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Background: Type-1 diabetes (T1D) is defined as a heterogeneous autoimmune disease. Immune system related factors are important in the pathogenesis of T1D. Chemokines are important factors in the pathogenesis of several autoimmune diseases, including T1D. They are potent chemotactic cytokines with various functions such as maturation, trafficking of leukocytes, angiogenesis, and homing of stem cells. Therefore, the current study was aimed to examine whether expression of CC chemokines CCL2, CCL5, and CXCL11 is associated with disease duration and complications in Iranian T1D patients. Methods: In this experimental study, blood samples were collected from 108 T1D patients and 189 healthy controls in EDTA pre-coated tubes. The serum levels of CC chemokines were measured by ELISA. Demographic data were also collected along with experimental examinations in a questionnaire which was designed specifically for this study. Results: Results of the present study demonstrated that the expression of CCL2 was decreased while CCL5 and CCL11 were increased in T1D patients in comparison to controls. These results demonstrated that CCL2, CCL5, and CCL11 were elevated in T1D patients with duration of disease. Again, our findings demonstrated that CCL2, CCL5, and CCL11 were elevated in T1D patients with age. But there was not a significant difference between circulating level of CC chemokines studied in T1D patients regarding their gender and they have followed a similar pattern of expression in both genders. Our findings also showed that all three CC chemokines were elevated in T1D patients suffering from diabetes complications. Conclusions: According to the results of our study, elevated levels of CCL5 and CCL11 are in parallel with decreased level of CCL2 and are useful tools in the differential diagnosis of T1D from other types of metabolic disorders. Elevated levels of these CC chemokines probably could be implicated as predictive factors for occurrence of T1D complications. These results may also re-emphasize the prominent therapeutic role(s) of these CC chemokines in control of either T1D or its associated complications.

Background: Type-1 diabetes (T1D) is characterized as a heterogenous autoimmune disease. Immune system factors are important in the pathogenesis of T1D. Chemokines as crucial members of the immune system are key factors in the pathogenesis of several autoimmune diseases, including T1D. They are potent chemotactic cytokines with various functions varied from maturation, trafficking of leukocytes, to angiogenesis, angiostasis, and homing of stem cells. Therefore, the current study was aimed to examine if the expression of pro-angiogenic CXC chemokines like CXCL1 and anti-angiogenic chemochines such as CXCL9 are associated with duration and complications of T1D in Iranian diabetic patients. Methods: In this experimental study, blood samples were collected from 209 T1D patients and 189 healthy controls. The serum levels of CXCL1 and CXCL9 were measured by ELISA. Demographic data were also collected on a questionnaire which was designed specifically for this study. Results: Increased plasma levels of chemokines studied (CXCL1 and CXCL9) were observed in T1D patients compared to controls. Current findings also demonstrated that there was a close association between chemokines and complications of T1D and chemokines were elevated in T1D patients suffering complications. Conclusions: Our results probably suggest that the serum levels of CXCL1 and CXCL9 play important roles in T1D pathogenesis. It is also worth noting that these factors are useful prognostic and/or diagnostic biological markers in T1D patients.

Stroke is a major cause of mortality and long-term disability in adults. Transient receptor potential vanilloid-1 (TRPV1) plays a crucial role in neuroinflammation. In this study, the effects of TRPV1 agonist (capsaicin) and antagonist (AMG9810) on cerebral ischemia were investigated. Forty male Wistar rats were assigned to the following experimental groups: sham, vehicle) ischemic), AMG9810 (selective TRPV1 antagonist, 0.5 mg/kg; 3 h after stroke), and capsaicin (1 mg/kg; 3 h after stroke). Stroke was induced by permanent middle cerebral artery occlusion and neurological deficits were evaluated 1, 3, and 7 days after stroke. Then, infarct volume, brain edema, body temperature, mRNA expression of TRPV1, and serum concentrations of tumor necrosis factor-alpha (TNF-α) and IL-10 were measured. Compared to the vehicle group, AMG9810 significantly decreased the infarct volume (P < 0.01). Latency for the removal of sticky labels from the forepaw and the hanging time were significantly decreased and increased, respectively, following administration of AMG9810 (P < 0.01 and P < 0.001 vs. vehicle) 3 and 7 days after stroke. Compared to the sham group, the mRNA expression of TRPV1 was significantly increased in vehicle group (P < 0.01). Administration of AMG9810 significantly increased the anti-inflammatory cytokine IL-10 and decreased the inflammatory cytokine TNF-α (P < 0.05). Moreover, our results indicate that AMG9810 might a promising candidate for the hypothermic treatment of stroke. The findings also suggest a key role for AMG9810 in reducing inflammation after stroke and imply that TRPV1 could be a potential target for the treatment of ischemic stroke.

Metformin (Met) has been shown to have pleiotropic effects such as neuroprotective, antioxidant, and anti-inflammatory properties making that a potential candidate for the treatment of central nervous system (CNS) disorders. This study was designed to investigate the possible effect of Met on the d-galactose (d-gal)-induced aging in ovariectomized mice. The female mice underwent bilateral ovariectomy. d-gal was administered orally at a dose of 500 mg/kg, and Met was administrated orally at doses of 1 and 10 mg/kg for 6 weeks. Anxiety-like behavior was evaluated by the elevated plus-maze. Physical power was assessed by vertical grid holding test and forced swimming capacity test. The brains were assessed for the level of superoxide dismutase (SOD) and brain-derived neurotrophic factor (BDNF). Ovariectomy caused anxiety and declined the physical power as well as BDNF and SOD levels. d-gal administration in ovariectomized mice exacerbated these deleterious effects. Met hampered the anxiety-like behavior and strengthened the physical power of d-gal-treated ovariectomized mice. Met also increased the SOD and BDNF levels in the brains of d-gal-treated ovariectomized animals. Based on the obtained results, we suggest Met administration as a novel therapeutic approach for the treatment of age-related conditions in the absence of female sex hormones.

Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is antiinflammatory, anti-apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro-inflammatory cytokines like TNF-α, IL-1α, IL-1β, and IL-6. It also inhibits the transcription factor nuclear NF-κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase

Our results demonstrated that Tro has protective effects against CP-induced nephrotoxicity through improving the biochemical indices and the oxidative stress parameters.

Immune responses are the main causes of immune system-related diseases such as hypersensitivities and autoimmunity. It has also been established that cytokines play key roles in the regulation of immune responses which have been shown to be important in the pathogenesis of the diseases. IL-10, the main anti-inflammatory cytokine, is produced by several immune cells such as T regulatory and Th2 lymphocytes, activated macrophages, B regulatory lymphocytes as well as other cell types. It plays a key role in the regulation of immune responses after microbe elimination (homeostasis) and against self-antigens to prevent hypersensitivity and autoimmune diseases, respectively. Studies showed that a single nucleotide polymorphism (SNP) at the -592 position of IL-10 is associated with its regulation of expression. This review addresses the recent information regarding the association of the polymorphism at position -592 of IL-10 with immune-related diseases including type 2 diabetes with and without nephropathy, multiple sclerosis, and asthma with an emphasize on Iranian patients.