Several environmental and genetic factors are believed to influence the onset of diabetes and its complications. It has also been established that cytokines play a key role in the pathogenesis of type 2 diabetes. Previous studies have revealed that the polymorphism at the stromal-derived factor 1β (SDF-1β) 3'A regulates the expression of SDF-1 (CXCL12). This study was aimed to explore this polymorphism in parallel with SDF-1 serum levels in type 2 diabetic patients. In this assessment, peripheral blood samples were collected from 200 type 2 diabetic patients and 200 healthy controls. DNA was extracted, and a PCR-RFLP screening was applied to examine the SDF-1β 3'A polymorphism. We also applied the ELISA technique to measure serum levels of SDF-1. Our results showed that there were no significant correlations between SDF-1β 3'Α polymorphism in type 2 diabetic patients when compared to controls. However, our results showed that the serum levels of SDF-1 were significantly increased in the patients when compared to controls. Based on the results of this study, we concluded that SDF-1β 3'Α polymorphism does not play a role in the pathogenesis of type 2 diabetes but that elevated serum levels of SDF-1 may be important for the etiology of type 2 diabetes but are unrelated to the SDF-1β 3'Α polymorphism.

The results suggested that the pathophysiological status of both mother and infant are involved in prematurity. Moreover, these findings suggest an inflammatory response in pre-term labor, which probably is controlled by inducible chemokines such as CXCL10.

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.

Immune responses are extensively accepted as primitive etiological leading causes involved in immune system diseases. It is now well established that chemokines as the main arms of the immune system play critical roles in the regulation of immune responses in the pathogenesis of different diseases. Several environmental and genetic elements of the immune system are also believed to potentially affect both the onsets of immunological diseases. The stromal cell-derived factor-1 alpha (SDF-1α) which in new nomenclature is nominated as C-X-C motif ligand 12 (CXCL12) is involved in the development and progression of immune responses. The CXCL12 is an extensively active chemokine that serves as a recruiter for migration and trafficking of leukocytes and hematopoietic progenitor cells. Patients suffering type 2 diabetes (T2D) that ascribe heterozygous SDF-1 3'A genotype (801G/A in the 3' untranslated region) have increased insulin-dependent mobilization of adult progenitor cells, which are known to participate in angiogenesis and vascular repair. Conversely, homing of progenitor cells contributes to the diabetes vascular complications. Because carriers of the SDF-1 3'A genotype show increased levels of the CXCL12 messenger RNA (mRNA) in their peripheral blood mononuclear cells. Genetic variations of CXCL12 gene might affect trafficking of inflammatory cells or defected precursors and hence induced tendency to diabetic complications. The SDF-1 3'A genetic variation of CXCL12 influences the development of late vascular diabetic complications, and previous studies reported that this genetic variation regulates the expression of CXCL12. Therefore, the main goal of the present study was to collect the most recent reports regarding the relation between serum concentrations and SDF-1 3'A genetic variation of CXCL12 in T2D.

Immune system-related factors are important in pathogenesis of multiple sclerosis. The CXC chemokine SDF-1α (CXCL12) is involved in the immune responses. Hence, the aim of this study was to investigate the association between serum levels of SDF-1α (CXCL12) and its gene polymorphisms at position +801 with multiple sclerosis. In this experimental study, blood samples were collected from 100 multiple sclerosis patients and 100 healthy controls on EDTA pre-coated tubes. DNA was extracted and DNA samples were analyzed for SDF-1α (CXCL12) polymorphisms using PCR-RLFP in patients and controls. The serum levels of SDF-1α (CXCL12) were measured by ELISA. Demographic data were also collected by a questionnaire which was designed specifically for this study. Our results showed a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of SDF-1α (CXCL12). Our results also showed that serum levels of SDF-1α (CXCL12) were markedly higher in patients than healthy controls, but no association was observed between SDF-1α (CXCL12) polymorphism and its serum levels. The results of this study might suggest the serum levels of SDF-1α (CXCL12) and its polymorphism play an important role in pathogenesis of multiple sclerosis. It is also worth noting that these factors could probably use as pivotal biological markers in the diagnosis of MS.

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.

Aim and objectives: Natural products and derivatives of medicinal vegetation can play an important role to the cure tumor. The Present study was focused to determine the effect of Cornus mass L. extract on the induction of apoptosis in AGS gastric carcinoma cell line in compared to L929 cells. Methods: In this experimental study, AGS and L929 cells were cultured and treated with different concentrations (0-10 mg/ml) of Cornus mass L. extract for 48 and 72 hours. Cell proliferation was assessed by MTT assay. The optical density of the colored solution was quantified at 570 nm wavelengths by an ELISA Reader. Making use of the apoptosis detection kit of Annexin V-FITC, PI and double staining with Annexin V-FITC were carried out for flow cytometry investigations. Data were analyzed by ANOVA. Variations with a P-value less than 0.05 were considered significant. Results: shows a noticeable deviation among various concentrations of extract when cells were treated for 48, 72 h declined cell viability in AGS cell line in comparison L929 cell lines in a dose and time-dependent manner (P < 0.05). This extract also displayed approximately several-fold increased anti-cancer potency in AGS compared to L929 cells. The IC 50 value in AGS cells (evaluated after 48,72h) of the extract against AGS cells was 5/44, 2/44 mg/ml (p≤0.05). The analysis results of flow cytometry indicated that apoptosis was induced by the extract in AGS cells treated, compared with L929 cells. Conclusion: Each of our results implicates the reality that Cornus mass L. extract acts as a novel, potent inhibitor of cancer proliferation in in vitro. This may result in developing a promising therapeutic agent for the treatment of indole-sensitive cancers.

The indole-3-carbinol (I3C) displays anti-cancer/proliferative activities against human cancer cells. Cellular proliferation is an event associated with the progress and its continuation. This manifest is described by variation in expression and/or functions of genes that are related with cell cycle relevant proteins. The constitutive activation of several signal transduction pathways stimulates cells proliferation as well. The immediate stages in cancer development are accompanied by a fibrogenic response and the progression of the hypoxic environment is in favor of survival and proliferatory functions of cancer stem cells. A main part for prevention of in cancer cells death may manifest through altering cell metabolism. Cellular proliferation and metastasis are reported to be supported with increased generation of responsible hormones (in hormone dependent malignancies), and further promotion the angiogenesis, with epithelial to mesenchymal transition. This may be facilitated by progression of autophagy phenomenon, as well as via taking cues from neighboring stromal cells. Several signaling pathways in association with various factors specific for cellular viability, including hypoxia inducible factor 1, NF-κB, insulin-like growth factor 1 (IGF-1) receptor, Human foreskin fibroblasts (HFF-1), phosphoinositide 3 kinase/Akt, Wnt, cell cycle related protein, with androgen and estrogen receptor signaling are reported to be inhibited by I3C. These evidences, in association with bioinformatics data represent very important information for describing signaling pathways in parallel with molecular targets that may serve as markers for early diagnosis and/or critical targets for designing and development of novel therapeutic regimes alone or combined with drugs, to prevent tumor formation and further progression. In particular, I3C and DIM have been extensively investigated for their importance against numbers human cancers both in vitro and in vivo. We aimed the present manuscript, current study, to review anticancer properties and the miscellaneous mechanisms underlying the antitumorigenicity in an in-depth study for broadening the I3C treating marvel.