The development of resistance to traditional antifungal therapies has necessitated the exploration of alternative treatment strategies to effectively manage fungal infections, particularly those induced by Candida albicans (C. albicans). This research investigates the possibility of integrating silver nanoparticles (AgNPs) with Terbinafine to improve antifungal effectiveness. Terbinafine, while potent, faces challenges with specific fungal strains, highlighting the need for strategies to enhance its treatment efficacy. Silver nanoparticles were produced through a light-activated, gelatin-based method, resulting in particle sizes ranging from 56.8 nm to 66.2 nm, confirmed by dynamic light scattering and scanning electron microscopy. Stability studies indicated that AgNPs produced with 30 mg of silver nitrate (AgNO₃) exhibited the greatest stability over 60 days across different temperature conditions. The analysis through UV-visible spectrophotometry revealed a notable shift in the absorption spectra as AgNO₃ concentrations increased, which was associated with a strengthening of plasmon resonance. The effectiveness of the AgNPs and Terbinafine combination was assessed against three strains of C. albicans (ATCC 10231, ATCC 90028, and ATCC 18804). Terbinafine demonstrated strong antifungal properties with minimum inhibitory concentrations (MIC) values ranging from 2–4 µg/mL, whereas AgNPs on their own displayed moderate effectiveness. The integrated formulation notably enhanced effectiveness, especially against strain ATCC 90028, revealing a synergistic effect (FIFi = 0.369). These results were complemented by the findings of the time-to-kill assay, where the same strain showed a 3.2 log₁₀ CFU/mL decrease in viable cell count. The process by which AgNPs boost activity entails the disruption of the fungal cell membrane and its internal components, probably as a result of silver ion release and the generation of free radicals. The results indicate that the combination of Terbinafine and AgNPs may act as a powerful alternative for addressing resistant fungal infections, presenting an encouraging direction for future antifungal treatments.

Tuberculosis (TB), caused by bacteria of the Mycobacterium tuberculosis complex (MTBC), remains a global health challenge, exacerbated by multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. This study employs whole-genome sequencing (WGS) to characterise genetic mutations associated with pyrazinamide (PZA) and fluoroquinolone (FQ) resistance in MDR-TB isolates from KPK. MDR and pre-XDR TB samples were collected and processed at the Provincial Tuberculosis Reference Laboratory under Biosafety Level III conditions. Samples underwent microscopy, GeneXpert MTB/RIF assay, culture, and drug susceptibility testing. DNA was extracted from positive cultures and subjected to WGS. Bioinformatics tools were used to analyse sequencing data, identify resistance-associated mutations, and assess genetic diversity among isolates. Out of the 78 MTBC isolates analysed, 67 (85.9 %) were identified as MDR-TB, with 48 categorized as pre-XDR, while 11 were drug-susceptible. The isolates predominantly came from young patients (mean age: 29.5 years, SD ±12.64), with a higher proportion of female patients (61.53 %). Mutations in the pncA gene, associated with PZA resistance, were identified in 51 isolates. Resistance to fluoroquinolones was linked to mutations in the gyrA and gyrB genes in 48 isolates. WGS confirmed PZA resistance in 51 isolates, 39 (76.47 %) of which also exhibited FQ resistance. Phylogenetic analysis revealed that Lineage 3 (L3) was predominant (58.97 %), followed by L4, L2, and L1 strains. The clustering of drug-resistant strains within L3 suggests ongoing localized transmission. These findings underscore the urgent need for targeted interventions, including enhanced molecular surveillance and tailored treatment strategies, to combat MDR-TB in KPK.

Background: Leishmaniasis is a neglected tropical disease with limited treatment options, characterized by high toxicity, rising resistance, and poor affordability of currently available drugs. Plant-derived bioactive compounds represent a promising alternative, offering potential for safer, more cost-effective therapeutics. Anchusa arvensis (Boraginaceae) has long been used in traditional medicine and is reported to possess diverse pharmacological properties, yet its anti-leishmanial potential remains underexplored. Objective: This study aimed to evaluate the anti-leishmanial efficacy, drug-likeness, and safety profiles of two key phytoconstituents from A. arvensis—p-methoxy catechol and uvaol—using an integrated approach combining in silico network pharmacology, molecular docking, ADMET prediction, and in vitro assays. Methods: Computational tools including PASS Online, SwissADME, pkCSM, FAME3, GLORY, Pred-hERG, and Endocrine Disruptome were used to predict pharmacokinetics, toxicity, and drug-likeness. Molecular docking was performed against the Leishmania tropica leishmanolysin (gp63; PDB ID: 1LML), followed by molecular dynamics simulation to assess complex stability. In vitro anti-leishmanial activity was tested against L. tropica promastigotes using MTT assays, with glucantime as a reference drug. Results: p-Methoxy catechol exhibited favorable drug-likeness (Lipinski compliant), low predicted toxicity, and strong activity as an inhibitor of aspulvinone dimethylallyltransferase and chlordecone reductase. Uvaol demonstrated additional hepatoprotective and anti-inflammatory potentials but showed moderate risks of hepatotoxicity and skin sensitization. Molecular docking revealed binding energies of −5.74 kcal/mol (p-methoxy catechol) and −9.0 kcal/mol (uvaol), with stable hydrogen bonding at key gp63 residues. In vitro assays confirmed significant anti-leishmanial activity with IC₅₀ values of 5.60 µg/mL (p-methoxy catechol) and 16.17 µg/mL (uvaol), compared to 0.78 µg/mL for glucantime. Conclusion: The findings establish p-methoxy catechol as a potent, safe, and druggable candidate, while uvaol offers complementary therapeutic value through multi-target pharmacology. Both compounds represent promising leads for the development of affordable plant-based anti-leishmanial therapies, aligning with global health goals to combat neglected tropical diseases.

Background: Chronic kidney disease (CKD) is a progressive condition associated with substantial morbidity, polypharmacy, and altered drug pharmacokinetics, placing patients at high risk of drug-related problems (DRPs). Non-dialysis CKD (ND-CKD) patients, in particular, face increased vulnerability to adverse drug events and drug–drug interactions (DDIs), necessitating proactive pharmaceutical care. Objective: This study aimed to evaluate the prevalence, causes, and clinical outcomes of DRPs in ND-CKD patients, assess the nature and acceptance of pharmacist-led interventions, and identify associations between Pharmaceutical Care Network Europe (PCNE) domains and DRP outcomes. Methods: A cross-sectional study was conducted among 157 ND-CKD inpatients at Northwest General Hospital, Peshawar. DRPs were identified and classified using PCNE version 9.1, and DDIs were analyzed via Lexicomp®. Data were analyzed using descriptive statistics and multivariate logistic regression. Results: A total of 254 DRPs were identified, predominantly due to inappropriate drug selection (42.91%) and patient-related factors (26.77%). Lexicomp® detected 157 DDIs, with Category C interactions most common (68.8%). Of 278 pharmacist interventions, 80.21% were accepted, and 44.96% of DRPs were completely resolved. Significant associations were found between DRP causes, intervention acceptance, and outcomes (p<0.05). Conclusion: DRPs are frequent in ND-CKD and predominantly preventable. Pharmacist-led interventions significantly improve therapeutic safety, highlighting the need for their integration into renal care.