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Melanoma occurs in various forms and body areas, not only in the cutis, but also in mucous membranes and the uvea. Rarer subtypes of that cancer differ in genomic aberrations, which cause their minor sensibility to regular cutaneous melanoma therapies. Therefore, it is essential to discover new strategies for treating rare forms of melanoma. In recent years, interest in applying CDK inhibitors (CDKIs) in cancer therapy has grown, as they are able to arrest the cell cycle and inhibit cell proliferation. Current studies highlight selective CDK4/6 inhibitors, like palbociclib or abemaciclib, as a very promising therapeutic option, since they were accepted by the FDA for advanced breast cancer treatment. However, cells of every subtype of melanoma do not react to CDKIs the same way, which is partly because of the genetic differences between them. Herein, we discuss the past and current research relevant to targeting various CDKs in mucosal, uveal and acral melanomas. We also briefly describe the issue of amelanotic and desmoplastic types of melanoma and the need to do more research to discover cell cycle dysregulations, which cause the growth of the mentioned forms of cancer.

Many studies have proven the involvement of the RhoA/ROCK pathway in autoimmune and cardiovascular diseases and the beneficial effects of its downregulation. Here, we examined whether the effect of simvastatin on experimental autoimmune myocarditis (EAM) may be through targeting the Ras homolog family member A/Rho-associated coiled-coil containing kinases (RhoA/ROCK) pathway and whether previously shown downregulation of metalloproteinase 9 (MMP-9) could be associated with MLC phosphorylation. Two doses of simvastatin were administered to experimental rats with autoimmune myocarditis by gastric gavage for 3 weeks, at the stage of development of the inflammatory process. Immunohistochemical staining for RhoA and ROCK1 was evaluated semi-quantitatively with H-score. The RhoA staining showed no significant differences in expression between the groups, but the ROCK1 expression was significantly upregulated in the hearts of the EAM group and was not downregulated by simvastatin. The Western blotting analysis of the last downstream product of the RhoA/ROCK axis, phosphorylated myosin light chain (phospho-MYL9), revealed that protein content increased in EAM hearts and it was prevented by the highest dose of simvastatin. Our findings suggest that the RhoA/ROCK pathway is upregulated in EAM, and simvastatin in EAM settings inhibits the RhoA/ROCK pathway at the stage of phosphorylation of myosin light chains and provides a new insight into the molecular pathology of autoimmune myocarditis.

Melanoma occurs in various forms and body areas, not only in the cutis, but also in mucous membranes and the uvea. Rarer subtypes of that cancer differ in genomic aberrations, which cause their minor sensibility to regular cutaneous melanoma therapies. Therefore, it is essential to discover new strategies for treating rare forms of melanoma. In recent years, interest in applying CDK inhibitors (CDKIs) in cancer therapy has grown, as they are able to arrest the cell cycle and inhibit cell proliferation. Current studies highlight selective CDK4/6 inhibitors, like palbociclib or abemaciclib, as a very promising therapeutic option, since they were accepted by the FDA for advanced breast cancer treatment. However, cells of every subtype of melanoma do not react to CDKIs the same way, which is partly because of the genetic differences between them. Herein, we discuss the past and current research relevant to targeting various CDKs in mucosal, uveal and acral melanomas. We also briefly describe the issue of amelanotic and desmoplastic types of melanoma and the need to do more research to discover cell cycle dysregulations, which cause the growth of the mentioned forms of cancer. [ABSTRACT FROM AUTHOR]

Glial cells are indispensable components of the peripheral nervous system (PNS), exerting diverse regulatory functions crucial for neuronal health and function. From myelination and synaptic modulation to immune regulation, glia actively participates in maintaining PNS homeostasis and responding to pathological insults. Further elucidating the roles of glial cells in peripheral nerve disorders holds promise for developing targeted therapeutic interventions to alleviate symptoms and improve patient outcomes. This article reviews the multifaceted functions of PNS glia in shaping nervous system function and their intricate involvement in various neuropathologies, including peripheral neuropathies, neuroinflammatory conditions, and gastrointestinal disorders. Understanding the underlying mechanisms of glial dysfunction offers opportunities for developing targeted therapeutic interventions aimed at preserving nerve function, attenuating neuroinflammation, and restoring gastrointestinal homeostasis. The expanding research on PNS glia underscores their indispensable roles and highlights the potential of therapeutic strategies targeting glial dysfunction in revolutionizing the management of nervous system disorders, offering hope for improved patient outcomes and quality of life.