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To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744–0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755–0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.

Abstract Background and objectives Behçet’s disease (BD) is an ongoing systemic vasculitis with mouth and genital ulceration and eye, skin, and systemic affection. It has considerable morbidity and mortality, and a high incidence and a higher male-to-female affection characterize Egypt. We aimed to evaluate liver x receptor messenger RNA beta (LXR β) and microRNA-146a (miR-146a) gene expression in Behçet’s disease cases in Egypt to relate them with clinicopathological features. Subject and method Eighty Egyptian individuals were split into two groups for the current study: Forty Behçet’s disease cases and forty healthy controls matched by age and gender from the Rheumatology Department at Helwan University Hospital, Egypt. The transformed score, also known as the Behçet’s Disease Current Activity Form (BDCAF), was utilized to measure disease activity. To assess the amounts of LXR β and miR-146a serum expression via real-time PCR, a blood sample was obtained. Results There was a downregulation of both LXR β and miR-146a levels that significantly differed between the BD group and the control group (p = 0.0001 and 0.0001, respectively). There is a noteworthy inverse relationship between the expression level of LXR β and BDCAF Patients Index (r = − 0.79 and p = 0.0001) was found. Regarding miR-146a, it had a reverse correlation with BDCAF Patients Index (r = − 0.89 and p = 0.0001). Conclusion LXR β and miR-146a were found to be significant non-invasive predictor biomarkers for Behçet’s disease and can indicate disease activity.

Background: Alopecia areata (AA) commonly displays as non-scarring, irregular hair loss. Experimental and clinical research have specifically implicated autoimmunity and genetics in the disruption of anagen hair follicles. AA patients' scalp lesions and peripheral blood mononuclear cells (PBMCs) exhibited an immune state imbalance. Numerous studies attempt to establish a connection between the occurrence and prognosis of AA and the epigenetic modulation of gene expression by long noncoding RNA (lncRNA) and microRNA (miRNA). The current study aimed to examine the serum levels of nuclear enriched abundant transcript 1 (NEAT1) and its target miRNA101 (miR-101) in AA and investigate the ability to use them as diagnostic biomarkers in the disease. Methods: Seventy-two AA patients were included in this prospective cohort study. Demographics, patient history, laboratory characteristics, and treatments were recorded. The miR-101 and NEAT1 levels were evaluated. Results: Serum NEAT1 levels were lower in AA patients, but there was no significant difference. However, there was no substantial disparity in NEAT1 level regarding other disease characteristics. There was a substantial positive association between NEAT1 and miR-101 levels among cases. On the other hand, the results showed a markedly low mean of miR-101 levels among patients, but the miR-101 marker shows no significant difference regarding different disease characteristics. The specificity and sensitivity test for the miR-101 marker shows a significant specificity of 60 % and sensitivity of 75 % with a p-value of 0.001 and a cut-off value of 0.897. Conclusions: The current research determined that miR-101 works as a diagnostic biomarker for AA.

Abstract Background Noncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet’s disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis. Methods Bioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values. Results The expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD. Conclusion Mechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures. Trial registration The protocol for the clinical studies was approved by Cairo University’s Faculty of Pharmacy’s Research Ethics Committee (approval number: BC 3590)

Abstract Background Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia. Methods The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction. Results High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5–45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2–9.8) (p = 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively. Conclusions The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

Abstract Background Diabetes mellitus is a disease that may result from interaction between environmental factors and a strong genetic component. The current study is aimed at exploring three single nucleotide polymorphisms to identify the associated ones with type 2 diabetes in the Egyptian society. The studied single nucleotide polymorphisms (rs10096097 in GOAT, rs6740584 in CREB1, and rs62521874 in MAFA) were examined via genotyping cases (n = 98) and irrelevant healthy subjects (n = 82). Results Associations were checked using dominant, recessive, genotypic, allelic, and Cochran–Armitage trend models. By comparing diabetic patients with controls, rs6740584 was associated with type 2 diabetes by employing all used models except the recessive model. Rs10096097 was connected with type 2 diabetes using the genotypic association, Cochran–Armitage trend test, and recessive model and not any other model. Rs62521874 was not linked with type 2 diabetes in all models. Moreover, haplotype association for rs10096097 and rs62521874 was conducted as these two single nucleotide polymorphisms were located on the same chromosome. The haplotype pattern rs10096097:G—rs62521874:A was identified as a biomarker for type 2 diabetes susceptibility in the Egyptian community. Conclusions The GOAT and CREB1 polymorphisms showed susceptibility to type 2 diabetes. Moreover, MAFA had no role in the disease except through the haplotype with GOAT polymorphism.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16–9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57–16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p

Abstract The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51–14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets’ expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren’t altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Background and aims: Systemic sclerosis (SSc) is a common autoimmune disorder involving the skin, blood vessels, and internal organs with an elusive pathophysiology. SSc is believed to be a genetically prone T-cell-mediated autoimmune disease. miRNAs and lncRNAs were thought to be involved in the etiology of several immunological diseases including SSc. This work aimed to assess the expression of miRNA-133, lncRNA-H19, PKM2, and TGF-β levels in SSc in comparison to controls and their relationship to the clinical course and severity of disease. Patients and methods: Fifty patients with SSc and 40 healthy age and sex-matched controls were included in this study. miRNA-133 and H19 expression levels were detected using quantitative RT-PCR while serum levels of PKM2 and TGF-β were measured using ELISA techniques. Patients’ clinical data and treatments received were extracted and correlated with proteins investigated. Results: Our results showed that miRNA-133 was significantly downregulated in SSc patients in comparison to controls (Mean + SD of SSc = 0.61 ± 0.22, Mean ± SD of HC = 0.97 ± 0.007, p = 0.003). However, there was significant upregulation of the serum expressions of all other tested biomarkers in SSc patients in comparison to controls; H19 (Mean + SD of SSc = 10.37 ± 3.13, Mean ± SD of HC = 1.01 ± 0.01, p = 0.0001), PKM2 (Mean + SD of SSc = 28.0 ± 4.84, Mean ± SD of HC = 16.19 ± 1.32, p = 0.005) and TGF-β (Mean + SD of SSc = 150.8 ± 6.36, Mean ± SD of HC = 23.83 ± 0.93, p = 0.0001). We also detected several correlations between serum levels of the investigated proteins in patients with SSc. Conclusion: Along with TGF-β, our results show that miRNA-133, H19, and PKM2 seem to be potential contributors to SSc pathogenesis and could be promising biomarkers in the diagnosis of SSc patients. The lncRNA-H19 correlations with TGF- β, miRNA-133, and PKM2 suggest a possible influential effect of this RNA molecule on the pathogenesis of SSc.

Abstract Background People of Mediterranean descent are primarily affected by the autoinflammatory genetic condition known as familial Mediterranean fever (FMF). The disease is resistant to colchicine therapy in 10–20% of patients. Numerous recent animal studies showed promising results of extra virgin olive oil (EVOO) to control inflammation. The objective of this study was to assess the effectiveness of combining EVOO with colchicine in the treatment of colchicine-resistant familial Mediterranean fever (CRFMF) patients. Results Both the frequency of episodes and inflammatory indicators significantly decreased after a three-month course of daily EVOO treatment with colchicine. The average erythrocyte sedimentation rate (ESR) of patients was 78.6 mm/h before the EVOO administration, and it dropped to 27.8 mm/h, after that. Additionally, after taking EVOO, the mean serum amyloid A (SAA) decreased from 123.82 mg/dl to 59.78 mg/L. Also, the average C-reactive protein (CRP) decreased from 34.22 to 7.84 mg/dl following its administration; the mean nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) level decreased from 134.92 to 64.23 pg/ml. The mean caspase-1 level decreased from 7.8 to 4.98 ng/ml; and the mean levels of cytokines, interleukin 6 (IL-6), interleukin 1 beta (IL-1 β), and tumor necrosis factor-alpha (TNF-α) decreased from 9.8, 18.14, and 52.7 pg/ml, respectively, to 5.95, 12.51, and 29.39 pg/ml. Finally following the administration of EVOO, there was a notable overall improvement in the quality of life of (CRFMF) patients. Conclusion EVOO demonstrated a significant positive impact when paired with the tolerated dosage of colchicine in the management of CRFMF. Improvements were observed in both clinical and laboratory settings, including a reduction in the attack frequency and serum levels of inflammatory markers, such as NLRP3, caspase-1, ESR, CRP, IL-1β, IL-6, and TNF-α without any negative side effects.

Abstract Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has a high incidence of spread. On January 30, 2020, the World Health Organization proclaimed a public health emergency of worldwide concern. More than 6.9 million deaths and more than 768 million confirmed cases had been reported worldwide as of June 18, 2023. This study included 51 patients and 50 age- and sex-matched healthy subjects. The present study aimed to identify the expression levels of lncRNA CASC2 and miRNA-21-5p (also known as miRNA-21) in COVID-19 patients and their relation to the clinicopathological characteristics of the disease. The expression levels of noncoding RNAs were measured by RT-PCR technique. Results detected that CASC2 was significantly downregulated while miRNA-21-5p was significantly upregulated in COVID-19 patients compared to healthy subjects. A significant negative correlation was found between CASC2 and miRNA-21-5p. ROC curve analysis used to distinguish COVID-19 patients from controls. MiRNA-21-p serum expression level had a significant positive association with temperature and PO2 (p = 0.04 for each). These findings indicate that CASC2 and miRNA-21-p might be used as potential diagnostic and therapeutic biomarkers in COVID-19.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Several studies demonstrated the role of lncRNAs and miRNAs in the pathogenesis of preeclampsia; the aim was to detect the expression profiles of serum LncRNA ANRIL, miR-186, miR-181a, and MTMR-3 in patients with preeclampsia. The study included 160 subjects divided into 80 subjects considered as a control group, 80 patients with preeclampsia. We found that there was a significant difference between the preeclampsia and control groups with up-regulation of miR-186 median (IQR) = 4, 29 (1.35–7.73) (P

Psoriasis is a persistent inflammatory skin disorder driven by T cells. The disease is characterized by aberrant keratinocytes (KCs) differentiation, epidermal proliferation, and excessive hyperplasia of veins and arteries. The purpose of the study was to identify the levels of circulating lnc-HULC, miR-122, and Sirtuin 1 (SIRT-1) in psoriatic patients, evaluate their possible roles as diagnostic biomarkers, and link their levels with the development of metabolic syndrome during psoriasis progression. This study included 176 participants. The subjects were divided into four groups, with 44 participants in each group. All patients have undergone a complete history taking and clinical examination. Laboratory investigations included Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides (TG), Fasting blood sugar (FBS), and cholesterol plasma levels. Serum levels of miR-122 and lnc-HULC were examined by qRT-PCR. Serum levels of SIRT-1 were examined by ELISA. The serum concentrations of lnc-HULC and miR-122 were significantly higher in psoriatic participants compared to controls. Psoriatic patients' serum concentrations of SIRT-1 were much lower than those of healthy individuals. There was a negative association between SIRT-1 concentration and BMI, disease duration, PASI score, LDL, and cholesterol levels. The blood levels of lnc-HULC, miR-122, and SIRT-1 in psoriasis patients provide a promising role as diagnostic biomarkers in patients with and without metabolic syndrome.

Background: Thyroid hormones (THs) signaling has profound effects on many physiological processes. The regulation of THs signaling in various tissues involves the action of microRNAs (miRNAs) on thyroid deiodinases and receptors. THs regulate the expression of certain miRNAs and their target messenger RNAs (mRNAs) in various tissues and cells. The modulation of miRNA levels by THs affects their functions in processes such as liver lipid metabolism, skin physiology, and muscle and heart performance.Aim: This research aimed to investigate miR-181b, miR-206, and miR-21 in the serum of patients with subclinical and overt hypothyroidism to determine their possible role in the diagnosis of the disease and their relationship to clinical disorders related to hypothyroidism.Methods: This study included ninety participants, divided evenly into three groups as follows: patients with overt hypothyroidism diagnosed clinically, radiologically, and by investigation, subclinical hypothyroid patients, and healthy volunteers. The patients had a thorough medical history and underwent a clinical examination. Laboratory tests included plasma cholesterol, LDL, HDL, TGs, liver and renal function tests, CBC, fasting insulin, HOMA-IR, HbA1c, TSH, and free T4. The serum levels of miR-21, miR-206, and miR-181b were measured using qRT-PCR.Results: miR-206 and miR-181b levels were higher in the subclinical group, followed by the hypothyroid and control groups. For miR-21, there was a significantly lower mean value in both the hypothyroid and subclinical groups than in the control group, with no difference between the two groups. Both miR-206 and miR-181b showed a significant negative association with albumin and free T4 levels and a significant direct association with GGT, ALT, AST, creatinine, uric acid, TGs, TC, LDL, TSH, thyroid volume, and CAP score. The same correlation pattern was observed for miR-181b, except that it was not significantly correlated with the TGs. For miR-21 levels, there was a significant positive correlation with albumin, free T4 level, and kPa score and a negative correlation with GGT, ALT, AST, creatinine, uric acid, HOMA-IR, HbA1c, TC, LDL, TSH, and CAP score. Cases with F1 kPa score and S2 CAP scores had significantly higher averages for miR-206 and miR-181b, with a p-value of 0.05. Moreover, miR-21 levels were significantly lower in the S2 CAP score group.Conclusion: These miRNAs (miR-206, miR-181b, and miR-21) may be used as diagnostic biomarkers for hypothyroidism. They may be used as therapeutic targets to control dyslipidemia and hepatic steatosis during hypothyroid disease.

Background. Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma where red rash exists on the skin. Understanding the role of miRNAs and ncRNAs in p53-response has become an open discussion, as they can regulate p53 or its downstream targets, and ncRNAs themselves. Objectives. To evaluate the serum levels of NEAT-1, miR-34a, and p53 in MF patients and its relation to healthy controls to indicate whether it has a potential role in the pathogenesis of the disease. Subjects and Methods. This prospective case-control study was carried out on 75 subjects subdivided into two groups, 35 MF patients (stages 1 and II) and 40 matched healthy controls. Their clinical investigations and serum biomarkers (NEAT-1, miR-34a, and p53) were measured. Results. There were significant elevations in the expression levels of both NEAT-1 (5.10 ± 1.16) and p53 (277.28 ± 62.02) in the serum of MF patients in comparison with controls (1.01 ± 0.031) and (194.29 ± 16.039), respectively, while the level of miR-34a tends to decrease in MF patients (0.24 ± 0.15). There are no significant difference between MF stages and the level of miR-34a, while in NEAT-1 and p53, there are significant differences with p value

Numerous malignancies, including colorectal and liver cancers, are ultimately more likely to occur in obese people, and chronic inflammatory conditions have been linked to this association. We are attempting to determine the clinical relevance of the mechanisms controlling the microRNA (miR-215 and miR-146a) expression and transforming growth factor-β (TGF-β)/interleukin-6 (IL-6) in a cross-link axis between obesity and colorectal cancer (CRC). Study participants were divided into four groups: healthy controls; obese without colorectal cancer; non-obese colorectal cancer; and obese with colorectal cancer. Obese and CRC patients had markedly higher expression of IL-6 and TGF-β, as well as tumor biomarkers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9), and alpha-fetoprotein (AFP) levels. The relative expression of microRNAs (miR-215 and miR-146a) was significantly lower in obese patients with colorectal cancer. BMI and the microRNAs(miR-215 and miR-146a) showed a substantial negative correlation. TGF-β was favorably linked with IL-6, cholesterol, triglyceride levels, and BMI. High levels of TGF-β and IL-6 in the blood indicate how intensely inflammation develops in obesity, which could increase the risk of colorectal cancer.

Abstract Background Colorectal malignant cells (CRC) are one of the world’s main causes of cancer mortality and morbidity. Notwithstanding the plenty of anti-CRC therapeutics, its prognosis remains not selective owing to cancer resistance to these therapeutics. Raloxifene (RX), a medication firstly used to treat osteoporosis, was recently licenced for the prevention of CRC. Unfortunately, due to medication resistance, many RX-based therapies are likely to become ineffective. Recently, we identified a novel method of administration to lengthen the half-life of RX by mixing it with chitosan (CS) and hyaluronic acid (HA). Thus, the rationale of the current study was to investigate how colon cancer cells were affected by RX-HA-CS nanoparticles (RX NPs) in terms of targetability, cytotoxicity, and epigenetic cascade alteration. Results RX NP had an entrapment efficiency (EE%) of 90.0 ± 8.12%. Compared to HCT 116 cells, Caco-2 cells were more susceptible to the cytotoxic effects of RX and its NP as well as they had a higher binding affinity to CD44 receptors compared to normal WI-38 cells. In comparison to the free RX, the RX NP’s cytotoxic fold changes in HCT 116 and Caco-2 cells were 2.16 and 2.52, respectively. Furthermore, the epigenetic cascade of some noncoding RNAs was examined. Moreover, particular protein concentrations were investigated in all tested cells after application of the proposed therapies. Our results showed that the RX NP recorded higher remarkable cytotoxic impact on CRC cells compared to the free RX. Intriguingly, it was hypothesized that RX nanoparticles attacked colon cancerous cells by up-regulating miR-944 and E-cadherin (ECN) expressions, while down-regulating the expressions of PPARγ, YKL-40, VEGF, H-19, LINC00641, HULC, HOTTIP, miR-92a, miR-200, and miR-21. Conclusions We may conclude that the RX NP effectively targets CRC cells in vitro via altering lncRNAs and miRNAs epigenetic cascade as well as cellular uptake through CD44-expressed CRC cells.

Background: Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension. Aim: While most studies in the field have focused on the functional roles of long noncoding RNAs (lncRNAs) NEAT1, GAS5, and HOTAIR in CVS, less attention has been paid to their clinical relevance to stroke incidence and prognosis. Also, a link has not yet been made between these lncRNAs and hypertension, our study aim was to investigate whether the expression of these lncRNAs differed between CVS with and without hypertension, as well as to compare each group to controls. Method: In total, 181 CVS patients were enrolled, including 91 chronic hypertensive patients with stroke, 90 stroke patients without hypertension, and 51 control subjects. blood samples were collected on the day of recruitment from patients with CVS and controls. Real-time qRT-PCR was used to detect the expression of target lncRNAs in serum. Results: When compared to controls, there was a statistically higher level of lncNEAT1 in each case group (median (IQR) = 3.68 (1.35–7.35) and 3.05 (0.95–6.45) for the hypertensive and non-hypertensive groups, respectively, with a significantly higher level in the hypertensive group (P = 0.04). When compared to controls, lncHOTAIR was significantly downregulated in all case groups (medians in hypertensive and non-hypertensive patients were 0.13, and 0.34, respectively), with a significantly lower level in the hypertensive group (P = 0.05). LncGAS5 levels in patients were significantly lower (median (IQR) = 0.16 (0.02–0.55) and 0.25 (0.03–0.99) for the hypertensive and non-hypertensive groups, respectively) compared to controls, with a significantly lower level in the hypertensive group (P = 0.02). There was a significant positive correlation between NEAT1 and GAS5, but a significant negative correlation between each with HOTAIR in both patients' groups. We also detected a significant negative correlation between each NEAT1 or GAS5 and NIHSS score while a significant positive correlation between HOTAIR and NIHSS. ROC curve analysis for GAS5 was able to differentiate patients with CVS hypertensive from patients with CVS non-hypertensive. Conclusion: Patients in each case group had statistically higher levels of NEAT1 and lower levels of HOTAIR and GAS5 compared to control levels, with higher significant NEAT1 but lower significant HOTAIR and GAS5 in the hypertensive group. Therefore, lncRNAs NEAT1, HOTAIR, and GAS5 could be used as diagnostic and prognostic biomarkers of CVS that correlate with NIHSS score and could produce a novel target for CVS therapy.

Abstract Introduction Essential oils (EOs) are complex structures and possess several pharmacological effects. Nanomedicine offers a solution for their major limitations, including poor solubility, volatility, and non–controlled release, preventing their clinical use. Methods Here, we developed a novel delivery system by nanoformulations that were prepared by impregnating savory essential oil (SA) into mesoporous silica nanoparticles (MSNs). The nanoformulations were characterized and examined for their anticancer activities on cancer cells (HepG2 liver and HL60 leukemia cells) and MRC5 normal cells. We further tested the mechanisms of action and possible molecular targets against HL60 cells. Results The results demonstrated that SA was governed by nanoformulations under the dual–trigger release of pH/glutathione, and it typically fit the Korsmeyer–Peppas kinetic model. The nanoformulations enhanced the anticancer effect against HepG2 cells and HL60 cells compared to SA but were less cytotoxic to MRC5 normal cells and regulated various molecular pathways of apoptosis. Most importantly, new results were obtained on the genetic regulation principle through the high inhibition of long noncoding RNAs (HOTAIR, HULC, CCAT1, and H19) and matrix metalloproteinases (MMP–2 and MMP–9), providing a novel leukemia target. Conclusions These results suggest potential impacts for nanoformulations composed of SA with a sustained release pattern controlled by dual–trigger release of pH/GSH that enhanced anticancer cells. This approach may offer a new route for using EOs as new targets for cancers and open the door for deep preclinical investigations.

Abstract The genetic and epigenetic architecture of clinical and subclinical hypothyroidism remains unclear. We investigated the impact of long noncoding RNA (LncRNA)-PAX8-AS1 and LAIR-2 genetic variants on the susceptibility to clinical and subclinical hypothyroidism, their influence on LncRNA-PAX8-AS1 and LAIR-2 expression and their potential as hypothyroid biomarkers. Hundred clinical hypothyroid patients, 110 subclinical hypothyroid patients, and 95 healthy controls were enrolled. Gene expression analysis and genotyping were performed by qPCR. LAIR-2 protein, a proinflammatory mediator, was tested by ELISA. Serum LncRNA-PAX8-AS1 was downregulated, whereas LAIR-2 mRNA and protein levels were upregulated in clinical and subclinical hypothyroid patients compared to healthy controls. LncRNA-PAX8-AS1 rs4848320 and rs1110839 were associated with increased risk of clinical hypothyroidism. Interestingly, both SNPs were associated with differential expression of serum LncRNA-PAX8-AS1 among clinical hypothyroid patients. LAIR-2 rs2287828 was associated with elevated risk of both clinical and subclinical hypothyroidism. Harboring the rs2287828 T allele augmented the LAIR-2 mRNA expression among clinical hypothyroid patients, while elevated both LAIR-2 mRNA and protein levels in subclinical hypothyroid patients. The rs4848320-rs1110839-rs2287828 TTT, CTT, and CGT haplotypes were associated with increased hypothyroid risk. Surprisingly, serum LncRNA-PAX8-AS1 and LAIR-2 mRNA expression demonstrated superior diagnostic accuracy for clinical hypothyroidism and turned out as independent predictors in the multivariate analysis. Conclusively, LncRNA-PAX8-AS1 and LAIR-2 genetic variants are novel genetic biomarkers of hypothyroidism that could alter the LncRNA-PAX8-AS1 and LAIR-2 expression. LncRNA-PAX8-AS1 and LAIR-2 expression profiles have the potential as effective diagnostic and prognostic indicators of hypothyroidism.

Key points 1. MIR146A (C allele) had a protective role in rheumatoid arthritis association. MTMR3 was associated with rheumatoid arthritis using the dominant, Co-dominant heterozygote and recessive models. MIR499/MIR499A had no association with rheumatoid arthritis.

Abstract New predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = − 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = − 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein–protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.

Abstract Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p

Objective: RNA-based mechanisms of epigenetic modification related to acute ischemic stroke (AIS) have been widely studied recently. The current work aimed to determine the potential roles of four ncRNAs (TUG1 and its target miR-21, NBAT1, and miR-335) as promising diagnostic biomarkers in AIS as well as their involvement in the disease pathogenesis.Methods: The levels of the studied lncRNAs and miRNAs were measured in the serum for two different groups, including patients with AIS (60) and healthy controls (60). All individuals were subjected to a full history investigation and clinical examination. Blood samples were tested for FBS, 2HPP, TAG, HDL, LDL, TSH, T3, and T4 levels.Results: The serum levels of TUG1 were significantly increased in AIS patients compared to control subjects. It is worthwhile to note that serum TUG1 levels were positively correlated with cholesterol, triglycerides, LDL, carotid IMT (Intima-media thickness), and miR-21, while they were negatively correlated with HDL levels. Our study showed that NBAT1 serum expression levels were elevated in AIS patients compared to controls. NBAT1 expression levels were observed to be positively correlated with triglycerides, TUG1, and miR-21. NBAT1 could distinguish between AIS patients and controls with a sensitivity of 100% and specificity of 100% at a cut-off point of 1.45. Regarding miR-335, we found that its expression levels were downregulated in AIS patients compared with healthy controls. It could distinguish between AIS patients and controls with a sensitivity of 73.3% and a specificity of 100% at a cut-off point of 0.796.Conclusion: Our results revealed that serum TUG1, miR-21, NBAT1, and miR-335 could be promising molecular diagnostic markers for AIS as these biomarkers could discriminate between AIS patients and healthy controls.

Abstract Background Behcet’s disease (BD) is a systemic inflammatory disease of the blood vessels and affects various body parts. This study aimed to determine the association of four single-nucleotide polymorphisms (SNPs) and BD in the Egyptian population using multiple statistical models and show the resulting associations along with previous studies of different populations. Four SNPs were examined for their association with BD: two SNPs from vitamin D receptor gene (FokI and BsmI) were selected and the other two were selected from miR-146a and miR-155. These four SNPs were selected for their association and role with BD in different populations and in the immune system. A marker check was conducted using the Hardy-Weinberg equilibrium and minor allele frequency. The associations were tested using four different statistical models: multiplicative, dominant, recessive, and codominant models. All statistical models used the odd’s ratio (OR) with confidence interval (CI) of 95% to evaluate the association of each SNP. Results BsmI showed association using the four models, while FokI did not show any association through any model. miR-155 showed association using the multiplicative and recessive models. miR-146a showed association using the multiplicative model only. Conclusions As a result, BsmI, miR-155, and miR-146a SNPs could have a role in the development of BD in the Egyptian population, while FokI could have a weak role, if any, in the development of BD in the Egyptian population.

Introduction The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet’s disease (BD) in the Egyptian population. Material and methods A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. Results The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728–103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928–182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013–6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet’s disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. Conclusions miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

Abstract Background It has been reported that Moringa oleifera (MO) has different medicinal properties. The aim of this study was to evaluate the hepatoprotective role of Moringa oleifera extract on acetaminophen-induced liver fibrosis in albino rats on a biochemical and histological basis. Forty male albino rats were divided into four groups: group I (control group), healthy rates; group II (acetaminophen group), rates received acetaminophen for induction of liver fibrosis; group III (treated group), liver fibrosis of rates treated with Moringa oleifera extract; and group IV (prophylactic group), rates treated with Moringa oleifera extract before and after induction of liver fibrosis. Serum liver function parameters were quantified using a spectrophotometer, while tumor necrosis factor α (TNF-α) and transformed growth factor beta (TGF- β) in liver tissue homogenate by means of enzyme-linked immunosorbent assay (ELISA), and expression of liver tissue TNF-α and TGF-genes was measured by real-time PCR after extraction and purification. Hepatic tissue was also evaluated under a microscope for histopathological changes. Results Our results showed a significant decrease in liver enzymes, TNF-α, and TGF-β in the treated and prophylactic groups compared to the acetaminophen group, and our biochemical data were consistent with the histopathological findings confirming the hepatoprotective effect of Moringa oleifera extract. Conclusions Biochemical parameters and histopathology results provide evidence that Moringa oleifera ethanolic extract has a great potential to prevent and improve liver damage due to its protective activity.

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke.Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays.Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke.Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.

Background: Psoriasis is a chronic skin disorder manifested by recurrent episodes of scaly, red, itchy skin patches that occur within apparently normal skin. Objectives: This study was performed to detect the expression of serum and tissue (lesion and non-lesion) LncRNA MALAT-1 and MiRNA-9 that might be used as biomarkers for psoriasis. Methods: Blood samples were obtained from 60 psoriasis patients and 40 controls, as well as 4 mm punch biopsy from lesional and non lesional skin of psoriatic patient and normal skin of healthy controls. Expression of LncRNA MALAT-1 and miRNNA-9 in serum and tissues was detected by real time qRT-PCR. Results: a statistically significant increase in the expression of MALAT-1 in lesional and non-lesional skin and serum of psoriatic patients in comparison to controls were detected. Moreover, there was statistically significant increase in serum MiRNA-9 in patients in comparison to controls, while its tissue level was significantly lower in patients. Conclusion: This study highlights the dysregulation of LncRNA MALAT-1 and miRNA-9 in psoriasis. Elevated expression of MALAT-1 in lesional skin of psoriatic patients compared to non-lesional skin may possibly contribute to the development of psoriatic plaques.

The human genome, which includes thousands of genes, represents a big data challenge. Rheumatoid arthritis (RA) is a complex autoimmune disease with a genetic basis. Many single-nucleotide polymorphism (SNP) association methods partition a genome into haplotype blocks. The aim of this genome wide association study (GWAS) was to select the most appropriate haplotype block partitioning method for the North American Rheumatoid Arthritis Consortium (NARAC) dataset. The methods used for the NARAC dataset were the individual SNP approach and the following haplotype block methods: the four-gamete test (FGT), confidence interval test (CIT), and solid spine of linkage disequilibrium (SSLD). The measured parameters that reflect the strength of the association between the biomarker and RA were the P-value after Bonferroni correction and other parameters used to compare the output of each haplotype block method. This work presents a comparison among the individual SNP approach and the three haplotype block methods to select the method that can detect all the significant SNPs when applied alone. The GWAS results from the NARAC dataset obtained with the different methods are presented. The individual SNP, CIT, FGT, and SSLD methods detected 541, 1516, 1551, and 1831 RA-associated SNPs respectively, and the individual SNP, FGT, CIT, and SSLD methods detected 65, 156, 159, and 450 significant SNPs respectively, that were not detected by the other methods. Three hundred eighty-three SNPs were discovered by the haplotype block methods and the individual SNP approach, while 1021 SNPs were discovered by all three haplotype block methods. The 383 SNPs detected by all the methods are promising candidates for studying RA susceptibility. A hybrid technique involving all four methods should be applied to detect the significant SNPs associated with RA in the NARAC dataset, but the SSLD method may be preferred because of its advantages when only one method was used. Keywords: Confidence interval test, Four-gamete test, Genome-wide association study, NARAC, Rheumatoid arthritis, Solid spine of linkage disequilibrium

Objectives. Periodontitis is characterized by inflammatory destruction of periodontal tissue, loss of attachment, and bone resorption. The increase in reactive oxygen species (ROS) is responsible for the oxidative damage occurring in periodontal tissues. Melatonin has important immunomodulatory, anti-inflammatory, and powerful antioxidant functions. The current study was carried out to evaluate the effect of topical melatonin gel as an adjunct to nonsurgical periodontal therapy. Methods. This split-mouth randomized controlled clinical trial was performed on 24 patients with grade II periodontitis. Two sites in each patient were randomly assigned; test sites were treated by nonsurgical therapy followed by intrapocket application of 5% melatonin gel. Control sites were treated by nonsurgical therapy followed by intrapocket application of placebo gel. Both the melatonin and placebo gel were applied weekly once for four weeks. Assessment of clinical parameters (PD and CAL) was done at baseline and 3 months after therapy. Total antioxidative capacity (TAC) and matrix metalloproteinase-9 (MMP-9) levels in GCF were also evaluated utilizing commercially available enzyme-linked immunosorbent assay kits (ELISA) at baseline and 3 months after therapy. Results. Treatment with topical melatonin was associated with a reduction in periodontal inflammation reflected as an improvement in the clinical periodontal parameters. Melatonin-treated sites showed a more statistically significant percent reduction in PD and more statistically significant percent gain in CAL than the control site. Additionally, a significant increase in TAC and a significant decrease in MMP-9 levels in GCF were found in melatonin-treated sites in comparison to control sites. Conclusions. The adjunctive use of topical melatonin gel with nonsurgical periodontal therapy has potent anti-inflammatory and antioxidant activity in the treatment of grade II periodontitis patients.

Polymorphisms of the renin-angiotensin system genes influence the pathogenesis of atherosclerosis and are connected with heart diseases. We explore the potential associations of ACE (I/D) and AGT (M235T) gene polymorphisms with coronary artery disease (CAD). A total of one hundred and twenty Egyptian patients (Sixty with CAD and sixty without CAD) and fifty healthy control subjects were included in the study. Genotyping of ACE (I/D) and AGT (M235T) were analyzed by the polymerase chain reaction (PCR) technique. Serum lipid profiles (total cholesterol, triglyceride, HDL-C) were measured by the enzymatic colorimetric method. Our data showed that the ACE D allele frequency (P

Objective: Long non-coding RNAs (lncRNAs) and their target microRNAs were documented in multiple studies to have a significant role in different joint disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA). The current work aimed to determine the potential role of lnc-PVT1 and miR-146a as promising biomarkers to distinguish between RA, OA patients, and healthy individuals. Methods: The expression levels of lnc-PVT1 and its target miR-146a in the serum were measured for three different groups, including patients with RA (40), OA patients (40), and healthy controls (HCs) (40). Participating individuals were subjected to a full history investigation and clinical examination. Blood samples were tested for ESR, RF, CBC, as well as liver and renal functions. Serum was used to detect the relative expression levels of lnc-PVT1 and miR-146a and we correlated the levels with RA and OA activity and severity signs. Results: Lnc-PVT1 expression level was greater among patients with RA compared to that of OA patients, with a fold change median of 2.62 and 0.22, respectively (p = 0.001). The miR-146a fold change was significantly demonstrated between the RA, OA, and HCs groups. There was no correlation between both biomarkers with the disease activity scales (DAS28) of RA, the Knee injury Osteoarthritis Outcome Score (KOOS), or any sign of detection of the disease severity of OA. Conclusions: lnc-PVT1 and miR-146a could be considered as promising biomarkers for the diagnosis of RA and OA and may have an important role as therapeutic targets in the future.

Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.

Background: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). Methods: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. Results: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). Conclusions: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.

Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field.

Background. Oral squamous cell carcinoma (OSCC) is the most common oral malignancy that preferentially spreads to the cervical lymph node which, when involved, complicates the anticancer therapy and threatens the patient life. It was suggested that lymph node metastasis may be facilitated by lymphangiogenesis. VEGF-C is one of the most important lymphangiogenic inducers that promotes the lymphatic vessels growth and supports the survival of adult lymphatic endothelial cells. Methods. Lymphatic vessels density (LVD) and LV morphometry were digitally evaluated using D2-40. The expression of VEGF-C was also assessed using immunohistochemistry and real-time polymerase chain reaction in 6 normal oral mucosa cases and 72 cases of OSCC. The correlation between LVD and LV morphometry, VEGF-C, and lymph node metastasis was statistically assessed. Results. A positive cytoplasmic expression of VEGF-C was detected in both epithelial and connective tissue cells in 97% of OSCC, while all normal tissues reacted negatively. A greater expression of VEGF-C was associated with larger and more dilated LV and lymph node metastasis but not with LVD. Conclusion. VEGF-C is actively involved in the invasion and metastasis of OSCC via inducing morphological changes in LV. VEGF-C may be a promising target for anticancer therapy.

Background. Tumor necrosis factor-alpha (TNF-α) is an important proinflammatory cytokine which plays an important role in the immunopathogenesis of Behcet’s disease (BD). B cell activating factor (BAFF) and its homolog A proliferation inducing ligand (APRIL) are members of the tumor necrosis factor family. BAFF binds to 3 receptors, B cell activating factor receptor (BAFF-R), transmembrane activator and calcium modulator ligand interactor (TACI), and B cell maturation antigen (BCMA) that are expressed by B cells. Objective. Estimation of the serum levels of TNF-α, APRIL, BAFF, and BCMA in patients with BD in an effort to evaluate their degree of involvement in the pathogenesis and development of BD. Patients and Methods. This study included 30 male patients fulfilling the international study group criteria for the diagnosis of BD. Twenty age-matched healthy male volunteers served as control. Serum samples were used for quantification of TNF-α, APRIL, BCMA, BAFF, and hsCRP using ELISA techniques. Results. The mean serum levels of TNF-α, APRIL, BCMA, and BAFF were more elevated in cases than in controls in a statistically significant manner (P

Objectives. This study evaluated IL-17 and IL-11 in gingival crevicular fluid (GCF) of generalized chronic periodontitis (GCP) and generalized aggressive periodontitis (GAgP) patients in relation to periodontopathic bacteria. Subjects and Methods. GCF samples were collected from 65 subjects including 25 CP, 25 GAgP, and 15 controls (C) and analyzed for IL-17 and IL-11 by an enzyme-linked immunosorbent assay. Molecular detection of bacteria in the dental plaque was determined by polymerase chain reaction. Results. The total amount of IL-17 was significantly higher in GAgP group than in GCP and C groups (P

To explore the feasibility of detecting salivary levels of IFN-γ, TNF-α, and sTNFR-2 from erosive oral lichen planus (ELP) patients for clinical application, 20 ELP patients were enrolled in the study as were 20 age-sex-matched controls. From all subjects, saliva level of the tested biomarkers was determined by ELISA. Salivary profiles were assessed in ELP patients by ELISA after being treated with prednisone. A significantly higher level of IFN-γ (P≤.01), TNF-α (P≤.0001), and sTNFR-2 (P≤.01) was detected in ELP patients before treatment than in controls. Following treatment, the salivary levels of IFN-γ (P≤.01), TNF-α (P≤.05), and sTNFR-2 (P≤.01) decreased significantly when compared to their pretreatment levels. This study demonstrated that salivary IFN-γ, TNF-α, and sTNFR-2 can be detectable in ELP patients and decreased significantly after treatment with prednisone, which may reveal the possibility of using these disease-related biomarkers in diagnosis and monitoring.

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population.