Summary Background Psoriasis is a chronic inflammatory disease that affects the skin. CD4+ CD28null cells are a subset of T lymphocytes associated with systemic inflammation and increased cardiovascular disease risk, and may be involved in the pathogenesis of psoriasis. Objectives To study the features of circulating CD4+ CD28null cells in patients with psoriasis, adjusted for the influence of known cardiovascular disease risk factors. Methods Forty‐two patients with psoriasis and 42 controls entered the study. Peripheral blood mononuclear cells were analysed for the frequency of CD4+ CD28null T lymphocytes and their expression of cytotoxic granules and homing receptors. Immunostaining for cutaneous cytotoxic granules was assessed in skin biopsies from 11 patients. Results There were no differences in the frequency of CD4+ CD28null T cells between groups in all situations analysed. However, there was an increased number of cells expressing cytotoxic granules and a decreased number expressing CXCR3 in ex vivo samples of patients with psoriasis. A negative correlation was observed between the frequency of ex vivo CD4+ CD28null cells and psoriasis severity. After clinical remission in nine patients, ex vivo CD4+ CD28null lymphocytes expressing cytotoxic granules decreased. Perforin‐, granzyme B‐ and granulysin‐containing cells were found in skin lesions. Patients with psoriasis also had increased plasma levels of C‐reactive protein. Conclusions These data suggest that cytotoxic cells, such as CD4+ CD28null lymphocytes, within an inflammatory environment may play a role in the pathogenesis of psoriasis.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules (21-24 nt) that negatively regulate gene expression, either by repression of translation or by degradation of messenger RNA. These molecules are involved in many important processes including cell differentiation, neurogenesis, formation of nervous system and others. Mesial temporal lobe epilepsy and epilepsy caused by cortical dysgenesis are among the leading causes of drug resistant epilepsy. OBJECTIVES: The objectives of this study were to characterize the expression profile of miRNAs and to investigate their regulation in mesial temporal lobe epilepsy (MTL) and in focal cortical dysplasias (FCDs). METHODS: Total RNA was extracted from hippocampal and neocortical tissue, maintained in paraffin or fresh-frozen, from patients who underwent surgery for seizure control. For comparison we used tissue obtained from autopsy. RNA was extracted and used in real time PCR reactions (157 miRNAs analyzed) or microarray chips (847 miRNAs analyzed). RESULTS: Bioinformatics analyzes identified three miRNAs with expression significantly different in patients with MTLE: let-7d, miR-29b and miR-30d; while in patients with FCDs we found 23 microRNAs differentially expressed. In addition, we found that different pathological forms of had different molecular signatures. CONCLUSIONS: The possible genes regulated by miRNAs with differential expression in tissue with mesial temporal sclerosis (MTS) are mainly related to neurogenesis and apoptosis. While in DCFs they were predominantly related to cell proliferation and migration. Our results demonstrate the importance of miRNA regulation the in molecular processes that lead to the lesions present in the MTS and the FCDs.

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