Association between vitamin d deficiencies in sarcoidosis with disease activity, course of disease and stages of lung involvements

Background: Despite negative association between 25-hydroxy vitamin D and incidence of many chronic respiratory diseases, this feature was not well studied in sarcoidosis. Current study investigated the association between 25-hydroxy vitamin D deficiency with sarcoidosis chronicity, disease activity, extra-pulmonary skin manifestations, urine calcium level and pulmonary function status in Iranian sarcoidosis patients. Results of this study along with future studies, will supply more effective programs for sarcoidosis treatment. Methods: Eighty sarcoidosis patients in two groups of insufficient serum level and sufficient serum level of 25-hydroxy vitamin D were studied. Course of sarcoidosis was defined as acute and chronic sarcoidosis. Pulmonary function test (PFT) was assessed by spirometry. Skin involvements were defined as biopsy proven skin sarcoidosis. 24-hour urine calcium level was used to specify the disease activity. Stages of lung involvements were obtained by CT-scan and chest X-ray. The statistical analyses were evaluated using Statistical Package for the Social Sciences. Results: A significant negative correlation was obtained between vitamin D deficiency in sarcoidosis patients and disease chronic course and stages two to four of lung involvements. Considering other parameters of the disease and vitamin D deficiency, no significant correlation was detected. Conclusions: In conclusion, results of the current study implies in the role of vitamin 25(OH)D deficiencies in predicting the course of chronic sarcoidosis. Furthermore, it was concluded that vitamin 25(OH)D deficiency can direct pulmonary sarcoidosis toward stage 2–4 of lung involvements

Effect of passive exposure to cigarette smoke on blood pressure in children and adolescents: A meta-analysis of epidemiologic studies

Background: Hypertension is an emerging disease in children and adolescents resulting in future morbidities. Cigarette smoking is one of the most studied contributing factors in this regard; however, there are contradictory results among different studies. Therefore, the present meta-analysis tends to assess the relationship between passive exposure to cigarette smoke and blood pressure in children and adolescents. Method: Medline, Embase, Scopus, EBSCO, and Web of Sciences were systematically reviewed for observational studies up to May, 2017, in which the relationship between cigarette smoking and hypertension were assessed in children and adolescents. The meta-analysis was performed with a fixed effect or random effects model according to the heterogeneity. Results: Twenty-nine studies were included in present meta-analysis incorporating 192,067 children and adolescents. Active smoking (pooled OR = 0.92; 95 CI: 0.79 to 1.05) or passive exposure to cigarette smoke (pooled OR = 1.01; 95 CI: 0.93 to 1.10) were not associated with developing hypertension in the study population. Despite the fact that active cigarette smoking did not significantly affect absolute level of systolic and diastolic blood pressure, it was shown that passive exposure to cigarette smoke leads to a significant increase in absolute level of systolic blood pressure (pooled coefficient = 0.26; 95 CI: 0.12 to 0.39). Conclusion: Both active and passive cigarette smoking were not associated with developing hypertension in children and adolescents. However, passive cigarette smoke was associated with higher level of systolic blood pressure in children and adolescents. © 2019 The Author(s)

Effect of mesenchymal stem cell-derived exosomes on the induction of mouse tolerogenic dendritic cells

Dendritic cells (DCs) orchestrate innate inflammatory responses and adaptive immunity through T‐cell activation via direct cell–cell interactions and/or cytokine production. Tolerogenic DCs (tolDCs) help maintain immunological tolerance through the induction of T‐cell unresponsiveness or apoptosis, and generation of regulatory T cells. Mesenchymal stromal cells (MSCs) are adult multipotent cells located within the stroma of bone marrow (BM), but they can be isolated from virtually all organs. Extracellular vesicles and exosomes are released from inflammatory cells and act as messengers enabling communication between cells. To investigate the effects of MSC‐derived exosomes on the induction of mouse tolDCs, murine adipose‐derived MSCs were isolated from C57BL/6 mice and exosomes isolated by ExoQuick‐TC kits. BM‐derived DCs (BMDCs) were prepared and cocultured with MSCs‐derived exosomes (100 μg/ml) for 72 hr. Mature BMDCs were derived by adding lipopolysaccharide (LPS; 0.1μg/ml) at Day 8 for 24 hr. The study groups were divided into (a) immature DC (iDC, Ctrl), (b) iDC + exosome (Exo), (c) iDC + LPS (LPS), and (d) iDC + exosome + LPS (EXO + LPS). Expression of CD11c, CD83, CD86, CD40, and MHCII on DCs was analyzed at Day 9. DC proliferation was assessed by coculture with carboxyfluorescein succinimidyl ester‐labeled BALB/C‐derived splenocytes p. Interleukin‐6 (IL‐6), IL‐10, and transforming growth factor‐β (TGF‐β) release were measured by enzyme‐linked immunosorbent assay. MSC‐derived exosomes decrease DC surface marker expression in cells treated with LPS, compared with control cells ( ≤ .05). MSC‐derived exosomes decrease IL‐6 release but augment IL‐10 and TGF‐β release (p ≤ .05). Lymphocyte proliferation was decreased (p ≤ .05) in the presence of DCs treated with MSC‐derived exosomes. CMSC‐derived exosomes suppress the maturation of BMDCs, suggesting that they may be important modulators of DC‐induced immune responses

The role of pattern recognition receptors in lung sarcoidosis

Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs). Due to the similar clinical and histopathological picture of sarcoidosis and tuberculosis, Mycobacterium tuberculosis antigens such early secreted antigen (ESAT-6), heat shock proteins (Mtb-HSP), catalase-peroxidase (katG) enzyme and superoxide dismutase A peptide (sodA) have been often considered as factors in the etiopathogenesis of sarcoidosis. Potential non-TB-associated PAMPs include lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria, peptidoglycan, lipoteichoic acid, bacterial DNA, viral DNA/RNA, chitin, flagellin, leucine-rich repeats (LRR), mannans in the yeast cell wall, and microbial HSPs. Furthermore, exogenous non-organic antigens such as metals, silica, pigments with/without aluminum in tattoos, pesticides, and pollen have been evoked as potential causes of sarcoidosis. Exposure of the airways to diverse infectious and non-infectious agents may be important in the pathogenesis of sarcoidosis. The current review provides and update on the role of PPRs and DAMPs in the pathogenesis of sarcoidsis

CD4:CD8 ratio: A valuable diagnostic parameter for pulmonary sarcoidosis

Sarcoidosis is a multi-organ disease and is characterized by sarcoidal noncaseating granuloma comprised of T-helper/inducer (CD4+) lymphocytes and scant cytotoxic (CD8+) T-lymphocytes. CD4+:CD8+ T-cell elevated ratio is a characteristic diagnostic parameter for sarcoidosis. This is the first report from Iran evaluating the CD4:CD8 ratio capability in differentiating pulmonary sarcoidosis from other interstitial lung diseases (ILDs) on a large cohort. Fifty pulmonary sarcoidosis patients and 50 non-sarcoidosis interstitial lung diseases (nsILDs) patients were included in the current study. Bronchoalveolar lavage (BAL) was performed using flexible fiberoptic bronchoscopy and flow cytometer. Non-sarcoidosis group was established by 50 components that were classified into eight subgroups. Fifty-two percent of sarcoidosis patients and 62% of non-sarcoidosis interstitial lung disease patients had normal spirometric results. The CD4/CD8 ratio was significantly higher in sarcoidosis than in non-sarcoidosis interstitial lung diseases (p 3.5 in 33.3%, 2.5-3.5 in 7.1%, 1.5-2.5 in 20.2% and < 1.5 in 39.4% of the entire study population. The best cut off point was 1.1 with the sensitivity of 92% and specificity of 80% for distinguishing sarcoidosis from other interstitial lung diseases. Performing bronchoalveolar lavage as the safe and rapid first step confirms the diagnosis of sarcoidosis in 92% of cases (current study sensitivity). Hence, performing an invasive procedure was required in a few patients only. Bronchoalveolar lavage flow cytometry in the assessment of clinical and radiological findings supplies an appropriate diagnostic adjunct for discriminating sarcoidosis from non-sarcoidosis interstitial lung diseases

Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR2 and TNF-α expression in mice

Background : Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural - based treatments. Toll - like receptors (TLRs) play an important role in evoking innate immunity agains t cancer cells. Zymosan, a known TLR - 2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae - derived z ymosan - modulated skin melanoma progression by regulation of TLR - 2 expression in peritoneal macrophages and serum TNF - level. Methods: Male C57BL/6 mice were divided into four groups: i) zymosan - treated (Z), ii) Melanoma - bearing mice (M), iii) Melanoma - bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10 g) daily for 4 consecutive days. Mice were CO 2 - euthanized and serum TNF - α level, TLR - 2 expression in peritoneal macrophages and tumor gro wth measured. Splenocytes were treated ex - vivo with zymosan to determine viability and proliferation. Results: Tumor weight significantly decreased following therapeutic dosing with zymosan ( P <0.05). This was associated with zymosan - induced upregulation of TLR - 2 and TNF - mRNA in peritoneal mac rophages and enhanced serum TNF - levels ( P <0.05). Splenocyte number and viability were increased in a concentration - dependent manner by zymosan. Conclusion s : Our study suggests that zymosan - induced upregulation of TL R - 2 and TNF - gene expression and of TNF - release ; together with increased level s of lymphocyte proliferation may play a role in the inhibition of melanoma progression

Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice

Background: Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural-based treatments. Toll-like receptors (TLRs) play an important role in evoking innate immunity against cancer cells. Zymosan, a known TLR-2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae-derived zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α level. Methods: Male C57BL/6 mice were divided into four groups: i) zymosan-treated (Z), ii) Melanoma-bearing mice (M), iii) Melanoma-bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10 μg) daily for 4 consecutive days. Mice were CO2-euthanized and serum TNF-α level, TLR-2 and TLR-4 expression in peritoneal macrophages and tumor growth measured. Splenocytes were treated ex-vivo with zymosan to determine viability and proliferation. Results: Tumor weight significantly decreased following therapeutic dosing with zymosan (P < 0.05). This was associated with zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α mRNA in peritoneal macrophages and enhanced serum TNF-α levels (P < 0.05). Splenocyte number and viability were increased in a concentration-dependent manner by zymosan. Conclusions: Our study suggests that zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α gene expression and of TNF-α release; together with increased level of lymphocyte proliferation may play a role in the inhibition of melanoma progression

Serum Exosomal miRNAs Are Associated with Active Pulmonary Tuberculosis

Introduction. Tuberculosis (TB) remains a major threat to human health. Due to the limited accuracy of the current TB diagnostic tests, it is critical to determine novel biomarkers for this disease. Circulating exosomes have been used as diagnostic biomarkers in various diseases. Objective of the Study. In this pilot study, we examined the expression of miRNAs as biomarker candidates for the diagnosis of TB infection. Methods. Serum-derived exosomes were isolated from TB patients and matched control subjects. The expression of miR-484, miR-425, and miR-96 was examined by RT-PCR methods. Results. The expression of miR-484, miR-425, and miR-96 were significantly increased in serum of TB patients which correlated with the TB infection level. A receiver operating characteristic (ROC) curve analysis showed the diagnostic potency of each individual serum exosomal miRNA with an area under the curve AUC=0.72 for miR-484 (p<0.05), 0.66 for miR-425 (p<0.05), and 0.62 for miR-96 (p<0.05). Conclusion. These results demonstrate that exosomal miRNAs have diagnostic potential in active tuberculosis. The diagnostic power may be improved when combined with conventional diagnostic markers