32 research outputs found
Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis
Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p<0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis
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
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Early Assessment of Molecular Progression and Response by Whole-genome Circulating Tumor DNA in Advanced Solid Tumors.
Treatment response assessment for patients with advanced solid tumors is complex and existing methods require greater precision. Current guidelines rely on imaging, which has known limitations, including the time required to show a deterministic change in target lesions. Serial changes in whole-genome (WG) circulating tumor DNA (ctDNA) were used to assess response or resistance to treatment early in the treatment course. Ninety-six patients with advanced cancer were prospectively enrolled (91 analyzed and 5 excluded), and blood was collected before and after initiation of a new, systemic treatment. Plasma cell-free DNA libraries were prepared for either WG or WG bisulfite sequencing. Longitudinal changes in the fraction of ctDNA were quantified to retrospectively identify molecular progression (MP) or major molecular response (MMR). Study endpoints were concordance with first follow-up imaging (FFUI) and stratification of progression-free survival (PFS) and overall survival (OS). Patients with MP (n = 13) had significantly shorter PFS (median 62 days vs. 310 days) and OS (255 days vs. not reached). Sensitivity for MP to identify clinical progression was 54% and specificity was 100%. MP calls were from samples taken a median of 28 days into treatment and 39 days before FFUI. Patients with MMR (n = 27) had significantly longer PFS and OS compared with those with neither call (n = 51). These results demonstrated that ctDNA changes early after treatment initiation inform response to treatment and correlate with long-term clinical outcomes. Once validated, molecular response assessment can enable early treatment change minimizing side effects and costs associated with additional cycles of ineffective treatment
Differential expressions of miRNAs evaluated in (a) chronic versus control, (b) acute versus control, and (c) acute versus chronic cases depend on miRNA microarray analysis (p<0.05, cut off = 2).
<p>Differential expressions of miRNAs evaluated in (a) chronic versus control, (b) acute versus control, and (c) acute versus chronic cases depend on miRNA microarray analysis (p<0.05, cut off = 2).</p
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 miRNAs that were differently regulated between acute and chronic brucellosis.
<p>List of miRNAs that were differently regulated between acute and chronic brucellosis.</p