No abstract

The use of nanosized particles has emerged to facilitate selective applications in medicine. Drug-delivery systems represent novel opportunities to provide stricter, focused, and fine-tuned therapy, enhancing the therapeutic efficacy of chemical agents at the molecular level while reducing their toxic effects. Melatonin (N-acetyl-5-methoxytriptamine) is a small indoleamine secreted essentially by the pineal gland during darkness, but also produced by most cells in a non-circadian manner from which it is not released into the blood. Although the therapeutic promise of melatonin is indisputable, aspects regarding optimal dosage, biotransformation and metabolism, route and time of administration, and targeted therapy remain to be examined for proper treatment results. Recently, prolonged release of melatonin has shown greater efficacy and safety when combined with a nanostructured formulation. This review summarizes the role of melatonin incorporated into different nanocarriers (e.g., lipid-based vesicles, polymeric vesicles, non-ionic surfactant-based vesicles, charge carriers in graphene, electro spun nanofibers, silica-based carriers, metallic and non-metallic nanocomposites) as drug delivery system platforms or multilevel determinations in various in vivo and in vitro experimental conditions. Melatonin incorporated into nanosized materials exhibits superior effectiveness in multiple diseases and pathological processes than does free melatonin; thus, such information has functional significance for clinical intervention.

Frequência do grupo sanguíneo DEA 1.1 em cães atendidos no Hospital Veterinário da UFMT (Sinop/MT), risco de sensibilização de cães DEA 1 negativos e da ocorrência de reação transfusional hemolítica por ocasião de uma segunda transfusão de sangue* DEA 1.1 blood group frequency in dogs attended at the veterinary hospital of UFMT (Sinop/MT), risk of DEA 1 negative dog sensitization and occurrence of hemolytic transfusion reaction in a second blood transfusion

Cell-to-cell communication is a broad and complex process associated with regular stimuli to maintain healthy cell interactions. One of the agents capable of cellular communication is known as an exosome, a subset of extracellular vesicles (EVs) released by the cell membrane. The exosome contains a wide range of functional proteins, mRNAs and miRNAs, which have the potential to interact with healthy or diseased cells in the body. On the other hand, melatonin also acts as a cellular communicator, produced and released by the pineal gland in a circadian way and also, non-circadian melatonin is derived from the mitochondria of all normal cells. In addition to exhibiting antioxidant, anti-inflammatory, anti-tumor and anti-aging activities, melatonin has recently been studied by its influence on exosomes. This review summarizes the relationship between exosomes and melatonin in various pathological processes. There is robust evidence that their combination ameliorates inflammation, ischemia-reperfusion injury, hepatic metabolic disturbance, cancer immunosuppression status, degenerative processes like chronic kidney disease, vascular calcification, ageing, ischemic brain injury, neurodegenerative diseases, obesity, colitis, wound healing and even embryonic development. Association of exosomes and melatonin represent a promising therapeutic tool, capable of interfering with basic molecular processes, such as oxidative stress and the inflammatory cascade, which support many pathophysiological aspects of diseases.

Prostate cancer is the second most common neoplasm among men, with a high mortality rate in advanced stages. Poly (ADP-ribose) polymerase (PARP) plays an important role in repair to DNA damage, being associated with resistance to tumor cell death. Conversely, Caspase-3 is a crucial mediator of programmed cell death, being highly expressed in apoptotic cells. The aim of the present study was to characterize the expression of PARP and Caspase-3 by immunohistochemistry in patients with advanced prostate cancer. PARP and Caspase-3 were independently correlated to patients' evolution, in accordance with the classification of prognostic groups. The increase in PARP expression was positively correlated with tumor patients with poor prognosis (P < 0.0001). In contrast, a decrease in Caspase-3 expression was identified in patients with poor prognosis, when compared with prostate cancer patients with good prognosis (P = 0.0007). Numerically, 92.3% of patients previously classified with poor prognosis showed higher PARP expression, while 93.75% of patients previously classified with good prognosis showed higher levels of Caspase-3. We conclude that PARP and Caspase-3 are potential prognostic markers for prostate cancer patients with different prognosis.