An Elevated mRNA Combined with Lower mRNA Level in Active Rheumatoid Arthritis Peripheral Blood.

We aimed to investigate the expression of pro-inflammatory cytokine genes , , , , and immunoregulatory genes , , and in the peripheral blood of patients with rheumatoid arthritis (RA) at messenger ribonucleic acid (mRNA) level. The total RNA was isolated from peripheral blood samples. Real-time quantitative PCR was used to perform TaqMan-based assays to quantify mRNAs from 8 target genes.

Navigating the Cytokine Seas: Targeting Cytokine Signaling Pathways in Cancer Therapy.

Cancer remains one of the leading causes of morbidity and mortality worldwide, necessitating continuous efforts to develop effective therapeutic strategies. Over the years, advancements in our understanding of the complex interplay between the immune system and cancer cells have led to the development of immunotherapies that revolutionize cancer treatment. Cytokines, as key regulators of the immune response, are involved in both the initiation and progression of cancer by affecting inflammation and manipulating multiple intracellular signaling pathways that regulate cell growth, proliferation, and migration.

Influence of and Promoter Polymorphisms on Serum Cytokine Levels in Development and Severity of RA.

In our study, we focused on the role of the immunosuppressive cytokines TGF-β1 and IL-10 in RA and, in particular, the influence of the -1082 A/G (rs1800896) and -509C/T (rs1800469) promoter polymorphisms on their levels as a prerequisite for RA and disease activity clinical features. We found significantly higher IL-10 and lower TGF-β1 serum levels in women with RA than in controls. Patients who carried the -1082AA and AG genotypes had significantly higher levels of lnIL-10 compared to GG in contrast to healthy women carrying the same genotypes.

Prevalence of Sensu Lato in Ticks Collected from Kaylaka Park in Pleven, Bulgaria.

We aimed to determine the presence and distribution of sensu lato (s.l.) in ticks collected from urbanized and wild areas in Kaylaka Park (Bulgaria).

Genetic variation of as a protective genotype for the development of colorectal cancer in men.

Background: The role of transforming growth factor beta (TGF-β) signaling, including both the cytokine and their receptors, in the etiology of colorectal cancer (CRC) has been of particular interest lately.

Aim: To investigate the association between promoter polymorphism in TGF-β receptor 2 TGF-ΒR2GA with a CRC risk in a cohort of Bulgarian patients using a case-control gene association study approach, as well as the protein levels of TGF-β1 in the peripheral blood.

Methods: A cohort of 184 CRC patients and 307 sex and age-matched healthy subjects were recruited in the study.

Comparisons of +3179G/A insulin-like growth factor 1 receptor gene distribution between two inflammatory arthritides and healthy adults.

Objectives: This study aims to investigate whether single nucleotide polymorphisms (SNPs) at the +3179G/A insulin-like growth factor 1 receptor (IGF-1R) locus were associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) genetic susceptibility and also explore age and sex distribution of the rs2229765 in healthy adults.

Patients And Methods: This cross-sectional study was conducted between September 2012 and October 2014. Seventy patients with RA (7 males, 63 females; mean age: 54±1 years; range, 32 to 78 years) and 56 with AS (44 males, 12 females; mean age: 38±9 years; range, 22 to 57 years) were genotyped using polymerase chain reaction-restriction fragment length polymorphism method.

The synergistic role of TNFA - 308G/A and IL10 - 1082A/G polymorphisms in ankylosing spondylitis.

Objective: Genetic polymorphisms of the cytokine genes could alter their protein expression, thus creating a genetic basis of dysregulated cytokine production and function, which render them as excellent candidates predisposing to autoimmune diseases. We investigated single nucleotide polymorphisms (SNPs) at TNFA - 308G/A and IL10 - 1082A/G locus to identify their involvement, separately or in combination, in determining susceptibility to ankylosing spondylitis (AS), as well as their functional connections with relevant serum cytokines and associations with disease characteristics.

Methods: Eighty-one AS patients and 215 healthy controls were genotyped by polymerase chain reaction-based method; 76 patients and sex-matched controls were also subjected to analysis of serum TNF-α and IL-10 levels by enzyme-linked immunosorbent assay.

Hypotheses and facts for genetic factors related to severe COVID-19.

Genome-wide association analysis allows the identification of potential candidate genes involved in the development of severe coronavirus disease 2019 (COVID-19). Hence, it seems that genetics matters here, as well. Nevertheless, the virus's nature, including its RNA structure, determines the rate of mutations leading to new viral strains with all epidemiological and clinical consequences.

A link between promoter polymorphisms of the transforming growth factor β1 (TGFB1) and TGF-β1 receptor II (TGFBR2) genes and relapsing-remitting multiple sclerosis.

Introduction: Multiple sclerosis (MS) is a chronic progressive autoimmune disease characterised by nerve demyelination, mediated by myelin-specific Th1 autoreactive cells. Transforming growth factor 1 (TGF-1) is a regulatory cytokine involved in MS aetiology by maintaining CD4+ cell differentiation and preventing autoimmune responses. Because of the important role of the TGF-1 signalling pathway in MS aetiopathogenesis, we aimed to investigate the association of two DNA polymorphisms: TGFB1C[-509]T and TGFBR2G[-875]A and their combined genotypes with the risk of MS development in a cohort of Bulgarian patients.

Association of polymorphism -308G/A in tumor necrosis factor-alpha gene () and TNF-α serum levels in patients with relapsing-remitting multiple sclerosis.

TNF-α is an important cytokine of the inflammatory response involved in the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). The aim of this study is to explore the association between the promoter polymorphism -308G/A in the gene (rs1800629) with genetic susceptibility to RRMS.: A group of 183 RRMS patients and 169 age and gender-matched healthy controls were enrolled in the study.

Association between TNFA, IL10 and IL18 promoter gene variants and cognitive functions in patients with relapsing-remitting multiple sclerosis.

Objectives: To investigate the relationship between TNFA-308G > A, IL10-1082A > G, IL18-607C > A, and cognitive functioning in relapsing-remitting multiple sclerosis (RRMS).

Results: In the patients' group: AG genotype of TNFA-308G > A was associated with higher serum tumor necrosis factor-alpha (TNF-alpha) than GG genotype, and higher TNF-alpha levels correlated with poorer results on Symbol Digit Modalities Test; CC genotype of IL18-607C > A was related to lower score on Isaacs test, compared to AC variant; AA genotype of IL10-1082A > G was associated with abnormally low results on Paced Auditory Series Addition Test.

Conclusions: TNFA-308G > A, IL10-1082A > G and IL18-607C > A gene variants may be associated with impaired cognitive functions in RRMS patients.

Interleukin-6 compared to the other Th17/Treg related cytokines in inflammatory bowel disease and colorectal cancer.

Background: The connection between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is well-established, as persistent intestinal inflammation plays a substantial role in both disorders. Cytokines may further influence the inflammation and the carcinogenesis process.

Aim: To compare cytokine patterns of active IBD patients with early and advanced CRC.

High interleukin-18 and low FOXP3 mRNAs in peripheral blood of women with severe systemic lupus erythematosus: a cross-sectional study.

Gene expression analysis of peripheral blood cells may provide valuable information about the triggered molecular processes in systemic lupus erythematosus (SLE). The study aimed to quantify the mRNA in peripheral blood of seven target genes, including inflammatory cytokine genes (IL23A, IL12B, TNFA, IL18), and T regulatory-related genes (FOXP3, TGFB1, IL10) in patients with SLE and to correlate expression levels with disease activity and/or clinical manifestations. The relative quantification of target genes was performed using real-time polymerase chain reaction in peripheral blood obtained from 28 adult SLE females and 17 healthy women.

Effect of a Small Selective Inhibitor of C-Jun N-Terminal Kinase on the Inducible mRNA Expression of Interleukin-6 and Interleukin-18.

Background: The expression of many inducible genes, involved in cell growth and differentiation as cytokine genes are regulated by receptor-activated intracellular signalling pathways, including the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase pathway.

Aim: We examined the involvement of the JNK signalling pathway in the regulation of the inducible interleukin-6 (IL-6) and interleukin-18 (IL-18) gene expression at the transcriptional level.

Methods: Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated with lipopolysaccharide (LPS) and C3 binding glycoprotein (C3bgp) with or without SP600125 and cultured for 6 h.

Impact of Polymorphisms on Genetic Susceptibility and IL-12p40 and IL-23 Serum Levels in Rheumatoid Arthritis.

The aim of this study was to evaluate the possible association of gene polymorphisms with serum levels of IL-12p40, IL-23 and genetic susceptibility to rheumatoid arthritis (RA) in the Bulgarian population. Genotyping for (rs17860508) and A/C - 3' UTR (rs3212227) polymorphisms was performed by polymerase chain reaction (PCR)-based methods in 125 RA patients and 239 healthy controls. The IL-23 and IL-12p40 serum levels were measured by enzyme-linked immunosorbent assay (ELISA).

SERUM LEVELS OF INTERLEUKIN - 23 AND INTERLEUKIN - 17 IN HASHIMOTO'S THYROIDITIS.

Context: Overproduction of proinflammatory cytokines plays a significant role in the pathogenesis of Hashimoto's thyroiditis (HT). Recent studies revealed a prominent role of newly discovered Th17 subset in the induction of autoimmune disorders and that the signaling induced by IL-23 on Th17 cells is crucial to obtain a pathogenic and sustained phenotype. The objective of this study was to provide the involvement of interleukin IL-23/IL-17 axis in pathologic processes.

n-3 polyunsaturated fatty acids provoke a specific transcriptional profile in rabbit adipose-derived stem cells in vitro.

Adipose-derived stem cells (ADSCs) possess multipotent properties, and their proper functionality is essential for further development of metabolic disorders. In the current study, we explored the impact of two n-3 LC-PUFAs (long-chain polyunsaturated fatty acids, DHA-docosahexaenoic; C22:6, and EPA-eicosapentaenoic; C20:5) on a specific profile of lipolytic-related gene expressions in the in vitro-differentiated subcutaneous and visceral ADSCs from rabbits. The subcutaneous and visceral ADSCs were obtained from 28-day-old New Zealand rabbits.

IL12B gene polymorphisms have sex-specific effects in relapsing-remitting multiple sclerosis.

IL-12-family cytokines play a pivotal role in neuroinflammation and neurodegeneration in relapsing-remitting multiple sclerosis (RRMS). The aim of the study was to evaluate whether two polymorphisms in IL12B gene, rs17860508 and rs3212227, are associated with RRMS, and to define their function effect on serum level of IL-12p40 and IL-23 and degree of disability in RRMS cases. In total 156 Bulgarian patients with Expanded Disability Status Scale score ranging from 1.

Genetic variations in the IL-12B gene in association with IL-23 and IL-12p40 serum levels in ankylosing spondylitis.

In the present study, we evaluated the implication of IL12Bpro (rs17860508) and IL12B 3' UTR A/C single nucleotide polymorphisms (SNPs) (rs3212227) for the ankylosing spondylitis (AS) development and the impact of IL12B genetic variations on IL-23 and IL-12p40 production and musculoskeletal disease characteristics. 80 patients with AS and 242 healthy controls were studied. Genotyping for the rs3212227 was performed by restriction fragment length polymorphisms-polymerase chain reaction (PCR) and for the rs17860508 by allele-specific PCR.

A Role of Cytokine Gene Polymorphisms in Cognitive Functioning.

The changes in cognitive functions that occur with aging and in various pathological conditions are a subject of growing interest. Experimental and clinical data justify the hypothesis about the influence the immune system exerts on cognitive processes. The balance between pro-inflammatory and anti-inflammatory cytokines has been established as a necessary factor for normal cognitive functioning.

Serum concentration of renin-angiotensin system components in association with ACE I/D polymorphism among hypertensive subjects in response to ACE inhibitor therapy.

Renin-angiotensin system (RAS) is a complex network of enzymes and peptides with the essential role in blood pressure control. The relationships between RAS components, RAS-related genetic polymorphisms and therapy response in essential hypertension (EH) were widely explored but the results were inconclusive. The aim of this study was to explore the functional role of ACE insertion/deletion (I/D) polymorphism on the systemic quantity of angiotensin-converting enzyme (ACE), its homolog - ACE2, chymase and angiotensin II in EH patients with respect to achieved therapeutic blood pressure control.

Transforming growth factor-β1 gene promoter -509C/T polymorphism in association with expression affects colorectal cancer development and depends on gender.

It is widely known that sporadic colorectal cancer (CRC) is age-related diseases with higher incidence rate among men. Transforming growth factor-β1 (TGF-β1) is a major immune regulatory cytokine with a great impact and dual role in gastrointestinal carcinogenesis. In this context, the aim of the study was to explore the role of circulating TGF-β1 and the -509C/T functional promoter polymorphism (rs1800469) within the TGF-β1 gene (TGFB1) in the susceptibility, progression, and prognosis of CRC among Bulgarian male and female patients.

The Role of Transforming Growth Factor-β1 Gene Polymorphism and Its Serum Levels in Hashimoto's Thyroiditis.

Background: TGF-β1 gene (TGFB1) is one of the target genes involved in genetic predisposition to autoimmune diseases, particularly Hashimoto's thyroiditis (HT).

Objective: In the present study, we attempted to investigate whether -509C/T SNP (rs1800469) in the promoter of TGFB1 is associated with the genetic susceptibility and clinical characteristics of Bulgarian patients with HT. We also analyzed serum TGF-β1 levels in different stages of the disease and its association with the -509C/T polymorphism in the TGFB1 promoter.