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.

Current and emerging trends of inorganic, organic and eco-friendly corrosion inhibitors.

Effective corrosion control strategies are highly desired to reduce the fate of corrosion. One widely adopted approach is the use of corrosion inhibitors, which can significantly mitigate the detrimental effects of corrosion. This systematic review provides a thorough analysis of corrosion inhibitors, including both inorganic and organic compounds. It explores the inhibition mechanisms, highlighting the remarkable inhibitive efficiency of organic compounds attributed to the presence of heteroatoms and conjugated π-electron systems. The review presents case studies and investigations of corrosion inhibitors, shedding light on their performance and application potential. Moreover, it compares the efficacy, compatibility, and sustainability of emerging environmentally friendly corrosion inhibitors, including biopolymers from natural resources as promising candidates. The review also highlights the potential of synergistic impacts between mixed corrosion inhibitors, particularly organic/organic systems, as a viable and advantageous choice for applications in challenging processing environments. The evaluation of inhibitors is discussed, encompassing weight loss (WL) analysis, electrochemical analysis, surface analysis, and quantum mechanical calculations. The review also discusses the thermodynamics and isotherms related to corrosion inhibition, further improving the understanding of inhibitor's behavior and mechanisms. This review serves as a valuable resource for researchers, engineers, and practitioners involved in corrosion control, offering insights and future directions for effective and environmentally friendly corrosion inhibition strategies.

Exploring AMR and virulence in Klebsiella pneumoniae isolated from humans and pet animals: A complement of phenotype by WGS-derived profiles in a One Health study in Egypt.

Klebsiella pneumoniae is a ubiquitous nosocomial pathogen associated with various types of infections in hospitalized patients and different animal species. In the current study, 49 Klebsiella strains isolated from humans, dogs, and cats were investigated using NGS technology. MALDI-TOF failed to identify newly discovered K. variicola and K. quasipneumoniae isolates correctly. MLST analysis revealed different sequence types among K. pneumoniae isolates, and the most frequent STs were ST29, ST219, and ST37. Three ST23 that are generally known as hypervirulent type were identified but they lacked major discriminatory determinants for hypervirulent K. pneumoniae (hvKp). K. pneumoniae isolates showed high diversity, and several isolates from humans and animals were assigned to the same ST and were almost identical. Isolates from humans exhibited more pronounced resistance patterns compared to the animal isolates. High levels of resistance were observed for piperacillin, trimethoprim/sulfamethoxazole, and cephalosporins, and resistance to carbapenem compounds was only found in isolates of human origin. Three strains of human origin were extensively drug-resistant (XDR). A diverse range of resistance genes primarily confer resistance to beta-lactams., phenicol/quinolone, aminoglycoside, macrolide, sulfonamides, and fosfomycin were identified in silico. However, there were inconsistencies between the phenotypic characterization of isolates and the set of resistance genes detected in silico in this set of Klebsiella isolates. Further research using a larger number of isolates from various sources is necessary to fully comprehend the relationship between the presence of antimicrobial resistance determinants and phenotypic data. It is also necessary to monitor the spread of K. pneumoniae from a One Health perspective in Egypt.

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.

Effective synthesis and characterization of citric acid cross-linking of modified ferrous metal-organic framework and chitosan nanocomposite sponge for Th(IV) elimination: Adsorption isotherms, kinetic analysis, and optimization by Box-Behnken design.

This research presents a novel nanocomposite of ferrous metal-organic framework (Fe(II)-MOF) that has been encapsulated with chitosan matrix, leading to the development of a new adsorbent referred to as NH2-Fe(II)-MOF@CSC composite sponge. This composite sponge has shown effectiveness in removing radioactive thorium (IV) contamination from water sources. The adsorbent underwent characterization using techniques including FTIR, PXRD, BET analysis, and SEM. The adsorbent has a high surface area of 1360.8 m2/g. The most effective conditions for adsorbing Th(IV) were found to be a pH of 5, using 0.02 g of adsorbent dose per 25 mL, and maintaining a contact time of 100 min. The composite sponge demonstrated an impressive maximum adsorption capacity of 618.8 mg/g for Th(IV). The adsorption process was fitted to Langmuir isothermally and kinetically fitted to pseudo-second-order. Nonetheless, the relatively low adsorption energy of 6.22 kJ/mol suggests that the main adsorption mechanism is physisorption, which is marked by weaker van der Waals forces. This discovery could have implications for the material's potential for easy regeneration. In the analysis of the influence of temperature on the adsorption of Th(IV), it was discovered that the adsorption process is endothermic because the positive ΔHo value was 24.48 kJ.mol-1. Furthermore, a positive ΔSo value of 87.46 J.mol-1 K-1 suggests the existence of disorder at the solid-solution interface. Conversely, a temperature rise resulted in a higher negatively charged ΔGo, indicating that the adsorption process is spontaneous. The research also examined the mechanism of interaction, such as π-π interaction, hydrogen bonding, pore filling, and electrostatic interaction. It was noted that the adsorbent can be efficiently used for a maximum of six cycles, demonstrating its economic viability. The adsorption outcomes were optimized using the Box Behnken design (BBD).

Design, synthesis and in vitro anti-proliferative evaluation of new pyridine-2,3-dihydrothiazole/thiazolidin-4-one hybrids as dual CDK2/GSK3ß kinase inhibitors.

Herein, the molecular hybridization drug discovery approach was used in the design and synthesis of twelve novel pyridine-2,3-dihydrothiazole hybrids (2a,b-5a,b and 13a,b-14a,b) and fourteen pyridine-thiazolidin-4-one hybrids (6a,b-12a,b) as anti-proliferative analogues targeting CDK2 and GSK3ß kinase inhibition. Almost all of the newly synthesized hybrids, including their precursors (1a,b), were evaluated for their anti-proliferative activity against three human cancer cell lines-MCF-7, HepG2 and HEp-2-as well as normal Vero cell lines. Both compounds 1a (pyridine-thiourea precursor) and 8a (pyridine-5-acetyl-thiazolidin-4-one hybrid) exhibited excellent anti-proliferative activity against HEp-2 (IC50 = 7.5 µg mL-1, 5.9 µg mL-1, respectively). Additionally, 13a (pyridine-5-(p-tolyldiazenyl-2,3-dihydrothiazole)) hybrid demonstrated excellent anti-proliferative activity against HepG2 (IC50 = 9.5 µg mL-1), with an acceptable safety profile against Vero (<45% inhibition at 100 µg mL-1) in the cases of 8a and 13a alone. The three promising anti-proliferative hybrids (1a, 8a, 13a) were selected for the assessment of their in vitro inhibitory kinase activity against CDK2/GSK3ß using roscovitine (IC50 = 0.88 µg mL-1) and CHIR-99021 (IC50 = 0.07 µg mL-1) as references, respectively. Compound 13a was the most potent dual CDK2/GSK3ß inhibitor (IC50 = 0.396 µg mL-1, 0.118 µg mL-1, respectively) followed by 8a (IC50 = 0.675 µg mL-1, 0.134 µg mL-1, respectively), and the weakest was 1a. To elucidate the mechanism of the most potent anti-proliferative 13a hybrid, further cell cycle analysis was performed revealing that it caused G1 cell cycle arrest and induced apoptosis. Moreover, it resulted in an increase in Bax and caspase-3 with a decrease in Bcl-2 levels in HepG2 cells compared with untreated cells. Finally, in silico drug likeness/ADME prediction for the three potent compounds as well as a molecular docking simulation study were conducted in order to explore the binding affinity and interactions in the binding site of each enzyme, which inspired their usage as anti-proliferative leads for further modification.

Comprehensive Genomic Analysis of Uropathogenic E. coli: Virulence Factors, Antimicrobial Resistance, and Mobile Genetic Elements.

Our whole-genome sequencing analysis of sixteen uropathogenic E. coli isolates revealed a concerning picture of multidrug resistance and potentially virulent bacteria. All isolates belonged to four distinct clonal groups, with the highly prevalent ST131 lineage being associated with extensive antibiotic resistance and virulence factors. Notably, all isolates exhibited multidrug resistance, with some resistant to as many as 12 antibiotics. Fluoroquinolone resistance stemmed primarily from efflux pumps and mutations in gyrase and topoisomerase genes. Additionally, we identified genes encoding resistance to extended-spectrum cephalosporins, trimethoprim/sulfamethoxazole, and various heavy metals. The presence of diverse plasmids and phages suggests the potential for horizontal gene transfer and the dissemination of virulence factors. All isolates harbored genomic islands containing virulence factors associated with adhesion, biofilm formation, and invasion. Genes essential for iron acquisition, flagella biosynthesis, secretion systems, and toxin production were also prevalent. Adding further complexity to understanding the isolates' genetic makeup, we identified CRISPR-Cas systems. This study underscores the need for continued genomic surveillance in understanding the pathogenic mechanisms and resistance profiles of uropathogenic E. coli to aid in developing targeted therapeutic strategies.

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.

One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents.

Aim: Pulmonary fibrosis is a life threating disease which requires an immediate treatment and due to the limited medications, this study focused on synthesizing a series of quinoline-based pyrimidodiazepines 4a-f as a novel antifibrotic hit.Materials & methods: The target compounds were synthesized via a one-pot reaction then investigated in a rat model of lung fibrosis induced by bleomycin (BLM).Results: Results revealed significant attenuation of the tested pro-inflammatory cytokines, fibrotic genes and apoptotic markers; however, Bcl-2 was upregulated, indicating a protective effect against fibrosis. Moreover, the molecular docking studies highlighted promising interactions between compounds 4b and 4c and specific amino acids within the protein pockets of caspase-3 (ARG341 and THR177), malondialdehyde (LYS195, LYS118 and ARG188) and TNF-α (SER99 and NME102).Conclusion: Compounds 4b and 4c emerge as promising candidates for further preclinical investigation as pulmonary antifibrotic agents.

[Box: see text].

The acquired pco gene cluster in Salmonella enterica mediates resistance to copper.

The pervasive environmental metal contamination has led to selection of heavy-metal resistance genes in bacteria. The pco and sil clusters are located on a mobile genetic element and linked to heavy-metal resistance. These clusters have been found in Salmonella enterica serovars isolated from human clinical cases and foods of animal origin. This may be due to the use of heavy metals, such as copper, in animal feed for their antimicrobial and growth promotion properties. The sil cluster can be found alone or in combination with pco cluster, either in the chromosome or on a plasmid. Previous reports have indicated that sil, but not pco, cluster contributes to copper resistance in S. enterica Typhimurium. However, the role of the pco cluster on the physiology of non-typhoidal S. enterica remains poorly understood. To understand the function of the pco gene cluster, a deletion mutant of pcoABCD genes was constructed using allelic exchange mutagenesis. Deletion of pcoABCD genes inhibited growth of S. enterica in high-copper medium, but only under anaerobic environment. Complementation of the mutant reversed the growth phenotype. The survival of S. enterica in RAW264.7 macrophages was not affected by the loss of pcoABCD genes. This study indicates that the acquired pco cluster is crucial for copper detoxification in S. enterica, but it is not essential for intracellular replication within macrophages.

Vanillin loaded-physically crosslinked PVA/chitosan/itaconic membranes for topical wound healing applications.

Vanillin loaded-physically crosslinked hydrogel membranes made of PVA/chitosan/itaconic acid (PVA-CS-IA) were prepared using freezing-thawing (F-T) cycle method. To ensure the entanglement of PVA-CS-IA chains, three F-T cycles were repeated. The polymeric chains entanglements were confirmed and characterized by different instrumental characterizations. Physicochemical properties for example, swelling ratio, mechanical characteristics, gel fraction percentage (GF%), hydrolytic degradation, and thermal stability of PVA-CS-IA membrane were discussed in detail. The findings showed that the swelling ratio, mechanical characteristics, and hydrolytic degradation of the crosslinked membranes enhanced with increasing CS-IA contents in membranes composition; however, GF% gradually declined with CS-IA content. Additionally, cell viability test using HFB-4 cell line and antimicrobial activity against Staphylococcus aureus and Escherichia coli were evaluated using MTT assay and the bacterium growth inhibition percentage method; respectively. Notably, with varying incubation durations and membrane concentrations, all examined constructed hydrogels showed significant cell survival percentages. The findings supported the notion that produced hydrogel membranes might be used in a professional setting as antibacterial dressings or biomaterials for quick wound healing rate.

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.

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.

One-step genome engineering in bee gut bacterial symbionts.

Mechanistic understanding of interactions in many host-microbe systems, including the honey bee microbiome, is limited by a lack of easy-to-use genome engineering approaches. To this end, we demonstrate a one-step genome engineering approach for making gene deletions and insertions in the chromosomes of honey bee gut bacterial symbionts. Electroporation of linear or non-replicating plasmid DNA containing an antibiotic resistance cassette flanked by regions with homology to a symbiont genome reliably results in chromosomal integration. This lightweight approach does not require expressing any exogenous recombination machinery. The high concentrations of large DNAs with long homology regions needed to make the process efficient can be readily produced using modern DNA synthesis and assembly methods. We use this approach to knock out genes, including genes involved in biofilm formation, and insert fluorescent protein genes into the chromosome of the betaproteobacterial bee gut symbiont Snodgrassella alvi. We are also able to engineer the genomes of multiple strains of S. alvi and another species, Snodgrassella communis, which is found in the bumble bee gut microbiome. Finally, we use the same method to engineer the chromosome of another bee symbiont, Bartonella apis, which is an alphaproteobacterium. As expected, gene knockout in S. alvi using this approach is recA-dependent, suggesting that this straightforward procedure can be applied to other microbes that lack convenient genome engineering methods. IMPORTANCE: Honey bees are ecologically and economically important crop pollinators with bacterial gut symbionts that influence their health. Microbiome-based strategies for studying or improving bee health have utilized wild-type or plasmid-engineered bacteria. We demonstrate that a straightforward, single-step method can be used to insert cassettes and replace genes in the chromosomes of multiple bee gut bacteria. This method can be used for investigating the mechanisms of host-microbe interactions in the bee gut community and stably engineering symbionts that benefit pollinator health.

Unveiling the photocatalytic potential of graphitic carbon nitride (g-C3N4): a state-of-the-art review.

Graphitic carbon nitride (g-C3N4)-based materials have emerged as promising photocatalysts due to their unique band structure, excellent stability, and environmental friendliness. This review provides a comprehensive and in-depth analysis of the current state of research on g-C3N4-based photocatalysts. The review summarizes several strategies to improve the photocatalytic performance of pristine g-C3N4, e.g., by creating heterojunctions, doping with non-metallic and metallic materials, co-catalyst loading, tuning catalyst morphology, metal deposition, and nitrogen-defect engineering. The review also highlights the various characterization techniques employed to elucidate the structural and physicochemical features of g-C3N4-based catalysts, as well as their applications of in photocatalytic degradation and hydrogen production, emphasizing their remarkable performance in pollutants' removal and clean energy generation. Furthermore, this review article investigates the effect of operational parameters on the catalytic activity and efficiency of g-C3N4-based catalysts, shedding light on the key factors that influence their performance. The review also provides insights into the photocatalytic pathways and reaction mechanisms involving g-C3N4 based photocatalysts. The review also identifies the research gaps and challenges in the field and presents prospects for the development and utilization of g-C3N4-based photocatalysts. Overall, this comprehensive review provides valuable insights into the synthesis, characterization, applications, and prospects of g-C3N4-based photocatalysts, offering guidance for future research and technological advancements in this rapidly growing field.

Synthesis of novel piperazine-based bis(thiazole)(1,3,4-thiadiazole) hybrids as anti-cancer agents through caspase-dependent apoptosis.

A series of novel piperazine-based bis(thiazoles) 13a-d were synthesized in moderate to good yields via reaction of the bis(thiosemicarbazones) 7a, b with an assortment of C-acetyl-N-aryl-hydrazonoyl chlorides 8a-f. Similar treatment of the bis(thiosemicarbazone) 7a, b with C-aryl-N-phenylhydrazonoyl chlorides 10a, b afforded the expected bis(thiadiazole) based piperazine products 13b-d in reasonable yields. Cyclization of 7a, b with two equivalents of α-haloketones 14a-d led to the production of the corresponding bis(4-arylthiazol)piperazine derivatives 15a-h in good yields. The structures of the synthesized compounds were confirmed from elemental and spectral data (FTIR, MALDI-TOF, 1H, and 13C NMR). The cytotoxicity of the new compounds was screened against hepatoblastoma (HepG2), human colorectal carcinoma (HCT 116), breast cancer (MCF-7), and Human Dermal Fibroblasts (HDF). Interestingly, all compounds showed promising cytotoxicity against most of the cell lines. Interestingly, compounds 7b, 9a, and 9i exhibited IC50 values of 3.5, 12.1, and 1.2 nM, respectively, causing inhibition of 89.7%, 83.7%, and 97.5%, compared to Erlotinib (IC50 = 1.3 nM, 97.8% inhibition). Compound 9i dramatically induced apoptotic cell death by 4.16-fold and necrosis cell death by 4.79-fold. Compound 9i upregulated the apoptosis-related genes and downregulated the Bcl-2 as an anti-apoptotic gene. Accordingly, the most promising EGFR-targeted chemotherapeutic agent to treat colon cancer was found to be compound 9i.

Investigation of plasmid-mediated quinolone resistance among extended-spectrum ß-lactamase isolates of E. coli and K. pneumoniae.

Escherichia coli and Klebsiella pneumoniae are important members of the Enterobacteriaceae family, involved in many infections. The increased resistance rate towards ß-lactams and fluoroquinolones -which are the main therapeutic options- limits their treatment options. This study aimed to assess the local resistance patterns against different antimicrobials and to determine the extended-spectrum ß-lactamase (ESBLs) producers. The study revealed that 36% of clinical isolates were ESBL producers, showing high resistance rates towards ß-lactams and non-ß-lactams, especially sulphamethoxazole-trimethoprim and fluoroquinolones. However, they were susceptible to chloramphenicol and doxycycline (33% and 20%; respectively). Also, the investigation aimed to screen the plasmid profile of quinolone-resistant ESBLs-producers and to detect the plasmid-mediated quinolone resistance genes including qnrA, qnrS, qnrB, qnrC, qnrD, and qnrVC. Moreover, the conjugative plasmid among the quinolone-resistant isolates was elucidated. The results showed that extracted plasmids of sizes ranging from ≈0.9 to 21.23 Kb, divided into 7 plasmid patterns were detected. A plasmid of approximately 21.23 Kb was found in all isolates and the QnrS gene was the most predominant gene. Moreover, the frequency of transconjugation within the same genus was higher than that recorded between different genera; where 68% of E. coli isolates transferred the resistance genes compared to Klebsiella isolates (36.6%). Plasmid profiles of transconjugants demonstrated great similarity, where 21.23 Kb plasmid was detected in all transconjugants. Since these transconjugants were quinolone-resistant ESBL producers, it has been suggested that quinolone resistance determinants might be carried on that plasmid.

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.

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.

Monoclonal IgY antibodies: advancements and limitations for immunodiagnosis and immunotherapy applications.

Due to their high specificity and scalability, Monoclonal IgY antibodies have emerged as a valuable alternative to traditional polyclonal IgY antibodies. This abstract provides an overview of the production and purification methods of monoclonal IgY antibodies, highlights their advantages over polyclonal IgY antibodies, and discusses their recent applications. Monoclonal recombinant IgY antibodies, in contrast to polyclonal IgY antibodies, offer several benefits. such as derived from a single B-cell clone, monoclonal antibodies exhibit superior specificity, ensuring consistent and reliable results. Furthermore, it explores the suitability of monoclonal IgY antibodies for low- and middle-income countries, considering their cost-effectiveness and accessibility. We also discussed future directions and challenges in using polyclonal IgY and monoclonal IgY antibodies. In conclusion, monoclonal IgY antibodies offer substantial advantages over polyclonal IgY antibodies regarding specificity, scalability, and consistent performance. Their recent applications in diagnostics, therapeutics, and research highlight their versatility.

Chicken egg yolk antibodies (IgY) and monoclonal antibodies: advancements and limitations for immunodiagnosis and immunotherapy applications Chicken egg yolk antibodies (IgY antibodies) and monoclonal antibodies (mAbs) are two types of antibodies used in medical applications. IgY antibodies are cost-effective, stable, and specific, with the advantage of not triggering harmful immune responses. However, they may have limitations in identifying certain target areas and availability. On the other hand, mAbs are highly specific and can detect multiple target areas on antigens, but their production is expensive and may cause immune responses. Despite these drawbacks, both IgY antibodies and mAbs show promise in various applications such as infectious disease diagnosis, cancer treatment, and autoimmune disorders. Ongoing developments in antibody technology are likely to expand their applications in immunology. This review provides an overview of the strengths and limitations of IgY antibodies and mAbs in immunodiagnosis and immunotherapy, as well as their role in pandemic control.