role of IL-2 in the balance of Th17 and Tregs and elucidate the underlying mechanisms of enhanced Th17 differentiation in primary Sjögren’s syndrome (pSS) patients.MethodsThis study involved 31 pSS patients, 7 Sicca patients, and 31 healthy subjects. Th17 and Treg cells were determined by flow cytometry, and IL-17A was detected by immunohistochemistry. IL-2 and IL-6 levels were assessed by ELISA and qPCR. p-STAT5 and p-STAT3 in salivary glands (SGs) were evaluated by immunohistochemistry and flow cytometry. The binding of STAT5 and STAT3 to the Il17a gene locus was measured by chromatin immunoprecipitation.ResultsWe found that the percentage of Th17 cells was increased in the periphery and SG of pSS patients when compared with healthy subjects, but the Treg cells was unchanged. Meanwhile, the IL-2 level was reduced, and the IL-6 and IL-17A level was increased in the plasma of pSS patients. The ratio of IL-2 and IL-6 level was also decreased and IL-2 level was negatively correlated with the level of IL-17A. The expression of Il6 and Il17a mRNA was significantly increased, whereas Foxp3, Tgfb1, Tnfa, and Ifng mRNA were comparable. Furthermore, the level of STAT5 phosphorylation (p-STAT5) was reduced and p-STAT3 was enhanced in the SGs and in peripheral CD4+ T cells of pSS patients. In vitro IL-2 treatment-induced STAT5 competed with STAT3 binding in human Il17a locus, leading to decreased Th17 differentiation, which was associated with the reduced transcription activation marker H3K4me3.ConclusionOur findings demonstrated a Treg-independent upregulation of Th17 generation in pSS, which is likely due to a lack of IL-2-mediated suppression of Th17 differentiation. This study identified a novel mechanism of IL-2-mediated immune suppression in pSS