The neuroprotective effects of Chalcones from Ashitaba on cuprizone-induced demyelination via modulation of brain-derived neurotrophic factor and tumor necrosis factor α.

INTRODUCTION: Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. However, the limitations of available therapeutic strategies are frustrating, both in terms of their low efficacy and multiple side effects. Previous studies showed that natural compounds such as Chalcones possess neuroprotective effects on neurodegenerative disorders. However, few studies have so far been published on the potential effects of Chalcones on treating demyelinating disease. The present study was designed to investigate the effects of Chalcones from Ashitaba (ChA) on cuprizone-induced noxious changes in the C57BL6 mice model of MS. METHODS: The mice received normal diets (Control group: CNT), or Cuprizone-supplemented diets either without ChA (Cuprizone group: CPZ) or with low or high (300, 600 mg/kg/day) doses of ChA (ChA-treated groups: CPZ+ChA300/600). Brain-derived neurotrophic factor (BDNF) and tumor necrosis factor alpha (TNFα) levels, demyelination scores in the corpus callosum (CC), and cognitive impairment were evaluated using the enzyme-linked immunosorbent assay, histological, and Y-maze tests, respectively. RESULTS: The findings showed that ChA Co-treatment significantly reduced the extent of demyelination in the CC and the serum and brain levels of TNFα in the ChA-treated groups compared to the CPZ group. Besides, treatment with a higher dose of ChA significantly improved the behavioral responses and BDNF levels in the serum and brain of the CPZ+ChA600 group when compared with the CPZ group. CONCLUSION: The present study provided evidence for the neuroprotective effects of ChA on cuprizone-induced demyelination and behavioral dysfunction in C57BL/6 mice, possibly by modulating TNFα secretion and BDNF expression.

KIR gene content does not contribute to susceptibility to Graves' disease.

BACKGROUND: Killer cell immunoglobulin-like receptors (KIR) are expressed on NK cells and a subset of T cells. The variable KIR receptors along with their ligands, HLA class I, influence risk for autoimmune and malignant diseases. OBJECTIVE: To investigate the KIR gene profiles in relation to susceptibility to Graves' disease in patients with ophthalmopathy. METHODS: KIR genes profiles were analyzed in 90 patients presenting Graves' disease with ophthalmopathy representing upper eyelid retraction, swelling, redness, conjunctivitis, and bulging eyes and were compared with the KIR gene profiles of 112 healthy controls. The presence and absence of 11 variable KIR genes were characterized using a gene-specific PCR typing system. RESULTS: There was no significant difference in the distribution of KIR gene profiles between patients and controls. CONCLUSION: Our data show that none of the KIR genotypes contribute in susceptibility to Graves' disease; although the role of HLA ligand remains to be characterized.

Activating KIR2DS5 receptor is a risk for thyroid cancer.

Natural killer (NK) cells are key members of innate immunity against tumor and infection. Killer cell immunoglobulin-like receptor (KIR) genes regulates NK cell function, which varies substantially between individuals in the number and type. Specific KIRs are associated with certain diseases. Herein we investigated if KIR genes are associated with thyroid cancer risk. Eighty-five patients with thyroid cancer were characterized for the presence and absence of 11 variable KIR genes using a gene-specific PCR typing system, and compared with our recently published healthy control data. Overall, a trend toward more activating KIR receptors was observed in thyroid cancer patients compared to the healthy controls. Particularly, the activating KIR2DS5 gene was significantly increased in patients compared to the controls. Additionally, three other genes (3DS1-2DL5-2DS1) that are strongly linked to KIR2DS5 at the telomeric region of the KIR gene complex [called Telomeric 4 (T4) gene cluster] were also more predominant in the thyroid cancer patient group than in healthy controls. A similar trend of having more of the T4 gene cluster was also reported in a previous study with cervical neoplasia. Together, these data suggest that specific activating KIR genes in cancer patients could generate a chronic inflammatory condition resulting in a tumor microenvironment that may favor tumor growth.