ABSTRACT
This study investigates the novel application of Phenyl Boronic Acid Functionalized-Quercetin nanoparticles (PBA-Qt NPs) in the context of antibacterial and diabetic wound healing. The research reveals a multifaceted approach, encompassing physicochemical characterization, antioxidant activity, antibacterial potential, and wound healing efficacy. The purpose of the study was to improve wound healing and antibacterial effects of quercetin and its esterified nanoparticles with phenyl boronic acid (PBA-Qt) compared with phenytoin streptozotocin-induced diabetic rats as a model. PBA-Qt NPs were confirmed using TLC, SEM, and FTIR. They exhibited superior DPPH scavenging (84.2 ± 0.12 %) compared to PBA (59.00 ± 0.18 %) and quercetin (79.02 ± 0.17 %). PBA-Qt showed significant antimicrobial properties with ZOI against Gram-negative (30.34 ± 0.02) and Gram-positive bacteria (25.40 ± 0.03). The MIC for Pseudomonas aeruginosa was 1.41 ± 0.03 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. The MBC against Pseudomonas aeruginosa was 4.33 ± 0.02 µg/100 µL, and for Staphylococcus aureus, it was 8.25 ± 0.02 µg/100 µL. PBA-Qt NPs reduced MIC for both Gram-positive and Gram-negative bacteria compared to quercetin. They enhanced wound healing by 60-99 % in infected diabetic rats, outperforming phenytoin. PBA-Qt NPs stimulated angiogenesis, tissue repair, and regeneration, improving wound closure. In diabetic and non-diabetic wounds, PBA-Qt NPs demonstrated superior wound contraction and granulation tissue formation. In conclusion, PBA-Qt nanoparticles are promising for treating diabetic chronic wounds due to reduced irritation and enhanced antibacterial and wound-healing properties.
ABSTRACT
Thalassemia is one of the most prevalent genetic disorders worldwide. The present study aimed to explore the mutational spectrum of all hemoglobin (HB) encoding genes and to identify the potentially damaging and pathogenic variants in the beta (ß)-thalassemia major patients and thalassemia minor carriers of Southern Punjab, Pakistan. A total of 49 ß-thalassemia major patients and 49 carrier samples were screened for the identification of HBA1, HBA2, HBB, HBD, HBE1, HBG1 and HBG2 variants by NGS. PCR was performed for the amplification of HB encoding genes and the amplified product of 13 patients and 7 carrier samples were processed for the Sanger sequencing. Various bioinformatics tools and databases were employed to reveal the functional impact and pathogenicity potential of the observed variants. Results depicted a total of 20 variants of HB-related genes by NGS and 5 by Sanger sequencing in thalassemia patients. While 20 variants by NGS and 3 by Sanger were detected in carriers. Few known genetic variants of HB-encoding genes are being reported for the first time in Pakistani thalassemia patients and carriers. However, two novel HBB variants c.375A>C (p.P125P) and c.*61T>G and a novel variant of HBE1 (c.37A>T (p.T13S)) were also documented. Pathogenicity analysis predicted the pathogenic potential of HBB variants (c.47G>A (p.W16*), c.27-28insG (p. S10fs), and c.92+5G>C) for ß thalassemia. The study of functional impact indicated that these HBB variants result in the premature termination of translation leading to the loss of functional ß-globin protein. It is therefore suggested that the pathogenic HBB variants, identified during present study, can be employed for the diagnosis, carrier screening, and planning therapy of thalassemia.
