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.

"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).

Expression of microRNA-223 and microRNA-214 in gingival crevicular fluid of smoker and nonsmoker periodontitis patients, an observational diagnostic accuracy study.

OBJECTIVE: Periodontitis is a multifactorial disease that affects a wide range of populations. However, its pathogenesis remains unclear. miRNAs are now considered potential diagnostic markers for many inflammatory diseases. Thus, the aim of this study was to assess the expression of microRNA-223(miRNA-223) and microRNA-214 (miRNA-214) in gingival crevicular fluid (GCF) of smoker and nonsmoker with periodontitis. MATERIALS AND METHODS: We conducted a prospective study among 42 participants: 14 healthy controls, 14 nonsmoker periodontitis participants, and 14 smokers with periodontitis. Eligibility criteria for inclusion were consecutive adults, aged 20-60 years, with stage III periodontitis grade B/C and no systemic diseases. All consenting participants had gingival crevicular fluid samples collected after diagnosis to assess miRNA-214 and -223 by quantitative real-time polymerase chain reaction assay. RESULTS: ROC curve analyses for the non-smoker periodontitis group showed that miR-214 as a predictor in comparison to miR-223 had higher sensitivity [92.86%-64.29%], same specificity [100%], and a significantly higher area under the curve [0.974-0.796] respectively (p = 0.036). As for the smoker periodontitis group, a ROC curve with miR-214 as predictor in comparison to miR-223 had higher sensitivity [100%-71.43%], same specificity [100%], and a non-significantly higher area under the curve [1-0.872], respectively (p = 0.059). CONCLUSION: Both miRNA-214 and 223 are reliable potential diagnostic markers for periodontitis, with miRNA-214 being more accurate for smokers with periodontitis. CLINICAL RELEVANCE: Both miRNA-214 and 223 could be considered for potential chair-side diagnostics, by simply collecting GCF detecting the disease in its first steps and aid in preventing unrepairable damage.

"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.

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.

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.

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.

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.

Evaluating the role of tissue microRNA-27b as a diagnostic marker for oral lichen planus and possible correlation with CD8.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association of MiRNA-146a, MiRNA-499, IRAK1 and PADI4 Polymorphisms with Rheumatoid Arthritis in Egyptian Population.

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.

Single Nucleotide Polymorphism in SMAD7 and CHI3L1 and Colorectal Cancer Risk.

Colorectal cancer (CRC) is one of the leading cancers throughout the world. It represents the third most common cancer and the fourth in mortality. Most of CRC are sporadic, arise with no known high-penetrant genetic variation and with no previous family history. The etiology of sporadic CRC is considered to be multifactorial and arises from the interaction of genetic variants of low-penetrant genes and environmental risk factors. The most common well-studied genetic variation is single nucleotide polymorphisms (SNPs). SNP arises as a point mutation. If the frequency of the sequence variation reaches 1% or more in the population, it is referred to as polymorphism, but if it is lower than 1%, the allele is typically considered as a mutation. Lots of SNPs have been associated with CRC development and progression, for example, genes of TGF-ß1 and CHI3L1 pathways. TGF-ß1 is a pleiotropic cytokine with a dual role in cancer development and progression. TGF-ß1 mediates its actions through canonical and noncanonical pathways. The most important negative regulatory protein for TGF-ß1 activity is termed SMAD7. The production of TGF-ß can be controlled by another protein called YKL-40. YKL-40 is a glycoprotein with an important role in cancer initiation and metastasis. YKL-40 is encoded by the CHI3L1 gene. The aim of the present review is to give a brief introduction of CRC, SNP, and examples of some SNPs that have been documented to be associated with CRC. We also discuss two important signaling pathways TGF-ß1 and CHI3L1 that influence the incidence and progression of CRC.

Impact of microRNA-375 and its target gene SMAD-7 polymorphism on susceptibility of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) has a high morbidity and mortality. Many studies reported that mir-375 is frequently down-regulated in many cancers including esophageal cancer, hepatocellular carcinoma, breast cancer and leukemias. AIM: Our aim was to study the expression of microRNA-375 and its target gene SMAD-7 polymorphisms (rs4939827) in CRC patients in comparison to control subjects and to correlate these results with clinical data of patients to elucidate their role in pathogenesis and early diagnosis of CRC. MATERIAL AND METHODS: The present study was conducted on 122 subjects divided into 86 patients with CRC and 36 age- and sex-matched controls. The followings were done to all subjects: full history taking, full clinical examination, complete blood picture, serum (ALT, AST), serum albumin, CEA, TLC, PLT, and creatinine. Gene expression of miRNA-375 from serum was done by real-time PCR. Gene polymorphism SNPs of SMAD7 (rs4939827) was also done in DNA extracted from blood by real-time PCR. RESULTS: As regards the polymorphism of SMAD7, we found that CC (wild) genotype has high percentage in controls compared to CRC cases (36.1% vs 15.1%). Meanwhile, the mutant and heterozygotes genotypes showed high percentage among cases compared to controls (33.7%, and 51.2% respectively) vs (22.2%, and 41.7% respectively) with no significant statistical analysis. There was a statistically significant high T-allelic frequency among cases and C-allelic frequency among controls. There was a statistically significant association between fold change in micro RNA (-375) and the susceptibility to CRC as there is down-regulation of the microRNA-375 in CRC group with fold change in 0.42±0.27. CONCLUSION: Micro RNA-375 and rs4939827 SNP in SMAD7 could be considered as potential markers for detecting and early diagnosing CRC patients.

Are SMAD7 rs4939827 and CHI3L1 rs4950928 polymorphisms associated with colorectal cancer in Egyptian patients?

A wide variety of genes have been associated with colorectal cancer (CRC) development and progression. The SMAD7 gene encodes an intracellular protein, which inhibits the transforming growth factor beta (TGF-ß) signaling pathway, thereby having a key role in the control of neoplastic processes in various organs. The CHI3L1 gene encodes glycoprotein YKL-40, which plays a role in cell proliferation, anti-apoptosis, and angiogenesis. The present study aimed to evaluate the association of single nucleotide polymorphisms (SNPs) SMAD7 rs4939827 and CHI3L1 rs4950928, as well as circulating TGFß-1 and YKL-40 levels with CRC in an Egyptian population of 77 CRC patients and 36 healthy controls. Polymorphisms in the SMAD7 rs4939827 and the CHI3L1 rs4950928 genes were determined using the real-time polymerase chain reaction (RT-PCR). Both the SMAD7 rs4939827 TT genotype and the CHI3L1 rs4950928 C allele were associated with the rectal but not the colon cancer. In addition, the C allele of both SMAD7 rs4939827 and CHI3L1 rs4950928 was associated with increased serum levels of TGF-ß1 and YKL-40, respectively. In conclusion, our data suggest that SMAD7 rs4939827 and CHI3L1 rs4950928 SNPs have no significant association with CRC. A significant association of SNP in SMAD7 rs4939827 and CHI3L1 rs4950928 was revealed between the rectal cancer and colon cancer patients.

Single-nucleotide polymorphism of Toll-like receptor 4 and interleukin-10 in response to interferon-based therapy in Egyptian chronic hepatitis C patients.

Egypt has the highest prevalence of hepatitis C virus (HCV) in the world. It has been suggested that not only the virus but also the interaction between the virus and the host immune system is important in determining the course of the infection and the response to interferon (IFN)-based therapy. While the adaptive immune system plays a critical role in HCV infection, the innate immune system has only been recognized recently. Toll-like receptors (TLRs) form the cornerstone of the innate immune response. Interleukin-10 (IL-10) is one of the upstream regulators of TLR4. A possible interplay between TLR4 and IL-10 has been suggested. The present study aimed to investigate the role of single-nucleotide polymorphisms (SNPs) in TLR4 and IL-10-1082 and the expression levels of these proteins in predicting the response to treatment in chronic HCV patients. A total of 83 chronic HCV-infected Egyptian patients treated with peg-IFN-α2b-ribavirin combination therapy and 40 healthy subjects were included in this study. SNPs in the TLR4 rs2149356 and IL-10-1082 genes and their serum levels were assessed. Within the responders group, T/T and A/A genotypes were the significantly most frequent genotypes of TLR4 and IL-10-1082, respectively. Moreover, a higher frequency of T/T and A/A was found to be associated with lower serum TLR4 and IL-10 levels in our responder patients. In addition, subjects with the T/T genotype in the healthy control group had a lower serum TLR4 level than those with other genotypes. We conclude that the SNPs TLR4 rs2149356-T/T and IL-10-1082-A/A may be important predictors for HCV therapy.

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.

Influence of Diclofenac Potassium versus Prednisolone on Postendodontic Pain and Pulpal Interleukin-8 Expression in Symptomatic Irreversible Pulpitis Cases: A Randomized Placebo-controlled Trial.

AIM: This prospective, randomized, double-blind clinical trial investigated the impact of diclofenac potassium, prednisolone, and placebo as oral premedication on postendodontic pain and pulpal interleukin (IL)-8 expression in patients with irreversible pulpitis. METHODS: Thirty-six patients undergoing conventional endodontic treatment were assigned into one of 3 groups (n = 12). Pulpal blood samples were taken after access cavity preparation and stored until they were analyzed using enzyme-linked immunosorbent asssay for quantification of IL-8. Postendodontic pain was scored using the visual analogue scale. Outcome data were statistically analyzed using one-way analysis of variance, Kruskal-Wallis, Friedman's, Dunn's, Chi-square, and Fisher's exact tests and Spearman's correlation coefficient. The significance level (α) was set at 0.05. RESULTS: Apart from preoperative pain scores, all groups had similar baseline characteristics (P > .05). Immediate postendodontic pain scores had a significant difference between all groups (P < .05) where placebo group showed the highest score. There was no significant difference between all groups at 6 and 12 hours postoperatively (P > .05). Furthermore, there was no significant difference in the incidence of postendodontic pain and in mean IL-8 levels between the 3 groups (P > .05). CONCLUSIONS: The only impact the premedications had was on the immediate postendodontic pain intensity, and they had no influence on the later time points, incidence of postendodontic pain or pulpal IL-8 levels.

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.

Inhibitory effect of a standardized pomegranate fruit extract on Wnt signalling in 1, 2-dimethylhydrazine induced rat colon carcinogenesis.

BACKGROUND: De-regulation of Wnt signalling is increasingly being implicated in both experimental and human carcinogenesis including colon cancer. AIMS: Our goal was to identify possible dietary agents that block Wnt signalling as a step toward investigating new strategies for suppression of colon cancer. Pomegranate extract has emerged as an intriguing candidate due to its polyphenolic content. METHODS: We used a 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis model to investigate the expression pattern of the main key players in Wnt signalling by reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: Our results showed that many Wnt-target genes, e.g., Wnt5a, frizzled receptor (FRZ)-8, ß-catenin, T cell factor/lymphoid enhancer binding protein (Tcf4/Lef1), c-myc and cyclin D1, were up-regulated whereas adenomatous polyposis coli (APC) and axin1 exhibited down-regulation in colonic tissues of our DMH-colon cancer group compared with the normal group. Standardized pomegranate extract minimised all the aberrant alterations observed in the studied Wnt genes in colonic tissues of the DMH+pomegranate group as compared with the DMH-induced colon cancer group. This effect was also confirmed by the normalization of survival rate, inhibition of tumour incidence and a reduction of serum tumour marker carcinoembryonic antigen (CEA) level. Histopathological observations provided supportive evidence for the biochemical and molecular analyses. CONCLUSIONS: Standardized pomegranate extract holds great promise in the field of colon cancer prevention by dietary agents.