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Background: Diffuse large B-cell lymphoma (DLBCL) has heterogeneity in its behavior, and pathological and molecular identification. Hematopoiesis is regulated by microRNAs thus its aberrant expression predisposes to myeloid and lymphoid neoplasms the current research aimed to explore serum miR-26a-5p and miR-199b-5p in patients with DLBCL and to evaluate its correlation with clinicopathological features and treatment protocols of NHLs among Egyptian patients with Hepatitis C virus (HCV)Infection. Methods: We enrolled 60 participants; 30 patients with DLBCL and 30 healthy persons as the control group. all subjects were screened for the presence of HCV-RNA in both plasma and PBMCs. miR-26a-5p and miR-199b-5p levels were determined by RT-PCR. Results: Serum miR-26a-5p and miR-199b-5p level values were downregulated in DLBCL patients with HCV and OCI compared to non-HCV and controls. There were significantly higher values of both miR-26a-5p and miR-199b-5p levels in patients with complete response(n=15,50%) compared to partial response (n= 5,16.7%) and primary refractory (n=10,33.3%), p=0.001. Noteworthy, there were statistically significant negative correlations between miR-26a-5p, miR-199b-5p, LDH, and total bilirubin. Linear regression tests revealed that among examined associated variables, only LDH was the independent variable associated with miR-26a-5p and miR-199b-5p, P < 0.001. Conclusions:Serum miR-26a-5p and miR-199b-5p levels were down regulated in DLBCL patients, especially with HCV infection. Thus, these epigenetic markers could provide a new era of precision medicine to better refine diagnosis, prognostication, and rational treatment. [ABSTRACT FROM AUTHOR]

Background: Obesity induces neuroinflammatory effects on the central nervous system (CNS) through dysregulation of energy metabolism, inflammation, and immune responses. Obesity is associated with poor clinical response of multiple sclerosis (MS) to immune mediator drugs. We aimed to assess IL-17 serum and mRNA levels in MS patients and to explore the association of obesity with DMT response and IL-17 serum and mRNA levels in patients with MS. Methods: we examined 40 patients with MS, the diagnosis was according to the latest 2017 McDoland criteria, and 40 subjects as a control group. IL-17 mRNA and serum levels of IL-17 were determined by ELISA. Results: 40 patients with MS were included, of whom 15 (37.5%) were obese, and 25(62.5%) patients were lean. IL-17 mRNA level was significantly higher in the obese MS group (3.4±1.24) compared to the lean MS group (2.5±1.11) and control group (0.9±0.09), P <0 .001. Also, IL-17 level was significantly high in the obese group (46.75±12.2) compared to the lean group (36.23±9.2) and the control group (23.1±5.7), P <0 .001. MS patients treated with fingolimod had statistically significant lower levels of IL-17 mRNA and serum IL-17 compared to patients treated with Interferon beta-1a and b. These markers were associated with BMI, number of relapses in the last 2 years, Expanded Disability Status Scale (EDSS), ESR, and hs-CRP. Conclusions: IL-17 serum and mRNA levels were upregulated in MS patients, particularly obese patients. MS patients treated with fingolimod had statistically significant lower levels of IL-17 mRNA and serum IL-17 compared to other patients. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid cancer (PTC) is the most frequent endocrine cancer. Aberrant expression of miRNAs can increase the risk of thyroid cancer. We aimed to investigate the miR-126-3p and miR-146a-5p plasma levels in patients with thyroid nodules and to identify their associations with clinicopathological characteristics, and progression of PTC. Methods: We enrolled forty healthy control and forty patients with thyroid nodules; benign thyroid nodules (BTN), (n=30), and PTC(n=10). We analyzed miR-126-3p and miR-146a-5p levels by using real-time PCR. Results: miR-126-3p expression level was downregulated in PTC patients (0.40±0.11) compared with BTN (0.58±0.12) and healthy subjects (0.87±0.31), P<0.001*. Regarding miR-146a-5p, its level was upregulated in PTC patients (4.59±1.61) compared with BTN (3.77±0.96) and healthy subjects (0.99±0.41), Additionally, miR-126-3p and miR-146b-5p levels were significantly associated with tumor progression, lymph node metastasis, TNM staging, and thyroid function tests. The diagnostic power of miR-126-3p in the prediction of PTC, the AUC was 0.860 with a sensitivity of 60 % and specificity of 87.3% at cutoff values =0.49. miR-146a-5p level in the prediction of PTC, the AUC was 0.742 with a sensitivity of 80 % and specificity of 74.3% at cutoff values =3.4. Conclusions: miR-146a-5p and miR-126-3p levels were dysregulated in patients with PTC compared to patients with BTN and the control group. The dysregulated miRNAs were associated with clinicopathological features of PTC. [ABSTRACT FROM AUTHOR]

Background Unexplained infertility (UEI) is a complex pathological condition that involves environmental and genetic factors. Hashimoto's thyroiditis (HT) is the most common autoimmune disease in reproductive-age women. Circular RNAs (circRNAs) play a biological role in autoimmunity by regulating gene transcription. A previous study found upregulation of hsa_circ_0089172 in HT. We aimed in the current research to investigate the relative expression level of hsa_circ_0089172 in patients with HT and to assess its correlation with UEI among Egyptian women. Methods: Among 60 women with HT (35 fertile and 25 women with UEI) and 60 healthy subjects as the control group. all subjects were investigated in clinical, laboratory, and radiological. Hsa-circ-0089172 was examined by RT-PCR. Results: There were significantly higher values of hsa_circ_0089172 in UEI group (3.4±0.26) compared to fertile group (2.34±0.33) and control group (0.91±0.216), P <0. 001. Interestingly we observed that anti-TPO and anti TG values were the independent factors associated with hsa_circ_0089172 in the prediction of UEI. hsa_circ_0089172 exposed a significant predictive value of HT, with an AUC of 0.990 (C. I=0.973-1.000), sensitivity of 91.7%, and specificity of 87.1%. Regarding the prediction of UEI among women with HT, the AUC of hsa_circ_0089172 was 0.994(C.I=0.981-1.000), a sensitivity of 94.9%, and a specificity of 89. 3%, P <0 .001 Conclusions: hsa_circ_0089172 level was upregulated in HT patients, particularly patients with UEI. Moreover, it was positively correlated with TSH, anti-TPO, and anti-TG [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has been considered a T cell-mediated autoimmune demyelinating disorder. Nuclear factor κB (NF-κB) is one of the master transcription factors that regulate the activity of inflammatory cells the present study aimed to investigate the NFKB/P65 mRNA levels in patients with MS and to assess its role in the prediction of Hashimoto' thyroiditis (HT). Methods: 50 patients with clinically definite relapsing-remitting multiple sclerosis (according to the McDonald criteria 2017) compared to 50 healthy age and sex-matched controls. Thyroid serum antibodies, IgG index (IgG), and oligoclonal band (OCB) were assessed. The relative expression of NFKB/P65 mRNA was measured using real-time quantitative PCR. Results: there were significantly higher values of NFKB/P65 mRNA levels in patients with HT (2.4±0.54) compared to other patients without HT (1.3±1.45) and control group (0.8±0.17), p <0 .001. Significant associations were confirmed between NFKB/P65 mRNA correlated to thyroid autoimmunity and MS manifestations, p <0. 001. Linear regression revealed that only FT4 and TSH were independent variables correlated with NFKB/P65 mRNA, p < 0.001. Regarding prediction of MS, ROC curve revealed that the sensitivity of NFKB/P65 mRNA was 96 %, and specificity was 88% at cutoff 0.98 with (95% CI = 0.909-0.999). Concerning HT prediction, the cutoff 1.42 with (95% CI = 0.843-1.000)with a sensitivity of 93.8 % and, a specificity of 87.4%. Conclusions: NFKB/P65 mRNA increased in patients with MS more specifically in HT. Thus, NFKB/P65 mRNA could be used as noninvasive prediction markers of MS and HT. [ABSTRACT FROM AUTHOR]

Helicobacter pylori (HP) is an infection related to metabolic and autoimmune disease Hashimoto thyroiditis (HT). HP-modified microRNA (miRNA) expression leads to various disorders. We aimed to evaluate circulatory miR-146a-5p and miR-155-5p expression in HT and to investigate their correlations with the clinical profile of HT and HP infection. Methods: We enrolled 100 subjects; 50 participants as healthy control and 50 patients with HT. The diagnosis of HP-infection by-HP antigen in stool and antibodies against cytotoxic-associated gene A (Cag-A). We tested serum antibodies against thyroid antigens. We used Quantitative real-time RT-PCR for the assessment of serum miR-146a-5p and miR-155-5p. Results: Among 100 studied participants, patients inf*. Concerning had significantly higher values of miR-146a-5p (3.94±0.8), compared to HT patients without HP infection (1.84±0.3) and control group (0.98±0.1), p value<0.001*. Concerning miR-155-5p, there were statistically significant higher values in HP infection (3.61±2.2) compared to HT patients without HP infection (1.91±1.1) and control group (0.90±0.35), p value<0.001*. There were significantly positive correlations with nausea, vomiting, heartburn, anti-TPO, anti-TG, TSH, HP antigen, and Cag-A. On the opposing, they were negatively correlated with FT3 and FT4. linear regression analyses revealed that the only variables independently associated with miR-146a-5p were anti-TPO and FT4. Whereas the only variables independent associated with miR-155-5p were anti-TPO and FT3, p value<0.001*. Conclusion: miR-146a-5p and miR-155-5p overexpressed in patients with HT, more specifically in patients infected by HP and they were significantly correlated to gastrointestinal symptoms thyroid dysfunction, and autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Diabetic sensorimotor polyneuropathy (DSPN) is the most common complication of type 2 diabetes mellitus (T2DM) and the major cause of nontraumatic lower limb amputation. We aimed in the current research to investigate miR-191-5p as a noninvasive predictive biomarker of DSPN among patients recently diagnosed with T2DM in associations with clinical and electrophysiological tests. Methods: We conducted fifty cases recently diagnosed with T2DM and 50 healthy control subjects. contributors were evaluated by clinical and laboratory investigations in addition to nerve conduction studies. circulatory miR-191-5p assessed using the Real-Time PCR method. Results: miR-191-5p levels were lower in patients with DSPN compared to patients without DSPN and controls. Remarkably, miR-191-5p levels were significantly negatively correlated with cardiometabolic risk factors and neuropathy scores; Neuropathy Disability Score (NDS), Neuropathy Symptom Score (NSS), and Toronto Clinical Scoring System (TCSS), p <0.001*. The linear regression test revealed that TCSS, HbA1c, and LDL were the main independent variables against Mir-191-5p levels in patients with DSPN, p <0.001*. To assess the predictive values of miR-191-5p we applied the ROC curve the cutoff values of miR-191-5p as a predictive marker for DSPN was (0.559), with a sensitivity of (95%) and a specificity of (98.7%), with the AUC was 0.958 (0.922-0.993), p <0.001*). Conclusion: circulating miR-191-5p was significantly downregulated in patients recently diagnosed with T2DM, more specifically in patients with DSPN, and it could be used as a biomarker for predicting diabetes and DSPN. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot ulcer (DFU) is one of the most distressing complications in patients with type 2 diabetes mellitus (T2DM). Vascular endothelial growth factor (VEGF) is a strong angiogenic factor associated with wound healing and development. This study aimed to investigate the VEGF mRNA and miR-200b levels in patients with T2DM and to discover their relations with the clinicopathological and anatomical distribution of DFU. Methods: This case-control study enrolled 70 patients with T2DM and 70 healthy subjects as controls. Physical and neurological examination to assess Wagner classification. RT-PCR was done to assess VEGF mRNA and miR- 200b expression levels. Results: There were significantly higher values of VEGF mRNA levels in patients with DFU (3.13±1.87) compared to patients without DFU (2.41±0.197) and controls (1.07±0.363), with P value <0.001* Additionally, miR-200b levels were significantly higher in patients with DFU (3.48±1.47) compared to patients without DFU (2.94±0.187) and controls (1.13±0.37), with P value <0.001*. The power of VEGF mRNA and miR-200b levels as a diagnostic marker for DFU were projected (2.5 and 3.1, respectively), which yielded a sensitivity of (77.1% and 74.3, respectively) and a specificity of (77.3% and 75.2%), with the AUC at (0.886 and 0.845, respectively). The size of DFU in cm was 3.5±0.421 and the number of ulcers was 2.45±0.433. Conclusions: The VEGF mRNA and miR-200b levels were significantly higher in patients with T2DM, particularly those with DFU. Consequently, we believed that VEGF mRNA and miR-200b might serve as promising predictive biomarkers for diabetes and DFU. [ABSTRACT FROM AUTHOR]

Background: Infected diabetic foot ulcer (IDFU) is among the most common complications of Type 2 diabetes mellitus (T2DM), significantly leading to lower extremity amputation. Tumor Necrosis Factor-alpha (TNF-α) is a cytokine with pleiotropic effects on different tissues. This study aimed to investigate TNF-α mRNA and serum levels in Egyptian patients with diabetic foot ulcers in correlation with the risk and severity of IDFU. Methods: We enrolled 100 patients with T2DM and 100 healthy subjects. All patients were subjected to thorough history taking, complete clinical and neurological assessment, and foot ulcers were examined for size, site, and duration. The level of TNF-α was measured using an Enzyme-linked immunosorbent assay, and the TNF-α mRNA level was determined by quantitative real-time PCR. Results: there were significantly higher values of TNF -α mRNA and serum levels in patients with DFU (4.69±0.97,19.7±6.12, P ˂0.001* respectively) compared to controls (0.92±0.084,3.57±0.52, P ˂0.001* respectively). There were significantly higher values of TNF -α mRNA and serum levels in patients with IDFU (4.98±0.52,22.98±5.56, P ˂0.001* respectively) compared to patients without IDFU (3.8±1.41,9.95±1.42, P ˂0.001* respectively). Serum and TNF-α mRNA levels were significantly positively correlated with the duration of diabetes, BMI, HbA1c, ESR, and WBC. Linear regression tests revealed that duration of diabetes, BMI, and WBC were the main predictors of serum TNF-α levels, but only ESR was the main predictor of TNF-α mRNA levels, P ˂0.001*. Conclusions: TNF-α mRNA and serum levels are elevated in DFU and IDFU and positively correlate with the risk and severity of IDFU. [ABSTRACT FROM AUTHOR]