The microRNA expression signature of CD4+ T cells in the transition of brucellosis into chronicity.

Brucellosis is a serious infectious disease that continues to be a significant cause of morbidity worldwide and across all ages. Despite early diagnosis and treatment, 10-30% of patients develop chronic brucellosis. Although there have been recent advances in our knowledge of Brucella virulence factors and hosts' immune response to the infection, there is a lack of clear data regarding how the infection bypasses the immune system and becomes chronic. The present study investigated immunological factors and their roles in the transition of brucellosis from an acute to a chronic infection in CD4+ T cells. CD4+ T cells sorted from peripheral blood samples of patients with acute or chronic brucellosis and healthy controls using flow cytometry as well as more than 2000 miRNAs were screened using the GeneSpring GX (Agilent) 13.0 miRNA microarray software and were validated using reverse transcription polymerase chain reaction (RT-qPCR). Compared to acute cases, the expression levels of 28 miRNAs were significantly altered in chronic cases. Apart from one miRNA (miR-4649-3p), 27 miRNAs were not expressed in the acute cases (p 2). According to KEGG pathway analysis, these miRNAs are involved in the regulation of target genes that were previously involved in the MAPK signalling pathway, regulation of the actin cytoskeleton, endocytosis, and protein processing in the endoplasmic reticulum. This indicates the potential role of these miRNAs in the development of chronic brucellosis. We suggest that these miRNAs can be used as markers to determine the transition of the disease into chronicity. This is the first study of miRNA expression that analyses human CD4+ T cells to clarify the mechanism of chronicity in brucellosis

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Depression and anxiety have unique contributions to somatic complaints in depression, irritable bowel syndrome and inflammatory bowel diseases

OBJECTIVE: In this study we aim to investigate the effects of somatic and related symptoms (SARS), alexithymia, hypochondriasis, anxiety and depression on patients with major depressive disorder, irritable bowel syndrome, inflammatory bowel disease which are the representative diseases of brain gut axis (BGA). METHOD: Sex and age similar groups of participants with major depressive disorder (MDD) (n = 102), irritable bowel syndrome (IBS) (n = 51), inflammatory bowel diseases (IBDs) (n = 54), and control group (n = 67) were included into this study. Depression and IBS were diagnosed according to DSM-5 and ROME 4 criteria, respectively. IBDs were established according to endoscopic, histological, and radiographic investigations. In all participants, somatic and related symptoms were evaluated by self-report scales including Bradford Somatic Inventory (BSI), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Whiteley Index (WI), The 20-item Toronto Alexithymia Scale (TAS-20), Somatosensory Amplification Scale (SAS). RESULTS: BSI, BDI, BAI, WI, TAS-20 and SAS scores were found to be highest in patients with MDD; scores of patients with IBS and IBDs were similar but higher than the control group. Gastrointestinal somatic symptoms including nausea, stomach burning, abdominal ache and stomach swelling were observed in more than half of the patients with MDD. The most common extra-intestinal somatic symptoms were, headache and neck pain and/or tension, and leg pain in IBS patients. However leg pain, weakness and lack of energy, and neck pain/tension were highest in IBDs patients. While the strongest correlation determined was between the BSI and anxiety scores in MDD (p < .001, r = .688) and IBS group; (p < .001, r = .51), in IBDs patients, BSI scores were more significantly correlated with depressive scores instead of anxiety (p < .001, r = .712 vs. r = .705, p < .001). CONCLUSION: Our study demonstrates that SARS are commonly observed in the representative diseases of BGA. Extra-intestinal somatic symptoms are common in IBS, and IBDs, and also gastrointestinal somatic symptoms are common in patients with MDD. Assessment of somatic and related symptoms is quite important in the context of BGA

Pathway analysis of miR-483-3p according to KEGG function annotations.

<p>Pathway analysis of miR-483-3p according to KEGG function annotations.</p

List of significantly altered miRNA expressions in both acute and chronic brucellosis cases compared to control cases.

<p>List of significantly altered miRNA expressions in both acute and chronic brucellosis cases compared to control cases.</p

List of significantly altered miRNA expressions in chronic brucellosis cases.

<p>List of significantly altered miRNA expressions in chronic brucellosis cases.</p

List of miRNAs that were differently regulated between acute and chronic brucellosis.

<p>List of miRNAs that were differently regulated between acute and chronic brucellosis.</p

List of significantly altered miRNA expressions in acute brucellosis cases.

<p>List of significantly altered miRNA expressions in acute brucellosis cases.</p