scholarly journals Expression of ghrelin gene in peripheral blood mononuclear cells and plasma ghrelin concentrations in patients with metabolic syndrome.

2008 ◽  
Vol 158 (4) ◽  
pp. 499-510 ◽  
Author(s):  
Ursula Mager ◽  
Marjukka Kolehmainen ◽  
Vanessa D F de Mello ◽  
Ursula Schwab ◽  
David E Laaksonen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Weight Loss ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Control Group ◽  
Ghrelin Concentration ◽  
Peripheral Blood Mononuclear ◽  
Ghrelin Gene ◽  
Blood Mononuclear Cells

ObjectiveWe examined the expression of ghrelin and ghrelin receptors in peripheral blood mononuclear cells (PBMCs) and evaluated the effect of weight loss or exercise on plasma ghrelin concentrations in subjects with the metabolic syndrome.Design and methodsData from 75 overweight/obese subjects randomized to a weight loss, aerobic exercise, resistance exercise or control group for a 33-week intervention period were analysed. The plasma ghrelin concentrations and indices of insulin and glucose metabolism were assessed, and mRNA expression of ghrelin, its receptors and various cytokines in PBMCs was studied using real-time PCR.ResultsGhrelin and GH secretagogue receptor 1b were expressed in PBMCs of subjects with metabolic syndrome. Ghrelin gene expression correlated positively with the expressions of tumour necrosis factor-α (P<0.001), interleukin-1β (P<0.001) and interleukin-6 (P=0.026) during the study, but was not associated with the plasma ghrelin concentration. Genotype-specific ghrelin gene expression in PBMCs was found for the −604G/A and the −501A/C polymorphisms in the ghrelin gene. At baseline, the plasma ghrelin levels were associated with fasting serum insulin concentrations, insulin sensitivity index and high-density lipoprotein cholesterol. However, longitudinally weight, BMI or waist circumference and acute insulin response in i.v. glucose tolerance test were stronger predictors of the ghrelin concentration. Plasma ghrelin did not change over the study period in the weight reduction group, but it tended to decrease in the control group (P=0.050).ConclusionsGhrelin mRNA expression in PBMCs suggests an autocrine role for ghrelin within an immune microenvironment. Moderate long-term weight loss may prevent a decline in ghrelin concentration over time in individuals with metabolic syndrome.

scholarly journals An Isocaloric Nordic Diet Modulates RELA and TNFRSF1A Gene Expression in Peripheral Blood Mononuclear Cells in Individuals with Metabolic Syndrome—A SYSDIET Sub-Study

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2932 ◽  
Author(s):  
Stine M. Ulven ◽  
Kirsten B. Holven ◽  
Amanda Rundblad ◽  
Mari C. W. Myhrstad ◽  
Lena Leder ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Control Diet ◽  
Peripheral Blood Mononuclear ◽  
Nordic Diet ◽  
Blood Mononuclear Cells

A healthy dietary pattern is associated with a lower risk of metabolic syndrome (MetS) and reduced inflammation. To explore this at the molecular level, we investigated the effect of a Nordic diet (ND) on changes in the gene expression profiles of inflammatory and lipid-related genes in peripheral blood mononuclear cells (PBMCs) of individuals with MetS. We hypothesized that the intake of an ND compared to a control diet (CD) would alter the expression of inflammatory genes and genes involved in lipid metabolism. The individuals with MetS underwent an 18/24-week randomized intervention to compare a ND with a CD. Eighty-eight participants (66% women) were included in this sub-study of the larger SYSDIET study. Fasting PBMCs were collected before and after the intervention and changes in gene expression levels were measured using TaqMan Array Micro Fluidic Cards. Forty-eight pre-determined inflammatory and lipid related gene transcripts were analyzed. The expression level of the gene tumor necrosis factor (TNF) receptor superfamily member 1A (TNFRSF1A) was down-regulated (p = 0.004), whereas the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit, RELA proto-oncogene, was up-regulated (p = 0.016) in the ND group compared to the CD group. In conclusion, intake of an ND in individuals with the MetS may affect immune function.

scholarly journals The influence of adalimumab treatment on the systemic gene expression in patients with psoriatic arthritis – preliminary report

2021 ◽  
Author(s):  
Agata Krawczyk ◽  
Barbara Strzałka-Mrozik ◽  
Dominika Wcisło-Dziadecka ◽  
Magdalena Kimsa-Dudek ◽  
Celina Kruszniewska-Rajsa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Psoriatic Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Control Group ◽  
Systemic Effects ◽  
Peripheral Blood Mononuclear ◽  
Adalimumab Therapy ◽  
Blood Mononuclear Cells

IntroductionThe primary goal of psoriasis treatment is to reduce the inflammatory response and associated complications. In severe cases of psoriasis that are resistant to local treatment (e.g., keratolytic preparations) and at least two types of general treatment methods (e.g., retinoids and cyclosporine A), biological therapy is used. This study aimed to assess the systemic effects of adalimumab at a given stage of treatment in patients with psoriatic arthritis and evaluate how the drug can improve the clinical condition of the patients.Material and methodsThe study group consisted of patients with diagnosed psoriatic arthritis, while the control group consisted of individuals from whom peripheral blood mononuclear cells were obtained. The effects of the administration of adalimumab were assessed by analyzing the gene expression using oligonucleotide microarrays.ResultsThe apoptosis process was indicated as one of the overrepresented categories (the PANTHER classification system 13.1 program, overrepresentativity test, p < 0.05). The dermatological indexes decreased, indicating an improvement in the clinical conditions of the patients three months after the first dose of adalimumab.ConclusionsWe found that adalimumab affects apoptosis, which is crucial in the development and course of psoriasis. The differential gene expression in peripheral blood mononuclear cells of patients with psoriatic arthritis indicated the potential systemic effects of adalimumab therapy. The analyses of dermatological (the Psoriasis Area And Severity Index, body surface area and Dermatology Life Quality Index) and inflammatory (Biernacki’s reaction) parameters revealed the effectiveness of the therapy.

scholarly journals Differential Expression of MMP2 and TIMP2 in Peripheral Blood Mononuclear Cells After Roux-en-Y Gastric Bypass

2021 ◽  
Vol 8 ◽  
Author(s):  
Carla Barbosa Nonino ◽  
Natália Yumi Noronha ◽  
Maysa de Araújo Ferreira-Julio ◽  
Lígia Moriguchi Watanabe ◽  
Karen Francislaine Cassia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Ecm Remodeling ◽  
Blood Mononuclear Cells ◽  
Before And After

Matrix metalloproteinases (MMP) and their endogenous inhibitor, the tissue inhibitor of metalloproteinases (TIMP), are expressed in many different cell types and play an important role in physiologic and pathological degradation of extracellular matrix (ECM). Starting from these observations and considering the activation state of peripheral blood mononuclear cells (PBMCs) in obesity, we investigated the gene expression of metalloproteinases before and after Roux-en-Y gastric bypass (RYBG). The study was performed in the Ribeirão Preto Medical School University Hospital. Seventy-three women were divided into a study group (SG), composed of 53 individuals with severe obesity before and after 6 months of RYGB, and a control group (CG), composed of 20 normal-weight individuals. Anthropometric and body composition data were collected, and peripheral blood for ribonucleic acid (RNA) extraction. The biological samples were submitted to a quantitative real-time polymerase chain reaction to evaluate the expression of MMP2 and TIMP2 genes. Alterations in weight loss, body mass index (BMI), and fat mass (FM) were observed after 6 months of RYGB (p &lt; 0.05). A reduction of gene expression of TIMP2 was observed after 6 months of RYGB, contributing positively to the weight loss (R2 = 0.33 p = 0.04). The enrichment analyses highlighted the interaction between TIMP2 and MMP2 genes and the molecular pathways involving the ECM remodeling in the obesity condition. RYGB contributes significantly to weight loss, improved BMI, reduced FM, and reduced TIMP2 expression in PBMCs, which might contribute to the ECM remodeling in the obesity and could be useful as a circulating biomarker.

scholarly journals Transcriptomic changes in peripheral blood mononuclear cells with weight loss: systematic literature review and primary data synthesis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Kaitlin Day ◽  
Aimee L. Dordevic ◽  
Helen Truby ◽  
Melissa C. Southey ◽  
Susan Coort ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Transcriptomic Response ◽  
Low Responders ◽  
Blood Mononuclear Cells ◽  
Transcriptomic Changes

Abstract Background and objectives Peripheral blood mononuclear cells (PBMCs) have shown promise as a tissue sensitive to subtle and possibly systemic transcriptomic changes, and as such may be useful in identifying responses to weight loss interventions. The primary aim was to comprehensively evaluate the transcriptomic changes that may occur during weight loss and to determine if there is a consistent response across intervention types in human populations of all ages. Methods Included studies were randomised control trials or cohort studies that administered an intervention primarily designed to decrease weight in any overweight or obese human population. A systematic search of the literature was conducted to obtain studies and gene expression databases were interrogated to locate corresponding transcriptomic datasets. Datasets were normalised using the ArrayAnalysis online tool and differential gene expression was determined using the limma package in R. Over-represented pathways were explored using the PathVisio software. Heatmaps and hierarchical clustering were utilised to visualise gene expression. Results Seven papers met the inclusion criteria, five of which had raw gene expression data available. Of these, three could be grouped into high responders (HR, ≥ 5% body weight loss) and low responders (LR). No genes were consistently differentially expressed between high and low responders across studies. Adolescents had the largest transcriptomic response to weight loss followed by adults who underwent bariatric surgery. Seven pathways were altered in two out of four studies following the intervention and the pathway ‘cytoplasmic ribosomal proteins’ (WikiPathways: WP477) was altered between HR and LR at baseline in the two datasets with both groups. Pathways related to ‘toll-like receptor signalling’ were altered in HR response to the weight loss intervention in two out of three datasets. Conclusions Transcriptomic changes in PBMCs do occur in response to weight change. Transparent and standardised data reporting is needed to realise the potential of transcriptomics for investigating phenotypic features. Registration number PROSPERO: CRD42019106582

Changes of IL-4 and IFN-g expression in monocytes and T-helper lymphocytes while modeling of systemic juvenile idiopathic arthritis in Wistar rats

2018 ◽  
pp. 61-69
Author(s):  
В.Н. Сахаров ◽  
П.Ф. Литвицкий ◽  
Е.И. Алексеева ◽  
Н.А. Маянский ◽  
Р.Ш. Закиров
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Wistar Rats ◽  
Mononuclear Cells ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Treatment Groups ◽  
Blood Mononuclear Cells ◽  
T Helpers

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.

scholarly journals Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia

2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Critical Limb Ischemia ◽  
Diabetic Foot ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Limb Ischemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

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