Search

Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-33, a member of IL-1 cytokine family, is produced by various immune cells and acts as an alarm to alert the immune system after epithelial or endothelial cell damage during cell necrosis, infection, stress, and trauma. The biological functions of IL-33 largely depend on its ligation to the corresponding receptor, suppression of tumorigenicity 2 (ST2). The pathogenic roles of this cytokine have been implicated in several disorders, including allergic disease, cardiovascular disease, autoimmune disease, infectious disease, and cancers. However, alerted levels of IL-33 may result in either disease amelioration or progression. Genetic variations of IL33 gene may confer protective or susceptibility risk in the onset of autoimmune diseases. The purpose of this review is to discuss the involvement of IL-33 and ST2 in the pathogenesis of a variety of autoimmune disorders, such as autoimmune rheumatic, neurodegenerative, and endocrine diseases. [ABSTRACT FROM AUTHOR]

Cancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management. This study is focused on the role of CCL19 in cancer development. It has been shown that CCL19 exerts conflicting functions in the tumor microenvironment. Using CCL19-based therapies might introduce novel approaches in cancer treatment. [ABSTRACT FROM AUTHOR]

The immune checkpoint molecules are involved in the regulation of T cells in order to prevent them from attacking to sell tissues and play a role in the immune response homeostasis. Application of the immune checkpoint inhibitors (ICIs) has provided a promising therapeutic approach in pathologies where the immune system is suppressed. The extended utilization of ICIs in several cancers has caused immune-related side effects in the cardiovascular system like cardiomyopathy and myocarditis. Cardiac toxicity, one of the main side effects of the ICIs-based therapeutic approach, has less been concerned; however, during the last years, many cases of fatal heart failure and myocarditis have been reported in patients treated with ICIs. In this review article, we attempted to discuss the cardiac adverse effects of inhibiting different immune checkpoint molecules. [ABSTRACT FROM AUTHOR]

Cytokines are considered vital mediators of the immune system. Down‐ or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL‐26 is referred to as an identified member of the IL‐10 family and IL‐20 subfamily. Due to having a unique cationic structure, IL‐26 exerts diverse functions in several diseases. Since IL‐26 is mainly secreted from Th17, it is primarily considered a pro‐inflammatory cytokine. Upon binding to its receptor complex (IL‐10R1/IL‐20R2), IL‐26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL‐26 induces IL‐22‐producing cells, which consequently decrease cytotoxic T‐cell functions and promote tumour growth through activating anti‐apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease‐promoting mediator and might be considered a biomarker for disease prognosis. Although IL‐26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL‐26 might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL‐26 has been confirmed in other conditions, including graft‐versus‐host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL‐26 function should be elucidated. Collectively, it is hoped that the examination of IL‐26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases. [ABSTRACT FROM AUTHOR]

• CXCL14 leads to infiltration of immune cells and maturation of dendritic cells. • CXCL14 exerts a conflicting role in cancer. • Analysis of CXCL14 dysregulation might be helpful for cancer diagnosis. Cancer is a leading cause of death worldwide and imposes a substantial financial burden. Therefore, it is essential to develop cost-effective approaches to inhibit tumor growth and development. The imbalance of cytokines and chemokines play an important role among different mechanisms involved in cancer development. One of the strongly conserved chemokines that is constitutively expressed in skin epithelia is the chemokine CXCL14. As a member of the CXC subfamily of chemokines, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Moreover, dysregulation of CXCL14 in several cancers has been identified by several studies. Depending on the type or origin of the tumor and components of the tumor microenvironment, CXCL14 plays a conflicting role in cancer. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression. Hence, this review will elucidate what is known on the mechanisms of CXCL14 and its therapeutic approaches in tumor treatment. CXCL14 is a promising approach for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

The therapeutic and immunomodulatory potential of mesenchymal stem cells (MSCs) in rheumatoid arthritis (RA) has attracted considerable scientific attention in recent decades. This study aimed to evaluate the expression of genes encoding interleukin (IL)4 and IL10, as well as interferon-gamma (IFNG) and transforming growth factor beta (TGFB1) in refractory RA patients following intravenous injection of autologous bone marrow-derived MSCs (BM-MSCs). This study was registered in Iranian Registry of Clinical Trials (IRCT) (2015102824760N1) and ClinicalTrials.gov (identifier: NCT03333681). Blood samples were taken from 13 patients before and 1 and 6 months after the MSC injection to evaluate the clinical manifestations, paraclinical factors, and expression of IL4, IL10, IFNG, and TGFB1 genes employing the SYBR Green real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique. There was a significant increase in the expression of TGFB1 at 1 and 6 months after the MSC injection compared to that in the baseline, while the expression of IL4 and IL10 did not change significantly. On the other hand, the expression of IFNG increased significantly after 1 month but decreased significantly at 6 months compared to 1 month after the intervention. Nevertheless, it showed no significant decrease compared to the baseline. A significant decrease was observed for the expression of IFNG 6 months after the injection compared to that after 1 month, which was in concordance with the rise in the expression of the TGFB1 gene. A significant change in the gene expression of TGFB1 and IFNG in our study was consistent with the amelioration of clinical manifestations, suggesting a mechanism of action for MSCs in the treatment of RA.

Background: inflammatory chemokines such as CCL2 and CCL5 are involved in the progress of osteoarthritis. Crocin with antioxidant and anti-inflammatory properties can reduce the symptoms of osteoarthritis (OA). This study was performed investigate the effect of Krocina™, on the gene expressions and plasma levels of CCL2 and CCL5 in OA patients., Methods: The study included 35 patients that were randomized in the Krocina™ and placebo groups. The intervention was Krocina™ 15mg daily for four months. Clinical and paraclinical parameters were measured. CCL2 and CCL5 genes expression and plasma levels were determined using the SYBR Green Real-Time RT-PCR and Enzyme-linked Immunosorbent Assay (ELISA) techniques., Results: The C-reactive protein (CRP) value in the Krocina™ group and the visual analogue scale (VAS) value in the Krocina™ and placebo groups decreased significantly after the intervention. The gene expression of CCL2 in the Krocina™ and placebo groups decreased significantly. On the contrary, the gene expression of CCL5 in the Krocina™ and placebo groups increased significantly. Moreover, the plasma levels of CCL2 in the Krocina™ and placebo groups decreased meaningfully. There was no difference regarding the plasma levels of CCL5 within the Krocina™ and placebo groups before and after the intervention in either of the groups., Conclusion: Administration of Krocina™ reduced the clinical signs of inflammation and CRP and VAS value. Also, Krocina™ significantly decreased the plasma levels and gene expression of CCL2 in osteoarthritis patients.

The synovial- lining cells have been involved with rheumatoid arthritis (RA) through the secretion of various cytokines and chemokines. Increased levels of these cytokines and chemokines are seen first in the synovial and subsequently in the bloodstream of RA patients. The synovial and circulating levels of CXCL8, CXCL12, and CXCL13 are higher in the RA patients than in the healthy subjects, causing migration of immune cells to the joints, which is associated with increased joint destruction. We aimed to evaluate the effects of autologous mesenchymal stem cells intravenous administration on plasma levels of CXCL8, CXCL12 and CXCL13 at 1, 6, and 12 month follow-up periods in refractory RA patients. 13 patients with refractory RA received autologous mesenchymal stem cells (MSCs). The ELISA technique was used to evaluate the plasma level of these chemokines. CXCL8 levels were significantly decreased at month 6 after MSCs transplantation in comparison with pre-injection level, and the concentration of this chemokine was significantly increased at month 12 in comparison with the month 6 after injection (P <0.05). The levels of CXCL12 and CXCL13 were insignificantly decreased at months 1 and 6 after the MSCs transplantation. The interaction of MSCs after migration to the inflamed joints with CXCL8-producing cells could be one but not the only possible mechanism that reduces its production in the joints and subsequently in the plasma of RA patients. CXCL8 reduction as a consequence of MSCs application returned to pre-injection levels after 12 months. Therefore, increasing the dose of MSCs and replication of injections may maintain the potential anti-inflammatory effects of MSCs on the production of CXCL8 as an inflammatory mediator in patients with refractory RA.

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by altered bowel habits and abdominal pain in the absence of a recognizable structural anomaly. The pathogenesis of IBS has been associated with inflammation and the expression of pro-inflammatory chemokines, such as CCL2 and CCL16. Our study aimed to investigate the relationship between the serum levels of CCL2 and CCL16 and IBS. Additionally, we examined how serum levels of these chemokines relate to IBS subtypes., Methods: Patients with IBS diagnosed according to the Rome III criteria participated in this study (n= 96). Healthy individuals with no history of allergic, autoimmune, chronic or active gastrointestinal infectious diseases were used as controls (n= 44). The serum levels of CCL2 and CCL16 was measured via enzyme-linked immunosorbent assay (ELISA)., Results: A significant decrease in the serum levels of CCL16 and CCL2 was observed in the patients with IBS. Additionally, the serum levels of CCL16 in IBS patients with diarrhea (D-IBS) was significantly higher than those with the mixed IBS (M-IBS) subtype., Conclusion: The significant increase in the serum levels of CCL-16 in patients with D-IBS compared to patients with M-IBS suggests that CCL-16 may be used as an immunological biomarker to differentiate between these two subtypes.