Vol 31, No 9 (2024)

Background: NLS-3 or (R, R) enantiomer of phacetoperane (levophacetoperane) is the reverse ester of methylphenidate, a well-documented psychostimulant marketed for the treatment of attention-deficit/hyperactivity disorder (ADHD) since the end of 1950s. Launched in Canada and Europe by Specia Rhône-Poulenc and Rhodia, marketed as Lidepran® (8228 R.P.), for the treatment of obesity and depression, phacetoperane became an increasingly popular psychiatric medication from 1959 to 1967. Previous data supported that the stimulant effect of phacetoperane differed from those of other medications acting on the catecholamine system (e.g., methylphenidate, amphetamine), with an advantage of benefit/risk balance. Method: The goal of this study is to characterize the binding profile of NLS-3 using in vitro and in vivo assays and hypothesize potential therapeutic uses considering all available data. Results: A complete binding profile assay confirmed the potential benefit of phacetoperane with a higher benefit/risk compared to other stimulants. NLS-3 synthesis resulted from phenylketone, which is also used for the synthesis of methylphenidate. It differs from that used by Rhône-Poulenc SA laboratories, allowing the possibility of individualizing several enantiomers not synthesized previously. The present review also confirmed extensive clinical use of the compound in almost one thousand children and adolescents in large dose ranges with fewer side effects versus comparative treatments. Furthermore, levophacetoperane was found to be generally well-tolerated by the subjects. Conclusion: NLS-3 could be a safer and more potent alternative to stimulants for patients with ADHD.

Quercetin (Qu, 3,5,7,3’, 4’-pentahydroxyflavanone) is a natural polyphenol compound abundantly found in health food or plant-based products. In recent decades, Qu has gained significant attention in the food, cosmetic, and pharmaceutic industries owning to its wide beneficial therapeutic properties such as antioxidant, anti-inflammatory and anticancer activities. Despite the favorable roles of Qu in cancer therapy due to its numerous impacts on the cell signaling axis, its poor chemical stability and bioavailability, low aqueous solubility as well as short biological half-life have limited its clinical application. Recently, drug delivery systems based on nanotechnology have been developed to overcome such limitations and enhance the Qu biodistribution following administration. Several investigations have indicated that the nano-formulation of Qu enjoys more remarkable anticancer effects than its free form. Furthermore, incorporating Qu in various nano-delivery systems improved its sustained release and stability, extended its circulation time, enhanced its accumulation at target sites, and increased its therapeutic efficiency. The purpose of this study was to provide a comprehensive review of the anticancer properties of various Qu nano-formulation to augment their effects on different malignancies. Various targeting strategies for improving Qu delivery, including nanoliposomes, lipids, polymeric, micelle, and inorganic nanoparticle NPs, have been discussed in this review. The results of the current study illustrated that a combination of appropriate nano encapsulation approaches with tumor-oriented targeting delivery might lead to establishing QU nanoparticles that can be a promising technique for cancer treatment.

Introduction:Thyroid carcinoma (TC) is currently the prevalent type of endocrine malignancy worldwide, having an incidence of around 15.5 per 100,000 people. However, the underlying mechanisms of TC tumorigenesis remain to be further elucidated.

Methods:Performing the database analyses, Platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) was found to be dysregulated in several carcinomas and might trigger tumor occurrence as well as the progression of TC. Clinicopathological information of patients from our local validated cohort and The Cancer Genome Atlas (TCGA) cohort also confirmed this hypothesis

Results:Our present research showed that elevated expression of PAFAH1B3 has a close association with worse behavior in papillary thyroid carcinoma (PTC). We utilized the small interfering RNA to obtain the PAFAH1B3-transfected PTC cell lines, including BCPAP, FTC-133, and TPC-1, and then further examined their biological function in vitro. Furthermore, gene set enrichment analysis suggested that PAFAH1B3 is implicated with epithelial-mesenchymal transition (EMT). Afterward, the western blotting assays aimed at EMT-related proteins were performed.

Conclusion:In short, our results revealed that silencing PAFAH1B3 could hinder the capabilities of proliferation, migration, and invasion of PTC cells. Increasing expression of PAFAH1B3 might be of quintessence with lymph node metastasis by triggering EMT in PTC patients