Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice.

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1ß, MCP-1, JNK1, and TGF-ß in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Examining the contribution of Notch signaling to lung disease development.

Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research.

Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review.

BACKGROUND: Systematic reviews and meta-analyses are instrumental in shaping clinical practice. However, their findings can sometimes be marred by discrepancies and potential biases, thereby diluting the strength of the evidence presented. Umbrella reviews serve to comprehensively assess and synthesise these reviews, offering a clearer insight into the quality of the evidence presented. In the context of the relationship between sperm DNA fragmentation (SDF) and assisted conception outcomes, there is a divergence in the literature. Some reviews suggest a clear cause-and-effect linkage, whereas others present conflicting or inconclusive results. OBJECTIVES: In this umbrella review we aimed to synthesise the evidence collated in systematic reviews and meta-analyses summarising the association of SDF with assisted reproductive technology (ART) outcomes. SEARCH STRATEGY: After preregistration (https://doi.org/10.17605/OSF.IO/6JHDP), we performed a comprehensive search of the PubMed, Scopus, Cochrane Library, Web of Science and Embase databases. We conducted a search for systematic reviews on the association between SDF and ART without any restrictions on language or publication date. SELECTION CRITERIA: Systematic reviews and meta-analyses assessing the association between SDF and ART outcomes were eligible. DATA COLLECTION AND ANALYSIS: We assessed the quality of the included reviews using AMSTAR 2 and ROBIS, and determined the degree of overlap of primary studies between reviews estimating the corrected covered area (CCA), adjusted for structural missingness. We evaluated the most recent reviews assessing the association of SDF with live birth, pregnancy, miscarriage, implantation, blastulation and fertilisation. The synthesis of evidence was harmonised across all included quantitative syntheses, re-estimating the odds ratio (eOR) in random-effects meta-analyses with 95% confidence intervals (95% CIs) and 95% prediction intervals (95% PIs). We categorised the evidence strength into convincing, highly suggestive, suggestive, weak or nonsignificant, according to the meta-analysis re-estimated P-value, total sample size, I2 statistic for heterogeneity, small study effect, excess significance bias and the largest study significance. MAIN RESULTS: We initially captured and screened 49 332 records. After excluding duplicate and ineligible articles, 22 systematic reviews, 15 of which were meta-analyses, were selected. The 22 reviews showed a moderate degree of overlap (adjusted CCA 9.2%) in their included studies (overall n = 428, with 180 unique studies). The 15 meta-analyses exhibited a high degree of overlap (adjusted CCA = 13.6%) in their included studies (overall n = 274, with 118 unique studies). AMSTAR 2 categorised the quality of evidence in 18 reviews as critically low and the quality of evidence in four reviews as low. ROBIS categorised all the reviews as having a high risk of bias. The re-estimated results showed that the association of SDF with live birth was weak in one and nonsignificant in four meta-analyses. Similarly, the association of SDF with pregnancy, miscarriage, implantation, blastulation and fertilisation was also weak or nonsignificant. The association of high SDF with different ART outcomes was also weak or nonsignificant for different interventions (IVF, ICSI and IUI) and tests. CONCLUSIONS: This umbrella review did not find convincing or suggestive evidence linking SDF with ART outcomes. Caution should be exercised in making any claims, policies or recommendations concerning SDF.

Detection and quantification of adenovirus, polyomavirus, and papillomavirus in urban sewage.

The objective of this study was to assess the occurrence and seasonal frequency of human adenovirus (HAdV), human polyomavirus (HPyV), and human papillomavirus (HPV) in urban sewage. The detection of these viruses was carried out by polymerase chain reaction (PCR), and then the viral concentrations in the positive samples were quantified by quantitative PCR (qPCR). Additionally, HAdV and HPyV genotyping was also performed by PCR. A total of 38/60 (63.3%) positive samples were found. HAdV was the most prevalent virus (26/60; 43.3%), followed by HPyV (21/60; 35%) and HPV (21/60; 35%). The viral concentrations ranged from 3.56 × 102 to 7.55 × 107 genome copies/L. The most common dual viral agents was found between HAdV and HPyV, in eight samples (8/38, 21%). HAdV types 40 and 41 as well as HPyV types JC and BK were identified, with HAdV-40 and HPyV JC being the most prevalent types. Furthermore, the detection rates of HAdV, HPyV, and HPV were higher during the winter season than the other seasons. The high prevalence of HAdV and HPyV supports their suitability as viral indicators of sewage contamination. Furthermore, this study demonstrates the advantages of environmental surveillance as a tool to elucidate the community-circulating viruses.

Autophagy-related gene and protein expressions during blastocyst development.

PURPOSE: This study aims to examine the expression of autophagic genes and proteins during blastocyst development and differentiation. METHODS: This is a prospective cohort study. Between March 2018 and November 2019, 30 females aged 30.13 ± 4.83 years underwent an intracytoplasmic sperm injection (ICSI) cycle at Madina Fertility Center. ICSI was used to develop and incubate 82 leftover embryos to day 5. Then, the embryos were divided into two groups based on their developmental structure: group D (n = 49) included embryos that developed into blastocysts, whereas group A (n = 33) included arrested embryos. These embryos were used to investigate the autophagic gene and protein expressions. The current study was approved by the Clinical Trial Ethical Committee of the Faculty of Medicine, Alexandria University, following the ethical standards of scientific research (Registration no. 0303721). RESULTS: Embryos that developed into blastocysts on day 5 (group D) had significantly higher relative expression of the LC3 gene (1.11 ± 0.52) and beclin-1 gene (1.43 ± 0.34) and beclin-1 protein expression (3.8 ± 0.028) than those that did not develop into blastocysts on day 5 (group A) [0.72 ± 0.18 (P = 0.03), 0.35 ± 0.12 (P = 0.0001), and 3.14 ± 0.05, (P = 0.0001), respectively]. In contrast, mTOR and PIK3C3 protein expression was significantly higher in group A (arrested embryos) than those in group D (developed embryos) (P = 0.007 and P = 0.0001, respectively). Furthermore, the expression of the eIF4E gene was significantly lower in group D embryos (0.32 ± 0.07) than that in group A embryos (4.38 ± 1.16) (P = 0.0001). CONCLUSIONS: This work identifies  autophagy as a well regulated process required to maintain cell allocation and differentiation during late preimplantation embryo developmental stages.

Glimepiride ameliorates renal toxicity induced by cadmium in mice: Modulation of Jun N terminal kinase (JNK)/nuclear factor kappa B (NF-κB) and phosphatidylinositol 3-kinases (PI3K)/protein kinase (AKT) pathways.

AIMS: Nephrotoxicity is one of the most serious health consequences of cadmium (Cd) toxic exposure. Cd was associated with nephrotoxicity through different mechanisms including apoptosis, inflammation, and oxidative stress. This study investigated the effects of glimepiride on renal inflammatory reactions and oxidative stress in response to Cd in mice animal model, pointing to the possible role of JNK/NF-кB and PI3K/AKT signaling. MATERIALS AND METHODS: Four groups of animals were created; the control group, the glimepiride group (4 mg/kg; i.p.), CdCl2 nephrotoxic group (6.5 mg/kg; i.p.), and the CdCl2/glimepiride group. On the other hand, molecular docking studies were used to investigate the affinity of glimepiride towards JNK, AKT, and PI3K targets. KEY FINDINGS: The CdCl2 group's serum creatinine and urea levels were found to have a significant increase when compared to the normal group. High expression of 8-OHDG, JNK, AKT, and NGAL was also detected in the CdCl2 group. In addition, coagulative necrosis of the renal tubules and increased immunostaining of NF-κB and PI3K. Furthermore, glimepiride significantly decreased the serum creatinine and urea level and alleviated the degenerative and necrotic changes within the renal tubules. Moreover, the renal NGAL and JNK were suppressed, and oxidants/antioxidants hemostasis was observed. SIGNIFICANCE: The available data show that glimepiride is an attractive strategy for improving the nephrotoxicity associated with CdCl2 through inhibition of JNK/NF-κB, PI3K/AKT inflammatory pathways. From the abovementioned results, glimepiride treatment might be a potential therapeutic approach to treat renal tissue against severe acute renal damage induced by the toxic effects of CdCl2.

Management of Adenoid Cystic Carcinoma of the Head and Neck: Experience of the National Cancer Institute, Egypt.

PURPOSE: This study presents the experience of the National Cancer Institute, Cairo University, in diagnosis and management of ACC of the head and neck. METHODS: This is a retrospective review of 57 patients with ACC managed during the period from January 2011 to January 2016. Data about the characteristics and management of the disease were recorded. All patients were followed up to detect the development of local recurrence and distant metastasis and their management. RESULTS: The mean age was 45.5 ± 15.1, with a femaleto-male ratio of 1.5:1. The minor salivary glands were affected in 61.4% of cases. Four patients (7%) were metastatic at presentation. The main presenting symptom was swelling, followed by pain. Surgical resection was performed in 48 patients (84.2%) followed by adjuvant radiotherapy in 36 of them. Four patients received radical radiotherapy. Treatment failed in 3 patients. Recurrences were recorded in 21 out of the 50 cured patients; 9 had locoregional recurrence, 9 had distant metastases, and 3 had both. The overall survival (OS) and disease-free survival (DFS) at three years were 79% and 57.1%, respectively. Surgical resection improved OS (p<0.001). Advanced T-stage, lymph node invasion, solid tumors, close or positive margins worsened OS. Adjuvant radiotherapy was associated with better DFS (p = 0.003), while solid tumors were associated with worse DFS. CONCLUSION: Despite aggressive management with radical surgery and adjuvant radiotherapy, recurrence affects 42% of the patients within three years. Patients with unresectable tumors have a poor prognosis. Adjuvant radiotherapy improves DFS but not OS.

A novel role of pirfenidone in attenuation acetic acid induced ulcerative colitis by modulation of TGF-ß1 / JNK1 pathway.

Colon diseases are a major health burden, particularly ulcerative colitis, in both men and women worldwide. Environmental and genetic factors in various colonic pathologies influence the onset and outcome of diseases. As the evidence from recent research is considered, the importance of inflammation in the onset, progression, and outcome is gaining more traction. The goal of this study was to see if pirfenidone could treat ulcerative colitis (UC) and if so, what mechanisms were involved. By intracolonic instillation [2 ml, 3 percent v/v acetic acid (AA)], ulcerative colitis was induced. Pirfenidone was administered to rats in different experimental groups (125 or 250 and 500 mg/kg, orally) for two weeks. Compared to normal group, the AA group showed an increase in colon weight, length, body weight, clinical evaluation, and macroscopic scoring of UC, serum lactate dehydrogenase, C-reactive protein, malondialdehyde, while decreasing serum total antioxidant capacity. Significant increases in colon Jun N terminal kinase1 (JNK1), transforming growth factor-beta (TGF-ß1), interleukin 1 beta (IL1ß), and Caspase-3 content. Furthermore, immunohistochemical staining revealed increased nuclear factor kappa B (NF-κB) expression along with histopathological changes. Pirfenidone inhibited inflammatory biomarkers release and restored oxidants/antioxidants hemostasis. In a dose-dependent manner, pirfenidone treatment showed a significantly decrease in all of these parameters. In addition, pirfenidone has significantly preserved the histopathological architecture of tissues. Current data demonstrate that Pirfenidone protects against AA-induced UC by modulating the TGF-ß1/JNK1 and Caspase-3 pathways. Pirfenidone's antioxidant, anti-inflammatory, and anti-apoptotic properties are thought to be responsible for its therapeutic benefit.

Pornography Use Prevalence and Associated Factors in Arab Countries: A Multinational Cross-Sectional Study of 15,027 Individuals.

BACKGROUND: There has been a tangible increase in pornography consumption during the past decade, with the absence of a large-scale study of Arab countries. AIM: The present study aimed to assess the prevalence of pornography viewing and its associated risk factors in Arab countries. METHODS: A large cross-sectional online survey was carried out recruiting participants without restrictions on the age, socioeconomic level, job, or educational level. Multivariable logistic regression analysis was performed to identify possible risk factors for viewing porn and results were expressed as odds ratios (ORs) and 95% confidence interval (95% CI). OUTCOMES: Main outcomes were pornography viewing (first exposure and frequency), the perceptions of this act, use of spare time, physical activity (exercising), and frequency of psychiatrist visits. RESULTS: The final number of participants included in the study was 15027 participants with a mean age ± standard deviation of 23.82 years ± 24.99. Most of the participants were men (84.56%), living with parents (81.71%), and 60.51% university graduates. There were statistically significant differences (P < .001) in the attitude and practice of men compared with women throughout all tested variables. Frequent pornography viewing was associated with male gender (OR [95% CI] = 7.08 [6.43 to 7.81]; P < .001) and age group ≤15 years (OR [95% CI] = 1.33 [1.01 to 1.75]; P = .044). By contrast, higher education was inversely associated with viewing rates reaching the lowest level in PhD awardees (OR [95% CI] = 0.36 [0.26 to 0.51]; P = .003). It was also noted that regular exercising (OR [95% CI] = 0.66 [0.58 to 0.74]; P < .001) was associated with a reduction in pornography viewing rates. CLINICAL IMPLICATIONS: Young age, male gender, and lower educational level are all predictors for higher pornography viewing and should be considered when designing public health intervention in a related context. STRENGTHS AND LIMITATIONS: This is the first large-scale multi-national survey to be conducted in Arab countries to investigate pornography viewing. The main limitations were the cross-sectional design (cannot indicate causality) and the self-report nature (liable to social desirability and recall bias). CONCLUSION: Pornography viewing is common in Arab countries and associated with some personal and behavioral factors. Eljawad MA, Se'eda H, Ghozy S, et al. Pornography Use Prevalence and Associated Factors in Arab Countries: A Multinational Cross-Sectional Study of 15,027 Individuals. J Sex Med 2021;18:539-548.

A Novel Role of Dapagliflozin in Mitigation of Acetic Acid-Induced Ulcerative Colitis by Modulation of Monocyte Chemoattractant Protein 1 (MCP-1)/Nuclear Factor-Kappa B (NF-κB)/Interleukin-18 (IL-18).

Colon illnesses, particularly ulcerative colitis, are considered a major cause of death in both men and women around the world. The present study investigated the underlying molecular mechanisms for the potential anti-inflammatory effect of Dapagliflozin (DAPA) against ulcerative colitis (UC) induced by intracolonic instillation of 3% v/v acetic acid (AA). DAPA was administered to rats (1 mg/kg, orally) for two weeks during the treatment regimen. Interestingly, compared to the normal group, a marked increase in the index of colon/body weight, colon weight/colon length ratio, serum lactate dehydrogenase (LDH), and C-reactive protein (CRP), besides decrease in the serum total antioxidant capacity (TAC), were reported in the AA control group (p ˂ 0.05). Elevation in colon monocyte chemoattractant protein (MCP1), Interleukin 18 (IL-18), and inflammasome contents were also reported in the AA control group in comparison with the normal group. In addition, colon-specimen immunohistochemical staining revealed increased expression of nuclear factor-kappa B (NF-κB) and Caspase-3 with histopathological changes. Moreover, DAPA significantly (p ˂ 0.05) reduced the colon/body weight index, colon weight/colon length ratio, clinical evaluation, and macroscopic scoring of UC, and preserved the histopathological architecture of tissues. The inflammatory biomarkers, including colon MCP1, IL-18, inflammasome, Caspase-3, and NF-κB, were suppressed following DAPA treatment and oxidants/antioxidants hemostasis was also restored. Collectively, the present data demonstrate that DAPA represents an attractive approach to ameliorating ulcerative colitis through inhibiting MCP1/NF-κB/IL-18 pathways, thus preserving colon function. Antioxidant, anti-inflammatory, and anti-apoptotic properties of DAPA are implicated in its observed therapeutic benefits.

Geothermal application of spectral gamma ray logging in the South Kansas Subsurface, USA.

Spectral gamma ray (SGR) is a logging tool that allows computation of the radioactive heat produced through radioactive decay of uranium, thorium and potassium within rocks. Radioactive heat-producing rocks are common targets for geothermal exploration. Gamma rays have longer half-length life in comparison to other radiations generated during radioactive decay. This characteristic allows the gamma rays to permeate far enough through the media to be measured by a logging tool. Radioactive heat production in this study was computed using spectral gamma ray and density logs. High-temperature geothermal reservoirs could provide heat that could be used to produce electricity from steam turbines. To provide domestic hot water, space heating, or process hot water, both low- and high-temperature geothermal systems could be used. This article is a case study illustrating subsurface radioactive heat production (A) calculated using well log data recorded in 48 wells located at 16 counties in the South Kansas State, USA. The results show that radioactive heat production (A) varies from approximately 0.1 to more than 10 µW/m3, whereas the average arithmetic mean is 1.15 µW/m3 and the average standard deviation is 0.57 µW/m3, which varies with lithology. The high measurements of radioactive heat production (A) in the studied rocks are predominantly related to the respective increase in uranium content in both shale and carbonate formations that could be future geothermal targets.

Robust contour propagation using deep learning and image registration for online adaptive proton therapy of prostate cancer.

PURPOSE: To develop and validate a robust and accurate registration pipeline for automatic contour propagation for online adaptive Intensity-Modulated Proton Therapy (IMPT) of prostate cancer using elastix software and deep learning. METHODS: A three-dimensional (3D) Convolutional Neural Network was trained for automatic bladder segmentation of the computed tomography (CT) scans. The automatic bladder segmentation alongside the computed tomography (CT) scan is jointly optimized to add explicit knowledge about the underlying anatomy to the registration algorithm. We included three datasets from different institutes and CT manufacturers. The first was used for training and testing the ConvNet, where the second and the third were used for evaluation of the proposed pipeline. The system performance was quantified geometrically using the dice similarity coefficient (DSC), the mean surface distance (MSD), and the 95% Hausdorff distance (HD). The propagated contours were validated clinically through generating the associated IMPT plans and compare it with the IMPT plans based on the manual delineations. Propagated contours were considered clinically acceptable if their treatment plans met the dosimetric coverage constraints on the manual contours. RESULTS: The bladder segmentation network achieved a DSC of 88% and 82% on the test datasets. The proposed registration pipeline achieved a MSD of 1.29 ± 0.39, 1.48 ± 1.16, and 1.49 ± 0.44 mm for the prostate, seminal vesicles, and lymph nodes, respectively, on the second dataset and a MSD of 2.31 ± 1.92 and 1.76 ± 1.39 mm for the prostate and seminal vesicles on the third dataset. The automatically propagated contours met the dose coverage constraints in 86%, 91%, and 99% of the cases for the prostate, seminal vesicles, and lymph nodes, respectively. A Conservative Success Rate (CSR) of 80% was obtained, compared to 65% when only using intensity-based registration. CONCLUSION: The proposed registration pipeline obtained highly promising results for generating treatment plans adapted to the daily anatomy. With 80% of the automatically generated treatment plans directly usable without manual correction, a substantial improvement in system robustness was reached compared to a previous approach. The proposed method therefore facilitates more precise proton therapy of prostate cancer, potentially leading to fewer treatment-related adverse side effects.

Survival of E. coli O157:H7, Salmonella Typhimurium, HAdV2 and MNV-1 in river water under dark conditions and varying storage temperatures.

The ability of Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, Human adenovirus serotype 2 (HAdV2) and Murine Norovirus 1 (MNV-1) to survive in river water at -20, 4, room temperature (~24 °C) and 37 °C, were evaluated under dark conditions. The tested surface water was obtained from the main Nile River in the Dokki area, Giza and sterilized by autoclaving. The pathogens were inoculated separately in the autoclaved river water. Each microcosm was sampled and the test microorganisms counted after zero (immediately following inoculation), 1, 7, 15, 30, 60, 90 and 120 days. Physicochemical parameters including pH, turbidity, electrical conductivity, dissolved oxygen, total dissolved solids, total alkalinity, biological oxygen demand, chemical oxygen demand, nitrates and nitrites, and sulphate, were also measured. For HAdV2, the highest decay rates were observed at 37 °C and room temperature compared to 4 and -20 °C. A similar trend was found for the MNV-1, although unlike the HAdV2, the decay rate was higher at -20 than at 4 °C. Also, 4 °C was the best temperature for the survival of MNV-1 (T90 = 76.9 days), E. coli O157:H7 (T90 = 103 days) and Salmonella Typhimurium (T90 = 105 days). The least survival of the pathogens, except MNV-1, was recorded at 37 °C. These results indicate that under dark conditions and low temperatures, enteric pathogens could be stable for extended periods. No significant statistical correlation was observed between the experimental temperatures and the infectivity of the viral particles. This study provided useful information about the stability of these pathogens in the Nile River water and could serve as an early warning when considering the water of the river for agricultural irrigation or household use in areas with limited or no access to potable water.

Combining several interventions to reduce the incidence of OHSS: A prospective cohort study.

OBJECTIVE: To assess the outcome of using low-dose aspirin, dopamine agonist and triggering ovulation by low dose of HCG in combination with GnRH agonist in fixed GnRH antagonist protocol in patients at risk of OHSS. STUDY DESIGN: This prospective cohort study was conducted on 50 infertile women who were at high risk of OHSS. They received low dose aspirin from first day of stimulation, cabergoline 0.5mg daily from the day of HCG for 8days and low dose of HCG (2500 IU) in combination with GnRH agonist for final oocyte maturation in fixed GnRH antagonist protocol. RESULTS: The study was conducted on 50 cases and all of them completed the study protocol. The clinical pregnancy rate was 40% (20 cases of 50) and no cases developed severe or critical OHSS. Only 8% (4 cases) developed moderate OHSS. CONCLUSION: Combining aspirin, cabergoline, and triggering with low dose of HCG in combination with GnRH agonist produced excellent clinical pregnancy rate, and decreased hospital admissions with severe or critical OHSS.

Surface Expression and Genetic Variants of Toll-like Receptor 2 in Pulmonary Tuberculosis Patients.

Innate immunity plays an important role in the host defense against Mycobacterium tuberculosis (M. tuberculosis). Toll-like receptor-2 (TLR2) is the main receptor and one of central components in initiation of innate immunity against M. tuberculosis. The study aimed to evaluate TLR2 surface expression on peripheral blood monocytes and study its association with variants in TLR2 597T/C single nucleotide polymorphisms (SNPs) in patients with pulmonary tuberculosis. Fifty pulmonary tuberculosis patients and 50 healthy controls were investigated for TLR2 expression on CD14+ monocytes by flow cytometry and TLR2 597T/C genotyping by Tetra primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR). A significant increase (P < 0.001) in TLR 2 expression was detected in tuberculosis patients compared to controls. TLR2 597 TC and CC genotypes were higher in pulmonary tuberculosis patients (OR =2.79, 95% CI =1.02-7.95 and OR =4.26, 95% CI =0.40-214.00) respectively. Genotype TT was associated with reduced risk of being a case of pulmonary tuberculosis. There was no association of TLR2 surface expression on monocytes in pulmonary tuberculosis patients with different TLR2 597T/C genotypes. It is concluded that elevated expression of TLR2 on CD14+ monocytes in pulmonary tuberculosis patients confirms the role of TLR2 in host defense against M. tuberculosis. 597T/C polymorphism of TLR 2 gene may be a risk factor for susceptibility to pulmonary tuberculosis in a sample Egyptian population.