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Despite the increased proof that long noncoding RNAs (lncRNAs) can control gene expression and broadly affect the normal physiological and disease conditions, the part of lncRNAs in rheumatoid arthritis (RA) is not well known. This study aimed to assess the serum expression levels of lnc-Cox2 and HOTAIR in RA and to investigate their role as novel noninvasive biomarkers in diagnosis of RA. Also, their relations with the levels of interleukin (IL)-6 and matrix metalloproteinase (MMP)-9 and with other clinicolaboratory data in RA patients were analyzed. LncRNAs-Cox2 and HOTAIR expression levels were detected in serum by real-time quantitative polymerase chain reaction. Both IL-6 and MMP-9 levels in serum were measured by enzyme-linked immunosorbent assay. The mRNA expression of lncRNA-Cox2 and HOTAIR was significantly upregulated in RA patients compared with healthy controls. Serum levels of both IL-6 and MMP-9 were significantly higher in RA patients than in healthy subjects (P 0.001 each). Receiver operating characteristic (ROC) curve demonstrated that lncRNA-Cox2 and HOTAIR could discriminate RA patients from healthy controls. HOTAIR (not lnc-Cox2) was observed to be an independent predictor for RA using multiple logistic regression analysis. We concluded that lnc-Cox2 and HOTAIR serum expression levels can be used as novel noninvasive biomarkers for the diagnosis of RA.

Populations' allele frequency studies are one of the major topics of Population genetics. In this research, an Allele Frequency Quality Control System (AFQCS) is proposed as a verification tool for populations' genetics data. This system visualizes and analyses statistically the allele frequencies of 15 Short Tandem Repeats (STRs) autosomal loci based on 65 previously published population genetics studies. Allele Frequency Trajectories (AFTs) for all addressed populations were plotted. The AFTs showed a distinct trend for each locus, which was used to build a global reference template for these loci. Pearson's Correlation Coefficient Matrices (CCM) generated for each locus were used to calculate different statistical parameters to assess the genetic populations' relationships, such as histogram, median, interquartile range, and p-value. P-values and interquartile ranges supported the visualization results by indicating the presence of a global AFT pattern for each locus. The novel developed AFTs template illuminates the idea of the first quality control system for testing new datasets, based on the high genetic similarity among populations. From CCMs statistical results, wide spectrums recorded in loci TH01, D13S317, D2S1338, D18S51, and FGA indicate significant populations' genetics heterogeneity.

Background: Various therapeutic agents have been described for alopecia areata but none is satisfactory. The use of ultraviolet A phototherapy in phototoxic regimens has emerged lately with promisi...

Aim of work To determine level of ischemia-modified albumin (IMA) in patients with Behçet’s disease (BD) and to assess its role in disease manifestations and activity. Patients and methods The study included 48 patients with BD and 38 matched controls. Disease activity was estimated by the BD current activity form. Serum IMA was measured. Results Mean age of the patients was 33.8±7.9 years. There were 42 males and six females, and the disease duration was 52.9±48.8 months. The serum IMA level was significantly increased in the patients with BD (50.9±12.9 U/ml) compared with the control (7.76±1.6 U/ml) (P

Background Microneedling is an evolving approach in the treatment of postburn scars based on the principle of collagen induction and neovascularization. Objective To evaluate and compare the clinical and histopathological outcome of microneedling versus ablative fractional CO2 laser targeting atrophic postburn scars. Patients and methods Twenty-five patients with atrophic postburn scars were included in this study. Each patient received four treatment sessions of both microneedling and fractional CO2 laser with 4-week interval. Histopathological and histochemical evaluations of collagen and elastic fibers were done. Quantitative morphometric studies were also performed. Results A significant increase in collagen deposition was detected after fractional CO2 laser therapy. A significant increase in elastic fiber deposition was detected after both laser therapy and microneedling with fractional CO2 laser showing more significant results than microneedling. Conclusion Ablative fractional CO2 laser is more effective than microneedling in the treatment of atrophic postburn scars; however, microneedling did show a significant increase in elastic fiber deposition and thus can be a promising therapeutic approach when combined with other treatment modalities.

Background The role of the long non-coding RNAs (lncRNAs) in the pathogenesis of systemic lupus erythematosus (SLE) is mostly unknown, despite increasing evidence that lncRNAs extensively participate in physiological and pathological conditions. Aim To detect the level of lncRNA-Cox2, HOTAIR, IL-6, and MMP-9 in the serum of SLE patients and to correlate these levels with disease activity and patients’ clinical and laboratory data to evaluate the value of these biomarkers for SLE diagnosis and assessment of disease activity. Methods Blood samples from 58 SLE patients, and 60 healthy controls (HCs) were used for detection of lncRNAs-Cox2 and HOTAIR expression levels by real-time polymerase chain reaction. Both IL-6 and MMP-9 serum levels were assayed by enzyme-linked immunosorbent assay. Lupus activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results The serum expression levels of lncRNA-Cox2 and HOTAIR were significantly up-regulated in SLE patients vs HCs (fold change [median (IQR) was 1.29(0.81–1.71, PP = 0.038) for lncRNA-Cox2 and HOTAIR, respectively. Serum levels of both IL-6 and MMP-9 were significantly high in SLE patients compared with HCs (P≤0.001 for each). The up-regulated lncRNA-Cox2 was positively associated with the presence of neurological manifestations in SLE patients (P = 0.007). Furthermore, HOTAIR expression level had significantly positive correlation with IL-6 (r = 0.578, P(r = 0.762, Pr = 0.296, P = 0.024) and proteinuria (r = 0.287, P = 0.035). LncRNA-Cox2 showed sensitivity and specificity 72.4%, and 100.0% respectively. HOTAIR sensitivity was 60.3%, and specificity was 100.0%. By multiple logistic regression analysis, lncRNA-Cox2 and HOTAIR were found as SLE independent predictors. Conclusion LncRNA-COX2 and HOTAIR can be used as new non-invasive biomarkers for the diagnosis of SLE.

Colorectal cancer (CRC) is major aliment around the word, with a cumulative rate of mortality. Metformin (MT) was recently approved as anticancer drug against solid tumors, such as CRC. Resistance to MT therapy remains to be a challenging matter facing the development of possible anti-cancer strategy. To circumvent this problem, MT nano-encapsulation has been introduced to sensitize resistant cancer cells. The purpose of the current study is to explore the MT's aptitude encapsulated in lecithin (LC) and chitosan (CS) nanoparticles to inhibit CRC proliferation through modulations of long noncoding RNAs (lncRNAs), micro RNAs (miRNAs), and some biochemical markers.Cytotoxic screenings of the newly synthesized MT-based regimens; MT, MT-LC NPs (NP1), MT-CS NPs (NP2), and MT-LC-CS NPs (NP3) against colorectal cancerous Caco-2 and HCT116 cell lines versus normal WI-38 cells were performed. The epigenetic mechanistic effects of these proposed regimens on lncRNAs and miRNAs were investigated. Additionally, some protein levels were assessed in CRC cells upon treatments; YKL-40, PPARγ, E-cadherin (ECN), and VEGF. We resulted that NP1 recorded the highest significant cytotoxic effect on CRC cells. HCT116 cells were more sensitive to the NP1 compared to Caco-2 cells. Intriguingly, it was suggested that NP1 tackled the CRC cells through down-regulation of the H19, HOTTIP, HULC, LINC00641, miR-200, miR-92a, miR-21, YKL-40, PPARγ, and VEGF expressions, as well as up-regulation of the miR-944 and ECN expressions.We concluded that the NP1 can potentially be cytotoxic to CRC cells in-vitro by modulating noncoding RNA.

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 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.

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 &lt, 0.001, p &lt, 0.001, and p &lt, 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 &lt, 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 &lt, 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 &lt, 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.

Genetic variants in microRNAs (miRNAs) can alter the miRNAs expression and/or function, accordingly, affecting the related biological pathways and disease risk. Dysregulation of miR-155 and miR-146a expression levels has been well-described in viral hepatitis B (HBV). In the current study, we aimed to assess rs767649 T/A and rs57095329 A/G polymorphisms in miR-155, and miR-146a genes, respectively, as risk factors for Chronic HBV (CHBV) in the Egyptian population. Also, we aimed to do in silico analysis to investigate the molecules that primarily target these miRNAs. One hundred patients diagnosed as CHBV and one hundred age and sex-matched controls with evidence of past HBV infection were genotyped for miR-155 (rs767649) and miR-146a (rs57095329) using real-time polymerase chain reaction. The rs767649 AT and AA genotypes in CHBV patients confer four folds and ten folds risk respectively, as compared to control subjects [(AOR = 4.245 (95%CI 2.009–8.970), pppp = 0.004] and [AOR = 5.604 (95%CI 2.157–14.563), p

AIM To assess the effect of Neem versus 2.5% NaOCl as root canal irrigants on the intensity of post-operative pain and amount of endotoxins following root canal treatment of mandibular molars with necrotic pulps. METHODOLOGY This parallel, prospective, double-blinded, randomized controlled trial with allocation ratio 1:1 was conducted in the out-patient clinic of the Endodontic Department, Faculty of Dentistry, Cairo University, Egypt. Fifty healthy patients with mandibular molars with necrotic pulps were randomly assigned into two equal groups using computer software. In the intervention group, root canals were irrigated using Neem; whilst 2.5% NaOCl was used in the control group. A standard root canal treatment was performed in two visits using ProTaper Next rotary files, with no intracanal medication. Pain intensity was assessed using a numerical rating scale (NRS) 6, 12, 24 and 48 h following instrumentation and canal filling. Endotoxin samples were collected using three paper points before and after canal instrumentation and a sandwich ELISA method was used to quantify the level of endotoxins. Demographic, baseline, and outcome data were collected and analysed using chi-square tests (for the comparisons of categorical variables), Mann-Whitney tests (for non-normally distributed variables) and Student's t tests (for normally distributed variables), A P-value

Background Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system (CNS). Long non-coding RNAs (lncRNAs) were believed to play a role in the pathogenesis of neurological disorders including MS. lincR-Ccr2-5′AS is expressed in the T helper2 (Th2) lineage. TNF-α heterogeneous nuclear ribonucleoprotein L (THRIL) causes the induction of TNF-α and regulates innate immune response and inflammation. We investigated the expression of lincR-Ccr2-5′AS and THRIL in MS to clarify their association with MS risk and the clinical features. Results LincR-Ccr2-5′AS was significantly downregulated in MS patients (fold change = 0.43±0.29, p = 0.03). The expression level was significantly low in patients with motor weakness and optic neuritis, patients with Expanded Disability Status Scale (EDSS) ≥5.5, and treatment-naïve patients. THRIL was significantly upregulated in MS patients (fold change = 6.18±2, p = 0.02). Its expression was significantly higher in patients with relapsing-remitting multiple sclerosis (RRMS), patients with motor weakness, patients with EDSS ≤5, and patients who received interferon. Conclusion Our results showed the downregulation of lincR-Ccr2-5′AS and the upregulation of lncRNA THRIL in MS patients. This differential expression of both lncRNAs may have an important role in MS pathogenesis.

It is quite clear that the ability to perceive taste sensations significantly affects food choice, which consequently affects health status in the long term. Gustatory dysfunction is a neglected symptom among the depressed patients and those under antidepressants therapy, although these patients are suspectable to oral problems, due to general self-negligence related to mental disease, fear of dental treatment, and side effects of varied medications utilized in psychiatry. This study is aimed at assessing gustatory thresholds (detection and recognition thresholds) among a sample of 30 depressed Egyptian adults under antidepressants therapy for at least 3 months or psychotherapy with age ranging from 20 to 50 years old, seeking the Psychiatric Clinic at the Faculty of Medicine, Cairo University, Egypt. These patients were distributed into three equal groups (tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRIs), and psychotherapy) and were assessed for gustatory detection and recognition thresholds using the filter paper disc method through a scoring system. The participants were also divided into normal taste group in which both the detection and recognition scores were 1, while the scores from 2 till 5 were considered as hypogeusia group and the score of 6 was considered as dysgeusia group. The TCA group was statistically significant from the other 2 groups in sweet detection thresholds ( p = 0.043) and sweet recognition thresholds ( p = 0.007). Hypogeusia for sweet was statistically significant ( p = 0.041), where it was more common among TCA (70%) than both SSRIs and the psychotherapy group (20%). Gustatory dysfunction was found to be mostly associated with TCA followed by SSRIs particularly for sweet taste thresholds. More attention has to be given to taste changes among these patients as oral health affects general health by causing considerable pain and by changing what people eat, their speech, and their quality of life and wellbeing. Proper awareness and evaluation of this problem will improve the quality of life for the depressed patients and avoid unnecessary treatment. This trial is registered with ClinicalTrials.gov ID: NCT03599011.

Background: This randomised, prospective, controlled trial aimed to assess the effect of reciprocatingsingle-file and rotary instrumentation on the intensity of postoperative pain and the amount of endotoxins inprimarily infected root canals.Methodology: Forty participants were randomly assigned into two equal groups according to root canalinstrumentation technique (n = 20), control group: root canals were instrumented using ProTaper Next rotarysystem and intervention group: canals were instrumented using WaveOne Gold reciprocating instrumentationsystem. Root canal treatment was carried out on two visits and postoperative pain of participants wasmeasured using a numerical rating scale (NRS) at predetermined time intervals 6, 12, 24, 48 hours afterinstrumentation and obturation appointments. Quantification of endotoxins was done using the Sandwich-ELISA method at predetermined time intervals (after access cavity preparation and after completion ofinstrumentation). Pain score data were summarised as mean and standard deviation.Results: No statistically significant difference was noted between the single-file reciprocating system(WaveOne Gold) and the multiple-file rotary system (ProTaper Next) regarding postoperative pain andreduction in the amount of endotoxins (P > 0.05).Conclusion: Both single-file reciprocating instruments and multi-file rotary instruments resulted in mild tomoderate postoperative pain and comparable reduction of endotoxins level.

Keloids result from uncontrolled inflammation and fibrosis during wound healing. Vitamin D can regulate skin proliferation and inflammation. Fibroblasts are vitamin D-responsive target cells and are source of koebnerisin (an antimicrobial peptide released during inflammation and wound healing). This study aimed to assess the levels and correlations between the serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin (S100A15) in patients with keloids. Nineteen patients with keloids and 20 matched controls were recruited. From each keloid patient, a serum sample and two biopsies were taken from the keloid (lesional) (Tissue A) and from normal skin (non-lesional) (Tissue B). From controls, a serum sample and a tissue biopsy from normal skin were taken. Serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin were measured in retrieved samples using ELISA. Results revealed a significantly lower serum 25-Hydroxyvitamin D, tissue vitamin D receptors, as well as, serum and tissue koebnerisin in keloid patients compared to controls. Tissue 25-Hydroxyvitamin D was significantly lower in keloidal skin biopsy (Tissue A) compared to non-lesional normal skin biopsy (Tissue B). Tissue koebnerisin showed a significant positive correlation with tissue vitamin D receptors, and a significant negative correlation with tissue 25-Hydroxyvitamin D. There was a significant negative correlation between serum 25-Hydroxyvitamin D and duration of keloid. Accordingly, low serum and tissue 25-Hydroxyvitamin D and deficient tissue vitamin D receptors contribute to the pathogenesis of keloids. This can be partly mediated by dysregulation of the antimicrobial peptide; koebnerisin. Artificial antimicrobial peptides and koebnerisin-modifying drugs, for example, vitamin D and TNF-α inhibitors can have a role in keloid prevention and treatment.

Background: Recent studies have demonstrated negative associations of serum uric acid (SUA) with serum 25 hydroxy vitamin D (25 [OH] vit D) among CKD patients. Objective: The aim of the study was to look for the impact of hypouricemic therapy using allopurinol on serum level of 25 (OH) vit D in CKD patients. Cases and Methods: Seventy-two CKD stage 3–5 patients were selected to this study. Patients with SUA above 7 mg/dL were allocated to hypouricemic therapy using allopurinol (group I). A control group of cases not suffering marked increase in SUA were included as control group (group II). All cases were followed up for 3 months. Serum Cr, SUA, ionized calcium (SiCa), phosphorus, 25 (OH) vitD, parathyroid hormone (PTH), and 24-h urine protein were estimated at entry and by the end of the study. Results: At least 20 cases completed the study in each group. Serum 25 (OH) vit D significantly increased in group I (26.4 [14.1] vs. 39.6 [14.8] at entry vs. at end of the study, p < 0.001). In addition, SUA, PTH, and urine protein significantly decreased (11 [1.6] vs. 3.95 [0.58] mg/dL, 267.5 [97.5] vs. 225.5 [153] ng/mL, and 2.7 [1.18] vs. 1.5 [1.08] gm/day, p < 0.001, = 0.043, and p < 0.001 and = 0.007, respectively). Conclusion: This study supports a negative causal relationship between SUA and serum 25 (OH) vit D. Further studies are still needed to confirm this conclusion.

Heat-shock proteins (HSPs) are a group of proteins that function to protect cells and tissues against different types of damage. The aim of this work was to study the relationship between the genetic variation in HSP70 genes and the risk for development of nephropathy in Egyptian patients with Type 2 diabetes mellitus (DM). This study was carried out on 90 patients divided into three groups: 30 patients of Type 2 DM with nephropathy (Group I), 30 patients of Type 2 DM without nephropathy (Group II) with duration of diabetes > 10 years in both patient groups, and 30 healthy persons, who served as controls (Group III). All the studied patients were submitted to full history taking, complete clinical examination, and laboratory investigations including fasting blood glucose, glycated hemoglobin, renal function tests, and urinary albumin- to-creatinine ratio. HSP70-1 -110 AC, +190 G/C, HSP70-2 +1267 A/G, and shock protein70- hom +2437 T/C gene polymorphism were determined using the polymerase chain reaction- restriction fragment length polymorphism technique (PCR-RFLP). The results of the present study showed a highly statistically significant difference between Group I and Group II regarding family history, systolic and diastolic blood pressure, and duration of diabetes. There was a significant difference in the distribution of C allele of HSP70-1 -110A/C and +190 G/C and G allele of HSP70-2+1267A/G with more frequent detection in nephropathy group versus other groups, while there was no significant difference in genotype and allele distributions among the three studied groups for the HSP70-hom. It can be concluded that the C allele distribution of (HSP70-1 -110 A/C and HSP70+190 C/G) and the G allele distribution of HSP70-2 +1267A/G are associated with the susceptibility to renal complications in Egyptian patients with Type 2 DM.

Multiple Sclerosis (MS) is an autoimmune disease that severely impacts the central nervous system. Thanks to the evolutionary genetic information studied and published, researches have started to study MS from a genetic perspective. This paper provides a study of six single-nucleotide polymorphisms (SNPs)—MIR137HG (rs1625579), GAS5 (rs2067079), MIR3142HG (rs57095329), MIR146A (rs2910164), MIR155HG (rs767649) and IRAK1 (rs3027898)—and demonstrates their association with MS. This study was applied over an Egyptian dataset of 38 MS patients and 35 controls. Hence, different models were applied, Dominant, Recessive and Genotypic models along with Fisher’s Exact method, Basic case–control analysis and Logistic regression analysis. This paper shows that the SNPs rs1625579, rs57095329, rs767649 and rs3027898 are associated with MS (p value

Background: Systemic Lupus Erythematous (SLE) is a chronic systemic autoimmune disorder whose diagnosis depends on combination of multiple factors. Circulating lncRNAs could serve as diagnostic non...

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 AC and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 AC single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868

Background Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. MicroRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data. Methods One hundred and twenty Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively. Results Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC = 0.85, whereas serum APRIL superiorly distinguished the two groups with AUC = 1 (sensitivity and specificity = 100% at cutoff> 4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction. Conclusion Our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.

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.

MicroRNAs (miRNAs) have critical roles in colorectal cancer (CRC) tumorigenesis and development. It has been reported that Eph receptor A7 (EphA7) was a potential target of miR-944 which is transcriptionally activated in cancer. The aim of this study was to explore the expression profile of miR-944 and its target gene EPHA7 in the serum of Egyptian CRC patients. 150 CRC patients, 50 adenomatous polyps (AP) patients, and 100 healthy controls were included. Serum miR-944 was downregulated (0.304 ± 0.0512) while serum EPHA7 was upregulated (3.163 ± 0.610) in CRC and AP patients versus controls and discriminated aganst these groups by Receiver operating characteristic curve (ROC) analysis. miR-944 presented the highest diagnostic accuracy for CRC patients from control (AUC = 0.90). Moreover obvious prognostic power in distinguishing AP from CRC (AUC = 0.87). In conclusion, miR-944 and EPHA7 are potential genetic markers of CRC predisposition and novel potential non-invasive diagnostic biomarkers for CRC.

The pathogenesis of multiple sclerosis (MS) is influenced by the interaction of genetic and epigenetic mechanisms. The long noncoding RNA GAS5 acts as a competing endogenous RNA for microRNA-137 and is involved in demyelination. We investigated the association of GAS5 and miR-137 expression and their polymorphisms with MS susceptibility. One hundred and eight MS patients and 104 healthy controls were included. Expression analysis and genotyping of GAS5-rs2067079 and miR-137-rs1625579 single nucleotide polymorphisms were performed by qPCR. Serum GAS5 was upregulated, while serum miR-137 was downregulated in MS compared with the controls. Serum miR-137 was an excellent discriminator of MS patients from the controls (AUC = 0.97) and a negative independent predictor of MS in multivariate logistic analysis. Serum GAS5 expression was positively correlated with the expanded disability status scale scores in the relapsing-remitting MS patients. The rs2067079TT minor homozygote genotype was associated with an increased MS risk, while the rs1625579G minor allele was protective. rs1625579 showed an age-specific effect, while the rs2067079 affected the MS risk in gender- and age-specific manners. In MS patients, rs2067079TT was associated with a higher serum GAS5 than other genotypes, while serum miR-137 did not differ between rs1625579 genotypes. Our results suggest serum GAS5 and miR-137 as MS biomarkers, with miR-137 as a negative predictor of MS risk and GAS5 as a marker of MS severity. We propose rs2067079 and rs1625579 as novel genetic markers of MS susceptibility, and at least, rs2067079 possibly impacts the crosstalk between GAS5 and miR-137.

Background The present study investigated the serum detectability and the diagnostic implications of long non-coding RNAs; nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) in viral hepatitis C (HCV) and HCV-associated hepatocellular carcinoma (HCC). Methods The study included twenty healthy controls, forty non-malignant HCV patients and forty HCV-associated HCC patients. The study assessed liver function tests, the antioxidant status, serum alpha fetoprotein, p53, NEAT1 and TUG1. Results Diminished serum expression of NEAT1 and TUG1 was observed in HCV and HCV-associated HCC and was closely associated with deregulated liver function and elevated AFP levels. A model of NEAT1, TUG1 and AFP accurately differentiated between HCC patients and healthy controls with sensitivity greater than that of AFP alone. Additionally, the diagnostic performance of a model of TUG1, p53 and AFP was superior to that of each marker alone for predicting HCC in HCV patients. Conclusion Significant alterations in the serum expression of NEAT1 and TUG1 in HCV and HCV-associated HCC patients were recorded. We propose NEAT1 and TUG1 as non-invasive, cost-effective and complementary biomarkers that improve the diagnostic characteristics of AFP.

Background: Lichen planus (LP) is a chronic autoimmune inflammatory mucocutaneous disease. Interleukin (IL)-17 is the signature cytokine of T-helper 17 cells, involved in the aetiology of many autoimmune and inflammatory disorders. Vitamin D has an immune-regulatory role and suppresses IL-17 production via direct transcriptional inhibition of IL-17 gene expression. Objective: To explore the relationship of IL-17 and vitamin D levels with LP, and the possible inter-relationship between IL-17 and vitamin D. Methods: The study enrolled 30 patients with LP and 30 healthy controls. Blood samples and skin biopsies were taken from all participants for evaluation of serum vitamin D, and serum and tissue IL-17 levels using enzyme-linked immunosorbent assay (ELISA). Results: Patients had significantly higher serum and tissue IL-17 (p < 0.001 for both), as well as significantly lower serum vitamin D levels and more deficient patterns of vitamin D status than controls (p < 0.001 for both). In the patient group, there was a statistically significant positive correlation between extent of the disease and serum IL-17. There was no direct statistical correlation between IL-17 levels and serum vitamin D in either patients or controls. Conclusion: This study confirms a previously suggested role of IL-17 in the pathogenesis of LP and suggests its relation to the extent and severity of the disease. We also found an association between vitamin D deficiency and LP. However, a direct relationship between IL-17 and vitamin D deficiency could not be clarified.

Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system. It was previously demonstrated that miR-155 and miR-146a served a vital role in the pathophysiology of MS, and single nucleotide polymorphisms in miR-155 and miR-146a were found to be associated with the susceptibility to different autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and type I diabetes. The aim of the present study was to analyze the association between susceptibility to MS and two genetic polymorphisms (miR-155 rs767649 A>T and miR-146a rs57095329 A>G) in a cohort of Egyptian patients. The presence of the two polymorphisms were analyzed in 114 patients with MS and 152 healthy controls using quantitative PCR. The present study demonstrated for the first time that: The TT genotype and T allele in miR-155 (rs767649 A>T) polymorphism were associated with an increased risk of MS; the miR-146a (rs57095329 A>G) mutated G allele conferred protection against the development of MS in all genetic models; miR-155 rs767649 A>T was a risk associated polymorphism of MS in females, but not in males; and miR-155 rs767649 AT/TT and miR-146a rs57095329 GG genotypes showed significantly higher distributions among patients with higher Expanded Disability Status Scale scores and secondary progressive MS subgroups. Therefore, miR-155 rs767649 polymorphism may confer susceptibility to MS, whereas miR-146a rs57095329 may be protective against MS in an Egyptian cohort.

ObjectiveTo investigate the effect of local injection of platelet-rich plasma (PRP) on the rate of orthodontic tooth movement.Materials and MethodsSixteen female patients were randomly allocated in a split-mouth study design to receive PRP injections with CaCl2 activating solution on one side (intervention side) while the other side received CaCl2 injection only (control side). Canine retraction was performed on 0.017 × 0.025-inch stainless steel archwire applying 1.5 N retraction force. PRP and CaCl2 injections were done at 0, 3, and 6 weeks. The duration of the study was 4 months. Data were collected from digitized models. Assessment of pain accompanying the procedure was done using a visual analogue scale.ResultsThe rate of canine retraction was faster on the intervention side in the first 2 months, with a statistically significant difference in the first month (P = .049). On the other hand, the rate was statistically significantly slower on the intervention side in the third month following cessation of PRP injections (P = .02). Pain increased following injections on both sides.ConclusionsPRP showed a positive potential to accelerate the rate of tooth movement when injected in the first 2 months. Repeated injections of PRP to maintain a steady rate of accelerated tooth movement warrant further investigation.

Background: This study investigates the presence of interleukin (IL)-33 and osteoprotegerin (OPG) in saliva and gingival crevicular fluid (GCF) samples of patients with chronic periodontitis and whether or not they are correlated with diabetes mellitus. Methods: Sixty subjects were included in this study: 20 chronic periodontitis patients (CP), 20 diabetic chronic periodontitis patients (CPDM) and 20 systemically and periodontally healthy subjects. GCF and saliva samples were collected from all participants. Enzyme linked immunosorbent assay (ELISA) kits were used for assaying IL-33 and OPG levels. Analysis of variance was used to compare means of the CP and CP-DM groups with the control. Correlation analyses were performed to find the value of Spearman's correlation. A receiver operating characteristic (ROC) curve was constructed to determine the cut-off values of the markers to differentiate between the groups. Areas under the ROC curve (AUCs) were compared using z-statistic. Results: IL-33, in both GCF and saliva, was significantly higher in the CP and CP-DM groups compared to the control, and significantly higher in the CP-DM group compared to the CP group in saliva. On the other hand, the level of OPG in GCF and saliva was significantly lower in the CP and CP-DM groups compared to the control, but was of no significance when comparing the CP-DM and CP groups. Conclusion: IL-33 seems to play a role in the pathogenesis of periodontal disease, while OPG may have a protective function. Diabetes may affect and influence the expression of IL-33. Thus, they could be utilized as diagnostic biomarkers for chronic periodontitis either in saliva or GCF.

Noncoding RNAs are emerging biomarkers for many diseases including diabetic retinopathy (DR). This study aimed to measure the expression levels of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in DR patients. A total of 80 patients diagnosed as type 2 diabetes (T2D) and 81 healthy subjects were recruited in this study. T2D patients were divided into three groups: nondiabetic retinopathy (NDR) group (30 patients), nonproliferative diabetic retinopathy (NPDR) group (30 patients), and proliferative diabetic retinopathy (PDR) group (20 patients). Quantitative real-time polymerase chain reaction (PCR) was used to assess the expression of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1. We found a significant decrease in serum miR-20b and a significant increase in serum HOTAIR and MALAT1 in NDR patients compared to healthy subjects. Also, we revealed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in each of NPDR and PDR groups when compared with healthy subjects. Furthermore, we reported a significant decrease in miR-20b and miR-17-3p and a significant increase in HOTAIR and MALAT1in DR as well as in PDR patients when compared with NDR patients. However, on comparing NPDR with NDR patients, no significant difference was observed regarding the expression levels of miR-20b and miR-17-3p, in contrast, significant elevation of serum HOTAIR and MALAT1 was found in NPDR. Moreover, we observed a significant decrease in serum miR-20b and miR-17-3p and a significant increase in serum HOTAIR and MALAT1 in PDR group relative to NPDR group. Receiver operating characteristic (ROC) curve was used for evaluating the diagnostic value of the examined serum noncoding RNAs as novel biochemical indicators detecting severity of DR. Our analyses suggested that the examined serum noncoding RNAs may discriminate DR (PDR and NPDR) from NDR. Furthermore, these noncoding RNAs (less importantly miR-17) can be used as promising novel biomarkers for prediction DR severity, distinguishing PDR from NPDR patients. We can conclude that serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 may be used as noninvasive biomarkers for screening of DR and early diagnosis of PDR. © 2018 IUBMB Life, 71(3):310-320, 2019.

MicroRNA-27b (miR27b) is a small, non-coding RNA that is involved in physiological keratinocyte differentiation and regulating inflammatory processes. We performed this study to investigate the value of miR27b as a diagnostic marker for oral lichen planus (OLP) and the correlation between CD8 (cytotoxic T-cell marker) and miR27b tissue expression in OLP patients.Forty participants (including 20 OLP patients and 20 controls) underwent oral biopsy. The obtained specimens were examined by immunostaining and quantitative RT-PCR for CD8 and miR27b tissue expression, respectively. We used the Spearman rank correlation test to evaluate the correlation between both variables.Our analysis showed that in comparison with healthy tissues, OLP tissue samples exhibited significantly higher CD8 levels (P 0.01), as well as a significant downregulation of miR27b expression (P 0.0001). Upon comparing different OLP subgroups, no significant difference was detected in terms of miR27b expression; however, the tissue levels of CD8 varied significantly (highest in the erosive subgroup and lowest in the papular/plaque/reticular subgroup). The Spearman rank analysis showed a negative correlation between tissue expression of miR27b and CD8; however, this was not statistically significant (P 0.05). Further, the receiver operating characteristic curve of tissue miR27b as an OLP biomarker revealed 100% sensitivity and 65% specificity at cutoff value of 4.4.This study demonstrated increased CD8 levels and downregulation of miR27b in OLP tissues, compared to healthy tissues. Moreover, it revealed the potential of miR27b as an OLP disease biomarker. The possible negative correlation between CD8 and miR27b tissue expression requires further investigation in larger studies.

Objectives This study aims to assess the role of transforming growth factor-beta 1 (TGF-β1) in systemic lupus erythematosus (SLE). Patients and methods The study included 40 female SLE patients (mean age 25.5±6.2 years; range 15 to 39 years) diagnosed according to the American College of Rheumatology criteria and 30 female healthy controls (mean age 26.2±5.9 years; range 16 to 39 years). Disease activity was assessed using SLE Disease Activity Index. Patients were diagnosed with lupus nephritis if they met the criteria for renal disorder. SLE patients and controls were compared in terms of TGF-β1, low and high density lipoprotein, and triglyceride levels. Results Mean serum TGF-β1 level of patients with SLE was 1385.7±483.1 pg/mL, with a significant difference compared to control group (2079.6±125.4 pg/mL; p

Single-nucleotide polymorphisms (SNPs) in microRNA-146a (miRNA-146a) can be associated with the development of immune-system dysfunctions.The aim of this work is to correlate SNPs of miRNA-146a and its target gene, IRAK1, with susceptibility, clinical manifestations, and diseases progression in patients with systemic lupus erythematous (SLE) and multiple sclerosis (MS). Genotyping for miRNA-146a (rs2910164) and its target gene IRAK1 (rs3027898) was performed using real-time polymerase chain reaction (RT-PCR) in 80 patients with SLE and 70 patients with MS, as well as 120 healthy control individuals. A statistically significant difference was found between the frequencies of the genotypes and alleles of miRNA-146a (rs2910164) and IRAK1 (rs3027898), compared with the control group. Also, whereas the mutant allele G of miRNA-146a may be a factor in the pathogenesis of lupus nephritis, the mutant allele C of IRAK1 may play a role in lupus arthritis. Both genes may contribute to the susceptibility of patients to SLE and MS.

Background The bone represents one of the most common sites of metastases in breast cancer. The aim of the current study was to evaluate the diagnostic potential of several circulating markers to detect metastasis to bones in patients with breast cancer. Patients and Methods Receptor activator of Nuclear Factor-kappa β (NF-Kβ) ligand (RANKL), osteoprotegrin (OPG), vitamin D (VIT D), Chitinase-3-like protein 1; also known as YKL-40, topoisomerase IIα (TOPO2a), and human epidermal growth factor receptor 2 (HER2) were measured in blood samples obtained from 122 patients with breast cancer and 25 healthy controls. Results All biomarkers were significantly elevated in patients with breast cancer with bone metastasis compared with nonmetastatic patients except YKL-40. RANKL had the highest diagnostic performance for bone metastasis detection with an area under the curve of 97.3, a sensitivity of 85%, and a specificity of 98.6%. Furthermore, logistic regression analysis resulted in a model of RANKL combined with HER2 that had even higher discriminatory power of metastasis to bones than that of RANKL alone. Overall correct classification of the model was 98.9%. Conclusion We recommend that measuring RANKL together with HER2 can be routinely applied to allow early detection of bone metastases in patients with breast cancer.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder affecting the peripheral joints. Different microRNAs had been investigated in RA including miRNA-146a meanwhile, miRNA-499 there were no studies to prove its expression in RA serum samples. This study was performed to investigate expression of both miRNAs-146a and -499 and their polymorphisms in Egyptian patients with RA and to evaluate their relationship with clinico-pathological data. The present study includes 108 subjects classified into two main groups: 52 RA patients and 56 unrelated healthy controls. RA patients were subclassified according to DAS28 score into inactive (23 patients) and active (29 patients). Quantitative expression of serum miRNA-146a, miRNA-499 as well as their Genotyping rs2910164 (C/G) and rs3746444 (T/C), respectively, were done to all subjects using real-time PCR. Serum miRNA-146a and -499 were significantly over expressed in RA patients, but they were not correlated to disease activity. Serum miRNA-146a was negatively correlated with anti-nuclear antibodies (ANA). miRNA-146a (rs2910164) genotyping revealed that the GG genotype and the frequency of the G allele were significantly higher in RA patients compared to the controls. miRNA-499 (rs3746444), genotyping revealed that the CC genotype and the frequency of the C allele were significantly higher. It can be concluded that both miRNAs-146a and -499 can be used as diagnostic markers for RA patients. Both miRNA-146a (rs2710164) and miRNA-499 (rs3746444) were significantly associated with RA susceptibility. The C allele of miRNA-146a (rs2710164) can be considered to be protective. On the other hand, the C allele of miRNA-499 (rs3746444) was significantly associated with RA susceptibility.

Objective: This investigation was conducted to measure the levels of serum and salivary YKL- 40 and IL-8 in patients suffering from OLP and OSCC to assess their potential role as biomarkers of oral cancer. Methods: Forty five subjects with age ranging from 30 to 70 years were distributed into 3 groups; 15 patients having atrophic and/or erosive OLP, 15 patients suffering from OSCC and 15 systemically healthy control individuals.YKL-40 and IL-8 were identified in serum and saliva samples utilizing enzyme-linked immunosorbent assays. Results: Serum YKL-40 and salivary levels of YKL-40 and IL-8 in patients with OSCC and OLP were significantly higher than the healthy control group. In order to differentiate patients having OLP from those suffering from OSCC, our study utilized the analysis of the receiver operating curve (ROC) which showed an AUC of 0.878, 0.789, 0.789 and 0.7 for serum YKL-40, salivary YKL-40, serum IL-8, and salivary IL-8, respectively. Serum YKL-40 had the highest diagnostic accuracy revealing 93 % sensitivity and 73 % specificity. That has been followed by salivary YKL-40 and serum IL-8, both revealing a good diagnostic accuracy with 93%, 80 % sensitivity, and 60%, 73.3 % specificity respectively. Salivary IL- 8 as well yielded a good diagnostic accuracy and revealed degrees of sensitivity (80%) and specificity (63%). Cut off values of the biomarkers under investigation has been selected according to the distribution of sensitivities and specificities Conclusion: YKL-40 and IL-8 might be counted as biomarkers for identifying cancerous changes of OLP and the initial stage of OSCC.

Background: the aim of the present study was to evaluate the levels of some biological markers; interleukin 1B (IL1B), interleukin 6 (IL6), interleukin 8 (IL8) and prostaglandin(PG) in the gingival crevicular fluids (GCF) in patients with periodontal disease during early stage of orthodontic tooth movement. Subjects and methods: The study included 9 subjects with age range 23-45 years, with periodontally affected teeth submitted to orthodontic treatment at the orthodontic department faculty of dentistry, Al-azhar University,Girls branch. Fixed appliances were inserted, nickel titanium light archwires were used for levelling and alignment. Gingival crevicular fluid (GCF) samples were collected from the healthy and periodontally affected teeth with paper points at base line, 3 days, 1,2,3,4 weeks from starting of orthodontic treatment. Results: during the test period, the levels of IL 6 in healthy teeth and periodontally affected teeth gradually increased after 3 days and 1 week, then gradually decreased after 2 and 3 weeks, Comparing healthy and periodontally affected teeth revealed a higher levels in periodontally affected teeth.. The mean value of IL 8 gradually increased after 3 days and 1 week, then gradually decreased after 2 and 3 weeks. the mean value of IL 1B was gradually increased after 3 days and 1 week, then gradually decreased after 2 and 3 week. PG showed gradual increase after 3 days and 1 week, then gradually decreased after 2, 3 and 4weeks. Comparing healthy and periodontally affected teeth revealed a higher levels in periodontally affected teeth. Conclusion: Our findings suggested that the orthodontic movement of periodontally compromised teeth result in significant changes in the levels of certain biological markers in the GCF as compared to healthy teeth.

Context: Studying the link between prolactin and autoimmunity has gained much ground over the past years. Its role played in alopecia areata (AA) is not clear yet, as previous reports yielded controversial results. Aims: This study aimed to measure the serum level of prolactin and to detect the expression of its receptor in AA, in an attempt to highlight its possible role in the pathogenesis of this disease. Subjects and Methods: A case-control study of 30 AA patients and 20 controls from outpatient clinic were undertaken. Every patient was subjected to history taking and clinical examination to determine the severity of alopecia tool (SALT) score. Blood samples were taken from patients and controls to determine the serum prolactin level. Scalp biopsies were obtained from the lesional skin of patients and normal skin of controls for assessment of the prolactin receptor. Statistical Analysis: Depending upon the type of data, t-test, analysis of variance test, Chi-square, receiver operator characteristic curve were undertaken. Results: On comparing the serum prolactin level between patients and controls, no significant difference was found, while the mean tissue level of prolactin receptor was significantly higher in patients than in controls. In patients, a significant positive correlation was found between the prolactin receptor and the SALT score. Conclusions: Prolactin plays a role in AA, and this role is probably through the prolactin receptors rather than the serum prolactin level.

Background/Aims: Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting up to 1% of the population worldwide. The aim of the present study was to investigate whether miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 polymorphisms are associated with susceptibility to RA in Egyptians and whether they influence disease severity and activity. Methods: The study was performed on 104 unrelated RA patients and 112 healthy subjects. RA patients were further subdivided into active and inactive RA groups. Polymorphisms were genotyped by using real-time polymerase chain reaction with TaqMan allelic discrimination assay. Results: Significant differences in the frequency of miRNA-146a rs2910164, miRNA-499 rs3746444, IRAK1 rs3027898 and PADI4 rs1748033 alleles and genotypes were observed between RA patients and controls. Only CA and AA genotypes of IRAK1 rs3027898 shows a significant difference between active and inactive subgroups. MiRNA-146a rs2910164 and IRAK1 rs3027898 polymorphisms were a risk factor for predisposition to RA in codominant and dominant tested inheritance models, while, the miRNA-499 rs3746444 and PADI4 rs1748033 polymorphisms were a risk factor in codominant and recessive one. CG and GG genotypes of miRNA-146a rs2910164 were associated with positive erosions. CA genotype of IRAK1 rs3027898 was associated with low disease activity and negative erosions, while, the AA genotype was associated with high disease activity. CC genotype of PADI4 rs1748033 was associated with negative rheumatoid factor. Conclusion: The 4 studied SNPs were likely to play an important role in the susceptibility to RA and can influence disease severity and activity in Egyptian population.

Background Acute ischemic stroke (AIS) is a chief cause of mortality and debility worldwide. Maternally expressed gene 3 (MEG3), is highly expressed in brain and was found to be upregulated after AIS. Single nucleotide polymorphisms (SNPs) in MEG3 have been associated with various diseases. The current study aimed to detect whether MEG3 SNPs, rs941576 and rs7158663, are associated with AIS risk in Egyptians. Subjects and methods samples were withdrawn from Egyptian subjects, 177 AIS patients and 73 controls, and genomic DNA was extracted to perform genotyping for rs941576 and rs7158663 using TaqMan Assays. Results A significantly higher risk of AIS was associated with rs941576 GG genotype before and after adjusting to age, gender, hypertension, and diabetes mellitus in the co-dominant (GG vs. AA: adjusted OR = 18.94, 95% CI: 2.38–50.52, P = 0.021) and dominant models (GG vs. AG + AA: adjusted OR = 18.095, 95% CI: 2.32–41.00, P = 0.006) and with G allele (G vs. A: adjusted OR = 2.20, 95% CI: 1.31–3.64, P = 0.003). Combined genotypes rs941576/rs7158663: AA/GG and GG/AA, in the co-dominant model, and GG/AG + AA, in the dominant model, were significantly more frequent in AIS than in control, 7.9% vs. 1.4%,11.3% vs 0% and 16.9% vs 1.4%, respectively. Furthermore, logistic regression analysis identified hypertension (OR (95%CI) = 7.48(2.64–21.22), P Conclusion The association between MEG3 rs941576, and AIS risk suggests that it may act as potential risk factor for AIS and be used in AIS prognosis in the future.

Aims Breast cancer is the most severe malignant tumor in women. Chemokines and their receptors appear to be implicated in tumorigenesis and metastatic pattern. Also the scavenger atypical chemokine receptors are emerging as crucial regulators for the availability of chemokines. Therefore the aim of the present study is to evaluate the expression of CCR7, ACKR4 and their ligand; CCL21 in human breast cancer. Main methods In this study, RT-PCR was done to detect the expression of CCR7 and ACKR4 in 50 non-metastatic and 30 metastatic breast cancer tissue. Also CCL21 level in the serum of study group was detected by ELISA. The expression of all markers is compared to 80 control healthy individual. Key findings Our results revealed the increase in expression of CCR7 and CCL21 level in metastatic group compared to non-metastatic and control groups while ACKR4 expression is significantly increased in breast tissues of non-metastatic patients compared to both control and metastatic groups. Also there was significant positive correlation between CCR7 expression and CCL21 level in cancer patients and significant negative correlation between ACKR4 and both CCR-7 and CCL21 in both non-metastatic and metastatic cancer groups. Significance Thus, it might be elucidating that ACKR4 and CCR7 could be a novel target for tumor therapy as targeting the chemokine-receptors axis might represent a powerful tool to prevent infiltration and metastasis and consequently improve cancer prognosis and treatment.

The impact of HULC rs7763881 on colorectal cancer (CRC) susceptibility is not yet known. Also, the biological function of the cancer-related rs6983267 remains unclear. We investigated the association of these SNPs with the risk of CRC and adenomatous polyps (AP), their correlation with CCAT2 and HULC expression, and the potential of serum CCAT2 and HULC as biomarkers for CRC. 120 CRC patients, 30 AP patients, and 96 healthy controls were included. Genotyping and serum lncRNAs were assayed by qPCR. Studied SNPs were not associated with AP susceptibility. rs6983267 GG was associated with increased CRC risk, whereas rs7763881 AC was protective. rs7763881 and rs6983267 CT haplotype was protective. Serum CCAT2 and HULC were upregulated in CRC and AP patients versus controls and discriminated these groups by ROC analysis. rs6983267 GG and rs7763881 AA patients demonstrated higher serum CCAT2 and HULC compared with GT/TT and AC, respectively. rs6983267 and serum HULC predicted CRC diagnosis among non-CRC groups (AP + controls) by multivariate analysis. Studied SNPs or serum long noncoding RNAs weren’t correlated with nodal or distant metastasis. In conclusion, rs6983267 and rs7763881 are potential genetic markers of CRC predisposition and correlate with serum CCAT2 and HULC, two novel potential non-invasive diagnostic biomarkers for CRC.

Aim of the work To assess the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and its -863 C/A and 1031 T/C promoter polymorphism in systemic lupus erythematosus (SLE) patients and find any association to disease activity and damage. Patients and methods Forty-two female SLE patients and 30 age and gender matched healthy control were included. Systemic Lupus Erythematosus Disease Activity Index and the Systemic Lupus International Collaboration Clinics-damage index were assessed. Serum TNF-α levels were measured and genotyped for TNF-α-863 C/A and 1031 T/C promoters. Results The SLE patients had a mean age of 28.5 ± 7.6 years and disease duration 3.3 ± 2.9 years. The mean serum TNF-α level in the SLE patients (8.2 ± 9.8 pg/ml) was significantly higher than in the control (3.5 ± 2.6 pg/ml) (p = 0.005). The TNF-α-863AA genotype was significantly frequent (52.4%) in the SLE patients compared to control (23.3%) (p = 0.012). Those patients had a significantly increased proteinuria and a tendency to a higher serum TNF-α level. Patients with TNF-α-1031 CC genotype had a significantly increased serum TNF-α levels (p = 0.002) and frequency of mucocutaneous manifestations (p = 0.03) as well as a higher frequency of lupus nephritis (LN) compared to those with TT genotype (p = 0.04). Only serum TNF-α level would predict the disease activity. Conclusion TNF-α-863 promoter gene polymorphism may be considered as a genetic marker for SLE susceptibility and its AA genotype was associated with LN and with high serum TNF-α production. The TNF-α-1031 AA genotype was related to an increased serum TNF-α level as well as to mucocutaneous manifestations and LN.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor that is deregulated in obesity. PPARγ exerts diverse antineoplastic effects. Attempting to determine the clinical relevance of the epigenetic mechanisms controlling the expression PPARγ and susceptibility to colorectal cancer (CRC) in obese subjects, this study investigated the role of some microRNAs and DNA methylation on the deregulation of PPARγ. Seventy CRC patients (34 obese and 36 lean), 22 obese and 24 lean healthy controls were included. MicroRNA levels were measured in serum. PPARγ promoter methylation was evaluated in peripheral blood mononuclear cells (PBMC). PPARγ level was evaluated by measuring mRNA level in PBMC and protein level in serum. The tested microRNAs (miR-27b, 130b and 138) were significantly upregulated in obese and CRC patients. Obese and CRC patients had significantly low levels of PPARγ. A significant negative correlation was found between PPARγ levels and the studied microRNAs. There was a significant PPARγ promoter hypermethylation in CRC patients that correlated to low PPARγ levels. Our results suggest that upregulation of microRNAs 27b, 130b and 138 is associated with susceptibility to CRC in obese subjects through PPARγ downregulation. Hypermethylation of PPARγ gene promoter is associated with CRC through suppression of PPARγ regardless of BMI.

Ulcerative colitis is a serious premalignant condition with a confusing multifactorial pathogenesis. It should warrant all attention by researchers, for exploration of new prophylactic or therapeutic drugs targeting its pathophysiology. The current study was conducted to study the possible role of tadalafil and its potential actions in ulcerative colitis rat model, induced by acetic acid. Forty eight male Wistar albino rats were classified into 6 groups: control group, acetic acid (AA)-ulcerated group, AA-ulcerated + tadalafil (1 mg/kg/day), AA-ulcerated + tadalafil (5 mg/kg/day), AA-ulcerated + tadalafil (10 mg/kg/day) and AA-ulcerated + sulfasalazine 100 mg/kg/day groups. Tissue malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were determined. Also, caspase-3 gene expression was measured as an indicator of apoptosis. Histopathological examination of the colonic tissue was also done. In addition, serum levels of interleukin (IL)-1β and tumour necrosis factor (TNF)-α were measured. In AA-ulcerated group, there was significant elevation in tissue MDA levels and MPO activity with upregulation of caspase 3 gene expression. Meanwhile, AA caused decreases in the SOD activities. Also, AA induced elevation in the serum IL-1β and TNF- α levels. Pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/days guarded against changes in these parameters. Its effects were dose-dependent. According to the results, pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/day exerted dose-dependent beneficial effects against AA-induced damage of the colon, possibly by exerting anti-inflammatory and antioxidant effects. Also, reduction of apoptosis proved to be one of the contributing protective mechanisms of actions. Key words: Tadalafil, ulcerative colitis, rats, acetic acid, anti-apoptotic.

Background: The present study was conducted to evaluate the levels of interleukin (IL) – 17 in gingival crevicular fluid (GCF) and placental tissue samples of pregnant females as a possible marker in determining whether or not an association exists between chronic periodontitis and preterm labor. Methods: This case-control study included a random sample of 40 female patients, aged 18 to 35 years, who were assigned to one of the following four groups (10 subjects each): group 1 included patients who underwent spontaneous preterm birth (PB) and were diagnosed with chronic periodontitis upon clinical examination (preterm/periodontitis); group 2 included patients who underwent spontaneous PB and who had a healthy periodontium upon clinical examination (preterm/healthy periodontium); group 3 included patients who underwent spontaneous normal term birth and were diagnosed with chronic periodontitis upon clinical examination (term/periodontitis); and group 4 included patients who underwent spontaneous normal term birth and who had a healthy periodontium upon clinical examination (term/healthy periodontium). GCF and placental tissue samples were obtained from each patient and IL-17 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GCF levels of IL-17 were significantly higher (P=0.010) in patients with chronic periodontitis compared to those with a healthy periodontium. No significant differences were observed in IL-17 levels in placental tissue samples of all study groups. Conclusion: An association between chronic periodontitis and preterm labor could not be established based on IL-17 levels measured in the present study.