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Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system (CNS). The pathogenesis of MS is characterized by neuronal axonal degeneration and demyelination. Among the genes that raises MS risk are the HLA-class II genes. The goals of this study were to investigate the role of the HLA-DRB1 and HLA-DQB1 genes (for the first time) in Jordanian MS patients and their association with MS disease. The association of these genes with other clinical features, such as optic neuritis, sensory impairment, and brainstem symptoms in MS patients was investigated as well using PCR-SSP techniques. Our findings indicated an association between HLA-DRB1 * 03:01 ( Pc = 0.01) and HLA-DRB1 * 04:01 ( Pc = 0.004) alleles with Jordanian MS patients. In addition, a significant linkage between HLA-DRB1 * 15:01 and HLA-DQB1 * 06:01 alleles ( Pc ≤ 0.001 and Pc = 0.012, respectively) were presented among Jordanian MS patients with optic neuritis compared to Jordanian MS patients without optic neuritis. Moreover, HLA-DQB1 * 05:01 and HLA-DQB1 * 06:02 alleles ( Pc ≤ 0.001 and Pc = 0.006, respectively) was found to be related with sensory impairment in MS patients. Additionally, HLA-DRB1 * 07:01 allele indicates a positive correlation in MS patients with brainstem symptoms ( Pc < 0.001). Moreover, our results indicated that there is no association on the HLA-DRB1 ~ HLA-DQB1 haplotype level and MS disease. Knowing the genes that are linked to MS, they may facilitate MS diagnosis, prevention, and treatment at earlier stage. Also, these results may serve in the development of more potent therapeutic regimens for MS and its related complications, such as optic neuritis, sensory impairment, and brainstem symptoms.

Alzheimer’s disease (AD) is a polygenic multifactorial neurodegenerative disease that, after decades of research and development, is still without a cure. There are some symptomatic treatments to manage the psychological symptoms but none of these drugs can halt disease progression. Additionally, over the last few years, many anti-AD drugs failed in late stages of clinical trials and many hypotheses surfaced to explain these failures, including the lack of clear understanding of disease pathways and processes. Recently, different epigenetic factors have been implicated in AD pathogenesis; thus, they could serve as promising AD diagnostic biomarkers. Additionally, network biology approaches have been suggested as effective tools to study AD on the systems level and discover multi-target-directed ligands as novel treatments for AD. Herein, we provide a comprehensive review on Alzheimer’s disease pathophysiology to provide a better understanding of disease pathogenesis hypotheses and decipher the role of genetic and epigenetic factors in disease development and progression. We also provide an overview of disease biomarkers and drug targets and suggest network biology approaches as new tools for identifying novel biomarkers and drugs. We also posit that the application of machine learning and artificial intelligence to mining Alzheimer’s disease multi-omics data will facilitate drug and biomarker discovery efforts and lead to effective individualized anti-Alzheimer treatments.

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, and existing antivirals suffer from major limitations regarding drug resistance and a limited spectrum of activity. In fact, most approved antivirals are directly acting antiviral (DAA) drugs, which interfere with viral proteins and confer great selectivity towards their viral targets but suffer from resistance and limited spectrum. Nowadays, host-targeted antivirals (HTAs) are on the rise, in the drug discovery and development pipelines, in academia and in the pharmaceutical industry. These drugs target host proteins involved in the virus life cycle and are considered promising alternatives to DAAs due to their broader spectrum and lower potential for resistance. Herein, we discuss an important class of HTAs that modulate signal transduction pathways by targeting host kinases. Kinases are considered key enzymes that control virus-host interactions. We also provide a synopsis of the antiviral drug discovery and development pipeline detailing antiviral kinase targets, drug types, therapeutic classes for repurposed drugs, and top developing organizations. Furthermore, we detail the drug design and repurposing considerations, as well as the limitations and challenges, for kinase-targeted antivirals, including the choice of the binding sites, physicochemical properties, and drug combinations.

Mpox, previously known as monkeypox, is a zoonotic viral disease caused by the Mpox virus (MPXV), a member of the Orthopoxvirus genus. This disease is of significant concern due to its zoonotic transmission, which can be challenging to control, its ability to spread easily from person to person, the potential for severe symptoms or even fatality, and its history of frequent global outbreaks. Despite the growing threat, there is still limited research on the pathophysiology of the disease and available disease-modifying treatments. To address this gap, the latest developments in Mpox epidemiology, viral variant detection, and advanced diagnostic tools for accurate MPXV detection have been reviewed. Ongoing preventive measures, including vaccination strategies, have also been examined. Additionally, the genomic and proteomic characteristics of MPXV have been explored, and network and pathway enrichment analyses have been performed to identify potential therapeutic targets. The findings presented in this manuscript suggest the potential for novel disease-modifying treatments. Moreover, emerging technologies, such as artificial intelligence and \"big data,\" are playing a crucial role in advancing disease management and enhancing prevention strategies. This review emphasizes the evolving understanding of Mpox and MPXV variants and underscores the importance of continued research and public health initiatives to combat the disease and prevent future global outbreaks.

Fluoroquinolones, such as levofloxacin (LVX), are extended-spectrum drugs used for the treatment of bacterial infections. Several fluoroquinolone derivatives have shown promising antibacterial and anticancer activities. Our group has earlier synthesized and investigated thionated LVX analogs, compounds 2 and 3, on A549 (non-small cell lung cancer) cell line and showed promising anticancer activity. The mechanism of cytotoxicity may be, in part, via aldehyde dehydrogenase enzyme inhibition and antioxidation. In this study, compounds 2 and 3 were evaluated on prostate (PC-3), breast (MCF7), colorectal (Caco-2), and small cell lung cancer (H69 and H69AR) cell lines. The anticancer activity was measured using resazurin colorimetric method. Combination treatments with doxorubicin (DOX) were also employed and combination index (CI) value were calculated. Compound 3 possessed higher anticancer activity compared to compound 2 on the tested cancer cell lines. Compound 3 had the highest activity on PC-3 cells with IC50 value of 3.58 µM. DOX was also tested for comparison and had IC50 value of less than 0.5 µM in all tested cell lines except for H69AR (DOX-resistant form of H69), which was 4.62 µM. Combination treatment with DOX resulted in significant reduction of cell viability in PC-3, H69, and H69AR cells, with those on H69 and H69AR cells resulted in additive (CI = 1.0) and synergistic effects (CI = 0.6), respectively. Compound 3, a thionated LVX derivative, showed a promising anticancer activity, prompting its potential repurposing for cancer treatment as well as combination treatment with DOX on DOX-resistant cancer cells.

This study aimed to develop and evaluate thermoresponsive in situ microgels for the local ocular delivery of prednisolone (PRD) (PRD microgels) to improve drug bioavailability and prolong ocular drug residence time. Lipid nanosystems of PRD microemulsions (PRD-MEs) were prepared and evaluated at a drug concentration of 0.25–0.75%. PRD microgels were prepared by incorporating PRD-MEs into 10 and 12% Pluronic® F127 (F127) or combinations of 12% F127 and 1–10% Kolliphor®P188 (F68). PRD microgels were characterized for physicochemical, rheological, and mucoadhesive properties, eye irritation, and stability. Results showed that PRD-MEs were clear, miscible, thermodynamically stable, and spherical with droplet size (16.4 ± 2.2 nm), polydispersity index (0.24 ± 0.01), and zeta potential (−21.03 ± 1.24 mV). The PRD microgels were clear with pH (5.37–5.81), surface tension (30.96–38.90 mN/m), size, and zeta potential of mixed polymeric micelles (20.1–23.9 nm and −1.34 to −10.25 mV, respectively), phase transition temperature (25.3–36 °C), and gelation time (1.44–2.47 min). The FTIR spectra revealed chemical compatibility between PRD and microgel components. PRD microgels showed pseudoplastic flow, viscoelastic and mucoadhesive properties, absence of eye irritation, and drug content (99.3 to 106.3%) with a sustained drug release for 16–24 h. Microgels were physicochemically and rheologically stable for three to six months. Therefore, PRD microgels possess potential vehicles for local ocular delivery.

Marine sponges are known for their rich variety of secondary metabolites, many of which show potential for pharmaceutical applications. In this study, three deep-sea sponge species— Stelletta fibrosa , Dactylospongia elegans, and Haliclona manglaris —were identified using DNA barcoding, and their ethanolic extracts were tested for antibacterial activity. The extracts were evaluated against Gram-positive ( e.g. , Bacillus pumilus, Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus , MRSA) and Gram-negative bacteria ( e.g. , Escherichia coli and Klebsiella aerogenes) using the agar well diffusion method. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were also determined. Among the extracts, D. elegans exhibited the most potent antibacterial activity, with inhibition zones ranging from six to 21 mm against gram-positive bacteria and low MIC/MBC values from 0.25 to three mg/ml. Liquid chromatography-mass spectrometry (LC-MS/MS) analysis of D. elegans revealed the presence of bioactive compounds such as gallic acid, caffeic acid, bolinaquinone, dactyloquinone, and others, which are known for their antimicrobial properties. These findings suggest that D. elegans has promising antibacterial properties that could be valuable in combating antimicrobial resistance.

Fluoroquinolones, such as levofloxacin (LVX), are extended-spectrum drugs used for the treatment of bacterial infections. Several fluoroquinolone derivatives have shown promising antibacterial and anticancer activities. Our group has earlier synthesized and investigated thionated LVX analogs, compounds 2 and 3, on A549 (non-small cell lung cancer) cell line and showed promising anticancer activity. The mechanism of cytotoxicity may be, in part, via aldehyde dehydrogenase enzyme inhibition and antioxidation. In this study, compounds 2 and 3 were evaluated on prostate (PC-3), breast (MCF7), colorectal (Caco-2), and small cell lung cancer (H69 and H69AR) cell lines. The anticancer activity was measured using resazurin colorimetric method. Combination treatments with doxorubicin (DOX) were also employed and combination index (CI) value were calculated. Compound 3 possessed higher anticancer activity compared to compound 2 on the tested cancer cell lines. Compound 3 had the highest activity on PC-3 cells with IC.sub.50 value of 3.58 [micro]M. DOX was also tested for comparison and had IC.sub.50 value of less than 0.5 [micro]M in all tested cell lines except for H69AR (DOX-resistant form of H69), which was 4.62 [micro]M. Combination treatment with DOX resulted in significant reduction of cell viability in PC-3, H69, and H69AR cells, with those on H69 and H69AR cells resulted in additive (CI = 1.0) and synergistic effects (CI = 0.6), respectively. Compound 3, a thionated LVX derivative, showed a promising anticancer activity, prompting its potential repurposing for cancer treatment as well as combination treatment with DOX on DOX-resistant cancer cells.

Hydrogels are crosslinked polymer chains that form a three-dimensional network, widely used for wound dressing due to their ability to absorb significant amounts of fluid. This study aimed to develop a hydrogel patch for wound dressing with self-healing properties, particularly for joints and stretchable body parts, providing a physical barrier while maintaining an optimal environment for wound healing. Polyvinyl alcohol (PVA) and sodium carboxymethyl cellulose (Na CMC) were crosslinked with borax, which reacts with the active hydroxyl groups in both polymers to form a hydrogel. The patches were loaded with ciprofloxacin HCl (CIP), a broad-spectrum antibiotic used to prevent and treat various types of wound infections. Hydrogels were subjected to rheological, morphological, antimicrobial, self-healing, ex vivo release, swelling, cytotoxicity, wound healing, and stability studies. The hydrogels exhibited shear-thinning, thixotropic, and viscoelastic properties. Microscopic images of the CIP hydrogel patch showed a porous, crosslinked matrix. The antimicrobial activity of the patch revealed antibacterial effectiveness against five types of Gram-positive and Gram-negative bacteria, demonstrating a minimum inhibitory concentration of 0.05 μg/mL against E. coli. The swelling percentage was found to be 337.4 ± 12.7%. The cumulative CIP release percentage reached 103.7 ± 3.7% after 3 h, followed by zero-order release kinetics. The stability studies revealed that the crossover point shifted toward higher frequencies after 3 months of storage at room temperature, suggesting a relaxation in the hydrogel bonds. The cytotoxicity study revealed that the CIP hydrogel patch is non-cytotoxic. Additionally, the in vivo study demonstrated that the CIP hydrogel patch possesses wound-healing ability. Therefore, the CIP PVA/Na CMC/Borax patch could be used in wound dressing.

The coronavirus disease-2019 (COVID-19) pandemic is a public health emergency of international concern. This pandemic poses a challenge to research and scientific community. In this study, we developed and tested content reliability and content validity of a questionnaire designed for evaluating the readiness and willingness of researchers to participate in virology research in Jordan. The survey was hosted on an online platform, and the link was emailed. A total of 332 participants from universities across Jordan completed the survey. For factor analysis, Kaiser-Meyer-Olkin value (KMO) and Bartlett’s Test of Sphericity were conducted. Furthermore, exploratory factor analysis (EFA) with parallel analysis and scree plots were conducted to evaluate the most suitable model for the data. The result of the EFA suggested a 5-factor model would fit the survey. Data showed that the lowest means were for researchers’ readiness to conduct virology research and readiness for virology research with means of 2.07 and 2.95, respectively. Moreover, years of experience and speciality had a significant effect on the readiness and willingness of virology research in Jordan. In conclusion, readiness for research and researchers should be addressed and authorities should pay attention to these shortcomings in virology research.