Melatonin and oral diseases: possible therapeutic roles based on cellular mechanisms.

Oral diseases, including periodontal disorders, oral cancer, periodontitis, and mucositis are the major challenges for both patients and healthcare providers. These conditions often involve inflammation, oxidative stress, and impaired cellular processes, leading to symptoms ranging from discomfort to severe debilitation. Conventional treatments for such oral diseases exhibit constraints, prompting the investigation of innovative therapeutic approaches. Considering the anti-inflammatory, anti-oxidant, and anti-cancer effects of melatonin, this study was carried out to investigate the potential protective effects of melatonin in mitigating the severity of oral diseases. Studies indicate that melatonin influences the differentiation of periodontal stem cells, inhibits oral cancer progression, reduces inflammation associated with periodontitis, and alleviates the severity of oral mucositis. Melatonin has demonstrated potential efficacy in both preclinical and clinical investigations; however, findings are frequently heterogeneous and contingent upon contextual factors. This review provides a comprehensiveoverview of current state of knowledge in this domain, elucidating the multifaceted role that melatonin may assume in combatingoral diseases. Further research should be directed toward determining the most effective dosing, timing, and administration methods for melatonin-based therapies for oral diseases.

Recent advances on small molecules in osteogenic differentiation of stem cells and the underlying signaling pathways.

Bone-related diseases are major contributors to morbidity and mortality in elderly people and the current treatments result in insufficient healing and several complications. One of the promising areas of research for healing bone fractures and skeletal defects is regenerative medicine using stem cells. Differentiating stem cells using agents that shift cell development towards the preferred lineage requires activation of certain intracellular signaling pathways, many of which are known to induce osteogenesis during embryological stages. Imitating embryological bone formation through activation of these signaling pathways has been the focus of many osteogenic studies. Activation of osteogenic signaling can be done by using small molecules. Several of these agents, e.g., statins, metformin, adenosine, and dexamethasone have other clinical uses but have also shown osteogenic capacities. On the other hand, some other molecules such as T63 and tetrahydroquinolines are not as well recognized in the clinic. Osteogenic small molecules exert their effects through the activation of signaling pathways known to be related to osteogenesis. These pathways include more well-known pathways including BMP/Smad, Wnt, and Hedgehog as well as ancillary pathways including estrogen signaling and neuropeptide signaling. In this paper, we review the recent data on small molecule-mediated osteogenic differentiation, possible adjunctive agents with these molecules, and the signaling pathways through which each small molecule exerts its effects.

Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats.

Chronic exposure to toxic inorganic arsenic results in the adverse health effects including skin lesions, cardiovascular diseases, diabetes, neurological disorders, and liver and kidney diseases. Gallic acid (GA) is an important phenolic compound, which could protect different tissues from oxidative stress induced damage. The present study investigated effects of GA against sodium arsenite (SA)-induced renal and hepatic toxicity. Thirty-five rats were randomly divided in to five groups; group 1 was treated with normal saline (2 ml/kg/day, p.o.; for 21 days); group 2 was exposed to SA (10 mg/kg/day, p.o.; for 14 days); groups 3 and 4 were treated with GA (10 and 30 mg/kg/day, respectively; for 7 days) prior to exposure to SA, and treatment was continued up to 21 days in parallel with SA administration; group 5 was treated with GA (30 mg/kg/day, p.o.; for 21 days). The level of MDA, IL-1ß, NO and glutathione (GSH) and the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) were evaluated in kidney and liver tissues. Histopathological parameters and serum levels of ALT, AST, ALP, Cr and BUN were also assessed. Treatment with GA remarkably improved SA-induced alteration of hematological and histopathological parameters; these protective effects were associated with the reduction of SA-induced elevation of MDA, IL-1ß and NO levels as well as reduction of GSH level and GPx, SOD and CAT activity. Our results suggest that GA may inhibit SA-induced kidney and liver toxicity through scavenging reactive free radicals and increasing intracellular antioxidant capacity.

Anti-candidal activity of Astragalus verus in the in vitro and in vivo guinea pig models of cutaneous and systemic candidiasis

This study was design to evaluate the anti-candidal activity of Astragalus verus Olivier, Fabaceae (Av). The GC/MS analysis of essential oils of Av showed that aqueous extract contains thymol while hexadecanoic acid, 1,2-benzenedicarboxylic acid, diisooctyl ester and phytol were found as major components of methanol and acetone extracts. The aqueous extract showed anti-candidal activity in the concentration 320 mg/mL using disc diffusion method and its minimum inhibitory concentration (MIC) was 160 mg/mL. To induce cutaneous candidiasis, the dorsum of immunocompromised guinea pigs was infected with Candida albicans and animals were divided into five groups (n=5 for each): NC, received a vehicle; PC, received topical ketoconazole 2% and three other groups which received topical 10, 20 and 40% aqueous extract of Av. On ninth day postinfection, skins were cultured and colony forming unite per gram (CFU/g) skin was recorded. Systemic candidiasis was obtained by intravenous inoculation of C. albicans, 4000 CFU/g body weight. Here, animals have been divided into five groups like cutaneous candidiasis but their medications have been delivered in drinking water for ten days before induction of infection. On second day postinfection, all internal tissues were taken for determining CFU/g tissue. The aqueous extract (40%) prevented heavy burden of C. albicans in tissues and skin in oral and topical application, respectively. The results indicate that Av represents a potential source of anti-candidal drug.