scholarly journals Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population

2022 ◽  
Vol 12 ◽  
Author(s):  
Shahnawaz D. Jadeja ◽  
Jayvadan Vaishnav ◽  
Ankit H. Bharti ◽  
Rasheedunnisa Begum
Keyword(s):  
Er Stress ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Interleukin 17A ◽  
Immune Mediated ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Polymerase Chain ◽  
Perilesional Skin

Vitiligo is an autoimmune skin disorder defined by the destruction of functional epidermal melanocytes. It is a multifactorial and polygenic disorder caused due to oxidative stress, endoplasmic reticulum (ER) stress, and autoimmunity, among other factors. In the present study, we aimed to investigate the association of X-box Binding Protein 1 (XBP1) and Interleukin-17A (IL-17A) polymorphisms and monitor their systemic as well as skin expression levels in vitiligo patients from Gujarat population in India. XBP1 rs2269577 G/C, IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 312 controls and 276 vitiligo patients. Transcript levels of spliced (sXBP1), unspliced XBP1 (uXBP1) and IL17A from peripheral blood mononuclear cells (PBMCs) as well as spliced and unspliced XBP1 from skin samples were analyzed by qPCR. IL-17A protein levels in suction-induced blister fluid (SBF) from the skin of study subjects were estimated by ELISA. The results revealed that genotype (p=0.010) and allele (p=0.014) frequencies of XBP1 rs2269577 G/C polymorphism were significantly different, however, no significant difference was observed in frequencies of IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms in control and patient population. Gene expression analysis revealed that sXBP1 and IL17A levels were significantly higher in PBMCs of generalized (p=0.030 and p=0.039, respectively) and active (p=0.024 and p=0.017, respectively) vitiligo patients. Moreover, we observed a significantly elevated sXBP1 expression (p=0.037) as well as IL-17A protein levels (p=0.009) in perilesional skin of vitiligo patients as compared to controls. Overall, these findings suggest XBP1 and IL17A play an important role in vitiligo and further substantiate the involvement of ER stress in exacerbating immune-mediated vitiligo pathogenesis.

scholarly journals Characterising Cytokine Gene Expression Signatures in Patients with Severe Sepsis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Robert Grealy ◽  
Mary White ◽  
Patrick Stordeur ◽  
Dermot Kelleher ◽  
Derek G. Doherty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Severe Sepsis ◽  
Organ Failure ◽  
Prospective Observational Study ◽  
Mononuclear Cells ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Polymerase Chain

Introduction. Severe sepsis in humans may be related to an underlying profound immune suppressive state. We investigated the link between gene expression of immune regulatory cytokines and the range of illness severity in patients with infection and severe sepsis.Methods. A prospective observational study included 54 ICU patients with severe sepsis, 53 patients with infection without organ failure, and 20 healthy controls. Gene expression in peripheral blood mononuclear cells (PBMC) was measured using real-time polymerase chain reaction.Results. Infection differed from health by decreased expression of the IL2, and IL23 and greater expression of IL10 and IL27. Severe sepsis differed from infection by having decreased IL7, IL23, IFNγ, and TNFαgene expression. An algorithm utilising mRNA copy number for TNFα, IFNγ, IL7, IL10, and IL23 accurately distinguished sepsis from severe sepsis with a receiver operator characteristic value of 0.88. Gene expression was similar with gram-positive and gram-negative infection and was similar following medical and surgical severe sepsis. Severity of organ failure was associated with serum IL6 protein levels but not with any index of cytokine gene expression in PBMCs.Conclusions. Immune regulatory cytokine gene expression in PBMC provides a robust method of modelling patients’ response to infection.

scholarly journals Novel mutations in the WFS1 gene are associated with Wolfram syndrome and systemic inflammation

2021 ◽  
Author(s):  
Eleonora Panfili ◽  
Giada Mondanelli ◽  
Ciriana Orabona ◽  
Maria L Belladonna ◽  
Marco Gargaro ◽  
...  
Keyword(s):  
Er Stress ◽  
Mononuclear Cells ◽  
Autosomal Recessive Disorder ◽  
Wolfram Syndrome ◽  
Therapeutic Interventions ◽  
T Helper 17 ◽  
Gene Encoding ◽  
Peripheral Blood Mononuclear ◽  
Inflammatory State ◽  
Wfs1 Gene

Abstract Mutations in the WFS1 gene, encoding wolframin (WFS1), cause endoplasmic reticulum (ER) stress and are associated with a rare autosomal-recessive disorder known as Wolfram syndrome (WS). WS is clinically characterized by childhood-onset diabetes mellitus, optic atrophy, deafness, diabetes insipidus and neurological signs. We identified two novel WFS1 mutations in a patient with WS, namely, c.316-1G > A (in intron 3) and c.757A > T (in exon 7). Both mutations, located in the N-terminal region of the protein, were predicted to generate a truncated and inactive form of WFS1. We found that although the WFS1 protein was not expressed in peripheral blood mononuclear cells (PBMCs) of the proband, no constitutive ER stress activation could be detected in those cells. In contrast, WS proband’s PBMCs produced very high levels of proinflammatory cytokines (i.e. TNF-α, IL-1β, and IL-6) in the absence of any stimulus. WFS1 silencing in PBMCs from control subjects by means of small RNA interference also induced a pronounced proinflammatory cytokine profile. The same cytokines were also significantly higher in sera from the WS patient as compared to matched healthy controls. Moreover, the chronic inflammatory state was associated with a dominance of proinflammatory T helper 17 (Th17)-type cells over regulatory T (Treg) lymphocytes in the WS PBMCs. The identification of a state of systemic chronic inflammation associated with WFS1 deficiency may pave the way to innovative and personalized therapeutic interventions in WS.

scholarly journals Peripheral Blood Mononuclear Cells Antioxidant Adaptations to Regular Physical Activity in Elderly People

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1555 ◽  
Author(s):  
Carla Busquets-Cortés ◽  
Xavier Capó ◽  
Maria Bibiloni ◽  
Miquel Martorell ◽  
Miguel Ferrer ◽  
...  
Keyword(s):  
Physical Activity ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Regular Physical Activity ◽  
Antioxidant Defenses ◽  
Active Lifestyle ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Blood Mononuclear Cells

Regular physical activity prescription is a key point for healthy aging and chronic disease management and prevention. Our aim was to evaluate the antioxidant defense system and the mitochondrial status in peripheral blood mononuclear cells (PBMCs) and the level of oxidative damage in plasma in active, intermediate and inactive elderly. In total, 127 healthy men and women >55 years old participated in the study and were classified according on their level of declared physical activity. A more active lifestyle was accompanied by lower weight, fat mass and body mass index when compared to a more sedentary life-style. Active participants exhibited lower circulating PBMCs than inactive peers. Participants who reported higher levels of exercise had increased antioxidant protein levels when compared to more sedentary partakers. Carbonylated protein levels exhibited similar behavior, accompanied by a significant raise in expression of cytochrome c oxidase subunit IV in PBMCs. No significant changes were found in the activities of antioxidant enzymes and in the expression of structural (MitND5) and mitochondrial dynamic-related (PGC1α and Mitofusins1/2.) proteins. Active lifestyle and daily activities exert beneficial effects on body composition and it enhances the antioxidant defenses and oxidative metabolism capabilities in PBMCs from healthy elderly.

scholarly journals Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

Cholesterol ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Zahra Tavoosi ◽  
Hemen Moradi-Sardareh ◽  
Massoud Saidijam ◽  
Reza Yadegarazari ◽  
Shiva Borzuei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Mononuclear Cells ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Regulation Mechanism ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Abca1 Expression

ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

scholarly journals H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Chien-Hung Chin ◽  
Chang-Chun Hsiao ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Mononuclear Cells ◽  
Gene Promoter ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Reactive Protein ◽  
Primary Snoring ◽  
Obstructive Sleep

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

scholarly journals Intrathymic Plasmablasts Are Affected in Patients With Myasthenia Gravis With Active Disease

2021 ◽  
Vol 8 (6) ◽  
pp. e1087
Author(s):  
Yohei Yamamoto ◽  
Naoko Matsui ◽  
Akiyuki Uzawa ◽  
Yukiko Ozawa ◽  
Tetsuya Kanai ◽  
...  
Keyword(s):  
B Cells ◽  
Myasthenia Gravis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Young Patients ◽  
B Lymphopoiesis ◽  
Peripheral Blood Mononuclear ◽  
Follicular Helper ◽  
Significant Difference ◽  
Cxcr5 Expression

Background and ObjectivesTo investigate intrathymic B lymphopoiesis in patients with myasthenia gravis (MG) and explore thymus pathology associated with clinical impact.MethodsThymic lymphocytes from 15 young patients without MG, 22 adult patients without MG, 14 patients with MG without thymoma, and 11 patients with MG with thymoma were subjected to flow cytometry analysis of T follicular helper (Tfh), naive B, memory B, plasmablasts, CD19+B220high thymic B cells, B-cell activating factor receptor, and C-X-C chemokine receptor 5 (CXCR5). Peripheral blood mononuclear cells of 16 healthy subjects and 21 untreated patients with MG were also analyzed. Immunologic values were compared, and correlations between relevant values and clinical parameters were evaluated.ResultsThe frequencies of circulating and intrathymic plasmablasts were significantly higher in patients with MG than controls. On the other hand, the frequency of CD19+B220high thymic B cells was not increased in MG thymus. We observed a significant increase in CXCR5 expression on plasmablasts in MG thymus and an increased frequency of intrathymic plasmablasts that was correlated with preoperative disease activity. The frequency of intrathymic Tfh cells was significantly lower in patients who received immunosuppressive (IS) therapy than those without IS therapy. However, there was no significant difference in the frequency of intrathymic plasmablasts irrespective of IS therapy.DiscussionOur findings confirmed a correlation between increased frequency of intrathymic plasmablasts and disease activity before thymectomy. We postulate that activated intrathymic plasmablasts endow pathogenic capacity in MG.

scholarly journals MDR1 polymorphisms are not related to Xeliri and Xelox chemoresistance in colorectal cancer

2019 ◽  
Author(s):  
Ayat B. Al-Ghafari ◽  
Areej M. Alqahtani ◽  
Suzan N. Alturki ◽  
Huda Abdulaziz Al Doghaither ◽  
Hanaa M. Tashkandi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Response ◽  
Fragment Length Polymorphism ◽  
Protective Role ◽  
Genotype Distribution ◽  
Chain Reaction ◽  
P Glycoprotein ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Polymerase Chain

Abstract Background Multidrug resistance member 1 (MDR1) is located on chromosome 7 and encodes P-glycoprotein (Pgp), which is universally accepted as a drug resistance biomarker. MDR1 polymorphisms may change either the protein expression or function, suggesting its possible association with cancers, including colorectal cancer (CRC). Thus, this study aimed to determine the effects of MDR1 polymorphisms on the drug response of Saudi CRC patients.Methods DNA samples were obtained from 62 CRC patients and 100 healthy controls. The genotypes and allele frequencies of the MDR1 polymorphisms G2677T and T1236C were determined by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).Results No significant difference was observed in the genotype distribution and allele frequency of T1236C between the CRC the patients and the controls. However, G2677T was found to play a highly significant protective role against the progression of CRC. Moreover, the results showed that none of the genotypes in SNPs T1236C and G2677T affected chemoresistance to Xeliri and Xelox.Conclusions T1236C in the MDR1 gene is not related to CRC risk, and G2677T protects against the development of CRC. Both MDR1 polymorphisms are not associated with the risk of chemoresistance.

scholarly journals Metabolic Syndrome Is Associated with Oxidative Stress and Proinflammatory State

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 236 ◽  
Author(s):  
Margalida Monserrat-Mesquida ◽  
Magdalena Quetglas-Llabrés ◽  
Xavier Capó ◽  
Cristina Bouzas ◽  
David Mateos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Mononuclear Cells ◽  
Antioxidant Defenses ◽  
Peripheral Blood Mononuclear ◽  
Protein Levels ◽  
Inflammatory Parameters ◽  
Increased Risk ◽  
Factor Α

Metabolic syndrome (MetS) is associated with increased risk of developing diabetes and cardiovascular diseases. MetS is also characterized by an increase of oxidative stress which contributes to impaired inflammation, vascular function, and atherosclerosis. The aim was to assess the oxidative stress and inflammatory markers in plasma and PBMCs in adults with or without MetS. Antioxidant and inflammatory parameters were measured in peripheral blood mononuclear cells (PBMCs) of 80 men and 80 women over 55 to 80-years-old residing in the Balearic Islands without previously documented cardiovascular disease. Circulating leukocytes, neutrophils, lymphocytes, basophils, and monocytes were higher in MetS subjects with respect to those without MetS. Plasma levels of malondialdehyde, tumor necrosis factor α (TNFα), and interleukin 6 (IL-6) levels were higher in MetS subjects in both genders, but the superoxide dismutase activity was lower. The myeloperoxidase plasma activity was higher in the MetS male subjects. Higher activities and protein levels of catalase and glutathione reductase in PBMCs were observed in MetS subjects in both genders. Obtained data show that MetS is associated with oxidative stress and a proinflammatory state and with high antioxidant defenses in PBMCs probably derived from a pre-activation state of immune cells.

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