Alzheimer’s disease (AD) is characterized by the presence of β-amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in the brain. The prevalence of the disease is increasing and is expected to reach 141 million cases by 2050. Despite the risk factors associated with the disease, there is no known causative agent for AD. Clinical trials with many drugs have failed over the years, and no therapeutic has been approved for AD. There is increasing evidence that pathogens are found in the brains of AD patients and controls, such as human herpes simplex virus-1 (HSV-1). Given the lack of a human model, the route for pathogen entry into the brain remains open for scrutiny and may include entry via a disturbed blood–brain barrier or the olfactory nasal route. Many factors can contribute to the pathogenicity of HSV-1, such as the ability of HSV-1 to remain latent, tau protein phosphorylation, increased accumulation of Aβ invivo and in vitro, and repeated cycle of reactivation if immunocompromised. Intriguingly, valacyclovir, a widely used drug for the treatment of HSV-1 and HSV-2 infection, has shown patient improvement in cognition compared to controls in AD clinical studies. We discuss the potential role of HSV-1 in AD pathogenesis and argue for further studies to investigate this relationship.

Alzheimer’s disease (AD) is a neurodegenerative disease that is known to accumulate amyloid-β (Aβ) and tau protein. Clinical studies have not identified pathogenesis mechanisms or produced an effective cure for AD. The Aβ monoclonal antibody lecanemab reduces Aβ plaque formation for the treatment of AD, but more studies are required to increase the effectiveness of drugs to reduce cognitive decline. The lack of AD therapy targets and evidence of an association with an acute neuroinflammatory response caused by several bacteria and viruses in some individuals has led to the establishment of the infection hypothesis during the last 10 years. How pathogens cross the blood–brain barrier is highly topical and is seen to be pivotal in proving the hypothesis. This review summarizes the possible role of the gut microbiome in the pathogenesis of AD and feasible therapeutic approaches and current research limitations.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing infections ranging from skin disorders to severe conditions like infective endocarditis. Its evolving resistance, including resistance to β-lactams and last-resort antibiotics, such as vancomycin, daptomycin, and linezolid, necessitates alternative therapies. This study investigates the synergistic efficacy of vancomycin and 3-hydrazinoquinoxaline-2-thiol (3HL) against 23 clinical MRSA isolates. Susceptibility testing was performed using broth microdilution and checkerboard assays, while in silico analyses assessed interactions between vancomycin and 3HL. Vancomycin exhibited minimum inhibitory concentrations (MICs) ranging from 0.25 to 1 µg/mL, whereas 3HL showed higher MICs of 16–32 µg/mL. Synergistic interactions were confirmed via checkerboard assays, with fractional inhibitory concentration index (FICI) values between 0.236 and 0.5, indicating enhanced vancomycin efficacy. Notably, vancomycin MICs decreased significantly when combined with 3HL. In silico docking revealed interactions with penicillin-binding protein 2a (PBP2a), suggesting promising therapeutic potential. Vancomycin exhibited superior docking scores (−8.9 kcal/mol) and stabilizing hydrogen bonds, effectively targeting key protein grooves. Both compounds demonstrated potential for overcoming PBP2a’s structural occlusions, suggesting their role in combating β-lactam-resistant strains through targeted protein inhibition and structural stabilization.

Bacterial infections remain a significant cause of mortality worldwide, further aggravated by the escalating issue of antibiotic resistance. Extended-Spectrum Beta-Lactamases (ESBLs) pose a substantial challenge, capable of hydrolyzing various beta-lactam antibiotics. The slow pace of drug discovery, coupled with the rapid emergence of drug-resistant bacteria, underscores the urgent need for innovative therapeutic solutions. Thymoquinone (TQ), derived from the seeds of Nigella sativa, has demonstrated notable antibacterial activity against Gram-negative bacteria, including Escherichia coli and Pseudomonas aeruginosa. Previous research has established the efficacy of quinoxaline derivatives, such as 3-hydrazinoquinoxaline-2-thiol (3HQ), against Methicillin-Resistant Staphylococcus aureus (MRSA). This study investigates the potential synergy between 3HQ and TQ against various clinical strains of ESBL. The minimum inhibitory concentrations (MICs) of TQ and 3HQ were evaluated against 18 clinical ESBL strains, revealing MIC values ranging from 16 to 128 µg/mL for both compounds. Furthermore, the interaction between TQ and 3HQ was assessed using a checkerboard assay, which demonstrated a 100% synergistic interaction, with a fractional inhibitory concentration index (FICI) of less than 0.5 against the ESBL strains. Docking and molecular dynamics simulations indicated that TQ exhibits a strong binding affinity and interaction profile comparable to that of RPX-7063. In contrast, 3-hydrazinoquinoxaline-2-thiol targets a different active site, potentially enhancing thymoquinone's binding efficiency. Collectively, these compounds may effectively inhibit CTX-M-15, as evidenced by their docking scores and interaction profiles. Further investigations, including in vivo studies, are essential to validate these findings. This research suggests a promising strategy for developing more effective treatments for ESBL infections, emphasizing the need for in vivo validation.

To assess the prevalence, temporal trends, and diagnostic concordance of transfusion-transmitted viruses (TTVs) using combined serological and nucleic acid testing (NAT) in a large donor population in Jeddah, Saudi Arabia. This retrospective study analysed all blood donations screened from 2019 to 2024 at King Fahad Armed Forces Hospital, using serological assays and NAT. Prevalence estimates were calculated with 95% confidence intervals. Temporal trends were evaluated using generalised estimating equations logistic regression. Multivariable logistic regression identified predictors of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) positivity. Diagnostic agreement between serology and NAT was assessed using Cohen’s kappa statistic. Among 48,151 donors, seroprevalence was 0.4% for HBsAg, 0.3% for HCV Ab, 0.1% for HIV Ab, and 0.02% for HTLV Ab. HBc Ab was detected in 4.7%. NAT identified HBV and HCV in 0.2% and 0.1%, respectively. Logistic regression showed a significant annual decline in HBsAg and NAT-HBV. Older age and non-Saudi nationality were linked to higher HBsAg and HCV positivity. Concordance between serology and NAT was substantial for HIV but negligible for HBV and HCV. TTVs rates are low and declining, but HBV/HCV concordance underscores the need for continued dual testing to ensure transfusion safety.

Introduction: Multidrug resistant (MDR) bacteria are one of the most important current threats to public health. Therefore, serious concerns were raised about the effectiveness of traditional antibiotics. Cisplatin, a chemotherapeutic agent that is used mainly in cancer treatment, has recently attracted attention and popularity for its potential antibacterial properties. Our study aim is to evaluate the antibacterial properties of cisplatin against several common MDR and non-MDR Gram-positive strains, including Methicillin-Resistant Staphylococcus aureus (MRSA), Methicillin-Susceptible Staphylococcus aureus (MSSA), Coagulase-Negative Staphylococcus (CoNS), and Vancomycin-Resistant Enterococcus (VRE). Methodology: Cisplatin's Minimum Inhibitory Concentration (MIC) was calculated through standard microdilution methods. Results: Our findings indicated that cisplatin had a minimum inhibitory concentration (MIC) of 256 µg/mL across all tested bacterial strains, reflecting its limited antibacterial efficacy in its currently available formulation. However, although the MIC values were high, this study explored cisplatin’s activity against these bacterial strains which uncovers a potential gap about cisplatin clinical effectiveness and indicates that further enhancement is required. Conclusions: These results confirm that cisplatin antibacterial activity has not been extensively explored against these resistant strains. Cisplatin alone shows limited efficacy based on the relatively high MIC values observed. However, combination therapy with other antibiotics may improve its therapeutic potential. Additionally, novel delivery systems—nanoparticle formulations, for instance—could enhance antibacterial activity while reducing toxicity. Future investigations should evaluate these approaches in more detail.