Melanin-The Éminence Grise of Melanoma and Parkinson's Disease Development.

A common feature of Parkinson's disease (PD) and melanoma is their starting points being based on cells capable of converting tyrosine into melanin. Melanocytes produce two types of melanin: eumelanin and pheomelanin. These dyes are designed to protect epidermal cells from the harmful effects of UV radiation. Neurones of the substantia nigra, which degenerate during PD, produce neuromelanin, the physiological role of which is not fully explained. This article discusses the potential role of melanins in the pathogenesis of both diseases. Melanins, due to their ability to accumulate toxic substances, may become their sources over time. The use of glutathione for the synthesis of pheomelanins and neuromelanins may reduce the antioxidant capacity of cells, leading to an excessive synthesis of free radicals. This study also tested the hypothesis that certain drugs used in the treatment of PD (L-DOPA, MAO-B and COMT inhibitors, and amantadine), aimed at increasing dopamine concentration, could potentially contribute to the development of melanoma. The role and properties of melanins should continue to be researched. Whether excessive melanin synthesis or its accumulation in the extracellular space may be factors initiating the development of diseases remains an open question.

Can Bee Venom Be Used as Anticancer Agent in Modern Medicine?

Honey bee venom in its composition contains many biologically active peptides and enzymes that are effective in the fight against diseases of various etiologies. The history of the use of bee venom for medicinal purposes dates back thousands of years. There are many reports in the literature on the pharmacological properties of bee venom and/or its main components, e.g., anti-arthritic, anti-inflammatory, anti-microbial or neuroprotective properties. In addition, both crude venom and melittin exhibit cytotoxic activity against a wide range of tumor cells, with significant anti-metastatic activity in pre-clinical studies. Due to the constantly increasing incidence of cancer, the development of new therapeutic strategies in oncology is a particular challenge for modern medicine. A review paper discusses the various properties of bee venom with an emphasis on its anticancer properties. For this purpose, the PubMed database was searched, and publications related to "bee", "venom", "cancer" from the last 10 years were selected.

Insight into Glutamatergic Involvement in Rewarding Effects of Mephedrone in Rats: In Vivo and Ex Vivo Study.

Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.

Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases.

BACKGROUND: There is a growing evidence that matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinases) play an important role in the pathogenesis of numerous disorders, especially with inflammatory etiology and extracellular matrix (ECM) remodeling. Despite the fact that gelatinases involve in liver cirrhosis is provided in the literature, their role in the pathogenesis of chronic pancreatitis and non-specific inflammatory bowel diseases is still under investigation. DATA SOURCES: We carried out a PubMed search of English-language articles relevant to the involvement of gelatinases in the pathogenesis of liver fibrosis, pancreatitis, and non-specific inflammatory bowel diseases. RESULTS: The decreased activity of gelatinases, especially MMP-2, is related to the development of liver fibrosis, probably due to the decrease of capability for ECM remodeling. Similar situation can be found in chronic pancreatitis; however, reports on this matter are rare. The presence of non-specific inflammatory bowel diseases results in MMP-9 activity elevation. CONCLUSION: The fluctuation of gelatinases activity during liver fibrosis, chronic pancreatitis and non-specific inflammatory bowel diseases is observed, but the exact role of these enzymes demands further studies.

The significance of matrix metalloproteinase (MMP)-2 and MMP-9 in the ischemic stroke.

There is a continuous urgent need to explore the pathogenesis and biochemical changes within the infarcted area during acute ischemic stroke (IS). Matrix metalloproteinases (MMPs), prevailing extracellular endopeptideses, can digest proteins located extracellulary, e.g. collagen, proteoglycans, elastin or fibronectin. Among MMPs, gelatinases (MMP-2 and MMP-9) are the most investigated enzymes. Gelatinases possess the ability to active numerous pro-inflammatory agents as chemokine CXCL-8, interleukin 1ß or tumor necrosis factor α. Moreover, due to digestion of collagen type IV (the component of basal membranes) and tight junction proteins (TJPs) they facilitate to cross the endothelium by leukocytes. Due to the significant role of gelatinases during brain ischemia, their selective inhibition seems to be an interesting kind of treatment of acute stroke. The synthetic inhibitors of gelatineses decrease the infarct volume in animal models of IS. In clinical practice statins, the lipid-lowering drugs possess the ability to inhibit the activity of MMP-9 during acute IS. This review briefly provides the most important information about the involvement of MMP-2 and MMP-9 in the pathogenesis of brain ischemia.