AB0237 Positive Correlation of ULK1 and MMP-9 versus Negative Correlation of Mtor and Tnfα Baseline Gene Expressions in the Peripheral Blood with the Disease Activity and Joint Destruction Indices Registered in Rheumatoid Arthritic Patients after Treatment

BackgroundNon−small-cell lung cancer (NSCLC) is the major type of lung cancer. MicroRNAs (miRNAs) are novel markers and targets in cancer therapy and can act as both tumor suppressors and oncogenes and affect immune function. The aim of this study was to investigate the expression of miR146a and miR155 in linked to blood immune cell phenotypes and serum cytokines in NSCLC patients.MethodsThirty-three NSCLC patients and 30 healthy subjects were enrolled in this study. The allele frequencies of potential DNA polymorphisms were studied using polymerase chain reaction (PCR)–restriction fragment length polymorphism (PCR-RFLP) analysis in peripheral blood samples. Quantitative reverse transcription PCR (qRT-PCR) was used to measure the expression of miR-146a and miR-155 in peripheral blood mononuclear cells (PBMCs). Serum cytokine (IL-1β, IL-6, TNF-α, TGF-β, IL-4, IFN-γ) levels were determined by ELISA. The frequency of circulating CD3+CTLA-4+ and CD4+CD25+FOXP3+ (T regulatory cells/Treg) expression was measured by flow cytometry.ResultsmiR-146a was significantly downregulated in PBMC of NSCLC patients (P ≤ 0.001). Moreover, IL-6 and TGF-β levels were elevated in NSCLC patients (P ≤ 0.001, P ≤ 0.018, respectively). CD3+ CTLA-4+ and Treg cells frequencies were higher in patients than in control subjects (P ≤ 0.0001, P ≤ 0.0001, respectively). There was a positive correlation between miR-155 and IL-1β levels (r=0.567, p ≤ 0.001) and a negative correlation between miR-146a and TGF-β levels (r=-0.376, P ≤ 0.031) in NSCLC patients. No significant differences were found in the relative expression of miR-146a and miR-155, cytokine levels or immune cell numbers according to miR-146a and miR-155 (GG/GC/CC, TT/AT/AA) genotypes. However, there was a positive correlation between miR-146a and IL-1β levels (r=0.74, P ≤ 0.009) in GG subjects and a positive correlation between miR-146a expression and CD3+CTLA4+ cell frequency (r=0.79, P ≤ 0.01) in CC genotyped subjects. Conversely, a negative correlation between miR-146a expression and Treg cell frequency (r=−0.87, P ≤ 0.05) was observed with the GG genotype. A positive correlation between miR-155 and IL-1β expression (r=0.58, p ≤ 0.009) in the TT genotype and between miR-155 expression and CD3+CTLA-4 cell frequency (r=0.75, P ≤ 0.01) was observed in the AT genotype.ConclusionsThe current data suggest that the miR-146a expression in PBMC and serum TGF-β and IL-1β levels may act as blood markers in NSCLC patients. Further study is needed to elucidate the link between immune cells and serum miR146 at early disease stages.

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Altered Frequencies of CD4+ CD25+ Foxp3+ and CD8+ CD25+ Foxp3+ Regulatory T Cells in Pre-eclampsia

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v17i6.618 ◽

2019 ◽

Cited By ~ 2

Author(s):

Maryam Zare ◽

Mehrnoosh Doroudchi ◽

Behrouz Gharesi-Fard

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Regulatory T Cells ◽

Negative Correlation ◽

Peripheral Blood ◽

Pregnancy Complications ◽

Treg Cells ◽

Positive Correlation ◽

Blood Pressures ◽

In Pregnancy

Regulatory T cells are of utmost importance for tolerating the fetus. In some pregnancy complications such as pre-eclampsia, the frequency of CD4+CD25+Foxp3+ regulatory T cells is altered, but there is no consistency regarding the results. Besides, little is known about the frequency of CD8+CD25+Foxp3+ Treg cells in pregnancy complications. Therefore, we aimed to investigate the frequency of both CD4+ and CD8+ regulatory T cells in the peripheral blood of women afflicted by preeclampsia. Ten non-pregnant, ten healthy pregnant, and ten preeclamptic women participated in this study. Four colors flow cytometry method was used to identify the frequency of the CD4+ and CD8+ regulatory T cells in the peripheral blood. Results indicated that the frequencies of CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+ cells were significantly lower in preeclamptic women compared to healthy pregnant and non-pregnant ones (p<0.05). A positive correlation was also observed between CD4+ and CD8+ regulatory T cells (R=0.532, p=0.002). Moreover, CD4+ regulatory T cells negatively correlated with systolic and diastolic blood pressures (R=-0.760 and -0.753, respectively; p<0.001). CD8+ regulatory T cells also had a negative correlation with systolic (R=-0.503, p=0.001) and diastolic (R=-0.590, p=0.005) blood pressures. In conclusion, a reduction in the frequencies of both CD4+ CD25+ Foxp3+ and CD8+CD25+Foxp3+ regulatory T cells might be important in the pathogenesis of pre-eclampsia.

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Glycated Albumin, a Marker for RA associated Coronary Artery Athelosclerosis

QJM ◽

10.1093/qjmed/hcaa064.007 ◽

2020 ◽

Vol 113 (Supplement_1) ◽

Author(s):

M R Y Eskander ◽

H ELsebaie ◽

N Assaf ◽

N Elgharbawy ◽

L Allam

Keyword(s):

Coronary Artery ◽

Disease Activity ◽

Negative Correlation ◽

Significant Positive Correlation ◽

Glycated Albumin ◽

Enzyme Linked Immunosorbent Assay ◽

Carotid Imt ◽

Positive Correlation ◽

Das 28 ◽

The Mean

Abstract Objectives to detect the value of serum Glycated Albumin measurement as a marker for RA associated coronary artery atherosclerosis and also a marker for RA disease activity. Patients and Methods serum GA using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of RA were measured in 30 RA patients and 15 age and sex matched controls known to have established coronary artery disease. Disease activity was assessed using the DAS-28 score. Carotid ultrasound was done to both groups to measure the carotid IMT. Results A significantly higher serum GA level on comparing RA patients and controls (T = 5.096, P < 0.001). Serum GA had a significant positive correlation with ESR (r = 0.546, P < 0.002) and CRP (r = 0.768, P < 0.001), a significant positive correlation with DAS-28 (r = 0.532 , P < 0.002), a significant positive correlation with mean carotid IMT (r = 0.471, P = 0.019). The mean carotid IMT showed a highly significant positive correlation with the disease duration (r = 0.645, P < 0.001), a positive correlation with severe disease activity (r = 0.771, P = 0.015), but negative correlation with mild and moderate disease activity (r = 0.500, P = 0.667) and ( r = 0.452, P = 0.059) respectively. Another significant positive correlation was found between the mean carotid IMT and the LDL (r = 0.408, P = 0.025) but negative correlation with total cholesterol and HDL (r = 0.120, P = 0.527) and (r = -0.250, P = 0.183). On comparing the mean carotid IMT with the presence of soft atheromatous plaque it gave negative results with positive correlation (T = -3.273, P = 0.003) Conclusion Serum GA is a specific and sensitive biomarker for detection of subclinical atherosclerosis and disease activity in RA.

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Differences in Mammalian Target of Rapamycin Gene Expression in the Peripheral Blood and Articular Cartilages of Osteoarthritic Patients and Disease Activity

Arthritis ◽

10.1155/2013/461486 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 26

Author(s):

Elena V. Tchetina ◽

A. Robin Poole ◽

Elena M. Zaitseva ◽

Eugeniya P. Sharapova ◽

Natalya G. Kashevarova ◽

...

Keyword(s):

Gene Expression ◽

Disease Activity ◽

Peripheral Blood ◽

Caspase 3 ◽

Joint Destruction ◽

Mammalian Target Of Rapamycin ◽

Joint Stiffness ◽

P70 S6k ◽

Articular Cartilages ◽

End Stage

The gene expression of mTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, and TNFα was measured in the peripheral blood of osteoarthritic (OA) patients at different stages of the disease aiming to establish a gene expression profile that might indicate the activity of the disease and joint destruction. Whole blood of 65 OA outpatients, 27 end-stage OA patients, 27 healthy volunteers, and knee articular cartilages of 28 end-stage OA patients and 26 healthy subjects were examined. OA outpatients were subjected to clinical testing, ultrasonography, and radiographic and WOMAC scoring. Protein levels of p70-S6K, p21, and caspase 3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. Upregulation of mTOR gene expression was observed in PBMCs of 42 OA outpatients (“High mTOR expression subset”) and in PBMCs and articular cartilages of all end-stage OA patients. A positive correlation between mTOR gene expression in PBMCs and cartilage was observed in the end-stage OA patients. 23 OA outpatients in the “Low mTOR expression subset” exhibited significantly lower mTOR gene expression in PBMCs compared to healthy controls. These “Low mTOR” subset subjects experienced significantly more pain upon walking, and standing and increased total joint stiffness versus “High mTOR” subset, while the latter more often exhibited synovitis. The protein concentrations of p70-S6K, p21, and caspase 3 in PBMCs were significantly lower in the “Low” subset versus “High” subset and end-stage subjects. Increases in the expression of mTOR in PBMCs of OA patients are related to disease activity, being associated with synovitis more than with pain.

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Rheumatoid Factor Positivity Is Associated with Increased Joint Destruction and Upregulation ofMatrix Metalloproteinase 9andCathepsin KGene Expression in the Peripheral Blood in Rheumatoid Arthritic Patients Treated with Methotrexate

International Journal of Rheumatology ◽

10.1155/2013/457876 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Elena V. Tchetina ◽

Natalia V. Demidova ◽

Dmitry E. Karateev ◽

Eugeny L. Nasonov

Keyword(s):

Gene Expression ◽

Rheumatoid Factor ◽

Peripheral Blood ◽

Caspase 3 ◽

Joint Destruction ◽

Previous History ◽

Cathepsin K ◽

Tissue Destruction ◽

Rheumatoid Arthritic

We evaluated changes in gene expression ofmTOR,p21,caspase-3,ULK1,TNFα, matrix metalloproteinase(MMP)-9, andcathepsin Kin the whole blood of rheumatoid arthritic (RA) patients treated with methotrexate (MTX) in relation to their rheumatoid factor status, clinical, immunological, and radiological parameters, and therapeutic response after a 24-month follow-up. The study group consisted of 35 control subjects and 33 RA patients without previous history of MTX treatment. Gene expression was measured using real-time RT-PCR. Decreased disease activity in patients at the end of the study was associated with significant downregulation ofTNFαexpression. Downregulation ofmTORwas observed in seronegative patients, while no significant changes in the expression ofp21,ULK1, orcaspase-3were noted in any RA patients at the end of the study. The increase in erosion numbers observed in the seropositive patients at the end of the follow-up was accompanied by upregulation ofMMP-9andcathepsin K, while seronegative patients demonstrated an absence of significant changes inMMP-9andcathepsin Kexpression and no increase in the erosion score. Our results suggest that increased expression ofMMP-9andcathepsin Kgenes in the peripheral blood might indicate higher bone tissue destruction activity in RA patients treated with methotrexate. The clinical study registration number is 0120.0810610.

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Reactive Thrombocytosis – Aetiology And Relationship with Different Hematological Parameters, ESR, CRP in Infections

Annals of Pathology and Laboratory Medicine ◽

10.21276/apalm.2761 ◽

2020 ◽

Vol 7 (8) ◽

pp. A409-415

Author(s):

Bhavana Garg ◽

Menka Shah

Keyword(s):

Platelet Count ◽

Disease Activity ◽

Negative Correlation ◽

Bacterial Infections ◽

Hematological Parameters ◽

Significant Negative Correlation ◽

Deficiency Anemia ◽

Reactive Thrombocytosis ◽

Positive Correlation ◽

Low Degree

Background: The measurements of platelet count, mean platelet volume (MPV), WBC are routinely available nowadays. The aim of this study was to determine aetiology and relationship of these parameters whether they were associated with the known markers of disease activity, erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) in infections. Methods: This descriptive study was done on 500 patients with platelet count > 450,000/ μl and the cause being reactive. Platelet count, WBC, MPV, ESR, and CRP were measured at the time of hospitalization. Result: Most common cause of reactive thrombocytosis was Infections (28.8%), Tissue damage (16.4%), Iron deficiency anemia (16.2%), Malignancy (9.6%) and Inflammation (9.4%). In infections, bacterial infections (88%) were found to be more common. There was low degree of positive correlation between reactive thrombocytosis and WBC (r = 0.124, P >0.05) , ESR ( r = .147, P= 0.07) , MPV ( r = .077, P >0.05) in infections. There was significant negative correlation between reactive thrombocytosis and CRP in infections (r = -.199, P= 0.017). Conclusion: This study demonstrated a higher level of platelet count and lower MPV in all the patients having reactive thrombocytosis irrespective of it’s etiology. There was low degree of positive correlation between platelet count and WBC, ESR and MPV in infections and a significant negative correlation with CRP. We propose that platelet parameters may be considered as reliable markers for assessment of disease activity.

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Correlation of Phraseological Semantic Fields in Russian Study of Aphorisms

Известия Смоленского государственного университета ◽

10.35785/2072-9464-2020-51-3-60-71 ◽

2020 ◽

pp. 60-71

Author(s):

Anshelika Korolkova

Keyword(s):

Negative Correlation ◽

Semantic Field ◽

Positive Correlation ◽

Classical Study ◽

Semantic Fields ◽

Zero Correlation ◽

Russian Study

The article deals with the interconnection and interdependence of phraseological semantic fields of Russian study of aphorisms in synchronic and in diachronic approaches. The correlation of phraseological semantic fields of Russian study of aphorisms is considered as their interdependence due to various factors (linguistic and extra-linguistic ones). The correlation of the phraseological semantic fields of Russian study of aphorisms is manifested in the existence of many antinomies. The natural linguistic antinomies of life / death / immortality or war / peace, or good / evil, or friend / enemy, or villainy / nobility are reflected in Russian aphorisms and have entered the corresponding phraseological semantic fields. The corpus of Russian study of aphorisms containsnot only antinomic aphorisms, but also antinomic relations that extend to the level of language and speech. Therefore, in Russian study of aphorisms there are phraseological semantic fields that implement these antinomies. In addition to the antinomic phraseological semantic fields in the corpus of classical Russian study of aphorisms there are other types of correlations. The keywords (concepts) of many phraseological semantic fields are closely thematically connected. When the number of units from one field is changed, the number of units in another phraseological semantic field also changes. Most phraseological semantic fields of Russian study of aphorisms do not show a zero correlation in either synchronic or diachronic approaches. This is due to, first of all, the universality of the aphoristic theme, with all the ideological and thematic uniqueness of the sayings used by Russian writers. However, a few phraseological and semantic fields of aphorisms by Russian writers may show a negative correlation, which is due to the diversity of the thematic groups that comprise them. A positive correlation of phraseological semantic fields, the most significant in the number of their constituent components, shows deep internal linguistic systemic connections in Russian classical study of aphorisms.

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Immunoregulatory Role of Interleukin-37 in Rheumatoid Arthritis; Relation to Disease Activity and Joint Destruction

The Medical Journal of Cairo University ◽

10.21608/mjcu.2018.60305 ◽

2018 ◽

Vol 86 (September) ◽

pp. 3341-3348

Author(s):

DALIA B. EL-BOHOTY, M.Sc.; DOAA S. AL-ASHKAR, M.D. ◽

MAALY M. MABROUK, M.D.; HALA M. NAGY, M.D.

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Joint Destruction

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Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity

Current Chemical Biology ◽

10.2174/2212796813666181219124924 ◽

2019 ◽

Vol 13 (2) ◽

pp. 140-148

Author(s):

Mai Nasser ◽

Noha M. Hazem ◽

Amany Atwa ◽

Amina Baiomy

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Autoimmune Diseases ◽

Disease Activity ◽

Mrna Expression ◽

Disease Activity Score ◽

Activity Score ◽

Tlr2 Expression ◽

Positive Correlation ◽

Tlr2 Mrna

Background: Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematic disease. It affects joints and bones. The exact etiology of RA is still unclear. Varied genetic and environmental factors have been associated with the increased risk for RA. Overactivation of Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseases including RA. Objective: The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritis patients and investigate its correlation with the disease activity. Materials and Methods: This study included 60 patients and 20 healthy individuals. The patients were diagnosed with RA according to the 2010 American College of Rheumatology/ European League Against Rheumatism criteria (ACR/EULAR). All included subjects did not have any joint disorders and /or autoimmune diseases. RA disease activity was determined by the disease activity score of 28 joints. Whole blood was collected from all participants. Total RNA extraction was done. TLR2 mRNA expression was assessed by reverse transcription-PCR (RT-PCR). Results: TLR2 mRNA expression was found to be significantly higher in RA patients compared to healthy controls. Also, a strong positive correlation was found between TLR2 expression level and the disease activity score. A non significant positive correlation was found between TLR2 expression and serum Rheumatoid Factor (RF) level. Conclusion: TLR2 pathway may have an important role in RA pathogenesis and could be a new biomarker for diagnosis and monitoring disease activity.

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