Advances in Regenerative Dentistry: A Systematic Review of Harnessing Wnt/ß-Catenin in Dentin-Pulp Regeneration.

Dentin pulp has a complex function as a major unit in maintaining the vitality of teeth. In this sense, the Wnt/ß-Catenin pathway has a vital part in tooth development, maintenance, repair, and regeneration by controlling physiological activities such as growth, differentiation, and migration. This pathway consists of a network of proteins, such as Wnt signaling molecules, which interact with receptors of targeted cells and play a role in development and adult tissue homeostasis. The Wnt signals are specific spatiotemporally, suggesting its intricate mechanism in development, regulation, repair, and regeneration by the formation of tertiary dentin. This review provides an overview of the recent advances in the Wnt/ß-Catenin signaling pathway in dentin and pulp regeneration, how different proteins, molecules, and ligands influence this pathway, either upregulating or silencing it, and how it may be used in the future for clinical dentistry, in vital pulp therapy as an effective treatment for dental caries, as an alternative approach for root canal therapy, and to provide a path for therapeutic and regenerative dentistry.

Exploration of newly synthesized amantadine-thiourea conjugates for their DNA binding, anti-elastase, and anti-glioma potentials.

Three newly synthesized amantadine thiourea conjugates namely MS-1 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)benzamide, MS-2 N-(((3 s,5 s,7 s)-adamantan-1-yl)carbamothioyl)-4-methylbenzamide and MS-3 N-((3 s,5 s,7 s)-adamantan-1-ylcarbamothioyl)-4-chlorobenzamide were investigated for their structures, bindings (DNA/ elastase), and for their impact on healthy and cancerous cells. Theoretical (DFT/docking) and experimental {UV-visible (UV-), fluorescence (Flu-), and cyclic voltammetry (CV)} studies indicated binding interactions of each conjugate with DNA and elastase enzyme. Theoretically and experimentally calculated binding parameters for conjugate - DNA interaction revealed MS-3 - DNA to have most significant binding with comparatively greater values of binding parameters {(Kb/M-1: docking, 3.8 × 105; UV-, 5.95 × 103; Flu-,1.55 × 105; CV, 1.52 × 104), (∆G/ kJmol-1: docking, -32.09; UV-, -22.40; Flu-,-30.81; CV, -24.82)}. The docked structures, greater bindings site size values (n), and the trend in DNA viscosity changes in the presence of each conjugate concentration confirmed a mixed binding mode of interaction among them. Conjugate - elastase binding by docking agreed with the experimental anti-elastase findings. Cytotoxicity studies of each tested conjugate demonstrated greater cytotoxicity for cancerous (MG-U87) cells in comparison to control, while for the normal (HEK-293) cells the cytotoxicity was found comparatively low. Overall exploration suggested that MS-3 is the most effective candidate for DNA binding, anti-elastase, and for anti-glioma activities.

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding ability of fluorinated drug target proteins has also been reported in some cases. An emerging line of research on F substitution has been addressed by using 18F as a radiolabel tracer atom in the extremely sensitive methodology of positron emission tomography (PET) imaging. This review aims to report on the fluorinated drugs approved by the US Food and Drug Administration (FDA) from 2016 to 2022. It cites selected examples from a variety of therapeutic and diagnostic drugs. FDA-approved drugs in this period have a variety of heterocyclic cores, including pyrrole, pyrazole, imidazole, triazole, pyridine, pyridone, pyridazine, pyrazine, pyrimidine, triazine, purine, indole, benzimidazole, isoquinoline, and quinoline appended with either F-18 or F-19. Some fluorinated oligonucleotides were also authorized by the FDA between 2019 and 2022.