Today, one of the most important challenges for physicians is the adequate treatment of infections due to multidrug resistant organism (MDR). Pseudomonas aeruginosa is considered an opportunistic organism causing different types of healthcare associated infections (HAIs). We aimed to investigate the MDR and pandrug resistance (PDR) rate in P. aeruginosa in our region and detect efflux-pump mexAB genes and the proposed binding interactions of five different categories of antimicrobial agents with the mexB pump. A total of 180 non-duplicated P. aeruginosa strains were isolated from patients with HAIs in the Suez Canal University Hospital. Phenotypically, minimum inhibitory concentration (MIC) was done for all MDR and PDR strains before and after addition of efflux pump inhibitor carbonyl cyanide m-chlorophenyl hydrazone (CCCP). Molecular detection of mexA and mexB genes was done by using polymerase chain reaction (PCR). Most of the isolated strains (126 strains) were MDR (70%); only 10 samples (5.5%) were PDR. MexA and mexB genes were detected in 88.2% (120 strains) and 70.5% (96 strains) of stains, respectively. All PDR strains (10 stains) carried both mexA and mexB genes. Efflux mexAB genes were detected in all MDR and PDR strains (136 strains). Molecular modeling studies were performed to investigate the modes of intermolecular binding interactions between the antimicrobial agents and mexB key amino acids that resulted in MDR and PDR. The current study reported high prevalence of MDR and PDR P. aeruginosa in patients with HAIs in the Suez Canal University Hospitals.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), which caused novel corona virus disease-2019 (COVID-19) pandemic, necessitated a global demand for studies related to genes and enzymes of SARS-CoV2. SARS-CoV2 infection depends on the host cell Angiotensin-Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease-2 (TMPRSS2), where the virus uses ACE2 for entry and TMPRSS2 for S protein priming. The TMPRSS2 gene encodes a Transmembrane Protease Serine-2 protein (TMPS2) that belongs to the serine protease family. There is no crystal structure available for TMPS2, therefore, a homology model was required to establish a putative 3D structure for the enzyme. A homology model was constructed using SWISS-MODEL and evaluations were performed through Ramachandran plots, Verify 3D and Protein Statistical Analysis (ProSA). Molecular dynamics simulations were employed to investigate the stability of the constructed model. Docking of TMPS2 inhibitors, camostat, nafamostat, gabexate, and sivelestat, using Molecular Operating Environment (MOE) software, into the constructed model was performed and the protein-ligand complexes were subjected to MD simulations and computational binding affinity calculations. These in silico studies determined the tertiary structure of TMPS2 amino acid sequence and predicted how ligands bind to the model, which is important for drug development for the prevention and treatment of COVID-19.

Introduction: The increasing incidence of methicillin resistance among Staphylococci has led to renewed interest in the usage of macrolide-lincosamide-streptogramin B (MLSB) antibiotics to treat S. aureus infections, with clindamycin being the preferable agent owing to its excellent pharmacokinetic properties. Inducible clindamycin resistance my lead to therapeutic failure. Aim: Detection of the prevalence of constitutive and inducible clindamycin resistance in clinical isolates of S. aureus to improve the clinical outcomes in patients. Methodology: A total of 176 non-duplicate staphylococcal isolates were isolated from different clinical samples. Methicillin resistance was detected using Cefoxitin disk diffusion (CDD) method. Phenotypic clindamycin resistance was performed for all isolates by D test. Polymerase Chain Reaction (PCR) assay were done for detection of erm resistance genes (ermA, ermB and ermC). Results: Out of 176 strains of S. aureus, 108 isolates (61.3%) were identified as MRSA. Erythromycin and clindamycin resistance was detected in 96 isolates (54.5%) and 68 isolates (38.6%) respectively. Clindamycin resistance (cMLSB) was significantly higher (p value < 0.001) in MRSA strains (56 isolates) compared to MSSA (12 isolates). Resistant genes were detected in 160 isolates (91%). The ermA gene was detected in 28 isolates (16%), the ermB gene was detected in 80 isolates (45.5%) (p < 0.001). Conclusions and recommendations: The frequency of constitutive and inducible clindamycin resistance in MRSA isolates emphasizes the need to use D test in routine antimicrobial susceptibility testing to detect the susceptibility to clindamycin as the inducible resistance phenotype can inhibit the action of clindamycin and affect the treatment efficacy.

Variants of the DEAD-Box Helicase 20 (DDX20), one of the microRNAs (miRNAs) machinery genes, can modulate miRNA/target gene expressions and, hence, influence cancer susceptibility and prognosis. Here, we aimed to unravel the association of DDX20 rs197412 T/C variant with colon cancer risk and/or prognosis in paired samples of 122 colon cancer and non-cancer tissue specimens by TaqMan allelic discrimination analysis. Structural/functional bioinformatic analyses were carried out, followed by a meta-analysis. We found that the T allele was more frequent in cancer tissues compared to control tissues (60.2% vs. 35.7%, p < 0.001). Furthermore, the T variant was highly frequent in primary tumors with evidence of recurrence (73% vs. 47.5%, p < 0.001). Genetic association models, adjusted by age and sex, revealed that the T allele was associated with a higher risk of developing colon cancer under heterozygote (T/C vs. C/C: OR = 2.35, 95%CI = 1.25–4.44, p < 0.001), homozygote (T/T vs. C/C: OR = 7.6, 95%CI = 3.5–16.8, p < 0.001), dominant (T/C-T/T vs. C/C: OR = 3.4, 95%CI = 1.87–8.5, p < 0.001), and recessive (T/T vs. C/C-T/C: OR = 4.42, 95%CI = 2.29–8.54, p = 0.001) models. Kaplan–Meier survival curves showed the shift in the C > T allele to be associated with poor disease-free survival. After adjusting covariates using a multivariate cox regression model, patients harboring C > T somatic mutation were 3.5 times more likely to develop a recurrence (p < 0.001). A meta-analysis of nine studies (including ours) showed a higher risk of CRC (81%) in subjects harboring the T/T genotype than in T/C + C/C genotypes, supporting the potential clinical utility of the specified study variant as a biomarker for risk stratification in CRC cases. However, results were not significant in non-colorectal cancers. In conclusion, the DDX20 rs197412 variant is associated with increased colon cancer risk and a higher likelihood of recurrence in the study population.

Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p < 0.001) compared to HCV-negative patients. TriNetX data analysis revealed that HCV-positive patients had a 53% lower risk of developing melanoma (RR = 0.470, 95% CI: 0.443–0.498, p < 0.001). However, HCV-positive melanoma patients had higher all-cause mortality (HR = 1.360, 95% CI: 1.189–1.556, p < 0.001). An in silico analysis identified key molecular players, including IL-6 and CTLA4, in the HCV-melanoma network. Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.