Design, synthesis, molecular modelling and biological evaluation of novel 6-amino-5-cyano-2-thiopyrimidine derivatives as potent anticancer agents against leukemia and apoptotic inducers.

Herein, a novel series of 6-amino-5-cyano-2-thiopyrimidines and condensed pyrimidines analogues were prepared. All the synthesized compounds (1a-c, 2a-c, 3a-c, 4a-r and 5a-c) were evaluated for in vitro anticancer activity by the National Cancer Institute (NCI; MD, USA) against 60 cell lines. Compound 1c showed promising anticancer activity and was selected for the five-dose testing. Results demonstrated that compound 1c possessed broad spectrum anti-cancer activity against the nine cancerous subpanels tested with selectivity ratio ranging from 0.7 to 39 at the GI50 level with high selectivity towards leukaemia. Mechanistic studies showed that Compound 1c showed comparable activity to Duvelisib against PI3Kδ (IC50 = 0.0034 and 0.0025 µM, respectively) and arrested cell cycle at the S phase and displayed significant increase in the early and late apoptosis in HL60 and leukaemia SR cells. The necrosis percentage showed a significant increase from 1.13% to 3.41% in compound 1c treated HL60 cells as well as from 1.51% to 4.72% in compound 1c treated leukaemia SR cells. Also, compound 1c triggered apoptosis by activating caspase 3, Bax, P53 and suppressing Bcl2. Moreover, 1c revealed a good safety profile against human normal lung fibroblast cell line (WI-38 cells). Molecular analysis of Duvelisib and compound 1c in PI3K was performed. Finally, these results suggest that 2-thiopyrimidine derivative 1c might serve as a model for designing novel anticancer drugs in the future.

Fractional CO2 laser versus 1064-nm long-pulsed Nd:YAG laser for inflammatory acne vulgaris treatment: a randomized clinical trial.

Acne vulgaris is challenging to treat for several individuals. Laser therapy may be a desirable alternative to traditional therapies with limited success. This study aimed to assess efficacy of fractional CO2 laser versus Nd:YAG laser for acne vulgaris therapy. Thirty cases with acne vulgaris underwent both fractional CO2 laser and Nd: YAG laser treatments in a randomized split face design at a 14-day interval for four sessions. The clinical efficacy was evaluated by counting acne lesions and utilizing the Global Acne Severity Scale (GEA Scale). GEAs decreased significantly after both fractional CO2 and Nd:YAG modalities after treatment and at a 3-month follow-up; fractional CO2 demonstrated significant more decrease in GEAs with (P = 0.006, 0.00 (respectively. Moreover, fractional CO2 showed a significantly higher satisfaction level (P = 0.004) and a better clinical improvement percentage regarding inflammatory and noninflammatory acne lesions (P = 0.007 and 0.000, respectively) after 3 months of follow-up. Apart from transient erythema, there were insignificant adverse effects concerning both treated sides. Fractional CO2 and Nd:YAG lasers are efficient physical modalities of acne treatment. However, fractional CO2 laser was more effective and more satisfying to the patients.

Novel 2-Thiouracil-5-Sulfonamide Derivatives: Design, Synthesis, Molecular Docking, and Biological Evaluation as Antioxidants with 15-LOX Inhibition.

New antioxidant agents are urgently required to combat oxidative stress, which is linked to the emergence of serious diseases. In an effort to discover potent antioxidant agents, a novel series of 2-thiouracil-5-sulfonamides (4-9) were designed and synthesized. In line with this approach, our target new compounds were prepared from methyl ketone derivative 3, which was used as a blocking unit for further synthesis of a novel series of chalcone derivatives 4a-d, thiosemicarbazone derivatives 5a-d, pyridine derivatives 6a-d and 7a-d, bromo acetyl derivative 8, and thiazole derivatives 9a-d. All compounds were evaluated as antioxidants against 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), lipid peroxidation, and 15-lipoxygenase (15-LOX) inhibition activity. Compounds 5c, 6d, 7d, 9b, 9c, and 9d demonstrated significant RSA in all three techniques in comparison with ascorbic acid and 15-LOX inhibitory effectiveness using quercetin as a standard. Molecular docking of compound 9b endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.

Evaluation of EZH2 and ERRα in colorectal carcinoma: an immunohistochemical study.

The combined immunohistochemical evaluation of EZH2 (enhancer of zeste homolog 2) and ERRα (estrogen-related receptor α), in relation to clinicopathological prognostic factors and patients' outcome, has not been performed yet in colorectal carcinoma (CRC). In order to achieve this aim, 120 samples were extracted; 60 cases of CRC; and 60 samples from normal colonic tissue. Our study showed that 63.3% and 38.3% of CRC cases reveal high EZH2 and high ERRα nuclear expression, respectively. 6.6% and 8.3% of normal colonic mucosa samples express low EZH2 and low ERRα nuclear expression, respectively. High EZH2 and high ERRα expression correlate with late tumor stages (p = 0.001 each), high grade (p = 0.001, p = 0.009 respectively), positive lymph node involvement (p = 0.001, p = 0.002 respectively) and larger tumor size (p = 0.001 each). There is a moderate highly statistically significant agreement (κ = 0.467, p = 0.001) between EZH2 and ERRα immunohistochemical expression. By Kaplan Meier analysis, high EZH2 and high ERRα show statistically significant shorter overall survival, and progression free survival than cases with low EZH2 and low ERRα immunohistochemical expression, respectively. Thus, EZH2 and ERRα might serve as potential promising prognostic markers in CRC.

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity.

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1-4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 µM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53-79%) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

Analysis of the expression profile of long non-coding RNAs MALAT1 and THRIL in children with immune thrombocytopenia.

BACKGROUND/AIMS: Pediatric immune thrombocytopenia (ITP) is an autoimmune disease; whose etiology is not exactly understood and seems to be highly multifactorial. Long non-coding RNAs (lncRNAs) are key regulators of different actions, which contribute to the development of many autoimmune diseases. To gain a further understanding, we estimated the relative expression of lncRNAs Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor-α (TNF-α) and heterogeneous nuclear ribonucleoprotein L (hnRNPL) immune-regulatory lncRNA (THRIL) in pediatric ITP. METHODS: In this case-control study, analysis of the expression profiles of these lncRNAs in blood samples from children with ITP and healthy controls (HCs) using quantitative real-time PCR was done. The association of MALAT1 and THRIL with ITP clinical features and their potential usage as non-invasive circulating biomarkers for ITP diagnosis was also evaluated. The receiver operating characteristic curve was constructed, and an area under the curve was analyzed. RESULTS: Both lncRNAs MALAT1 and THRIL were significantly upregulated in ITP patients in comparison to HCs ( p < .0001 and = .001 respectively). In addition, there was a positive significant correlation between the expression level of both biomarkers among patients (r = 0.745, p < .0001). At cutoff points of 1.17 and 1.27 for lncRNAs MALAT1and THRIL, respectively, both biomarkers had an excellent specificity (100% for both) and fair sensitivity (63.6 and 73.3% for lncRNAs MALAT1and THRIL, respectively). Improvement of biomarkers specificity was obtained by evaluation of the combined expression of both biomarkers. Serum lncRNAs MALAT1 and THRIL could be used as potential biomarkers in differentiating childhood ITP patients and HCs.

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.

Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal chemistry. Herein, we report the design, synthesis molecular modelling and biological evaluation of novel hybrids containing pyrazole, naphthalene and pyrazoline/isoxazoline moiety. Chalcones 2a-e were synthesized efficiently and were used as starting materials for synthesis of a variety of heterocycles. A novel series of pyrazoline 3a-e, phenylpyrazoline 4a-e, isoxazoline 5a-e and pyrazoline carbothioamide derivatives 6a-e were synthesized and screened for in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and superoxide radical scavenging assay as well as 15-lipoxygenase (15-LOX) inhibition activity. Compounds 3a, 4e, 5b, 5c, 6a, 6c, and 6e showed excellent radical scavenging activity in all three methods in comparison with ascorbic acid and 15-LOX inhibition potency using quercetin as standard then were subjected to in vivo study. Catalase (CAT) activity, glutathione (GSH) and malondialdehyde (MDA) levels were assayed in liver of treated rats. Compounds 5b, 5c, and 6e showed significant in vivo antioxidant potentials compared to control group at dose of 100 mg/kg B.W. Molecular docking of compound 6a endorsed its proper binding at the active site pocket of the human 15-LOX which explains its potent antioxidant activity in comparison with standard ascorbic acid.

Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent form of cancer. Various long non coding RNA (lncRNAs) and micro RNA have been confirmed to have a role in the progression of HCC. Our aim was to investigate for the first time the expression profile of serum level of LNC NEAT (nuclear enrich abundant transcript) and MiR-129-5p in HCC patients and their relations with patient's clinical and biochemical investigations rather than previous studies on tissue cell lines. Our study includes 72 subjects divided into 36 as control subjects and 36 patients with HCC. Complete physical and laboratory investigations were done on all subjects. RNAs were extracted from sera of all subjects. RNAs were reversed transcribed into cDNAs using Qiagen, Valenica, CA. Quantitative PCR (qPCR) was performed using Rotor gene Q System (Qiagen). Relative NEAT1 expression level was significantly increased in serum of HCC patients 4.7 (1.31-6.82) (p < .0001). Meanwhile MiR-129-5p relative expression level was significantly decreased in serum of HCC patients 0.17 (0.14-20) (p < .0001). Also there was negative significant correlation between the expression level of LNC NEAT and MiR-129-5p in HCC group (p < .0001). ROC curve analysis revealed that LNC NEAT; AUC = 0.981, p < .0001, cutoff value (1.02), sensitivity 100%, specificity 88.9%. MiR-129-5p; AUC = 0.997, p < .0001, cutoff value (0.43), sensitivity 100%, specificity 97.2%. Serum LNC NEAT and MiR-129-5p could be used as potential biomarkers for HCC cancer diagnosis and prognosis.

Overview and outcome of mucormycosis among children with cancer: Report from the Children's Cancer Hospital Egypt.

Mucormycosis represents a real challenge in immunocompromised patients. This study aimed to describe the clinical characteristics, treatment outcome and infection-related mortality in our patients at the Children's Cancer Hospital 57357, Cairo, Egypt. This is a retrospective study during the period 2007-2017. Data analysis included demographic data, risk factors, diagnostic workup, treatment and outcome. During the study period, 45 patients developed proven mucormycosis according to EORTC/MSG criteria (2008). Ninety percentof cases were of haematological malignancies. Liposomal amphotericin B was the mainstay of treatment. Posaconazole was used as secondary prophylaxis in 35% of cases. Combination antifungal was used in three cases with progressive mucormycosis. Surgical intervention was achievable in 50% of cases. Therapy was successful in 35 patients (66%). Complications related to mucormycosis were seen in five cases with disfigurement and perforated hard palate. Chemotherapy delay with subsequent relapse of primary malignancy was reported in one case. Mucormycosis-related mortality was 33% (15 cases). Mucormycosis is a major cause of mortality among patients with haematological malignancies. Early diagnosis of Mucormycosis infection, with rapid initiation of appropriate antifungal therapy and surgical intervention, whenever feasible, is the backbone of mucormycosis treatment.

Design, synthesis, molecular modelling, and biological evaluation of novel substituted pyrimidine derivatives as potential anticancer agents for hepatocellular carcinoma.

New anticancer agents are highly needed to overcome cancer cell resistance. A novel series of pyrimidine pyrazoline-anthracene derivatives (PPADs) (4a-t) were designed and synthesised. The anti-liver cancer activity of all compounds was screened in vitro against two hepatocellular carcinoma (HCC) cell lines (HepG2 and Huh-7) as well as normal fibroblast cells by resazurin assay. The designed compounds 4a-t showed a broad-spectrum anticancer activity against the two cell lines and their activity was more prominent on cancer compared to normal cells. Compound 4e showed high potency against HepG2 and Huh-7 cell lines ((IC50=5.34 and 6.13 µg/mL, respectively) comparable to that of doxorubicin (DOX) activities. A structure activity relationship (SAR) has been investigated and compounds 4e, 4i, 4m, and 4q were the most promising anticancer agents against tested cell lines. These compounds induced apoptosis in HepG2 and Huh-7 cells through significant activation of caspase 3/7 at all tested concentrations. In conclusion, 4e could be a potent anticancer drug.

The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats.

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.

Alleviation of antioxidant defense system by ozonized olive oil in DNBS-induced colitis in rats.

The aim of the study was to evaluate the potential protective effect of ozonized olive oil (OZO) in 2,4-dinitrobenzene sulphuric acid (DNBS) induced colitis in rats and to elucidate the role of some antioxidant defense system (superoxide dismutase "SOD," glutathione peroxidase "GSH-Px," and catalase "CAT") in these effects. The physicochemical parameters including viscosity, peroxide, and acid values of olive oil and OZO were evaluated. The animals were divided into several groups and the colitis was induced in the rats by intracolonic instillation of DNBS at dose of 15 mg/rat. Olive oil (OO) at dose of 6 mg/kg and OZO at doses of 3 and 6 mg/kg was administered orally for 7 days, starting the day before induction of colitis. Our results showed that macroscopic and microscopic damage scores were significantly reduced in a dose response manner in rats pretreated with OZO only. In contrast, CAT, GSH-Px, and SOD activities were significantly increased in the distal colon of inflamed animals pretreated with OZO with respect to control group dose dependently. Results demonstrate that OZO pretreatment exerts protective effects in DNBS induced colitis in rats and provide evidence that the protective effects of OZO are mediated by stimulation of some antioxidant enzymes.

Achieving integrated disease surveillance in the Eastern Mediterranean Region.

Access to reliable and timely information is key for healthcare decision-making at the regional, national and sub-national levels. However, lack of access to such information hampers to progress towards achievement of the Sustainable Development Goals (SDGs) in the Eastern Mediterranean Region (EMR), as indicated in the Regional Progress Report on Health-Related Sustainable Development Goals.

Combined microneedling with topical vitamin D3 or bimatoprost versus microneedling alone in the treatment of alopecia areata: A comparative randomized trial.

INTRODUCTION: Alopecia areata (AA) is a challenging disease with variable treatment outcomes. Hair follicles express vitamin D receptors. Therefore, vitamin D3 may be promising for AA treatment through immunomodulatory mechanisms. The efficacy of bimatoprost in scalp AA treatment was reported by few studies. OBJECTIVE: To evaluate the efficacy and safety of microneedling (MN) with topical vitamin D3 versus MN with bimatoprost in comparison with MN alone in the treatment of localized AA. PATIENTS AND METHODS: Seventy-five patients with localized AA were divided into three groups. The first group: 25 patients were treated with MN alone. The second group: 25 patients treated with MN combined with topical vitamin D3. The third group: 25 patients treated with MN combined with bimatoprost solution. The response was evaluated clinically and dermoscopically. RESULTS: At the end of the study, all groups showed a statistically significant decrease in the SALT score compared to the baseline. The clinical response (regrowth scale): vitamin D and bimatoprost groups showed a statistically significant higher regrowth scale compared to MN alone group (p-value = 0.000). After treatment, hair regrowth was significantly higher in MN combined with bimatoprost than in MN combined with topical vitamin D3. However, after 3 months of follow-up, there was no statistically significant difference between both groups. Side effects were mild and transient in all groups. CONCLUSION: Topical vitamin D3 and bimatoprost combined with MN are safe and effective therapeutic options for localized AA.

Carbapenem-Resistant Enterobacteriaceae (CRE) among Children with Cancer: Predictors of Mortality and Treatment Outcome.

Carbapenem-resistant Enterobacteriaceae (CRE) is an important emerging threat among pediatric cancer patients, with a high mortality rate. This retrospective study included all pediatric cancer patients with (CRE) bloodstream infections (BSIs) at a children's cancer hospital in Egypt (2013-2017). Two hundred and fifty-four pediatric cancer patients with CRE BSI were identified; 74% had hematological malignancies, and 26% had solid tumors. Acute myeloid leukemia was the most common hematological malignancy (50%). The main clinical features for acquiring CRE-BSI were previous antibiotics exposure (90%), profound neutropenia (84%), prolonged steroid use (45%), previous colonization with a resistant pathogen (35%), ICU admission within 90 days (28%), and central venous catheter use (24%). E. coli was the most common isolated pathogen (56%), followed by Klebsiella pneumoniae (37%). All isolates were resistant to carbapenem with an MIC < 4-8 µg/mL in 100 (45%) and >8 µg/mL in 153 (55%). The overall mortality rate was 57%, and 30 day mortality was reported in 30%. Upon multivariate analysis, for the patients with Klebsiella pneumoniae BSI, carbapenem resistance with an MIC > 8 µg/mL and associated typhlitis or pneumonia were predictors of poor outcome. In conclusion, CRE-BSI is a major threat among pediatric cancer patients in limited resource countries with limited options for treatment. Antimicrobial stewardship for early detection through routine screening, adequate empirical treatment, and timely adequate therapy may impact the outcome for such high-risk patient groups.

Evidence of intra-hepatic vascular proliferation remodeling early after cure in experimental schistosomiasis mansoni: an immunohistochemical descriptive study.

Experimental studies have demonstrated the occurrence of angiogenesis, blood vessels formation from pre-existing vessels, in the initial phase of bilharzial granuloma formation and during fibrosis progression in chronic hepatic schistosomiasis. Paradoxically, a recent work demonstrated an occurrence of angiogenesis during fibrosis regression months after curative treatment. Studies regarding the in situ kinetics of blood vessels in the phase of granuloma resolution and liver tissue healing early after treatment are lacking. The current work compared the kinetics of blood vessels by immunohistochemical staining using CD34, vascular endothelial growth factor (VEGF) and actin in the livers of normal control mice, Schistosoma mansoni infected mice and mice 2 weeks after curative treatment. The present study demonstrated a process of angiogenesis remodeling in the liver in the curative phase of hepatic schistosomiasis during the stage of granuloma resolution. Such finding raises the evidence of the importance and potential beneficial effect of vascular proliferation in the process of healing and restoration of liver tissue functions. Thus, blocking of angiogenesis may not represent the appropriate therapeutic target for the early treatment of schistosomal liver fibrosis.

Histological, immunohistochemical and radiographic evaluation of Amitriptyline administration on the periodontium of albino rats (An experimental study).

Background: Amitriptyline is a tricyclic antidepressant drug accustomed to treat depressive disorders. It recorded many side effects on different tissues. Objective: To investigate reaction of Albino rats' periodontium after oral administration of Amitriptyline histologically and radiographically. Methods: Fourteen adult male albino rats (150-200 g) were divided into two groups, control and experimental. Rats of experimental group received 10 mg/kg/day of Amitriptyline hydrochloride by oral gavage for four weeks. Mandibles were prepared for hematoxylin and eosin (H&E) and anti-osteopontin (Anti-OPN) immunohistochemistry staining. Bone mineral density was measured in mandibular alveolar bone. Statistical analysis for Anti-OPN and relative Hounsfield unit value (HU value) was performed using independent-samples t-test. Results: Gingiva of experimental group showed epithelial degeneration with pyknotic nuclei and disintegration in lamina propria. Areas of separation in alveolar bone and degeneration of some regions in cementum were seen with apparent increase in periodontal ligament (PDL) thickness and its detachment from bone and cementum at some regions. Immunohistochemical examination of experimental group showed apparently increased immunopositivity in gingiva, cementocytes, osteocytes, cementum, bone matrices, fibroblasts and PDL fibers when compared to control group. Statistical analysis revealed insignificant difference of Anti-OPN area% in gingiva between both studied groups. While there was statistical significant increase of Anti-OPN area% in the other periodontium tissues and high statistical significant decrease of relative HU value in experimental group when compared to control. Conclusions: Amitriptyline has destructive effect on periodontal tissues and statistically increases the expression of Anti-OPN in all periodontal tissues except gingiva and decreases bone mineral density.

Comparative study between fractional carbon dioxide laser versus retinoic acid chemical peel in the treatment of acanthosis nigricans.

BACKGROUND: Acanthosis nigricans (AN) is a common dermatological issue with several therapeutic modalities to treat. Despite retinoid is the first drug of choice in the treatment, the fractional-ablative carbon dioxide (CO2 ) laser has revealed as a promising procedure for the management of neck-AN, outstanding to its ability for superficial ablation of the skin surface, with trans-epidermal melanin elimination. OBJECTIVES: To decide whether fractional-ablative CO2 laser or retinoic acid (5%) peel is the more effective and safe choice for AN treatment. METHODS: In this study, twenty Egyptian cases with neck-AN were enrolled, where each case was exposed to four sessions with 2 weeks apart of both fractional CO2  laser on the right half of the neck and retinoic acid peel on the left half of the neck. Cases were assessed by a scoring system: Acanthosis Nigricans Area and Severity Index (ANASI) score, two blinded dermatologists, and dermoscopically before and one month after treatment. RESULTS: We found a highly statistically significant improvement among both treated groups regarding (ANASI) score and dermatologist's assessments. Bedside, the degree of sulci cutis, cristae cutis, brown-to-dark brown dots, and milia-like cysts, dermoscopic sign improvement was evident in both treated groups. However, fractional CO2 laser shows the superior result to retinoic acid peel in the treatment. CONCLUSION: Fractional CO2 laser and retinoic acid peel are considered effective modalities for neck-AN treatment. However, fractional CO2 laser was more effective.

The effect of Rutin hydrate on Glucocorticoids induced osteoporosis in mandibular alveolar bone in Albino rats (Radiological, histological and histochemical study).

Background: Glucocorticoids are used in different conditions such as autoimmune disorders and organ transplantation and their administration is the most common cause of secondary osteoporosis. Rutin is a flavonoid found in many plants. Flavonoids are natural products with various therapeutic and biological effects. Objective: Is to investigate the effect of Rutin Hydrate as a form of Rutin on glucocorticoid induced osteoporosis in mandibular alveolar bone radiologically, histologically and histochemically. Methods: Twenty-one adult male Albino rats were randomly divided into three groups. Group I (control), group II (osteoporotic) and group III (Rutin Hydrate treated). In both group II and III rats received 21 mg/kg of methylprednisolone daily for four weeks. Then group III received 50 mg/kg of rutin hydrate in distilled water daily for another four weeks. At the end of the experiment, mandibles were dissected for radiographic assessment, then processed for histological and histochemical examination and statistical analysis. Results: Radiologically, administration of Rutin Hydrate was able to enhance bone density than osteoporotic group. Histological examination revealed preserved cortical bone thickness that had been statistically proved. Apparently normal sized marrow cavities, some plump osteoblasts and normal osteocytes were seen in group III. Histochemical examination showed statistical increase in the area percentage of newly formed collagen in group III than group II. Conclusions: Rutin Hydrate was able to modify the radiological and histological picture of osteoporotic alveolar bone. This was achieved by the ability of Rutin Hydrate to increase bone density, preserve cortical plates thickness and enhance new collagen formation that was proved histochemically.

MiR-146a and miR-155 polymorphisms in Egyptian patients with Behcet's disease.

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