Green Tea Polyphenol (-)-Epicatechin Pretreatment Mitigates Hepatic Steatosis in an In Vitro MASLD Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is becoming more prominent globally due to an increase in the prevalence of obesity, dyslipidemia, and type 2 diabetes. A great deal of studies have proposed potential treatments for MASLD, with few of them demonstrating promising results. The aim of this study was to investigate the potential effects of (-)-epicatechin (EPI) on the development of MASLD in an in vitro model using the HepG2 cell line by determining the metabolic viability of the cells and the levels of PPARα, PPARγ, and GSH. HepG2 cells were pretreated with 10, 30, 50, and 100 µM EPI for 4 h to assess the potential effects of EPI on lipid metabolism. A MASLD cell culture model was established using HepG2 hepatocytes which were exposed to 1.5 mM oleic acid (OA) for 24 h. Moreover, colorimetric MTS assay was used in order to determine the metabolic viability of the cells, PPARα and PPARγ protein levels were determined using enzyme-linked immunosorbent assay (ELISA), and lipid accumulation was visualized using the Oil Red O Staining method. Also, the levels of intracellular glutathione (GSH) were measured to determine the level of oxidative stress. EPI was shown to increase the metabolic viability of the cells treated with OA. The metabolic viability of HepG2 cells, after 24 h incubation with OA, was significantly decreased, with a metabolic viability of 71%, compared to the cells pretreated with EPI, where the metabolic viability was 74-86% with respect to the concentration of EPI used in the experiment. Furthermore, the levels of PPARα, PPARγ, and GSH exhibited a decrease in response to increasing EPI concentrations. Pretreatment with EPI has demonstrated a great effect on the levels of PPARα, PPARγ, and GSH in vitro. Therefore, considering that EPI mediates lipid metabolism in MASLD, it should be considered a promising hepatoprotective agent in future research.

Glycylglycine promotes the solubility and antigenic utility of recombinant HCV structural proteins in a point-of-care immunoassay for detection of active viremia.

BACKGROUND: Although E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection. METHODS: The core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab-) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients' sera. The color intensity (OD450) and S/Co values were estimated. RESULTS: The integration of 0.1-0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab-sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection. CONCLUSION: The applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.

Unveiling the tyrosinase inhibitory potential of phenolics from Centaurium spicatum: Bridging in silico and in vitro perspectives.

Phenolics, abundant in plants, constitute a significant portion of phytoconstituents consumed in the human diet. The phytochemical screening of the aerial parts of Centaurium spicatum led to the isolation of five phenolics. The anti-tyrosinase activities of the isolated compounds were assessed through a combination of in vitro experiments and multiple in silico approaches. Docking and molecular dynamics (MD) simulation techniques were utilized to figure out the binding interactions of the isolated phytochemicals with tyrosinase. The findings from molecular docking analysis revealed that the isolated phenolics were able to bind effectively to tyrosinase and potentially inhibit substrate binding, consequently diminishing the catalytic activity of tyrosinase. Among isolated compounds, cichoric acid displayed the lowest binding energy and the highest extent of polar interactions with the target enzyme. Analysis of MD simulation trajectories indicated that equilibrium was reached within 30 ns for all complexes of tyrosinase with the isolated phenolics. Among the five ligands studied, cichoric acid exhibited the lowest interaction energies, rendering its complex with tyrosinase the most stable. Considering these collective findings, cichoric acid emerges as a promising candidate for the design and development of a potential tyrosinase inhibitor. Furthermore, the in vitro anti-tyrosinase activity assay unveiled significant variations among the isolated compounds. Notably, cichoric acid exhibited the most potent inhibitory effect, as evidenced by the lowest IC50 value (7.92 ± 1.32 µg/ml), followed by isorhamnetin and gentiopicrin. In contrast, sinapic acid demonstrated the least inhibitory activity against tyrosinase, with the highest IC50 value. Moreover, cichoric acid exhibited a mixed inhibition mode against the hydrolysis of l-DOPA catalyzed by tyrosinase, with Ki value of 1.64. Remarkably, these experimental findings align well with the outcomes of docking and MD simulations, underscoring the consistency and reliability of our computational predictions with the actual inhibitory potential observed in vitro.

Deciphering molecular mechanisms underlying the inhibition of ß-glucuronidase by xanthones from Centaurium spicatum.

Herein, we scrutinized the inhibitory potential of five xanthones and a flavonoid, sourced from Centaurium spicatum, against ß-glucuronidase activity. The results showed that gentisin and azaleatin emerged as the most potent inhibitors, with significantly lower IC50 values of 0.96 ± 0.10 and 0.57 ± 0.04 µM, respectively. The evaluation of enzyme kinetics unveiled that the isolated xanthones manifested inhibition of ß-glucuronidase through a mixed inhibition mode, whereas azaleatin exhibited a noncompetitive inhibition mechanism. The findings from molecular docking analysis unveiled that the compounds under investigation, particularly azaleatin, displayed comparatively diminished binding affinities towards ß-glucuronidase. Furthermore, the tested drugs were shown to occupy a common binding site as the employed reference drug. Our comprehensive Molecular Dynamics (MD) simulations analysis revealed consistent trajectories for the investigated drugs, wherein azaleatin and gentisin demonstrated notable stabilization of energy levels. Analysis of various MD parameters revealed that drugs with the lowest IC50 values maintained relatively stable interactions with ß-glucuronidase. These drugs were shown to exert notable alterations in their conformation or flexibility upon complexation with the target enzyme. Conversely, the flexibility and accessibility of ß-glucuronidase was reduced upon drug binding, particularly with azaleatin and gentisin, underscoring the stability of the drug-enzyme complexes. Analysis of Coul-SR and LJ-SR interaction energies unveiled consistent and stable interactions between certain isolated drugs and ß-glucuronidase. Azaleatin notably displayed the lowest average Coul-SR interaction energy, suggesting strong electrostatic interactions with the enzyme's active site and significant conformational variability during simulation. Remarkably, LJ-SR interaction energies across different xanthones complexes were more negative than their Coul-SR counterparts, emphasizing the predominant role of van der Waals interactions, encompassing attractive dispersion and repulsive forces, in stabilizing the drug-enzyme complexes rather than electrostatic interactions.

Comparison between stem cell therapy and stem cell derived exosomes on induced multiple sclerosis in dogs.

BACKGROUND: Multiple sclerosis (MS) is a chronic condition that primarily manifests as demyelination of neuronal axons in the central nervous system, due to the loss or attack of oligodendroglia cells that form myelin. Stem cell therapy has shown promising results for the treatment of MS due to its capability to halt the immune attack, stop apoptosis and axonal degeneration, and differentiate into oligodendrocytes. Stem cell-derived Exosomes (Exosomes) have shown great capabilities for neuronal diseases as they have growth factors, complex sets of miRNA, enzymes, proteins, major peptides, lipids, and macromolecules with anti-inflammatory, angiogenesis, and neurogenesis activities. METHODS: This study aimed to compare the healing properties of stem cells, against Exosomes for the treatment of an experimentally induced MS dog model. Dog models of MS received either a single treatment of stem cells or a single treatment of Exosomes intrathecally and the treatment process was evaluated clinically, radiologically, histopathologically, and electron microscopy and cerebrospinal fluid analysis. RESULTS: showed marked amelioration of the clinical signs in both treated groups compared to the control one, magnetic resonance scans showed the resolution of the hyperintense lesions at the end of the study period, the histopathology and electron microscopy showed marked healing properties and remyelination in treated groups with superiority of the stem cells compared to Exosomes. CONCLUSIONS: Although stem cell results were superior to Exosomes therapy; Exosomes have proven to be effective and safe important actors in myelin regeneration, and their use in diseases like MS helps to stimulate remyelination.

Predictive Value of Interleukin 6 and Interleukin 8 in Response to Treatment of Hepatitis C Virus.

BACKGROUND: Chronic hepatitis C (CHC) infection is a major public health problem in many low- and middle-income countries. The study aimed to find out how interleukin IL-6 and IL-8 levels in the blood affect the virological response to directacting antivirals (DAAs) and to find useful clinical or immunological markers for the response to HCV treatment. METHODS: CHC patients from a real Egyptian population (n = 4,300), who were treated during the Egyptian national initiative to eliminate HCV at the Sherbin Central Hospital, Dakahlia Governorate, Ministry of Health, Egypt, were enrolled in our study. They were all patients who did not obtain a sustained virological response (SVR) (n = 75; non-responder; the response rate was 98.26%), and a total of 100 patients were randomly selected from patients who obtained SVR (responder) and were age- and gender-matched (p > 0.05) with non-responder patients. Serum levels of IL-6 and IL-8 were measured by commercial ELISA kits. RESULTS: Non-responder patients were associated with significantly high levels of ALT, AST, ALP, and total bilirubin. Non-responders had significantly (p < 0.05) higher baseline IL-6 (16.7 ± 4.92 pg/mL) and IL-8 (37.81 ± 10.55 pg/mL) levels compared to responders (12.68 ± 2.06, 29.06 ± 5.94 pg/mL, respectively). There was a substantial (p < 0.05) association between the combination of two cytokines and a high likelihood of treatment failure, as indicated by all parameters examined, with the highest correlation values seen. CONCLUSIONS: The present study showed that increased IL-6 and IL-8 were associated with HCV treatment failure. Also, IL8 was associated with hepatic fibrosis.

New imidazole-2-thiones linked to acenaphythylenone as dual DNA intercalators and topoisomerase II inhibitors: structural optimization, docking, and apoptosis studies.

In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.

Genomic analysis of Brucella isolates from animals and humans, Türkiye, 2010 to 2020.

BackgroundBrucellosis is a bacterial zoonosis causing severe illness in humans and animals and leading to economic losses in the livestock production in Türkiye and other endemic countries.AimWe aimed at investigating genomic differences of Brucella isolates from animals and humans in Türkiye.MethodsWe used whole genome sequencing (WGS) to assess the genetic diversity of Brucella isolates from 41 provinces in Türkiye and compared with isolates from other countries. We applied allele-based typing and core genome single nucleotide polymorphism (cgSNP) determination.ResultsOf the 106 Turkish Brucella isolates included, 57 were B. abortus and 49 were B. melitensis. One B. melitensis and two B. abortus isolates were identified as vaccine strains. Most (n = 55) B. abortus isolates clustered in three major branches, with no spatial discernible pattern. Of the B. melitensis isolates, 48 were assigned to the Eastern Mediterranean lineage with no discernible patterns between host species, location and sampling date. The Turkish isolates clustered with isolates from neighbouring countries such as Greece and Syria, but some also with isolates from human patients in European countries, like Germany, Norway and Sweden, suggesting that the source may be travel-related.ConclusionSeveral B. melitensis and B. abortus lineages are circulating in Türkiye. To decrease the prevalence and prevent brucellosis in animals and humans, stricter control measures are needed, particularly in areas where humans and animals have close contact. Furthermore, illegal transportation of animals across borders should be more closely controlled and regulated.

Serum collagen IV as a predictor for response to direct-acting antivirals hepatitis C therapy.

Althoughchronic hepatitis C (CHC) therapies based on direct-acting antiviral (DAA) agents safely improved treatment effectiveness, some cases do not obtain sustained virological response (SVR) and, thus, evaluating factors that may be related to treatment failure is very important. We aimed to evaluate the association of baseline serum collagen IV with DAA treatment failure in Egyptian patients with CHC. A total of 175 CHC patients (100 responders and 75non-responders tosofosbuvir/daclatasvir) were included. Collagen IV was assessed using sensitive chemiluminescent immunoassay. There was distinctly higher (P < 0.0001) collagen IV in non-responders compared to responder patients as the median (interquartile range) were 19.02 (13.4-25.2) vs.9.7 (7.2-12.3) µg/L, respectively. Collagen IV has a good ability for distinguishing nonresponders from responder patients (AUC = 0.890) with sensitivity of 92%, specificity 72%, PPV 71.1%, NPV 92.3% and accuracy of 80.6%. Collagen IV was correlated (p < 0.05) with decreased albumin (r=-0.266), elevated APRI (r = 0.288), and elevated FIB-4 (r = 0.281) scores. In conclusion,these findings suggested the remarkable role of baseline collagen IV in the prediction of HCV DAAs treatment response. Thus, however further studies are needed, its measurement may improve treatment duration and the disease control.

Interferon-induced protein 44 (IFI44) and interferon regulatory factor 4 (IRF4) gene expression in rheumatoid arthritis.

BACKGROUND AND OBJECTIVES: The type I interferon (IFN) signature has been found to be overactivated in many systemic autoimmune diseases. This may be explained by impaired regulation of interferon-stimulated genes (ISGs) as well as interferon-induced protein 44 (IFI44) expression via their regulatory mechanisms via interferon regulatory factors (IRFs). PATIENTS AND METHODS: This case-control study includes two groups: 50 RA patients and 50 healthy controls. The quantification of IFI44 and IRF4 expression levels by the real-time PCR technique was estimated. Disease Activity Score-28 (DAS-28) was estimated for RA patients only. RESULTS: Among the RA patients, there were statistically significant increased ESR, CRP, TLC, RF, and anti-CCP levels (p value < 0.001) and significant increased expression of the IFI44 and IRF4 genes (p value < 0.001). There was a significant positive correlation between the IFI44 and IRF4, and there was a significant correlation between both and ESR and anti-CCP among RA patients. At a cutoff point of 1.95, IFI44 shows higher sensitivity and specificity values than IRF4 for the diagnosis of RA. CONCLUSION: IFI44 was more sensitive for RA diagnosis than IRF4. IFI44 and IRF4 overexpression could be promising predictors of RA diagnosis and might become useful clinical tools to guide therapeutic strategies.

Phytochemical Analysis and Anti-dyslipidemia and Antioxidant Activities of Pluchea dioscoridis: In Vitro, In Silico and In Vivo Studies.

Pluchea dioscoridis (L.) DC. is a flowering wild plant used traditionally in the treatment of rhematic disorders. This study investigated the phytochemical and in vitro radical scavenging activity (RSA), and in vivo anti-hyperlipidemic, antioxidant and anti-inflammatory properties of P. dioscoridis. The antihyperlipidemic efficacy was determined in a rat model of dyslipidemia. The extract and fractions of P. dioscoridis showed RSA with the ethyl acetate (EA) fraction exhibiting the most potent activity. The phytochemical analysis of P. dioscoridis EA fraction (PDEAF) led to the isolation of five compounds (lupeol, quercetin, lupeol acetate, stigmasterol, and syringic acid). To evaluate its anti-hyperlipidemic effect, three doses of PDEAF were supplemented to rats for 14 days and poloxamer-407 was administered on day 15 to induce dyslipidemia. All doses of PDEAF decreased plasma triglycerides, cholesterol, low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol (vLDL-C), and increased plasma lipoprotein lipase (LPL). PDEAF upregulated hepatic LDL receptor and suppressed 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, decreased lipid peroxidation and tumor necrosis factor (TNF)-α and enhanced reduced glutathione (GSH) and enzymatic antioxidants in dyslipidmeic rats. In silico findings revealed the binding affinity of the isolated compounds towards LPL, HMG-CoA reductase, and LDL receptor. In conclusion, P. dioscoridis is rich in phytoconstituents, exhibited RSA and its EA fraction effectively prevented acute dyslipidemia and its associated oxidative stress and inflammatory response.

Long-standing Nonunited Fracture Lateral Humeral Condyle in Children. Evaluating a Two-stage Surgical Treatment Strategy With Critical Review.

OBJECTIVE: This work aimed to evaluate the results of using a 2-stage surgical treatment strategy without doing anterior transposition of the ulnar nerve (ATUN) for cases with long-standing nonunited fracture lateral humeral condyle (LHC) in children, accompanied by a critical review. METHODS: A consecutive 12 children with a long-standing ">2 years" nonunited LHC with evident radiologic gross anatomic distortion of the elbow were included in this study. A 2-stage surgical treatment strategy was applied, wherein the first stage, open functional reduction, osteosynthesis, and iliac bone graft were done. Then after 6 months, the second stage surgery was carried out in the form of supracondylar humeral corrective osteotomy if the cubitus valgus angle was ≥20 degrees. ATUN was not done for any of the cases even with those having ulnar nerve dysfunction. RESULTS: Union took place in 11 out of the 12 cases after a mean follow-up period of 11 weeks (range: 8 to 14 wk; SD: 1.6). All the 7 cases showed preoperative ulnar nerve dysfunction and reported clinical recovery at the end of their follow-up. CONCLUSIONS: Two-stage surgical treatment strategy without ATUN is a convenient, reproducible, and successful line of treatment for children presented with longstanding nonunited LHC with anatomically distorted elbow. LEVEL OF EVIDENCE: Level IV-case series.

Supra-arcuate free fascial MS-TRAM, a modified technique to reduce donor site morbidity in obese population-comparative study.

BACKGROUND: Abdomen-based free flaps represent the gold standard option in the armamentarium of breast reconstruction. The natural evolution to more preservation with less invasive forms of these flaps has been driven by both patient and surgeon satisfaction. Nevertheless, obese patients are challenging due to the increased risk of compromised flap perfusion and donor site morbidity. This challenge is compounded by the prevalence of obesity worldwide, resulting in more free abdominal flaps being performed for breast reconstruction in obese patients. The authors present the outcomes of a modified supra-arcuate fascial muscle-sparing transverse rectus abdominus myocutaneous (FMS-TRAM) technique compared to standard muscle-sparing transverse rectus abdominus myocutaneous (MS-TRAM) technique to reduce the donor site morbidity while providing a well-vascularized large volume of autologous tissue. METHODS: A retrospective comparative data analysis was conducted at two centers: Cairo University Hospitals, Egypt, and University Hospitals Birmingham, United Kingdom. Standard MS-TRAM was performed in 65 patients between 2008 and 2011 (Group 1) versus 275 patients between 2011 and 2020 (Group 2) who underwent FMS-TRAM. The modified technique involved limiting the fascial incision to above or at the level of the arcuate line to preserve the integrity of the anterior rectus sheath caudally. All patients included were of the obese population (BMI≥30 kg/m2 ) and underwent unilateral post-mastectomy reconstruction. Patient demographics, comorbidities, operative details, and outcomes focusing on donor site morbidity and flap complications were recorded and compared between the two groups. RESULTS: The median age and BMI for Group 1 were 43 and 32, respectively. While for Group 2, they were 47 and 33, respectively. Flap weight ranged from 560 to 1470 g (Mean 705) for Group 1, while Group 2 ranged from 510 to 1560 (mean 715). The majority (280/340 [82%]) of the patients in both groups received radiotherapy. 7.7% of Group 1 were smokers, while in Group 2 it was 4.7%. The percentage of delayed versus immediate reconstruction in Group 1 was 60%/40%, while in Group 2, it was 43%/56%. The incidence of fat necrosis, partial necrosis, and total necrosis was 7.6%.1.5%, and 3%, respectively, for Group 1 and 8%, 1.4%, and 2.6%, respectively, for Group 2. The two-tailed p-value demonstrated a significant statistical difference (p < 0.00001) in donor site morbidity between both groups, with more bulge 20% (13/65) and hernia 1.5% (2/65) occurrence in Group 1 versus 1.9% (5/275) and 0.7% (2/275) in Group 2 respectively, over a follow-up period ranging from 24 to 60 months (mean 32). CONCLUSION: FMS-TRAM flaps are safe, robust, and reliable with less donor site morbidity while maintaining optimal flap perfusion for large volume flaps in obese patients with excellent, durable outcomes. It should be considered a valuable tool in the reconstructive armamentarium of breast reconstruction.

Association between hepatitis C virus genotype 4 and renal cell carcinoma: Molecular and virological studies.

Hepatitis C virus (HCV) is the most common infection worldwide. The correlation between HCV and renal cell carcinoma (RCC) is still mysterious. Therefore, the relationship between HCV and RCC was investigated. The study included 100 patients with RCC; 32 with HCV infection, and 68 without HCV infection. Expressions of viral proteins (NS3 and NS5A) were tested using an immune electron-microscope (IEM) and immunohistochemistry (IHC). IHC and quantitative real time-PCR investigated the presentation of human proteins TP53 and p21 genes. Transmission electron (TEM) detected viral-like particles in infected RCC tissues. The gene and protein expression of P53 was higher in HCV positive versus HCV negative patients and p21 was lower in HCV positive versus HCV negative in both tumor and normal tissue samples. Viral like particles were observed by TEM in the infected tumor and normal portion of the RCC tissues and the plasma samples. The IEM showed the depositions of NS3 and NS5A in infected renal tissues, while in noninfected samples, were not observed. The study hypothesizes that a correlation between HCV and RCC could exist through successfully detecting HCV-like particles, HCV proteins, and (p53 and p21) in RCC-infected patients.

Novel Disperse Dyes Based on Enaminones: Synthesis, Dyeing Performance on Polyester Fabrics, and Potential Biological Activities.

1-(3-aryl)-3-(dimethylamino)prop-2-en-1-one (enaminones) derivatives and the diazonium salt of para-chloroaniline were used to synthesize several novel disperse azo dyes with high yield and the use of an environmentally friendly approach. At 100 and 130 °C, we dyed polyester fabrics using the new synthesized disperse dyes. At various temperatures, the dyed fabrics' color intensity was assessed. The results we obtained showed that dyeing utilizing a high temperature method at 130 °C was enhanced than dyeing utilizing a low temperature method at 100 °C. Reusing dye baths once or twice was a way to achieve two goals at the same time. The first was obtaining a dyed product at no cost, and the second was a way to treat the wastewater of dyeing bath effluents and reuse it again. Good results were obtained for the fastness characteristics of polyester dyed with disperse dyes. When the disperse dyes were tested against certain types of microbes and cancer cells, they demonstrated good and encouraging findings for the potential to be used as antioxidants and antimicrobial agents.

Comparison of Direct Intraoral Scan and Traditional Impression for CAD/CAM Mandibular Overdenture Base: RCT on Peri-implant Marginal Bone Changes.

AIM: This study aimed to evaluate the impact of digital vs traditional impression techniques on peri-implant vertical bone resorption in the creation of mandibular overdenture bases supported by four implants using CAD/CAM technology. MATERIALS AND METHODS: Twenty edentulous patients were placed in four mandibular implants and randomly divided into groups: (A) the control group (CIG) (n = 10); patients obtained CAD/CAM denture base using conventional impression technique and group (B) the study (DIG) group (n = 10); patients obtained CAD/CAM denture base using digital impression technique. Peri-implant vertical bone height was measured immediately (T0), 6 (T6), and 12 (T12) months after insertion. Peri-implant vertical bone loss (VBL) was calculated first 6 months (T1), the second 6 months (T2), and 1 year (T3) after insertion. RESULTS: For both groups, the survival rates of inserted implants were 100%. The amount of VBL in the first year in both groups was within normal ranges. In both groups, VBL significantly decreased over time. The control group recorded significantly higher VBL than (DIG) group at T2 (p = 0.006) and at T3 (p = 0.005). CONCLUSION: Digital intraoral scanning technique may be considered a more beneficial registration method than traditional impression technique for the construction of CAD/CAM 4-implant-assisted overdenture base regarding the preservation of vertical bone levels. CLINICAL SIGNIFICANCE: Both digital intraoral scanners and conventional impression techniques can be used for the construction of CAD/CAM-implant-assisted overdenture bases regarding the preservation of peri-implant vertical bone resorption. How to cite this article: Seifeldeen AR, Aboelez MA, Gebreel AA, et al. Comparison of Direct Intraoral Scan and Traditional Impression for CAD/CAM Mandibular Overdenture Base: RCT on Peri-implant Marginal Bone Changes. J Contemp Dent Pract 2024;25(6):527-534.

Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis.

PURPOSE: Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. METHODOLOGY: Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. RESULTS: A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. CONCLUSION: This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.

Mechanistic aspects of reactive metabolite formation in clomethiazole catalyzed biotransformation by cytochrome P450 enzymes.

Clomethiazole (CLM), a sedative and anticonvulsant drug, is commonly employed for the treatment of alcohol withdrawal syndrome because it suppresses cytochrome P450 (P450) activity associated with the generation of free radicals and liver damage. The catalyzed biotransformation of thiazole-containing drugs by P450 is known to afford reactive metabolites. These metabolites can alter the biological functions of macromolecules and result in toxicity and adverse drug interactions. Multitargeted molecular modeling and quantum chemical DFT calculations were performed to explore the binding modes and molecular mechanisms underlying the mechanism-based inactivation (MBI) of P450 by CLM. The mechanistic details associated with reactive metabolite formation from further metabolic processes were extensively assessed. Seven possible routes were proposed for CLM-P450 biotransformation including CLM hydroxylation, sulfoxidation, N-oxidation, CN epoxidation (oxaziridine formation), and CC epoxidation. The results revealed a degree of preference for the C-N epoxidation pathway because of the low energy requirements of its rate-determining step (8.74 and 10.07 kcal mol-1 for LS and HS states, respectively). A kinetic competition for the CLM-methyl hydroxylation pathway was detected because the H-abstraction energy barrier was relatively comparable to the thermodynamically prevailing oxaziridine formation rate-determining step (12.58 and 14.52 kcal mol-1 for quartet and doublet states, respectively). Our studies assessed the mechanisms of covalent nucleophilic epoxide adduct formation through nucleophilic addition, hydrolysis of epoxidation products, and nonenzymatic degradation. CLM was shown to display P450-inhibitory activity by forming covalent adducts rather than further metabolization to reactive metabolites. The outcomes of molecular docking allowed assessing the binding profile of CLM with three human P450 isozymes, namely, CYP2E1, CYP3A4, and CYP2D6.

The role of blood groups, vaccine type and gender in predicting the severity of side effects among university students receiving COVID-19 vaccines.

On March 11th, 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) a pandemic. To control the pandemic, billions of vaccine doses have been administered worldwide. Predictors of COVID-19 vaccine-related side effects are inconsistently described in the literature. This study aimed to identify the predictors of side effects' severity after COVID-19 vaccination among young adult students at Taif University (TU) in Saudi Arabia. An online, anonymous questionnaire was used. Descriptive statistics were calculated for numerical and categorical variables. Possible correlations with other characteristics were identified using the chi-square test. The study included 760 young adult participants from TU. Pain at the injection site (54.7%), headache (45.0%), lethargy and fatigue (43.3%), and fever (37.5%) were the most frequently reported COVID-19 vaccine-related side effects after the first dose. The most frequent side effects were reported among the 20-25-year-old age group for all doses of all vaccines. Females experienced remarkably more side effects after the second (p < 0.001) and third doses (p = 0.002). Moreover, ABO blood groups significantly correlated with vaccine-related side effects after the second dose (p = 0.020). The participants' general health status correlated with the side effects after the first and second doses (p < 0.001 and 0.022, respectively). The predictors of COVID-19 vaccine-related side effects in young, vaccinated people were blood group B, female gender, vaccine type, and poor health status.

Association of endothelial nitric oxide synthase (Glu298Asp) gene polymorphism with radial artery spasm during cardiac catheterization in Egyptians.

BACKGROUND: Nitric oxide (NO) exerts diverse effects on the cardiovascular system. Impairment of NO production plays a key role in cerebral and coronary artery spasm. We aimed to explore the predicting factors of radial artery spasm (RAS) and the association of eNOS gene polymorphism (Glu298Asp) with RAS during cardiac catheterization. METHODS AND RESULTS: 200 patients underwent elective coronary angiography through a trans-radial approach. The subjects were genotyped to the Glu298Asp polymorphism (rs1799983) on the eNOS gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our results showed that the subjects with the TT genotype and T allele were significantly more likely to develop radial artery spasms (OR = 12.5, 4.6, P < 0.001 respectively). TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, radial tortuosity, and right radial access are independent predictors of radial spasm. CONCLUSION: The eNOS (Glu298Asp) gene polymorphism is associated with RAS during cardiac catheterization in Egyptians. TT genotype of eNOS Glu298Asp polymorphism, number of punctures, size of the radial sheath, right radial access, and tortuosity are independent predictors of RAS during cardiac catheterization.