Radon concentration in drinking water sources of the Main Campus of the University of Peshawar and surrounding areas, Khyber Pakhtunkhwa, Pakistan

Radon and its progenies in indoor environment have been identified as the main sources of radiation dose to the people from natural radioactive sources. Presence of radon in drinking water causes radiation related health hazards both through inhalation and ingestion. In this study 36 drinking water samples from taps, boreholes and deep tube wells within the Main Campus of the University of Peshawar and adjoining area were analyzed with RAD7 electronic device for radon content determination. These water samples have a mean, maximum and minimum radon value of 8.8 ± 0.8, 18.2 ± 1.0, and 1.6 ± 0.3 Bq L⁻¹, respectively. Eleven drinking water samples analyzed have radon levels in excess of the EPA recommended maximum contaminant level (MCL) of 11.1 Bq L⁻¹. These include 89% from tube wells, 8% from tap water, and 50% from shallow boreholes. Radon levels of about 31% of the total samples used by the inhabitants of the study area are higher than the EPA advised level of 11.1 Bq L⁻¹. The annual effective dose from radon in water due to its ingestion and inhalation per individual has also been estimated. The mean radon concentration and mean annual effective dose due to radon in water of this study have been compared with the mean radon concentration and mean annual effective dose of earlier investigators due to radon in water from different localities of India and Pakistan. The mean annual effective doses of all the samples are lower than the reference level of 0.1 mSv a⁻¹ for drinking water of WHO and EU Council. It has been concluded that drinking water of the study area is generally safe as far as radon related health hazards are concerned with the exception of a few isolated cases. It has been found that radon levels within the region have a positive correlation with depth of the water sources.     

Novasomes as Nano-Vesicular Carriers to Enhance Topical Delivery of Fluconazole: A New Approach to Treat Fungal Infections

The occurrence of fungal infections has increased over the past two decades. It is observed that superficial fungal infections are treated by conventional dosage forms, which are incapable of treating deep infections due to the barrier activity possessed by the stratum corneum of the skin. This is why the need for a topical preparation with advanced penetration techniques has arisen. This research aimed to encapsulate fluconazole (FLZ) in a novasome in order to improve the topical delivery. The novasomes were prepared using the ethanol injection technique and characterized for percent entrapment efficiency (EE), particle size (PS), zeta potential (ZP), drug release, Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and antifungal activity. The FN7 formulation with 94.45% EE, 110 nm PS and −24 ZP proved to be the best formulation. The FN7 formulation showed a 96% release of FLZ in 8 h. FTIR showed the compatibility of FLZ with excipients and DSC studies confirmed the thermal stability of FLZ in the developed formulation. The FN7 formulation showed superior inhibition of the growth of Candida albicans compared to the FLZ suspension using a resazurin reduction assay, suggesting high efficacy in inhibiting fungal growth.     

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Attenuates Breast Cancer Progression

Hydrogen sulfide (H₂S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H₂S production or exposure of H₂S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H₂S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H₂S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H₂S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H₂S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H₂S-based anti-tumor drugs to cure BC.