Parasitic diseases, caused by intestinal helminths, remain a very serious problem in both human and veterinary medicine. While searching for new nematicides we examined a series of 1,2,4-triazole derivatives 9–22, obtained during reactions of N³-substituted amidrazones with itaconic anhydride. Two groups of compounds, 9–16 and 17–22, differed in the position of the double bond on the methacrylic acid moiety. The toxicity of derivatives 9–22 and the anti-inflammatory activity of 12 and 19–22 were studied on peripheral blood mononuclear cells (PBMC). Antiproliferative activity of compounds 12 and 19–22 was tested cytometrically in PBMC cultures stimulated by phytohemagglutinin. The influence of derivatives 12 and 19–22 on the TNF-α, IL-6, IL-10 and IFN-γ production was determined by ELISA in lipopolysaccharide-stimulated PBMC cultures. Anthelmintic activity of compounds 10–22 was studied in the Rhabditis sp. nematodes model. Most compounds (11–22) proved to be non-toxic to human PBMC. Derivatives 19–22 showed anti-inflammatory activity by inhibiting the proliferation of lymphocytes. Moreover, compounds 12 and 19–22 significantly reduced the production of TNF-α and derivatives 19–21 decreased the level of INF-γ. The strongest anti-inflammatory activity was observed for compound 21. Compounds 12 and 14 demonstrated anthelmintic activity higher than albendazole and may become promising candidates for anthelmintic drugs.

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Heme is a ubiquitous compound of human tissues, and it is involved in cellular physiology and metabolism. Once released from the cell, free heme oxidizes to the ferric state (hemin). High levels of hemin can cause oxidative stress and inflammation if not neutralized immediately by specialized scavenger proteins. Human alpha1-antitrypsin (A1AT), an acute-phase glycoprotein and important inhibitor of neutrophil proteases, is also a hemin-binding protein. A short-term exposure of freshly isolated human blood neutrophils to 4 µM hemin results in cell spreading, surface expression of filament protein, vimentin, free radical production, expression of heme oxygenase-1 (HO-1), release of IL-8, and enhanced neutrophil adhesion to human endothelial cells. Consequently, the phosphorylation of protein kinase C (PKC) occurs after 25 min. Under the same experimental conditions, addition of 1 mg/ml A1AT markedly reduces or abolishes neutrophil-activating effects of hemin and prevents PKC phosphorylation. In a mouse model of acute kidney injury (AKI) plus injection of hemin, monotherapy with 4 mg/mouse A1AT significantly lowered serum levels of free hemin at 2 h after surgery. Moreover, a tendency toward lower AKI scores, reduced infiltration of neutrophils, and lower levels of serum chemokine [CXCL1/keratinocyte-derived chemokine (KC)] was observed. Our findings highlight A1AT as a potential serum scavenger of hemin and suggest that the commercial preparations of human plasma A1AT might prove to be useful therapeutics in conditions associated with hemolysis.

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC₅₀ (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022. A total of 41 articles based on 56 in vitro experiments met our eligibility criteria. Using a meta-analysis based on a random effect model, we evaluated the cytotoxicity of cisplatin (IC₅₀) after 48- or 72-h cell exposure. We found large differences between studies using a particular cell line. According to the random effect model, the 95% confidence intervals for IC₅₀ were extremely wide. The heterogeneity of cisplatin IC₅₀, as measured by the I² index for all cancer cell lines, was over 99.7% at culture times of 48 or 72 h. Therefore, the variability between studies is due to experimental heterogeneity rather than chance. Despite the higher IC₅₀ values after 48 h than after 72 h, the heterogeneity between the two culture periods did not differ significantly. This indicates that the duration of cultivation is not the main cause of heterogeneity. Therefore, the available data is diverse and not useful as a reference. We discuss possible reasons for the IC₅₀ heterogeneity and advise researchers to conduct preliminary testing before starting experiments and not to solely rely on the published data. We hope that this systematic meta-analysis will provide valuable information for researchers searching for new cancer drugs using cisplatin as a reference drug.

Depression is highly prevalent in COPD patients, and both diseases are believed to be associated with inflammation. The aim of this study was to elucidate the role of the immune system alterations in pathogenesis of depression in COPD patients. Blood was collected from patients diagnosed with chronic obstructive pulmonary disease and comorbid depressive symptoms [COPD + DS, (N = 13)], from individuals with either COPD (N = 16) or recurrent depressive disorder (rDD) alone (N = 15), and from healthy controls (N = 19). Surface phenotype expression of T regulatory and T effector cells was analyzed with a flow cytometry, and IL-2, IL-6, IL-8, IFN-γ, IL-17, and neopterin were detected with ELISA. We demonstrated that COPD, depression, and COPD with comorbid depression are associated with increased IL-6 levels when compared with healthy controls 42.2 ± 1.87, 40.9 ± 2.12, 41.7 ± 1.31, and 33.2 ± 1.23 pg/ml, respectively (p < 0.05). A significant increase in neopterin levels was observed both in rDD and COPD patients when compared with controls (15.69 ± 0.095, 13.98 ± 0.887 vs. 9.22 ± 0.466 nmol/l, p < 0.001 and p < 0.05, respectively). Concentrations of IFN-γ were significantly increased in COPD + DS patients when compared with controls (24.3 ± 1.49 and 17.8 ± 0.70 pg/ml, respectively, p < 0.05). IL-2 levels were highest in COPD + DS (3.20 ± 0.389 pg/ml) and differed significantly when this group was compared with controls (2.20 ± 0.184 pg/ml), p ≤ 0.05). In this study, we demonstrated for the first time that depressive symptoms in COPD patients may be related to inflammatory state as confirmed by increased levels of IL-6 both in COPD and depression and also in COPD with comorbid depressive symptoms, despite the fact that the patients were treated with anti-inflammatory drugs and/or antidepressants. We also identified IFN-γ and IL-2 as putative inflammatory agents associated with depressive symptoms in COPD patients. Prospective studies will need to confirm whether measuring IL-2 and IFN-γ can identify COPD patients at risk of depression. These findings suggest that T helper cell 1-derived cellular immune activation may play significant role in developing depressive symptoms in COPD patients.