Chronic Caffeine Consumption, Alone or Combined with Agomelatine or Quetiapine, Reduces the Maximum EEG Peak, As Linked to Cortical Neurodegeneration, Ovarian Estrogen Receptor Alpha, and Melatonin Receptor 2.

RATIONALE: Evidence of the effects of chronic caffeine (CAFF)-containing beverages, alone or in combination with agomelatine (AGO) or quetiapine (QUET), on electroencephalography (EEG), which is relevant to cognition, epileptogenesis, and ovarian function, remains lacking. Estrogenic, adenosinergic, and melatonergic signaling is possibly linked to the dynamics of these substances. OBJECTIVES: The brain and ovarian effects of CAFF were compared with those of AGO + CAFF and QUET + CAFF. The implications of estrogenic, adenosinergic, and melatonergic signaling and the brain-ovarian crosstalk were investigated. METHODS: Adult female rats were administered AGO (10 mg/kg), QUET (10 mg/kg), CAFF, AGO + CAFF, or QUET + CAFF, once daily for 8 weeks. EEG, estrous cycle progression, and microstructure of the brain and ovaries were examined. Brain and ovarian 17ß-estradiol (E2), antimullerian hormone (AMH), estrogen receptor alpha (E2Rα), adenosine receptor 2A (A2AR), and melatonin receptor 2 (MT2R) were assessed. RESULTS: CAFF, alone or combined with AGO or QUET, reduced the maximum EEG peak, which was positively linked to ovarian E2Rα, negatively correlated to cortical neurodegeneration and ovarian MT2R, and associated with cystic ovaries. A large corpus luteum emerged with AGO + CAFF and QUET + CAFF, antagonizing the CAFF-mediated increased ovarian A2AR and reduced cortical E2Rα. AGO + CAFF provoked TTP delay and increased ovarian AMH, while QUET + CAFF slowed source EEG frequency to δ range and increased brain E2. CONCLUSIONS: CAFF treatment triggered brain and ovarian derangements partially antagonized with concurrent AGO or QUET administration but with no overt affection of estrus cycle progression. Estrogenic, adenosinergic, and melatonergic signaling and brain-ovarian crosstalk may explain these effects.

"Outcome of non-surgical periodontal treatment on Gal-1 and Gal-3 GCF levels in periodontitis patients: a case-control study".

OBJECTIVES: This study aimed to explore the effect of nonsurgical periodontal treatment on Galectin-1 and -3 GCF levels in gingivitis and periodontitis stage III compared to periodontally healthy individuals, to determine whether they could serve as diagnostic markers / therapeutic targets for periodontitis and revealing their possible role in periodontal disease. MATERIALS AND METHODS: Forty-five systemically healthy participants were included and equally subdivided into three groups: gingivitis, periodontitis (stage III), and a periodontally healthy control group. The clinical parameters were recorded. Galectin-1 and -3 GCF levels were evaluated (before and after non-surgical treatment for periodontitis) using an enzyme linked immune-sorbent assay (ELISA) kit. Receiver operating characteristic (ROC) curve was performed to reveal sensitivity, specificity, predictive value, and diagnostic accuracy of both markers. RESULTS: The study showed statistical significance between different groups regarding Galectin-3 with higher values in periodontitis and the lowest values in healthy control. Also, Galectin-1 was significantly higher in the periodontitis/gingivitis groups than in the control group. Moreover, non-surgical periodontal treatment in periodontitis patients caused a statistical reduction in clinical parameters and biomarkers. ROC analysis revealed excellent diagnostic ability of both biomarkers in discriminating periodontitis/gingivitis against healthy individuals (100% diagnostic accuracy for Galectin-1 and 93% for Galectin-3, AUC > 0.9) and acceptable diagnostic ability between periodontitis participants against gingivitis (73% diagnostic accuracy for Gal-1 and 80% for Gal-3, AUC > 0.7). CONCLUSIONS: Both Galectin-1 and Galectin-3 seem to have outstanding diagnostic accuracy for the identification of periodontal disease, an acceptable ability to measure periodontal disease activity and the severity of inflammatory status. Additionally, they could serve as therapeutic targets to monitor treatment efficiency. CLINICALTRIAL: GOV REGISTRATION NUMBER: (NCT06038812).

IL-39 and IL-35 gingival crevicular fluid levels in diabetic patients with generalized periodontitis.

OBJECTIVES: This research was performed to investigate if there is a role for IL-39 in immunopathogenesis of both systemically healthy and diabetic periodontitis patients. Additionally, to explore if we can consider IL-39 and IL-35 as biomarkers for periodontitis activity. MATERIALS AND METHODS: A total of 38 periodontitis patients and 19 control volunteers were included in our study. The periodontitis patients were divided equally into (Group I), 19 patients with stage III grade C periodontitis with diabetes mellitus and (Group II), 19 patients with stage III grade B periodontitis and systemically healthy. Gingival crevicular fluid levels of each interleukin were measured pre- and postoperatively for all periodontitis patients as well as control subjects using ELISA. RESULTS: Our study results showed that the highest level for IL-39 was in diabetic periodontitis patients that decreased significantly postoperatively. However, the highest level for IL-35 was revealed in control group while the lowest value was registered in diabetic periodontitis patients and statistically increased after periodontal treatment. CONCLUSIONS: Based on the results of our research, both investigated biomarkers may have a potent role in pathogenesis of periodontitis. CLINICAL RELEVANCE: We could consider both interleukins as accurate diagnostic markers for periodontitis patients, regardless of diabetes mellitus association, as well as promising markers that can aid in the prevention and treatment of periodontitis patients worldwide.

Cytokine expression of IL-8 before and after root canal treatment in patients with symptomatic apical periodontitis: A clinical trial.

This study's objective was to compare the cytokine expression of IL-8 in periapical tissues of single-rooted teeth with symptomatic apical periodontitis (SAP) before and after root canal treatments. As well as, comparing IL-8 levels in peri-apical tissues between vital and necrotic teeth with SAP. METHODOLOGY: Thirty-six patients were allocated according to their pulp status into two experimental groups (n = 18) receiving the same treatment protocol; group 1: Vital pulps with SAP, and group 2: non-vital pulps with SAP. Conventional endodontic treatment was done on two visits; isolation and disinfection of the operative field were undertaken, and two-stage access cavity preparation was implemented. The first pre-instrumentation peri-apical sample (S1) was collected prior to cleaning and shaping procedures. A 2.5% NaOCl irrigation was used to thoroughly irrigate the canal after performing root canal preparation utilising the ProTaper Next (PTN) rotary system. After 1 week, the second post-instrumentation peri-apical sample (S2) was collected. Using an ELISA kit, the quantity of IL-8 was evaluated following the collection of all samples. RESULTS: In all pre-instrumentation samples, IL-8 was detected (100%). The level of IL-8 expression was significantly decreased from the S1 to S2 of all samples (p < 0.001). The intra-group comparison showed a statistically significant reduction in the level of IL-8 expression between S1 and S2 in both vital and non-vital groups where p < 0.001* in both groups. The inter-group comparison of levels of IL-8 expression (vital and non-vital) revealed a significant difference between both groups regarding the pretreatment sample with the higher levels of IL-8 shown in the non-vital group (p < 0.001). While in the post-treatment sample, both groups showed a significant reduction in the level of IL-8 expression but the difference between them was not statistically significant (p = 0.226). CONCLUSION: Root canal instrumentation seems to be efficient in decreasing the levels of anti-inflammatory cytokines, namely IL-8. Further research should clarify how intra-canal medicaments affect inflammatory mediator levels.

"Salivary LINC00657 and miRNA-106a as diagnostic biomarkers for oral squamous cell carcinoma, an observational diagnostic study".

BACKGROUND: Early detection and diagnosis of malignant tumors is critical for improving the survival rate and treatment outcomes of oral cancer. Thus, the current prospective investigation was designed to verify the role, sensitivity, and specificity of salivary LINC00657 and miRNA-106a as diagnostic markers in oral squamous cell carcinoma patients as compared to oral lichen planus (as an example of oral potentially malignant disorders) and normal individuals, and to show LINC00657 relation to miR-106a. METHODS: A total of 36 participants were included, subdivided into 3 groups: Group I: 12 patients diagnosed with oral squamous cell carcinoma (OSCC). Group II: 12 patients diagnosed with oral lichen planus (OLP). Group III: 12 systemically free individuals with no oral mucosal lesions. Unstimulated salivary samples were collected from all participants to evaluate level of LINC00657 and miR-106a in different groups using quantitative real-time PCR. RESULTS: OSCC showed the highest LINC00657 and lowest miR-106a fold change among included groups. Receiver Operating Characteristic (ROC) curve analysis of the two biomarkers for detecting OSCC revealed that LINC00657 had higher diagnostic accuracy (DA) (83.3%) compared to miR-106a (80.4%). As for detecting OLP, ROC analysis showed that miR-106a had higher (DA) (61%) compared to LINC00657 (52.5%). To discriminate OSCC from OLP, the diagnostic accuracy of both markers is the same (75%). Moreover, differentiating OSCC grades II and III, ROC analysis showed that miR-106a had lower (DA) (60%) compared to LINC00657 (DA) (83.3%). CONCLUSIONS: Salivary LINC00657 and miR-106a could be promising diagnostic markers for oral squamous cell carcinoma. Salivary LINC00657 may differentiate oral squamous cell carcinoma from oral potentially malignant disorders with considerable diagnostic accuracy. Moreover, low levels of salivary miR-106a could have the potential to indicate malignancy. TRIAL REGISTRATION: The study was retrospectively registered on clinicaltrial.gov with NCT05821179 (first trial registration in 26/3/2023), date of registration: 19/4/2023.

Galectin-1 (Gal-1) and Galectin-3 (Gal-3) levels in seminal plasma and serum in azoospermic patients versus fertile men: A cross-sectional study.

INTRODUCTION: Galectin-1 (Gal-1) and galectin-3 (Gal-3) are expressed by many immune cells and receive considerable attention in the context of immunity. We aimed to compare between seminal plasma and serum levels of Gal-1 and Gal-3 in azoospermic patients and fertile men. MATERIALS AND METHODS: This cross-sectional study was conducted at the andrology outpatient clinic from January (2022) to September (2022). A total of 90 participants were enrolled and divided into two equal groups: azoospermic and normal group. Semen analysis was done for all participants. Hormonal profile including FSH, LH, serum prolactin, total testosterone and estradiol was performed as well as assessment of serum and seminal levels of Gal-1 and Gal-3 by ELISA commercial kits. Finally, scrotal Duplex was done in standing and supine position. RESULTS: Serum and seminal levels of Gal-1 and Gal-3 were statistically significant higher in azoospermic patients compared with normal individuals (p < 0.001 for all). In addition, in healthy individuals there were statistically significant positive correlations between serum levels of Gal-1 and age, FSH, LH levels (r = 0.296, p = 0.005; r = 0.333, p = < 0.001; r = 0.312, p = 0.003, respectively) and serum levels of Gal-2 and FSH and LH (r = 0.436, p < 0.001; r = 0.350, p < 0.001, respectively), whereas serum Gal-3 showed a borderline positive correlation with age (r = 0.2, p = 0.059). Additionally, statistically significant positive correlations between seminal levels of Gal-1 and Gal-3 and free testosterone in healthy individuals were reported (r = 0.205, p = 0.053; r = 0.219, p = 0.038, respectively). On the other hand, there were negative correlations between serum and seminal levels of Gal-1 and Gal-3, total and progressive sperm motility, sperm count and abnormal sperm forms in healthy individuals (r = -0.382, p < 0.001; r = -0.405, p < 0.001; r = -0.376, p < 0.001; r = -0.364, p < 0.001) (r = -0.394, p < 0.001; r = -0.467, p < 0.001; r = -0.413, p < 0.001; r = -0.433, p < 0.001); (r = -0.372, p < 0.001; r = -0.377, p < 0.001; r = -0.317, p = 0.002; r = -0.311, p = 0.003)(r = -0.445, p < 0.001; r = -0.498, p < 0.001; r = -0.453, p < 0.001; r = -0.463, p < 0.001, respectively). Furthermore, statistically significant positive correlations between serum levels of Gal-1 and Gal-3 and age in azoospermic patients were reported (r = 0.511, p < 0.001; r = 0.390, p = 0.008, respectively). On the other hand, there were negative correlations between seminal Gal-1 and estradiol (E2) and seminal Gal-3 and FSH and LH in azoospermic patients (r= -0.318, p = 0.033; r = -0.322, p = 0.031; r = -0.477, p < 0.001, respectively). Also, negative correlations between serum Gal-3 and total and free testosterone in azoospermic patients were detected (r = -0.396, p = 0.007; r = -0.375, p = 0.011, respectively). CONCLUSIONS: Elevated serum and seminal levels of Gal-1 and Gal-3 have detrimental effects on spermatogenesis. Furthermore, the current study demonstrated potential regulatory effects of reproductive hormones on Gal-1 and Gal-3. Thus, future studies are needed to confirm such findings.

Frequency and risk factors of H. pylori infection among dental students: an observational cross-sectional study.

Despite Helicobacter pylori infection remains asymptomatic in most people, it is associated with an increased risk of gastric cancer. Considering Egypt had the highest prevalence of H. pylori in healthy asymptomatic population in adults and pediatric age in past studies and currently salivary ELISA could be used for diagnosis of Oral H. pylori infection. Moreover, some researchers speculated that dentists and dental students might be at a higher risk for oral H. pylori infection because they are the most frequently exposed ones to saliva and dental plaque. This study aimed to determine risk factors associated with frequency of H. pylori among a sample of dental students for better management of the disease. 83 participants, with age (21-25 years), attending Faculty of Dentistry, Fayoum University were recruited. A structured questionnaire was used to collect information on sociodemographic parameters and risk factors for H. pylori. Direct inquiry about dyspeptic symptoms were done. Saliva samples were collected and tested for H. pylori antibodies. Overall seroprevalence was 22.9%. Participants in internship were more prone to be positive (p = 0.005). 32.6% of urban residents versus 10.8% of rural were H. pylori positive (p = 0.019). 75.0% of previous history of H. pylori infection versus 14.1% of those with no history were H. pylori positive p < 0.001. 70% of positive H. pylori participants reported positive clinical symptoms that were statistically significant. This study suggests that middle income, previous history of H. pylori and clinical symptoms of dyspepsia are risk factors of oral H. pylori with a decline in its prevalence in Egypt.

Long Noncoding Rna GAS5 And Mir-137 And Two Of Their Genetic Polymorphisms Contribute To Acute Ischaemic Stroke Risk In An Egyptian Population.

Objectives: To assess the serum expression levels of long non-coding ribonucleic acid growth arrest specific-5 and micro-ribonucleic acid-137, and the different genotypes of long non-coding ribonucleic acid growth arrestspecific-5 rs2067079 (C>T) and micro-ribonucleic acid-137 rs1625579 (T>G) in acute ischaemic stroke patients. Method: The case-control study was conducted at Cairo University, Cairo, Egypt, from January to August 2020, and comprised adult acute ischaemic stroke patients of either gender selected from the stroke unit of the Neurology Department at Kasr Alainy Hospital of Cairo University. Healthy individuals matched for age and gender were enrolled as controls. Quantitative real-time polymerase chain reaction was used to quantify serum expression levels of long non-coding ribonucleic acid growth arrest specific-5 and micro-ribonucleic acid-137, and to genotype long non coding ribonucleic acid lncRNA growth arrest specific-5 rs2067079 and micro-ribonucleic acid-137 rs1625579 using TaqMan allelic discrimination. Data was analysed using SPSS 22. RESULTS: Of the 100 subjects, 50(50%) were patients; 34(68%) males and 16(32%) females with mean age 60.4±10.0 years. The remaining 50(50%) were controls; 28(56%) males and 22(44%) females with mean age 56.9±12.2 years (p>0.05). The patients had more smokers, more hypertensives and more diabetics than the controls (p<0.05). Long non-coding ribonucleic acid growth arrest specific-5 expression levels were significantly increased, while microribonucleic acid-137 expression levels were significantly reduced among the patients(p<0.05). Acute ischaemic stroke risk was significantly higher in patients with growth arrest specific-5 rs2067079 (C>T) recessive model (homozygous minor TT genotype), while micro-ribonucleic acid-137 rs1625579 (T>G) was protective against acute ischaemic stroke in allelic (G minor allele), codominant (GT genotype), dominant (GT+GG), and over-dominant (GT genotype) models (p<0.05). CONCLUSIONS: Long non-coding ribonucleic acid growth arrest specific-5 rs2067079 and micro-ribonucleic acid-137 rs1625579 may act as novel genetic markers of acute ischaemic stroke risk.

Expression of Long Noncoding RNA, HOTAIR, and MicroRNA-205 and Their Relation to Transforming Growth Factor ß1 in Patients with Alopecia Areata.

Introduction: Alopecia areata (AA) is a common autoimmune condition that affects anagen hair follicles. The most commonly recognized theory is that it is a T-cell-mediated autoimmune disorder in a genetically susceptible individual. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) were thought to play a function in the pathogenesis. The expression of lncRNA HOTAIR and miRNA-205 and their relation to transforming growth factor ß1 (TGF-ß1) in AA were not studied. Aim: The aim of the studywas to evaluate the role of miRNA-205, lncRNA, HOTAIR, and TGF-ß1 levels in AA pathogenesis, clinical course, and severity of AA. Methods: Two groups of subjects were included in this case-control study: 50 patients with AA and 50 healthy matched controls. miRNA-205 and lncRNA HOTAIR expression levels were assayed using quantitative RT-PCR, while serum levels of TGF-ß1 were assayed using ELISA techniques. Results: The serum expression of lncRNA HOTAIR was significantly downregulated in AA patients with a p value < 0.001, while the serum expression of both miRNA-205 and TGF-ß1 were significantly upregulated in patients. Discussion/Conclusion: This study highlights the potential role of high serum expression of miRNA-205 and TGF-ß1 and the low serum expression of lncRNA HOTAIR in AA pathogenesis. This could be used as a therapeutic target to treat AA.

Expression of Signal Transducer and Activator of Transcription-3 in Androgenetic Alopecia: A Case-Control Study.

BACKGROUND: Signal transducer and activator of transcription (STAT)-3 belongs to a group of latent transcription factors phosphorylated and activated by several protein tyrosine kinases, including members of Janus kinases (JAKs) family. It has been implicated that the JAK-STAT pathway activation could promote quiescence in the hair cycle, and topical treatment of mouse and human skin with JAK inhibitors was shown to result in rapid hair growth. OBJECTIVE: Our aim was to assess the tissue expression of STAT3 in patients with androgenetic alopecia and correlate it with disease severity and clinical parameters. METHODS: Twenty-five androgenetic alopecia patients who served as both cases and controls were included in this study. Full clinical examination was done and tissue STAT3 gene expression was then measured by real-time polymerase chain reaction. RESULTS: Scalp tissue affected by androgenetic alopecia shows significantly higher STAT3 gene expression levels compared to unaffected (androgen independent) areas (p < 0.001), but no statistically significant relation was found between tissue STAT3 expression level and severity of hair loss (p = 0.660). LIMITATIONS: Limited sample size. CONCLUSION: This study demonstrated an upregulation in STAT3 gene expression in androgenetic alopecia. Further studies are needed to assess the possible role of the JAK-STAT pathway in the pathogenesis of androgenetic alopecia.

Role of micro-RNA132 and its long non coding SOX2 in diagnosis of lupus nephritis.

BACKGROUND: The skin and the kidney are commonly affected in systemic lupus erythematosus (SLE) with similar molecular mechanisms. Although clinical indicators of renal injury in SLE are fairly uncontroversial, few biomarkers are reliable. The role of micro-RNAs (mi-RNAs) in lupus nephritis (LN) pathogenesis has been investigated to help in early diagnosis. PURPOSE: The aim of work is to evaluate miRNA132 and SOX2 expressions in SLE Egyptian patients; with and without nephritis, and the relation between miRNA132 and its long non-coding gene SOX2 in both patients groups. RESEARCH DESIGN: This is a case-control study involving 100 SLE patients with and without LN (LN and non-LN groups), and 50 age-and sex-matched healthy controls. The study was carried out to detect miRNA132 and SOX2 expression by quantitative Real-Time Polymerase chain reaction methods. The SLE disease activity index (SLEDAI) was assessed. RESULTS: SLEDAI increased in LN compared to non-LN. Micro-RNA132 expression was significantly increased in patient groups compared to controls (p<0.01) and increased in LN more than non-LN group (p<0.001). SOX2 significantly decreased in patient groups compared to controls (p<0.001), and was more in LN compared to non-LN group (p<0.001). There was a negative correlation between miRNA132 and SOX2 expression in both patient groups (p<0.001). CONCLUSION: miRNA132 and SOX2 may play a role in SLE activity and help in the early non-invasive diagnosis of LN.

MicroRNA-22 Level in Patients with Multiple Sclerosis and Its Relationship with Vitamin D and Vitamin D Receptor Levels.

INTRODUCTION: Multiple sclerosis (MS) is known to be a multifactorial disorder. Numerous observational studies have suggested the implication of multiple genetic and environmental factors in the pathogenesis of MS. The aim of this work was to evaluate expression of the microRNA-22 (miRNA-22) level, in relation to vitamin D (VD) and VD receptor (VDR) levels in patients with MS during remission state. METHODS: This case-control study was conducted in 50 patients with clinically definite MS and 50 age- and sex-matched healthy controls. miRNA-22 expression was assessed in both MS patients and controls using quantitative RT-PCR. The serum level of VD and VDR was assessed in both MS patients and controls using ELISA techniques. RESULTS: The miRNA-22 level was significantly downregulated in MS patients in comparison to controls (p value <0.001). MS patients had also significantly lower VD and VDR levels in comparison to controls (p value <0.001 and <0.001, respectively). Patients with secondary progressive MS (SPMS) have a significantly higher miRNA-22 level than patients with relapsing remitting MS (RRMS) (p value = 0.042). There was a statistically significant positive correlation between the miRNA-22 level and EDSS (p value = 0.033). There was also a statistically significant positive correlation between the miRNA-22 level and VDR level (p value = 0.002). CONCLUSION: The miRNA-22 level was significantly downregulated in MS patients, but it had a positive correlation with disability status. Patients with SPMS have a significantly higher miRNA-22 level than patients with RRMS. VD and VDR levels were significantly lower in MS patients than controls. The miRNA-22 level was positively correlated with the VDR level.

Serum Long Non-Coding RNAs PVT1, HOTAIR, and NEAT1 as Potential Biomarkers in Egyptian Women with Breast Cancer.

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.

Possible Relation between Vitamin D and Interleukin-17 in the Pathogenesis of Lichen Planus.

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.

Serum a proliferation-inducing ligand and MicroRNA-223 are associated with rheumatoid arthritis: diagnostic and prognostic implications.

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.

Heat Shock Protein 70 Gene Polymorphism in Egyptian Patients with Type 2 Diabetes Mellitus, with and without Nephropathy.

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.

Evaluation of serum and salivary transforming growth factor beta, vascular endothelial growth factor and tumor necrosis factor alpha in oral lichen planus / Evaluación sérica y salival del factor de crecimiento transformante beta, factor de crecimiento endotelial vascular y factor de necrosis tumoral alfa en liquen plano oral

Introduction: Lichen planus is one of the most common oral mucosal lesions. Transforming growth factor-ß (TGF- ß) has a marked effect on epithelial­mesenchymal transition and immune cells function. Vascular Endothelial Growth Factor (VEGF) is a key regulator of vasculogenesis and angiogenesis. Tumor necrosis factor-α (TNF-α) mediates T-lymphocyte homing and apoptosis of epithelial cells. Objetive: The present study was conducted in order to compare the expression of serum and salivary TGF- ß, VEGF, TNF-α between OLP patients and control individuals to investigate if saliva can be used as an alternative to serum for diagnostic purposes and for monitoring disease. Materials and Methods: 23 OLP patients and 23 control individuals were included to evaluate serum and salivary TGF-ß, VEGF, TNF-α using ELISA kits. Five milliliters of venous blood was collected and unstimulated saliva was collected by the spitting method. Results: Serum and salivary levels of TGF- ß, VEGF, TNF-α are higher in OLP patients compared to normal controls. Mean difference is higher in saliva than serum. Moreover, there was a significant difference in serum and salivary VEGF and TNF-α between symptomatic and asymptomatic groups. Conclusions: Saliva can be a used as a substitute for serum to evaluate levels of the assessed biomarkers.

Introducción: El liquen plano oral es una de las lesiones de la mucosa oral más comunes. El factor de crecimiento transformante ß (TGF-ß) tiene un efecto marcado sobre la transición epitelial-mesenquimal y la función de las células inmunes. El factor de crecimiento endotelial vascular (VEGF) es un regulador clave de la vasculogénesis y la angiogénesis. El factor de necrosis tumoral α (TNF-α) media la localización de los linfocitos T y la apoptosis de las células epiteliales. Objetivo: El presente estudio se realizó con el fin de comparar la expresión en suero y saliva de TGF-ß, VEGF, TNF-α entre pacientes con OLP y personas de control para investigar si la saliva se puede utilizar como alternativa al suero para fines de diagnóstico y monitoreo de la enfermedad. Material y Métodos: Se incluyeron 23 pacientes con OLP y 23 individuos control para evaluar los niéveles en suero y en saliva de TGF- ß, VEGF, TNF-α utilizando kits ELISA. Se recogieron cinco mililitros de sangre venosa y se recogió saliva no estimulada por el método de escupir. Resultado: Los niveles séricos y salivales de TGF-ß, VEGF, TNF-α son más altos en pacientes con OLP en comparación con los controles normales. La diferencia media es mayor en saliva que en suero. Además, hubo una diferencia significativa de VEGF y TNF-α en suero y saliva entre los grupos sintomáticos y asintomáticos. Conclusion: La saliva puede usarse como un sustituto del suero para evaluar los niveles de los biomarcadores estudiados

Possible Prognostic Potential of RANKL and OPG in Metastatic Breast Cancer Egyptian Females.

OBJECTIVES: Searching for sensitive, minimally invasive biomarkers that represent tumor-associated changes in the peripheral blood might enable the early diagnosis of breast cancer (BC) and monitoring of tumor progression. METHODS: Herein, we investigated the association of some circulating biomarkers with the risk of metastasis. In the current study, 115 BC patients which were subdivided into two groups: nonmetastatic breast cancer patients (NMBC) (n=83) and metastatic breast cancer patients (MBC) (n=32), and 79 apparently healthy controls were recruited. Serum protein levels of lysosomal protein transmembrane 4 beta (LAPTM4B), receptor activator of nuclear factor-kappa b (NF-Kb) ligand (RANKL), osteoprotegerin (OPG), vitamin D (VIT D), chitinase-3-like protein 1 (also known as YKL-40), and sirtuin 1 (SIRT1) were assessed in blood samples using ELISA technique. RESULTS: The results showed that RANKL and OPG had the highest diagnostic potential for MBC detection, with area under the curve values of 0.97 and 0.94, respectively. Moreover, logistic regression analysis showed that RANKL had the highest differentiation power in the discrimination of MBC from NMBC. CONCLUSION: The study highlighted that measuring RANKL and OPG may be helpful in the early detection of metastasis in Egyptian patients with BC.

Role of Serum miR-181b, Proinflammatory Cytokine, and Adhesion Molecules in Behçet's Disease.

Behçet's disease (BD) is a chronic multi-systemic inflammatory disease of uncertain pathogenesis and with no definitive diagnostic test. The aims of this study were to investigate serum levels of miR-181b in BD patients and to correlate this candidate biomarker with disease activity, cytokines, and adhesion molecules to identify new markers that can be used as a diagnostic tool for BD. Blood samples were collected from 96 participants who were classified according to their BD current activity form into 3 groups: healthy control, active BD, and inactive BD patients. MiR-181b was estimated by real-time polymerase chain reaction. However, high sensitive C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), E-selectin, and vascular cell adhesion molecule 1 (VCAM-1) levels were determined by enzyme-linked immunosorbent assay. Serum levels of miR-181b, hs-CRP, TNF-α, IL-6, E-selectin, and VCAM-1 were significantly higher in patients than in controls, but no significant difference was observed between the active and inactive BD groups. IL-6 was positively correlated with adhesion molecules, E-selectin, and VCAM-1. MiR-181b was positively correlated with hs-CRP, TNF-α, IL-6, and VCAM-1 in all subjects. In conclusion, miR-181b could play an important role in BD pathophysiology. MiR-181b could be utilized as potential biomarker for diagnosis and therapeutic targeting of BD. However, further studies with larger patient number are required to support these findings.