Interactions of melatonin with various signaling pathways: implications for cancer therapy

Melatonin is a neuro-hormone with conserved roles in evolution. Initially synthetized as an antioxidant molecule, it has gained prominence as a key molecule in the regulation of the circadian rhythm. Melatonin exerts its effect by binding to cytoplasmic and intra-nuclear receptors, and is able to regulate the expression of key mediators of different signaling pathways. This ability has led scholars to investigate the role of melatonin in reversing the process of carcinogenesis, a process in which many signaling pathways are involved, and regulating these pathways may be of clinical significance. In this review, the role of melatonin in regulating multiple signaling pathways with important roles in cancer progression is discussed, and evidence regarding the beneficence of targeting malignancies with this approach is presented

Etiologic Agents of Otomycosis in the North-Western Area of Iran

BACKGROUND: Otomycosis is a superficial fungal infection often involves the pinna and external auditory canal. It is a pathologic condition, with Candida and Aspergillus, the most common fungal species. It is common worldwide but more prevalent in tropical and subtropical countries. OBJECTIVES: The aim of this study was to determine the etiologic agents and local epidemiologic pattern of otomycosis in northwest Iran. PATIENTS AND METHODS: A series of 140 patients with clinically symptomatic otomycosis were studied in 21 cities, towns, and villages throughout northwest Iran between 2009 and 2011. Clinical samples were collected by swabs and then assessed by mycological investigation. RESULTS: Otomycosis was diagnosed in 129 cases (92%, 76 male, 53 female) with the highest prevalence of cases occurring in males between 21 - 40 years of age. From an etiological point of view, 116 patients (90%, 21 - 40 years old) were infected by saprophytic mold and 9 patients (7%) were infected by yeast. Three cases (2%) involved dermatophytes, and in one case (1%) the subject was infected with Eurotium (the perfect stage of Aspergillus fumigatus). Aspergillus niger was the most common mold that was isolated, followed by A. flavus, A. fumigatus, Penicillium spp., Fusarium spp., and Rhizopus spp. A total of 2 yeasts belonging to genus Candida, C. albicans and C. tropicalis, were isolated. CONCLUSIONS: Our study showed a high prevalence of otomycosis in the northwestern area of Iran. As such, proper diagnosis and treatment by aseptic techniques for this disease is urgently needed

Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: involvement of circadian clock genes

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most prevalent joint diseases. A such, they are important causes of pain and disability in a substantial proportion of the human population. A common characteristic of these diseases is the erosion of articular cartilage and consequently joint dysfunction. Melatonin has been proposed as a link between circadian rhythms and joint diseases including RA and OA. This hormone exerts a diversity of regulatory actions through binding to specific receptors and intracellular targets as well as having receptor-independent actions as a free radical scavenger. Cytoprotective effects of melatonin involve a myriad of prominent receptor-mediated pathways/molecules associated with inflammation, of which the role of omnipresent NF-κB signalling is crucial. Likewise, disturbance of circadian timekeeping is closely involved in the aetiology of inflammatory arthritis. Melatonin is shown to stimulate cartilage destruction/regeneration through direct/indirect modulation of the expression of the main circadian clock genes, such as BMAL, CRY and/or DEC2. In the current article, we review the effects of melatonin on RA and OA, focusing on its ability to regulate inflammatory pathways and circadian rhythms. We also review the possible protective effects of melatonin on RA and OA pathogenesis. Linked Articles: This article is part of a themed section on Recent Developments in Research of Melatonin and its Potential Therapeutic Applications. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc. © 2017 The British Pharmacological Societ

Therapeutic potential of polyphenols in cardiovascular diseases: Regulation of mTOR signaling pathway

Cardiovascular diseases comprise of non-communicable disorders that involve the heart and/or blood vessels and have become the leading cause of death worldwide with increased prevalence by age. mTOR is a serine/threonine-specific protein kinase which plays a central role in many physiological processes including cardiovascular diseases, and also integrates various proliferative signals, nutrient and energy abundance and stressful situations. mTOR also acts as central regulator during chronic stress, mitochondrial dysfunction and deregulated autophagy which are associated with senescence. Under oxidative stress, mTOR has been reported to exert protective effects regulating apoptosis and autophagy processes and favoring tissue repair. On the other hand, inhibition of mTOR has been suggested to have beneficial effects against atherosclerosis, cardiac hypertrophy and heart failure, and also in extending the lifespan. In this aspect, the use of drugs or natural compounds, which can target mTOR is an interesting approach in order to reduce the number of deaths caused by cardiovascular disease. In the present review, we intend to shed light on the possible effects and molecular mechanism of natural agents like polyphenols via regulating mTOR

Preparation and in-vitro evaluation of pH-responsive cationic cyclodextrin coated magnetic nanoparticles for delivery of methotrexate to the Saos-2 bone cancer cells

Osteosarcoma, as a common malignant neoplasm in children and adolescents, still remains a challenge for conventional therapeutic regimens. In the meantime advent of innovative and revolutionary techniques such as drug delivery systems and smart nano-biomaterials seems promising in tackling these complications. In this study, we designed a smart nano-system consisting of a magnetic inner core and polymeric outer shell with cationic moieties for targeted delivery and enhanced uptake of methotrexate anticancer agent for Saos-2 cell line. The designed nano-formulation was characterized and its drug loading capacity and drug release profile were studied as well that about 60 of methotrexate was released in the first 12 h. The efficacy of the nano-formulation in killing cancer cells was assessed using MTT, cellular uptake, and uptake flow-cytometry. Our in-vitro results confirmed the prepared nano-system has a potential for delivery of anticancer drugs against the Saos-2 cell line and suggests more investigations such as in-vivo tests to be implemented. © 2020 Elsevier B.V

Natural products, PGC-1α, and Duchenne muscular dystrophy

Peroxisome proliferator-activated receptor γ (PPARγ) is a transcriptional coactivator that binds to a diverse range of transcription factors. PPARγ coactivator 1 (PGC-1) coactivators possess an extensive range of biological effects in different tissues, and play a key part in the regulation of the oxidative metabolism, consequently modulating the production of reactive oxygen species, autophagy, and mitochondrial biogenesis. Owing to these findings, a large body of studies, aiming to establish the role of PGC-1 in the neuromuscular system, has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases. Among these, some evidence has shown that various signaling pathways linked to PGC-1α are deregulated in muscular dystrophy, leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species (ROS) production. In the light of these results, any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies. PGC-1α is influenced by different patho-physiological/pharmacological stimuli. Natural products have been reported to display modulatory effects on PPARγ activation with fewer side effects in comparison to synthetic drugs. Taken together, this review summarizes the current knowledge on Duchenne muscular dystrophy, focusing on the potential effects of natural compounds, acting as regulators of PGC-1α