The importance of the differences in immunoglobulin levels specific for melanin and tyrosinase in antitumor immunity in patients with melanoma

Melanom je visoko imunogeno maligno oboljenje. Melanomski antigeni imaju sposobnost imunizacije i stimulacije sinteze specifičnih antitela. Antitela specifična za iste, melanomske antigene, koji su prisutni kako na neoplastično transformisanim, tako i na neizmenjenim melanocitima, pronađeni su i kod bolesnika sa vitiligom. Pojava hipopigmentacija sličnih vitiligu kod bolesnika sa melanomom utiče na bolju prognozu preživljavanja, što ukazuje na značaj veze između tumorske imunosti i autoimunosti kod ovih bolesnika. Ćelije melanoma karakteriše povećano prisustvo melanina i tirozinaze, a u serumu bolesnika sa metastatskim melanomom uočena je tirozinazna aktivnost. Dipeptidil peptidaza IV (DPPIV/CD26) je transmembranski glikoprotein koji se eksprimira na površini limfocita, i predstavlja važan marker aktivacije ćelija imunskog sistema. Upravo su limfociti jedan od najznačajnijih izvora solubilne forme ovog proteina u serumu. DPPIV ima značajnu ulogu u regulaciji imunskih funkcija i procesu neoplastične transformacije. Osnovni cilj ovog istraživanja je bio da se ispitaju razlike u nivoima IgG, IgA i IgM klasa antitela specifičnih za melanin i tirozinazu u bolesnika sa melanomom u odnosu na bolesnike sa vitiligom i zdrave osobe. Od značaja je bilo i da se ispita postojanje razlika u humoralnom imunskom odgovoru između bolesnika sa melanomom bez metastaza i bolesnika sa melanomom i metastazama. S ciljem dodatne karakterizacije imunskog odgovora, određivan je procenat CD16+ i CD16+CD56+ limfocita, i CD89+ granulocita kod bolesnika sa melanomom, kao i bolesnika sa vitiligom i zdravih osoba, a zatim je ispitivana povezanost nivoa antitela i CD16/CD89+ ćelija u grupi bolesnika sa melanomom...Melanoma is a highly immunogenic malignancy. Melanoma antigens are capable of immunization and stimulation of the synthesis of specific antibodies. Antibodies specific for same, melanoma antigens, which are present both on the neoplastically transformed, as well as on the non-transformed melanocytes, were also found in patients with vitiligo. The presence of vitiligo-like hypopigmentations in patients with melanoma is associated with a better survival prognosis, indicating the importance of the link between tumor immunity and autoimmunity. The increased presence of melanin and tyrosinase is characteristic of melanoma cells, while the tyrosinase activity was observed in the sera of patients with metastatic melanoma. Dipeptidyl peptidase IV (DPPIV/CD26) is a transmembrane glycoprotein which is expressed on the surface of lymphocytes, and represents an important marker of activation of immune system cells. Lymphocytes represent one of the major sources of soluble form of this protein in the serum. DPPIV is implicated in the regulation of immune functions and neoplastic transformation. The main goal of this study was to examine the differences in the levels of IgG, IgA and IgM classes of antibodies specific for melanin and tyrosinase in patients with melanoma, compared with the group of patients with vitiligo and the group of healthy individuals. The examination of the presence of differences in the humoral immune response between patients with melanoma without metastases and patients with melanoma and metastases was also significant for our research. To further characterize the immune response, it was important to determine the percentage of CD16+ and CD16+CD56+ lymphocytes and CD89+ granulocytes in patients with melanoma, as well as patients with vitiligo and healthy persons, and also to investigate the connection between the levels of antibodies and CD16/CD89+ cells in the group of patients with melanoma..

Barks of Three Wild Pyrus Taxa: Phenolic Constituents, Antioxidant Activity, and in Vitro and in Silico Investigations of α-Amylase and α-Glucosidase Inhibition

Dry MeOH extracts of the twig barks of Pyrus communis subsp. pyraster, P. spinosa and their hybrid P.×jordanovii nothosubsp. velenovskyi, collected in wild in Serbia, were analyzed. By LC/MS, the contents of arbutin (99.9–131.0 mg/g), chlorogenic acid (2.2–6.3 mg/g), catechin (1.0–5.3 mg/g) and total dimeric and trimeric procyanidins (42.2–61.3 mg/g), including procyanidin B2 (8.9–17.2 mg/g), were determined. Colorimetri- cally, high contents of total phenolics (436.2–533.4 mg GAE/g) and tannins (339.4–425.7 mg GAE/g), as well as strong total antioxidant activities (FRAP values 4.5–5.9 mmol Fe2+ /g), and DPPH (SC50 = 6.6–7.1 μg/ml) and hydroxyl radical (SC50 = 447.1–727.7 μg/ml) scavenging abilities were revealed. In vitro, all extracts exhibited notable inhibition of α-amylase (IC50 = 310.8–617.7 μg/ml) and particularly strong inhibition of α-glucosidase (IC50 = 2.1–3.7 μg/ml). Molecular docking predicted that among identified compounds procyanidin B2 is the best inhibitor of these carbohydrate-digesting enzymes. Obtained results showed that the barks of investigated Pyrus hybrid and its parent taxa have similar composition and bioactivity