Evolutionary analysis of LMP-1 genetic diversity in EBV-associated nasopharyngeal carcinoma: Bioinformatic insights into oncogenic potential.

EBV latent membrane protein 1 (LMP-1) is an important oncogene involved in the induction and maintenance of EBV infection and the activation of several cell survival and proliferative pathways. The genetic diversity of LMP-1 has an important role in immunogenicity and tumorigenicity allowing escape from host cell immunity and more metastatic potential of LMP-1 variants. This study explored the evolutionary of LMP-1 in EBV-infected patients at an advanced stage of nasopharyngeal carcinoma (NPC). Detection of genetic variability in LMP-1 genes was carried out using Sanger sequencing. Bioinformatic analysis was conducted for translation and nucleotide alignment. Phylogenetic analysis was used to construct a Bayesian tree for a deeper understanding of the genetic relationships, evolutionary connections, and variations between sequences. Genetic characterization of LMP-1 in NPC patients revealed the detection of polymorphism in LMP-1 Sequences. Motifs were identified within three critical LMP-1 domains, such as PQQAT within CTAR1 and YYD within CTAR2. The presence of the JACK3 region at specific sites within CTAR3, as well as repeat regions at positions (122-132) and (133-143) within CTAR3, was also annotated. Additionally, several mutations were detected including 30 and 69 bp deletions, 33 bp repeats, and 15 bp insertion. Although LMP-1 strains appear to be genetically diverse, they are closely related to 3 reference strains: prototype B95.8, Med- 30 bp deletion, and Med + 30 bp deletion. In our study, one of the strains harboring the 30 bp deletion had both bone and bone marrow metastasis which could be attributed to the fact that LMP-1 is involved in tumor metastasis, evasion and migration of NPC cells. This study provided valuable insights into genetic variability in LMP-1 sequences of EBV in NPC patients. Further functional studies would provide a more comprehensive understanding of the molecular characteristics, epidemiology, and clinical implications of LMP-1 polymorphisms in EBV-related malignancies.

Green Biofabrication of Silver Nanoparticles of Potential Synergistic Activity with Antibacterial and Antifungal Agents against Some Nosocomial Pathogens.

Nosocomial bacterial and fungal infections are one of the main causes of high morbidity and mortality worldwide, owing to the high prevalence of multidrug-resistant microbial strains. Hence, the study aims to synthesize, characterize, and investigate the antifungal and antibacterial activity of silver nanoparticles (AgNPs) fabricated using Camellia sinensis leaves against nosocomial pathogens. The biogenic AgNPs revealed a small particle diameter of 35.761 ± 3.18 nm based on transmission electron microscope (TEM) graphs and a negative surface charge of -14.1 mV, revealing the repulsive forces between nanoparticles, which in turn indicated their colloidal stability. The disk diffusion assay confirmed that Escherichia coli was the most susceptible bacterial strain to the biogenic AgNPs (200 g/disk), while the lowest sensitive strain was found to be the Acinetobacter baumannii strain with relative inhibition zones of 36.14 ± 0.67 and 21.04 ± 0.19 mm, respectively. On the other hand, the biogenic AgNPs (200 µg/disk) exposed antifungal efficacy against Candida albicans strain with a relative inhibition zone of 18.16 ± 0.14 mm in diameter. The biogenic AgNPs exposed synergistic activity with both tigecycline and clotrimazole against A. baumannii and C. albicans, respectively. In conclusion, the biogenic AgNPs demonstrated distinct physicochemical properties and potential synergistic bioactivity with tigecycline, linezolid, and clotrimazole against gram-negative, gram-positive, and fungal strains, respectively. This is paving the way for the development of effective antimicrobial combinations for the effective management of nosocomial pathogens in intensive care units (ICUs) and health care settings.

Pepper Mild Mottle Virus as a Potential Indicator of Fecal Contamination in Influents of Wastewater Treatment Plants in Riyadh, Saudi Arabia.

Several indicators of fecal pollution in water resources are continuously monitored for their reliability and, of particular interest, their correlation to human enteric viruses-not justified by traditional bacterial indicators. Pepper mild mottle virus (PMMoV) has recently been proposed as a successful viral surrogate of human waterborne viruses; however, in Saudi Arabia there are no available data in terms of its prevalence and concentration in water bodies. The concentration of PMMoV in three different wastewater treatment plants (King Saud University (KSU), Manfoha (MN), and Embassy (EMB) wastewater treatment plants (WWTP)) was measured using qRT-PCR during a one-year period and compared to the human adenovirus (HAdV), which is highly persistent and considered an indicator for viral-mediated fecal contamination. PMMoV was found in ~94% of the entire wastewater samples (91.6-100%), with concentrations ranging from 62 to 3.5 × 107 genome copies/l (GC/l). However, HAdV was detected in 75% of raw water samples (~67-83%). The HAdV concentration ranged between 1.29 × 103 GC/L and 1.26 × 107 GC/L. Higher positive correlation between PMMoV and HAdV concentrations was detected at MN-WWTP (r = 0.6148) than at EMB-WWTP (r = 0.207). Despite the lack of PMMoV and HAdV seasonality, a higher positive correlation (r = 0.918) of PMMoV to HAdV was recorded at KSU-WWTP in comparison to EMB-WWTP (r = 0.6401) around the different seasons. Furthermore, meteorological factors showed no significant influence on PMMoV concentrations (p > 0.05), thus supporting the use of PMMoV as a possible fecal indicator of wastewater contamination and associated public health issues, particularly at MN-WWTP. However, a continuous monitoring of the PMMoV distribution pattern and concentration in other aquatic environments, as well as its correlation to other significant human enteric viruses, is essential for ensuring its reliability and reproducibility as a fecal pollution indicator.

Synergistic Antibacterial Proficiency of Green Bioformulated Zinc Oxide Nanoparticles with Potential Fosfomycin Synergism against Nosocomial Bacterial Pathogens.

The drug resistance of bacterial pathogens causes considerable morbidity and death globally, hence there is a crucial necessity for the development of effective antibacterial medicines to address the antibacterial resistance issue. The bioprepared zinc oxide nanoparticles (ZnO-NPs) were prepared utilizing the flower extract of Hibiscus sabdariffa and then characterized using different physicochemical techniques. The antibacterial effectiveness of the bioprepared ZnO-NPs and their synergism with fosfomycin were evaluated using disk diffusion assay against the concerned pathogens. Transmission electron microscopy (TEM) investigation of the bioprepared ZnO-NPs showed that their average particle size was 18.93 ± 2.65 nm. Escherichia coli expressed the highest sensitivity to the bioinspired ZnO-NPs with a suppressive zone of 22.54 ± 1.26 nm at a concentration of 50 µg/disk, whereas the maximum synergistic effect of the bioinspired ZnO-NPs with fosfomycin was noticed against Klebsiella pneumoniae strain with synergism ratio of 100.29%. In conclusion, the bioinspired ZnO-NPs demonstrated significant antibacterial and synergistic efficacy with fosfomycin against the concerned nosocomial bacterial pathogens, highlighting the potential of using the ZnO NPs-fosfomycin combination for effective control of nosocomial infections in intensive care units (ICUs) and health care settings. Furthermore, the biogenic ZnO-NPs' potential antibacterial action against food pathogens such as Salmonella typhimurium and E. coli indicates their potential usage in food packaging applications.

Synergistic Anticandidal Activities of Greenly Synthesized ZnO Nanomaterials with Commercial Antifungal Agents against Candidal Infections.

The high occurrence of mycological resistance to conventional antifungal agents results in significant illness and death rates among immunodeficient patients. In addition, the underprivileged therapeutic results of conventional antifungal agents, besides the potential toxicity resulting from long term therapy necessitate the fabrication of efficient antimicrobial combinations. Hence, the objective of the present investigation is to synthesize, characterize and investigate the anticandidal action of green zinc oxide nanoparticles (ZnO-NPs) formulated using Camellia sinensis leaf extract against three candidal pathogens. The eco-friendly synthesized ZnO-NPs were characterized utilizing different physicochemical methods and their anticandidal potency was tested utilizing a disk diffusion assay. In this setting, the size of the biofabricated ZnO-NPs was detected using transmission electron microscope (TEM) micrographs, recording an average particle size of 19.380 ± 2.14 nm. In addition, zeta potential analysis revealed that the ZnO-NPs surface charge was -4.72 mV. The biogenic ZnO-NPs reveal the highest anticandidal activity against the C. tropicalis strain, demonstrating relative suppressive zones measured at 35.16 ± 0.13 and 37.87 ± 0.24 mm in diameter for ZnO-NPs concentrations of 50 and 100 µg/disk, respectively. Excitingly, Candida glabrata showed a high susceptibility to the biofabricated ZnO nanomaterials at both ZnO-NPs' concentrations (50 and 100 µg/disk) compared to the control. Moreover, the biosynthesized ZnO-NPs revealed potential synergistic effectiveness with nystatin and terbinafine antifungal agents against the concerned strains. The maximum synergistic efficiency was noticed against the C. glabrata strain, demonstrating relative synergistic percentages of 23.02 and 45.9%, respectively. The biogenic ZnO-NPs revealed no hemolytic activity against human erythrocytes revealing their biosafety and hemocompatibility. Finally, the high anticandidal effectiveness of biogenic ZnO-NPs against the concerned candidal pathogens, as well as potential synergistic patterns with conventional antifungal agents such as nystatin and terbinafine, emphasize the prospective application of these combinations for the fabrication of biocompatible and highly efficient antifungal agents.

Anticandidal effectiveness of greenly synthesized zinc oxide nanoparticles against candidal pathogens.

Drug resistance of pathogenic candidal strains to conventional antifungal agents represents a significant health issue contributing to high morbidity worldwide. Hence, the aim of the current study focused on evaluating the antifungal and synergistic activities of the green synthesized zinc oxide nanoparticles formulated using Laurus nobilis leaf extract. The biogenic ZnONPs were hexagonal in shape with average particle size diameter of 37.98 nm and pure crystalline structure as detected by XRD data. The highest antifungal activity of biogenic ZnONPs was detected against Candida parapsilosis strain demonstrating relative inhibitory zone diameters of 17.13 ± 0.74 and 25.78 ± 0.47 mm, at the concentrations of 100 and 200 µg/disk, respectively. Moreover, the biogenic ZnONPs demonstrated the highest synergistic activity with clotrimazole antifungal agent against Candida glabrata followed by Candida auris strains. MTT assay revealed that the biogenic ZnONPs showed low toxicity demonstrating relative IC50 value of 774.45 µg/mL against normal lung fibroblast cells which further affirmed their biosafety for application. In conclusion, the bioinspired ZnONPs could be utilized for the formulation of effective antifungal agents against drug resistant candidal strains and also could be combined with antifungal agents to boost their antifungal efficiency.