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Objectives: To investigate whether (cluster of differentiation) CD40-1C>T (rs1883832) contributes to predisposition and treatment response of primary immune thrombocytopenia (pITP) in children., Methods: A case-control study that included 100 children with newly diagnosed pITP and 50 age- and sex-matched healthy controls. CD40 rs1883832 was genotyped using TaqMan allele discrimination real-time polymerase chain reaction (PCR). Patients were categorized into responders and non-responders according to their response to corticosteroids and thrombopoietin-receptor agonists (TPO-RA) at 3-month intervals., Results: The genotypic distribution of the CD40 rs1883832 was significantly different among cases and controls (CC 48% vs. 30%; CT 44% vs. 42%; TT 8% vs. 28%; p = .003). Compared with controls, children with newly diagnosed pITP had significantly higher C allele frequency (70% vs. 51%; odds ratio [OR] 2.2, 95% confidence interval [CI]: 1.3-3.8; p = .001). The association between C allele frequency and pITP risk was evident in females (OR 4.3, 95% CI: 2.1-8.8; p < .001), but not in males (OR 0.9, 95% CI: 0.4-2.1; p = .822). Compared with responders, the C allele frequency was significantly higher among non-responders to corticosteroids (87% vs. 66%; OR 3.4, 95% CI: 1.2-11.7; p = .012), but not to TPO-RA (92% vs. 85%; OR 2, 95% CI: 0.2-107; p = .550)., Conclusion: CD40 rs1883832 polymorphism may contribute to predisposition and response to upfront corticosteroids therapy of pediatric pITP. These findings improve our understanding of the compound pathophysiology of ITP, suggest important clinical potentials, and open the door for further research on the mechanistic role of CD40 rs1883832 in ITP development and progression., (© 2024 Wiley Periodicals LLC.)

Metabolic syndrome (MetS) is a worldwide public health challenge. Accumulating evidence implicates elevated serum ferritin and disruptions in iron metabolism as potential elements linked to an increased risk of MetS. This study investigates the relationship between iron homeostasis-including hepcidin levels, serum iron concentration, unsaturated iron-binding capacity (UIBC), and the hepcidin/ferritin (H/F) ratio-and MetS. In this descriptive cross-sectional study, 209 participants aged 24-70 were categorized into two groups: 103 with MetS and 106 without MetS. All participants underwent medical assessment, including anthropometric measures, indices of glycemic control, lipid profiles, and iron-related parameters. Participants were further stratified by the Homeostasis Model Assessment-Insulin Resistance index into three subgroups: insulin-sensitive (IS) (<1.9), early insulin resistance (EIR) (>1.9 to <2.9), and significant insulin resistance (SIR) (>2.9). Notable increments in serum ferritin and hepcidin were observed in the SIR group relative to the IS and EIR groups, with a significant association between metabolic parameters. The UIBC and serum ferritin emerged as significant predictors of MetS, particularly in men, with an area under the curve (AUC) of 0.753 and 0.792, respectively ( p ≤ 0.001). In contrast, hepcidin was notably correlated with MetS in women, with an AUC of 0.655 ( p = 0.007). The H/F ratio showed superior predictive capability for MetS across both sexes (at cutoff level = 0.67). Among women, this ratio had an AUC of 0.639 ( p = 0.015), and for men, it had an AUC of 0.792 ( p < 0.001). Hypertension proved an independent risk factor for MetS, affirming its role in metabolic dysregulation. The findings highlight a significant interconnection between iron homeostasis parameters and MetS, with sex-specific variations underscoring the importance of personalized diagnostic criteria. The crucial role of the H/F ratio and the UIBC as emerging predictive markers for MetS indicates their potential utility in identifying at-risk individuals. Further longitudinal research is essential to establish causality and explore the interplay between these biomarkers and MetS.

Helicobacter pylori (H. pylori) is a universal health intimidation as mentioned by the World Health Organization. The primary causal agent linked to a number of illnesses, including inflammation and the development of stomach ulcers, is Helicobacter pylori. Since, H. pylori develops antibiotic resistance quickly, current H. pylori treatment approaches are becoming less effective. Our research aims to highlight novel formulation antibiotics using CuO-NPs as catalysts and studied their activity as anti-helicobacter pylori supported by computational studies (POM analysis and molecular docking) software. They were designed for anti-Helicobacter Pylori action. All compounds revealed a bactericidal effect better than the reference McFarland standards., (© 2024. The Author(s).)

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory., (© 2023. The Author(s).)

Lactic acid bacteria (LAB) are of major concern due to their health benefits. Fermented food products comprise variable LAB demonstrating probiotic properties. Discovering and evaluating new probiotics in fermented food products poses a global economic and health importance. Therefore, the present work aimed to investigate and evaluate the probiotic potentials of LAB strains isolated from Egyptian fermented food. In this study, we isolated and functionally characterized 100 bacterial strains isolated from different Egyptian fermented food sources as probiotics. Only four LAB strains amongst the isolated LAB showed probiotic attributes and are considered to be safe for their implementation as feed or dietary supplements. Additionally, they were shown to exert antimicrobial activities against pathogenic bacteria and anticancer effects against the colon cancer cell line Caco-2. The Enterococcus massiliensis IS06 strain was exclusively reported in this study as a probiotic strain with high antimicrobial, antioxidant, and anti-colon cancer activity. Hitherto, few studies have focused on elucidating the impact of probiotic supplementation in vivo. Therefore, in the current study, the safety of the four strains was tested in vivo through the supplementation of rats with potential probiotic strains for 21 days. The results revealed that probiotic bacterial supplementation in rats did not adversely affect the general health of rats. The Lactiplantibacillus plantarum IS07 strain significantly increased the growth performance of rats. Furthermore, the four strains exhibited increased levels of antioxidants such as superoxide dismutase and glutathione in vivo. Consistently, all strains also showed high antioxidant activity of the superoxide dismutase enzyme in vitro. Overall, these findings demonstrated that these isolated potential probiotics harbor desirable characteristics and can be applied widely as feed additives for animals or as dietary supplements for humans to exert their health benefits and combat serious diseases., (© 2023. Springer Nature Limited.)

Current evidence supports the association of metabolic syndrome (MetS) with neuropathy. Limited data are available on proper strategies to control metabolic disorders and neuropathy among patients with type2 diabetes mellitus (T2DM). We aimed to determine hesperidin and diosmin efficacy individually and in combination among T2DM patients with neuropathy and meet MetS criteria. In this parallel-group designed trial, 129 T2DM patients with MetS and neuropathy were recruited and randomized to receive their oral hypoglycemics with either hesperidin (1g/day), or diosmin (1g/day), or combination of both or oral hypoglycemics without intervention for 12 weeks. Diabetic neuropathy was evaluated using Michigan Neuropathy Screening Instrument (MNSI) at baseline and after trial. Anthropometric parameters, blood glucose and lipid profile were also assessed before and after the intervention using paired student t-test within groups. The trial is registered at clinicaltrials.gov as NCT05243238. By completion of the trial duration, both hesperidin and diosmin groups showed significant reduction in blood glucose, triglycerides (TGs) and low density lipoprotein (LDL) from baseline (p<0.05). However, the magnitude of improvement in metabolic components significantly increased with hesperidin and diosmin combination. Although MNSI scores improved significantly in both groups, the reduction was more significant with the combination of hesperidin and diosmin. Moreover, the change in MNSI score was significantly correlated with the improvement in metabolic profile components including LDL, TGs and fasting blood glucose. Oral supplementation of hesperidin and diosmin was associated with improvement in metabolic syndrome and diabetic neuropathy and the combination of both was superior in efficacy.

On our way to discovering and developing compounds that have an antioxidant impact compared to ascorbic acid and other biological activities, we designed, synthesized, and evaluated a new series of heterocyclic moieties drugs ( 1 - 11 ) as antioxidants and antimicrobial agents. As starting moieties, these new candidates were derived from two promising heterocyclic compounds, imidazoldin-4-one and thiazol-4-one. Firstly, diphenylimidazol 1 was obtained because of the cyclo condensation one-pot ternary reaction of urea, aniline, and chloroacetic acid under thermal conditions. Out of this starting compound, we could design and create new vital rings such as purine and triazine as in compounds 5 and 6 , respectively. Secondly, the start thiazole derivative 7 was obtained from the intermolecular cyclization of thiourea, chloroacetic acid, p -nitobezaldehyde in the presence of sodium acetate. We synthesized various derivatives from this second starting compound 7 by being subjected to different reagents such as aniline, phenylenediamine, phenylhydrazine, and barbituric acid to yield 8 , 9 , 10 , and 11 , respectively. Using ascorbic acid as the standard compound, the pharmacological testing for antioxidant activity assessment of the produced derivatives was evaluated against ABTS (2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid). Candidate 6 exhibited the best activity as an antioxidant agent compared to ascorbic acid as a reference compound. Moreover, all compounds were evaluated as antimicrobial agents against a series of bacteria and fungi. Among all synthesized compounds, compound 6 achieved high efficiency against two types of fungi and four kinds of bacteria, as Clotrimazole and Ampicillin were used as the reference agents, respectively. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopical and elemental investigations.

Background: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population., Methods: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay., Results: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile., Conclusions: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes ( OCT4 , NANOG , and SOX2 ), G-protein-coupled chemokine receptor 4 ( CXCR4 ) and the ligand ( CXCL2 ), and alpha feto-protein ( AFP ) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method. In silico network analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG , CXCR4 and AFP were significantly up-regulated in HCC patients with late clinical stage. In contrast, SOX2 and CXCL2 were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.

Background: Human epididymis protein 4 (HE4) is a novel and specific biomarker for ovarian cancer. The aim of this study is to evaluate a new tumor marker, HE4, in comparison with CA125 in diagnosis of epithelial ovarian cancer (EOC) and benign gynecological diseases., Methods: CA125 and HE4 serum levels were determined in 30 patients with epithelial ovarian cancer (21 serous, 6 endometrioid and 3 mucinous tumors), 20 patients with benign gynecological diseases (8 patients with ovarian cyst, 5 patients with endometriosis, 4 patients with fibroid and 3 patients with pelvic inflammatory disease) and 20 healthy women. CA125 and HE4 cut-offs were 35 U/ml and 150 pmol/l, respectively., Results: Serum HE4 and CA125 concentrations were significantly higher in the ovarian cancer patients compared with those seen in patients with benign disease or in the healthy controls (p = 0.001 and p < 0.001 respectively). In the receiver operating characteristic analysis (ROC), the area under the curve (AUC) values for HE4 was 0.96 (95% confidence interval, 0.9-1.0) and CA125 was 0.82 (95% confidence interval, 0.7-0.94). Compared to CA125, HE4 had higher sensitivity (90% vs. 83.3%), specificity (95% vs. 85%), PPV (93.1% vs. 80.7%) and NPV (92.7% vs. 87.2%), the combination of HE4 + CA125 the sensitivity and PPV reached 96.7% and 97% respectively., Conclusion: Measuring serum HE4 concentrations along with CA125 concentrations may provide higher accuracy for detecting epithelial ovarian cancer., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1060413168685759.

Many cellular, preclinical and observational studies support a role of vitamin D in pathogenesis of type-1 diabetes mellitus (DM). The vitamin D receptor (VDR) locus has been studied in different populations for association with susceptibility to immune-mediated diseases, but with inconsistent findings in type-1 DM. This study aimed to investigate vitamin D status in patients with type-1 DM. We examined the frequency of VDR Fokl (rs10735810) gene polymorphism, and its association with serum 25-hydroxyvitamin D (25(OH) D) level in Egyptian patients with type-1 DM. 132 children with type-1 DM and 40 age and sex matched healthy control subjects were studied. VDR Fokl polymorphism was assessed using polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis. Diabetic children demonstrated lower circulating levels of 25(OH) D than the controls (13.4 +/- 7.6 vs 32.1 +/- 3.8ng/ml) (P < 0.01). Patients with deficient 25(OH) D showed lower calcium levels and higher HbA1c% than those with sufficient levels (8.1 +/- 2.1 versus 9.1 +/- 1.6 mg/dl & 9.9 +/- 2.5 versus 8.1 +/- 1.4%, respectively (P < 0.05). There was no significant difference in the genotype distribution or the allele frequencies of VDR Fokl between patients and controls. The odds ratio (OR) was 1.08 (P = 0.76), and the 95% confidence interval (CI) ranged from 0.64-1.85. The diabetic carriers of the ff genotype showed low serum levels of 25(OH) D and calcium when compared with the carriers of the F allele (9.1 +/- 4.4 vs 13.1 +/- 7 and 13.9 +/- 6.09 ng/ml & 8.1 +/- 2.1 vs 9.1 +/- 1.1 and 9.3 +/- 1.2 mg/dl, respectively) (P < 0.05). In conclusion, 84.8% of children with type-1 DM have low circulating levels of 25(OH) D. These patients have poor glycemic control (56.06%) than those with sufficient levels of 25(OH) D. Fokl polymorphism of VDR gene is associated with vitamin D deficiency but has no significant role in susceptibility to type-1 diabetes.