Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high­incidence adult male cancers (Review).

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

Magnetosomes as Potential Nanocarriers for Cancer Treatment.

Magnetotactic bacteria (MTBs) and their organelles, magnetosomes, are intriguing options that might fulfill the criteria of using bacterial magnetosomes (BMs). The ferromagnetic crystals contained in BMs can condition the magnetotaxis of MTBs, which is common in water storage facilities. This review provides an overview of the feasibility of using MTBs and BMs as nanocarriers in cancer treatment. More evidence suggests that MTBs and BMs can be used as natural nanocarriers for conventional anticancer medicines, antibodies, vaccine DNA, and siRNA. In addition to improving the stability of chemotherapeutics, their usage as transporters opens the possibilities for the targeted delivery of single ligands or combinations of ligands to malignant tumors. Magnetosome magnetite crystals are different from chemically made magnetite nanoparticles (NPs) because they are strong single-magnetic domains that stay magnetized even at room temperature. They also have a narrow size range and a uniform crystal morphology. These chemical and physical properties are essential for their usage in biotechnology and nanomedicine. Bioremediation, cell separation, DNA or antigen regeneration, therapeutic agents, enzyme immobilization, magnetic hyperthermia, and contrast enhancement of magnetic resonance are just a few examples of the many uses for magnetite-producing MTB, magnetite magnetosomes, and magnetosome magnetite crystals. From 2004 to 2022, data mining of the Scopus and Web of Science databases showed that most research using magnetite from MTB was carried out for biological reasons, such as in magnetic hyperthermia and drug delivery.

Characterization of ESKAPE pathogens in urinary tract infections among Jordanian patients.

INTRODUCTION: ESKAPE pathogens are a small group of pathogens of remarkable importance. The present study was carried out to determine the prevalence of ESKAPE pathogens in urinary tract infections (UTIs) and their antibiotic susceptibility patterns at the Jordan University of Science and Technology Health Center in Irbid, Jordan. METHODOLOGY: A one-year retrospective study was conducted from April 2021 to April 2022. A total of 444 samples of "clean-catch" (midstream) urine from outpatients were studied. RESULTS: Our study showed that the vast majority of urinary tract infected patients were females (92%) compared to males (8%) and were most frequent in the age group 21-30 years old. The most associated co-morbidities with UTIs were hypertension followed by diabetes mellitus and hypothyroidism. ESKAPE pathogens were responsible for about 87.4% of the UTIs in this study, and all were identified in the urine samples except Acinetobacter baumannii. In this study, isolates were most sensitive to levofloxacin, ciprofloxacin, and third-generation cephalosporin's and least sensitive to doxycycline, amoxicillin, and clindamycin. CONCLUSIONS: This research work has shown that patients with UTI-associated ESKAPE pathogens in Jordan are at high risk of antibiotic resistance. To the best of our knowledge, this is the first study in the region that studies the association between ESKAPE pathogens and UTIs.

Nanomaterials as a Potential Target for Infectious Parasitic Agents.

Despite the technological advancement in the era of personalized medicine and therapeutics development, infectious parasitic causative agents remain one of the most challenging areas of research and development. The disadvantages of conventional parasitic prevention and control are the emergence of multiple drug resistance as well as the non-specific targeting of intracellular parasites, which results in high dose concentration needs and subsequently intolerable cytotoxicity. Nanotechnology has attracted extensive interest to reduce medication therapy adverse effects including poor bioavailability and drug selectivity. Numerous nanomaterials-based delivery systems have previously been shown in animal models to be effective in the treatment of various parasitic infections. This review discusses a variety of nanomaterials-based antiparasitic procedures and techniques as well as the processes that allow them to be targeted to different parasitic infections. This review focuses on the key prerequisites for creating novel nanotechnology-based carriers as a potential option in parasite management, specifically in the context of human-related pathogenic parasitic agents.

Identification and characterization of bacteria isolated from patients with cystic fibrosis in Jordan.

BACKGROUND: Notable emergence of multidrug-resistant bacteria has become increasingly problematic worldwide. Most patients with cystic fibrosis (CF) suffer from chronic persistent infections with frequent occurrence of acute exacerbations. Routine screening of bacterial strains, epidemiological characteristics, and resistance patterns are particularly useful for patient management and maintenance of infection control procedures. METHODS: In this study, 43 pharyngeal samples were taken from patients with CF. Microbiological bacterial culture and identification, antimicrobial susceptibility testings, biofilm formation, including minimum biofilm eradication concentration (MBEC) and PCR for detecting resistance genes were performed. RESULTS: All samples were positive for bacterial growth. The predominant species were Staphylococcus aureus (41.86%; n = 18) and Pseudomonas aeruginosa (39.53%; n = 17). 30% of isolated bacteria were multidrug-resistant, resisting high concentrations of tested antibiotics. Among the 42 biofilm-forming isolates, 23.8% (n = 10) were strong biofilm formers. The occurance of resistance genes varied with blaKPC detected in 71% (n = 17) of all Gram-negative isolates and mecA found in 61% (n = 11) of all S. aureus strains. CONCLUSIONS: The majority of isolated bacteria were S. aureus and P. aeruginosa. The high frequency of antimicrobial resistance, the presence of resistance genes, and biofilm formation highlight the challenge in treatment and infection control measures in patients with CF.KEY MESSAGESStaphylococcus aureus and Pseudomonas aeruginosa are the most prevalent pathogens found in patients with CF in Jordan.Detection of antimicrobial resistance genes in patients with CF confirms that antimicrobial resistance patterns must always be monitored.Biofilm formation significantly increases the tolerance of bacteria to antimicrobial agents.

Protein-Based Drug Delivery Nanomedicine Platforms: Recent Developments.

BACKGROUND: Naturally occurring protein cages, both viral and non-viral assemblies, have been developed for various pharmaceutical applications. Protein cages are ideal platforms as they are compatible, biodegradable, bioavailable, and amenable to chemical and genetic modification to impart new functionalities for selective targeting or tracking of proteins. The ferritin/ apoferritin protein cage, plant-derived viral capsids, the small Heat shock protein, albumin, soy and whey protein, collagen, and gelatin have all been exploited and characterized as drugdelivery vehicles. Protein cages come in many shapes and types with unique features such as unmatched uniformity, size, and conjugations. OBJECTIVES: The recent strategic development of drug delivery will be covered in this review, emphasizing polymer-based, specifically protein-based, drug delivery nanomedicine platforms. The potential and drawbacks of each kind of protein-based drug-delivery system will also be highlighted. METHODS: Research examining the usability of nanomaterials in the pharmaceutical and medical sectors were identified by employing bibliographic databases and web search engines. RESULTS: Rings, tubes, and cages are unique protein structures that occur in the biological environment and might serve as building blocks for nanomachines. Furthermore, numerous virions can undergo reversible structural conformational changes that open or close gated pores, allowing customizable accessibility to their core and ideal delivery vehicles. CONCLUSION: Protein cages' biocompatibility and their ability to be precisely engineered indicate they have significant potential in drug delivery and intracellular administration.

Protein-based nanomaterials: a new tool for targeted drug delivery.

Protein nanomaterials are well-defined, hollow protein nanoparticles comprised of virus capsids, virus-like particles, ferritin, heat shock proteins, chaperonins and many more. Protein-based nanomaterials are formed by the self-assembly of protein subunits and have numerous desired properties as drug-delivery vehicles, including being optimally sized for endocytosis, nontoxic, biocompatible, biodegradable and functionalized at three separate interfaces (external, internal and intersubunit). As a result, protein nanomaterials have been intensively investigated as functional entities in bionanotechnology, including drug delivery, nanoreactors and templates for organic and inorganic nanomaterials. Several variables influence efficient administration, particularly active targeting, cellular uptake, the kinetics of the release and systemic elimination. This review examines the wide range of medicines, loading/release processes, targeted therapies and treatment effectiveness.

Mothers' Impressions and Beliefs About Taking a Booster Dose for COVID-19 Vaccine During Pregnancy and Lactation.

OBJECTIVES: This study aimed to explore perceptions and willingness to get coronavirus disease 2019 (COVID-19) booster vaccination among pregnant and lactating women in Jordan. METHODS: A cross-sectional study using a 29-item web-based questionnaire was conducted. Sociodemographic characteristics, vaccine acceptance, confidence in the booster dose of COVID-19 vaccine, perception of risk for COVID-19, and acceptance to participate in COVID-19 booster vaccine clinical trials were prospectively evaluated. Logistic regression was used to identify factors that might affect the participants' acceptance of a COVID-19 vaccine and their willingness to enroll in clinical trials of a booster dose of COVID-19 vaccine. RESULTS: Among all participants (pregnant and lactating women, n = 584), 328 (56.2%) intended to receive the booster dose of the COVID-19 vaccine. Predictors of booster dose acceptance were a medical-related degree (OR 1.62, CI 1.06-2.5, p = 0.028), income (OR 0.677, CI 0.52-0.88, p = 0.004), living residency (OR 0.44, CI 0.32-0.60, p < 0.001), knowing pregnant/lactating women previously infected with infectious microbe (OR 1.539, CI 1.07-2.23, p = 0.022), commitment to immunization for children (OR 3.01, CI 1.03-8.82, p = 0.044), receiving an influenza vaccine (OR 1.46, CI 1.04-2.05, p = 0.031), and worried about infectious microbes (OR 1.32, CI 1.15-1.52, p < 0.001). Among participants, only 22.9% were willing to participate in clinical trials of the booster dose of COVID-19 vaccine. The biggest motivator for participation was the participants' desire to help find the best vaccine during pregnancy/lactation (57.5%) while the main barrier towards participation was not wanting to expose themselves and their babies to more side effects (88.0%). CONCLUSION: This study reported reasonable acceptance of vaccination in a sample of pregnant/lactating women. Vaccination hesitancy for the booster dose was in-line with similar studies on the primary series around the globe, but the willingness to participate in clinical trials was lower than non-pregnant/non-lactating women.