Further evidence to support acute and chronic anti-inflammatory effects of Nasturtium officinale.

Background and purpose: Previously, we reported the anti-inflammatory properties of Nasturtium officinale (watercress) in several models of acute inflammation. This study was designed to explore the effects of topical and systemic administrations of N. officinale in the two chronic inflammatory models and to evaluate the role of TNF-α and IL-1ß in these effects. Experimental approach: Folin-Ciocalteu and aluminum chloride methods were used to estimate the extract's total phenol and flavonoid content, respectively. Carrageenan-induced paw edema was carried out and TNF-α and IL-1ß concentrations in the carrageenan-treated paw tissue were determined. Formalin injection into rat hind paws (7 days) and the application of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on mouse ears (9 days) were used to simulate chronic inflammation. Furthermore, a histological assessment of the inflamed tissues was carried out. Findings/Results: The extract's flavonoid and phenolic contents were 90.26 ± 4.81 mg rutin equivalents/g and 68 ± 8.16 gallic acid equivalents/g gallic acid, respectively. N. officinale pretreatment in all doses administered considerably decreased carrageenan-induced edema. The extract also reduced IL-1ß levels in carrageenan- treated paws while did not affect TNF-α levels. Oral and topical administrations of N. officinale considerably reserved the paw and ear edema. The extract also ameliorated the tissue injuries due to formalin and TPA challenges. Conclusion and implications: The data confirmed the topical and systemic anti-inflammatory effects of watercress against two chronic models of inflammation. They suggested that these properties are not related to TNF-α but could be attributed to inhibition of IL-1ß and inhibition of leukocyte infiltration.

The Relationship between Salivary and Serum IgA and IgG Levels and Dental Caries in Adults.

BACKGROUND: Dental caries is one of the most common microbial infectious diseases. The important method for as-sessment of oral health status is DMFT (Decayed, Missing, and Filled Teeth). Recent studies have shown conflicting results regarding the relationship of antibodies with dental caries. This study aimed to investigate the salivary and serum IgA and IgG levels in adult caries. METHODS: This cross-sectional study was conducted on 96 patients with dental caries who were referred to the specialized dental clinic in Yasuj. Based on the DMFT index, patients were divided into three groups. DMFT index in group 1, 2, and 3 were 0, 1 - 3, and more than 3, respectively. Salivary and serum levels of IgA and IgG were measured by nephelometric method. Data were analyzed using SPSS software, chisquared, and paired t-test. RESULTS: The mean salivary IgA level in group 1, 2, and 3 were 0.259 ± 0.118, 0.264 ± 0.175, and 0.169 ± 0.106 mg%, respectively (p = 0.001). Also, the mean salivary IgG level in group 1, 2, and 3 were 1.360 ± 316, 1.320 ± 0.350 and 1.320 ± 0.370 mg% (p = 0.929). The mean serum IgA level were 1.443 ± 0.433, 1.805 ± 0.518 and 1.790 ± 0.700 gr% in group 1, 2 and 3, respectively (p = 0.363). Also, the mean serum IgG level in group 1, 2, and 3 were 9.275 ± 1.899, 10.257 ± 1.658 and 10.589 ± 3.113 gr% (p = 0.451). CONCLUSIONS: This study showed that by decreasing the level of salivary IgA, the rate of dental caries and DMFT index increase and this indicates the protection mechanism against dental caries by IgA.

The emerging role of microRNA in regulating the mTOR signaling pathway in immune and inflammatory responses.

The mechanistic/mammalian target of rapamycin (mTOR) is considered to be an atypical protein kinase that plays a critical role in integrating different cellular and environmental inputs in the form of growth factors, nutrients and energy and, subsequently, in regulating different cellular events, including cell metabolism, survival, homeostasis, growth and cellular differentiation. Immunologically, mTOR is a critical regulator of immune function through integrating numerous signals from the immune microenvironment, which coordinates the functions of immune cells and T cell fate decisions. The crucial role of mTOR in immune responses has been lately even more appreciated. MicroRNAs (miRNAs) are endogenous, small, noncoding single-stranded RNAs that act as molecular regulators involved in multiple processes during immune cells development, homeostasis, activation and effector polarization. Several studies have recently indicated that a range of miRNAs are involved in regulating the phosphoinositide 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway by targeting multiple components of this signaling pathway and modulating the expression and function of these targets. Current evidence has revealed the interplay between miRNAs and the mTOR pathway circuits in various immune cell types. The expression of individual miRNA can affect the function of mTOR signaling to determine the cell fate decisions in immune responses through coordinating immune signaling and cell metabolism. Dysregulation of the mTOR pathway/miRNAs crosstalk has been reported in cancers and various immune-related diseases. Thus, expression profiles of dysregulated miRNAs could influence the mTOR pathway, resulting in the promotion of aberrant immunity. This review summarizes the latest information regarding the reciprocal role of the mTOR signaling pathway and miRNAs in orchestrating immune responses.

Plasma Levels and Gene Expression of RANK in Non-Alcoholic Fatty Liver Disease.

BACKGROUND: The pathobiology of initiation and progression of nonalcoholic fatty liver disease (NAFLD) has not been completely elucidated. It seems that the RANK/RANKL/OPG cytokine system play an etiologic role in pathogenesis of this disease. This study aimed to investigate the plasma content and gene expression of RANK in NAFLD patients as compared to healthy individuals. METHODS: This case-control work was performed on 63 patients with NAFLD and 25 healthy subjects. The plasma levels of RANK and biochemical parameters were measured using ELISA and colorimetric methods, respectively. Also, RANK mRNA content was evaluated by quantitative RT-PCR in peripheral blood mononuclear cells. RESULTS: RANK plasma contents were shown to be lower in NAFLD patients than in control subjects (1.02 ± 0.75 and 1.41 ± 1 ng/mL, respectively (p = 0.008)). The differences in gene expression of RANK between NAFLD patients and controls were significant (p = 0.001). In the NAFLD patients, RANK was inversely correlated with HDL. Logistic regression showed the association of RANK plasma content with the risk of NAFLD. Moreover, ROC curve analysis showed that RANK has a great ability to differentiate between NAFLD patients and controls. CONCLUSIONS: This study for the first time showed lower plasma and mRNA levels of RANK in NAFLD patients compared to control individuals. These results recommend a possible association between RANK and pathobiology of NAFLD.

Circulating Levels of Pro-inflammatory Cytokines in Patients with Nonalcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

BACKGROUND: Pro-inflammatory cytokines are associated with systemic inflammatory responses. OBJECTIVE: To investigate the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) in patients with non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) compared to healthy individuals. METHODS: This case-control study was conducted on 30 patients with NAFL, 30 patients with NASH, and 30 healthy volunteers. The plasma level of IL-1ß, IL-6, and TNF-α were determined by ELISA, and biochemical parameters were measured using colorimetric methods. RESULTS: IL-1ß and IL-6 levels were significantly higher in patients with NASH compared with NAFL and control group. However, TNF-α levels had no significant variations in NAFL and NASH patients compared to the control group (p=0.903 and p=0.960, respectively). CONCLUSION: Results showed that the levels of ALT activity and pro-inflammatory cytokines were higher in patients with NASH compared to control and NAFL subjects; Therefore, steatosis and inflammation develop as a result of excessive pro-inflammatory factors in NASH.

IL-21 and IL-21 receptor in the immunopathogenesis of multiple sclerosis.

Cytokines are considered important factors in the modulation of various immune responses. Among them, interleukin (IL)-21 is one of the major immune modulators, adjusting various immune responses by affecting various immune cells. It has been suggested that IL-21 may enhance autoimmunity through different mechanisms, such as development and activation of helper T (TH)-17 and follicular helper T (TFH) cells, activation of natural killer (NK) cells, enhancing B-cell differentiation and antibody secretion and suppression of regulatory T (Treg) cells. Moreover, IL-21 has also been suggested to be an inducer of autoimmunity when following treatment of MS patients with some therapeutics such as alemtuzumab. This review will seek to clarify the precise role of IL-21/IL-21R in the pathogenesis of MS and, in its animal model, experimental autoimmune encephalomyelitis (EAE).

The role of natural killer T cells in B cell malignancies.

Little is known regarding the precise role of different subsets of natural killer T (NKT) cells in the immunopathogenesis of cancer diseases, particularly hematopoietic malignancies. Although it is well known that NKT cells counteract tumor immunity, conflicting reports on the role of NKT cells in hematopoietic malignancies support more investigations to clarify the interactions between NKT cells and the tumor. Among the hematopoietic malignancies, B cell malignancies derive from different stages of B cell maturation in which T cells play a pivotal role. There is evidence which implies the protective role of some subsets of NKT cells in solid cancers as well as B cell malignancies. In this review, we will discuss recent advances about the immunobiology of NKT cells and their precise role in the immunopathogenesis and treatment of different B cell malignancies.

CTLA-4 gene promoter and exon 1 polymorphisms in Iranian patients with gastric and colorectal cancers.

BACKGROUND AND AIM: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by down-regulating T-cell activation. Effects of several polymorphisms in CTLA-4 on CTLA-4 expression and function have been previously documented. The aim of this study was to investigate the putative effect of CTLA-4 polymorphisms on susceptibility to gastric and colorectal cancers in an Iranian population. METHODS: A total of 155 patients (109 with colorectal cancer and 46 with gastric cancer) and 190 age- and sex-matched healthy controls were evaluated. Genotyping of -1722T/C, -1661A/G, and +49A/G were performed by PCR restriction fragment length polymorphism methods and of -318C/T by a PCR amplification refractory mutation system technique. RESULTS: No statistically significant differences were found in the genotype distribution and allele frequencies among patients and controls. Haplotype analysis demonstrated that the TACG haplotype (-1722T, -1661A, -318C, +49G) frequency was significant increased in patients with colorectal cancer (P = 0.009) and gastric cancer (P = 0.006) in comparison to the control group. In contrast, the TACA haplotype frequency was significantly decreased in patients with colorectal cancer (P = 0.02) and not significantly decreased in patients with gastric cancer (P = 0.13) compared to the control group. CONCLUSION: A positive association between CTLA-4 TACG haplotype and gastric and colorectal cancers was found in an Iranian population. A protective role for TACA haplotype is postulated.