The proper regeneration of vessel anastomoses in microvascular surgery is crucial for surgical safety. Pituitary adenylate cyclase-activating polypeptide (PACAP) can aid healing by decreasing inflammation, apoptosis and oxidative stress. In addition to hematological and hemorheological tests, we examined the biomechanical and histological features of vascular anastomoses with or without PACAP addition and/or using a hemostatic sponge (HS). End-to-end anastomoses were established on the right femoral arteries of rats. On the 21st postoperative day, femoral arteries were surgically removed for evaluation of tensile strength and for histological and molecular biological examination. Effects of PACAP were also investigated in tissue culture in vitro to avoid the effects of PACAP degrading enzymes. Surgical trauma and PACAP absorption altered laboratory parameters; most notably, the erythrocyte deformability decreased. Arterial wall thickness showed a reduction in the presence of HS, which was compensated by PACAP in both the tunica media and adventitia in vivo. The administration of PACAP elevated these parameters in vitro. In conclusion, the application of the neuropeptide augmented elastin expression while HS reduced it, but no significant alterations were detected in collagen type I expression. Elasticity and tensile strength increased in the PACAP group, while it decreased in the HS decreased. Their combined use was beneficial for vascular regeneration.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that plays significant regulatory roles in the differentiation of the central nervous system and peripheral organs. A lack of the neuropeptide can lead to abnormalities in long bone development. In callus formation, a possible signaling balance shift in PACAP KO mice has been demonstrated, but Notch signalization, with its potential connection with PACAP 1-38, has not been investigated in ossification. Our main goal was to show connections between PACAP and Notch signaling in osteogenesis. Notch signalization showed an elevation in the long bones of PACAP-gene-deficient mice, and it was also elevated during the PACAP 1-38 treatment of UMR-106 and MC3T3-E1 osteogenic cells. Moreover, the inhibition of Notch signaling was compensated by the addition of PACAP 1-38 in vitro. The inorganic and organic matrix production of UMR-106 cells was increased during PACAP 1-38 treatment under the inhibition of Notch signaling. As a possible common target, the expression and nuclear translocation of NFATc1 transcription factor was increased during the disturbance of PACAP and Notch signaling. Our results indicate a possible synergistic regulation during bone formation by PACAP and Notch signalization. The crosstalk between Notch and PACAP signaling pathways highlights the complexity of bone development and homeostasis.

Systemic sclerosis (SSc) is a complex autoimmune disease characterized by fibrosis, immune dysregulation, and vascular dysfunction, yet its pathogenesis remains incompletely understood. This study compares two widely used animal models of SSc—the bleomycin-induced fibrosis model and the collagen-V-induced autoimmune model—to evaluate their ability to replicate key disease features. In the bleomycin model, consistent cardiac fibrosis was observed across treatment groups despite variability in fibrosis in the skin and lungs, suggesting organ-specific differences in susceptibility. The collagen-V model demonstrated robust autoantibody production against collagen-V, confirming its utility in studying immune activation, though fibrosis was largely confined to the heart. While the bleomycin model excels at mimicking rapid fibrosis and is suitable for testing antifibrotic therapies, the collagen-V model provides insights into antigen-specific autoimmunity. Both models highlight the dynamic nature of fibrosis, where ECM deposition and degradation occur concurrently, complicating its use as a quantitative disease marker. Cardiac fibrosis emerged as a consistent feature in both models, emphasizing its relevance in SSc pathophysiology. Combining these models or refining their design through hybrid approaches, extended timelines, or sex and age adjustments could enhance their translational utility. These findings advance understanding of SSc mechanisms and inform therapeutic development for this challenging disease.

Background/Objectives: To prevent flap failure, adequate tissue perfusion and effective regenerative processes, undisturbed wound healing are essential, among others. To improve wound healing, various locally and systematically administered pharmacons can be used. This study investigated the effect of PACAP 1-38 (pituitary adenylate cyclase activating polypeptide) and BGP-15 (a nicotinic amidoxime derivative) on the healing of epigastric fasciocutaneous flaps exposed to ischemia–reperfusion (I/R). Methods: Wistar rats were randomly divided into control (no substance), PACAP 1-38, and BGP-15 groups. Groin flaps were prepared bilaterally. The left flap was exposed to 120 min of ischemia prior to suturing it back. We applied wound gels containing substances. Laboratory tests (hematology, erythrocyte deformability, and aggregation) were performed before surgery on the 1st, 3rd, and 7th postoperative days. Lastly, flap skin samples were taken for histological and tensile strength measurements. Results: Impaired erythrocyte deformability and enhanced aggregation were found because of flap I/R. The pharmacons were able to reduce the systemic micro-rheological impairment to varying degrees. The tensile strength increased in the areas of better perfusion. Conclusions: The anti-inflammatory effects of PACAP 1-38 and BPG-15, as well as the impact of PACAP 1-38 on collagen and elastic fiber composition, have been demonstrated.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a small neuropeptide detected first in the hypothalamo–hypophyseal system; recently, it has also been identified in peripheral organs and in tumours. It is well demonstrated that PACAP exerts cell- and tissue-protecting effects in various stressful conditions and helps to maintain tissue homeostasis. In melanoma, the anti-invasive effect of PACAP has been demonstrated; however, there is also existing sporadic data which proves PACAP plays a role in melanoma progression. The major goal of our study was to investigate the signalling targets of PACAP in A2058 and WM35 melanoma cell lines in vitro. Various molecular players of melanocyte differentiation and function responded to PACAP application. SOX9 expression increased while SOX10 expression decreased and CREB signalling did not change. The expression level of TYRP1 decreased, while DCT elevated, and MITF expression showed changes at the mRNA level and in its subcellular localisation. In contrast, the amount of hyaluronan (HA) and expressions of its synthases, as well as RHAMM, increased, indicating the role of PACAP in secretion of an HA-rich matrix. In parallel with these results, we detected elevated hyaluronidase2 (Hyal2) expression in the presence of PACAP. On the other hand, alfaV and beta3 integrin expressions did not alter significantly. Our results demonstrate that exogenous PACAP modulates the expression of multiple target molecules in melanoma cells. Some of the significantly responding molecules take part in hyaluronan homeostasis, suggesting an effect of PACAP on tumour matrix composition, through which it can modulate invasiveness of melanoma cells.