(1) Background: Poly(ADP-ribose) polymerase 1) (PARP1) is a pleiotropic enzyme involved in several cellular processes, e.g., DNA damage repair, regulation of mitosis, and immune response. Little is known about the role of PARP1 in melanoma development and progression. We aimed to investigate the prognostic significance of PARP1 expression in cutaneous melanoma through evaluation of mRNA and protein levels of PARP1 in normal melanocytes and melanoma cell lines, as well as in patients’ tissue material from surgical resections. (2) Methods: An in vitro model was based on two types of normal human melanocytes (HEMn-DP and HEMn-LP) and four melanoma cell lines (A375, WM1341D, Hs294T, and WM9). PARP1 mRNA gene expression was estimated using real-time polymerase chain reaction (RT-PCR), whereas the protein level of PARP1 was evaluated by fluorescence confocal microscopy and then confirmed by Western Blotting analysis. The expression of PARP1 was also assessed by immunohistochemistry in formalin-fixed paraffin-embedded tissues of 128 primary cutaneous melanoma patients and correlated with follow-up and clinicopathologic features. (3) Results: The in vitro study showed that melanoma cells exhibited significantly higher PARP1 expression at mRNA and protein levels than normal melanocytes. High PARP1 expression was also associated with the invasiveness of tumor cells. Elevated nuclear PARP1 expression in patients without nodal metastases strongly correlated with significantly shorter disease-free survival (p = 0.0015) and revealed a trend with shorter cancer-specific overall survival (p = 0.05). High PARP1 immunoreactivity in the lymph node-negative group of patients was significantly associated with higher Breslow tumor thickness, presence of ulceration, and a higher mitotic index (p = 0.0016, p = 0.023, and p < 0.001, respectively). In patients with nodal metastases, high PARP1 expression significantly correlated with the presence of microsatellitosis (p = 0.034), but we did not confirm the prognostic significance of PARP1 expression in these patients. In the entire analyzed group of patients (with and without nodal metastases at the time of diagnosis), PARP1 expression was associated with a high mitotic index (p = 0.001) and the presence of ulceration (p = 0.036). Moreover, in patients with elevated PARP1 expression, melanoma was more frequently located in the skin of the head and neck region (p = 0.015). In multivariate analysis, high PARP1 expression was an independent unfavorable prognosticator in lymph node-negative cutaneous melanoma patients. (4) Conclusions: In vitro molecular biology approaches demonstrated enhanced PARP1 expression in cutaneous melanoma. These results were confirmed by the immunohistochemical study with clinical parameter analysis, which showed that a high level of PARP1 correlated with unfavorable clinical outcome. These observations raise the potential role of PARP1 inhibitor-based therapy in cutaneous melanoma.

Background: The endocannabinoid system (ECS) is composed of cannabinoid receptors type 1 (CBR1) and type 2 (CBR2), cannabinoid-based ligands (endogenous chemically synthesized phytocannabinoids), and endogenous enzymes controlling their concentrations. Cannabinoid receptors (CBRs) have been identified in invertebrates and in almost all vertebrate species in the central and peripheral nervous system as well as in immune cells, where they control neuroimmune homeostasis. In humans, rodents, dogs, and cats, CBRs expression has been confirmed in the skin, and their expression and tissue distribution become disordered in pathological conditions. Cannabinoid receptors may be a possible therapeutic target in skin diseases. Objectives: To characterize the distribution and cellular expression of CBRs in the skin of horses under normal conditions. Animals: Fifteen healthy horses. Methods: Using full-thickness skin punch biopsy samples, skin-derived primary epidermal keratinocytes and dermal-derived cells, we performed analysis of Cnr1 and Cnr2 genes using real-time PCR and CBR1 and CBR2 protein expression by confocal microscopy and Western blotting. Results: Normal equine skin, including equine epidermal keratinocytes and dermal fibroblast-like cells, all exhibited constant gene and protein expression of CBRs. Conclusions and Clinical Importance: Our results represent a starting point for developing and translating new veterinary medicine-based pharmacotherapies using ECS as a possible target.

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, affecting approximately 1 of the total global population. Curcumin, a natural polyphenol is a substance that could potentially mitigate the course of this disease. To evaluate curcumins anti-inflammatory impact on synoviocytes in the RA model, a set of experiments was conducted on SW982 cells, stimulated by IL-1β, IL-6, or TNF-α to emulate inflammation. During the research, the curcumin effect was evaluated by measuring cell survivability, expression of MMP1 gene, subcellular localization of P70S6K1 protein, and its phosphorylated form and amount of produced IL-6 and TNF-α. Results of conducted experiments presented a positive impact of curcumin on synoviocytes in the RA model, by reducing SW982 cells survivability, decreasing levels of MMP1 gene expression and TNF-α protein production, which altogether confirm beneficial effects of the curcumin therapy in a RA in vitro model.

The endocannabinoid system (ECS) is a complex neuromodulatory network involved in maintaining physiological balance through interactions with various neurotransmitter and hormonal pathways. Its key components—cannabinoid receptors (CBRs)—are activated by endogenous ligands and exogenous cannabinoids such as those found in the Cannabis sativa plant. Although cannabinoids like cannabidiol (CBD) have garnered interest for their potential therapeutic effects, evidence regarding their safety, particularly for reproductive health, remains limited. This review summarizes the structure and molecular mechanisms of the ECS, its role in reproductive physiology—including its interactions with the hypothalamic–pituitary–gonadal axis (HPG axis), gametogenesis, implantation, and lactation—and the possible consequences of cannabinoid exposure for fertility. In addition, we focus on the involvement of the ECS and cannabinoids in breast cancer, highlighting emerging evidence on their dual role in tumor progression and therapy. These insights emphasize the need for further research to better define the therapeutic potential and risks associated with cannabinoid use in reproductive health and breast cancer.

Psoriasis, a chronic immune-mediated skin disorder affecting over 125 million people globally, is characterized by abnormal keratinocyte proliferation and immune cell infiltration. Photodynamic therapy (PDT) remains underutilized in the treatment of psoriasis despite its potential as a promising and effective therapeutic approach. This study aimed to explore the efficacy of zinc phthalocyanine (ZnPc) and its sugar conjugates as potential antipsoriatic agents. We successfully synthesized protected and unprotected sugar-conjugated zinc phthalocyanines and evaluated their potential against cytokine-stimulated HaCaT keratinocytes, as well as an established IMQ psoriasis-like in vivo model. Tetrasubstituted protected glucose–ZnPc (Glu-4-ZnPc-P) demonstrated superior phototoxicity (IC50 = 2.55 µM) compared to unprotected glucose conjugate (IC50 = 22.7 µM), protected galactose–ZnPc (IC50 = 7.13 µM), and free ZnPc in cytokine-stimulated HaCaT cells (IC50 = 5.84 µM). Cellular uptake analysis revealed that IL-17A, a cytokine that plays a central role in the pathogenesis of psoriasis, enhanced unprotected Glu-4-ZnPc uptake by 56.3%, while GLUT1 inhibitor BAY-876 reduced its accumulation by 23.8%. Intracellular ROS generation following Glu-4-ZnPc-P-PDT was significantly increased after stimulation with IL-17A, correlating with in vitro photocytotoxicity. In vivo PDT using Glu-4-ZnPc-P exhibited significant improvement in Psoriasis Area and Severity Index (PASI), inhibiting splenomegaly and restoring normal skin morphology. This study highlights sugar-conjugated zinc phthalocyanines as potential candidates for targeted PDT in psoriasis, providing a basis for further clinical investigations.