Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn₃O₄ NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn₃O₄ NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn₃O₄ NPs was accompanied by Ca²⁺ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn₃O₄ NP-induced eryptosis was calpain- and caspase-dependent.

Eryptosis is a type of regulated cell death of mature erythrocytes characterized by excessive Ca²⁺ accumulation followed by phosphatidylserine externalization. Eryptosis facilitates erythrophagocytosis resulting in eradication of damaged erythrocytes, which maintains the population of healthy erythrocytes in blood. Over recent years, a wide array of diseases has been reported to be linked to accelerated eryptosis, which leads to anemia. A growing number of studies furnish evidence that eryptosis is implicated in the pathogenesis of liver diseases. Herein, we summarize the current knowledge of eryptosis signaling, its physiological role, and the impact of eryptosis on anemia and hypercoagulation. In this article, upon systemically analyzing the PubMed-indexed publications, we also provide a comprehensive overview of the role of eryptosis in the spectrum of hepatic diseases, its contribution to the development of complications in liver pathology, metabolites (bilirubin, bile acids, etc.) that might trigger eryptosis in liver diseases, and eryptosis-inducing liver disease medications. Eryptosis in liver diseases contributes to anemia, hypercoagulation, and endothelial damage (via ferroptosis of endothelial cells). Treatment-associated anemia in liver diseases might be at least partly attributed to drug-induced eryptosis. Ultimately, we analyze the concept of inhibiting eryptosis pharmaceutically to prevent eryptosis-associated anemia and thrombosis in liver diseases.

A compelling body of evidence links pesticide exposure to human diseases. The liver plays a central role in the detoxification of pesticides, suggesting intense pesticide–liver cell interactions. A growing body of studies highlighted in this review supports the contribution of pesticides of various chemical classes to the development of non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), liver cirrhosis, viral hepatitis, hepatocellular carcinoma, etc., via disrupting lipid and carbohydrate metabolism and redox homeostasis, promoting endoplasmic reticulum stress and mitochondrial dysfunction, as well as stimulating apoptosis, fibrosis, and inflammation. In this review, we systematically illustrated an underappreciated mechanism of pesticide-induced overall and hepatic toxicity, i.e., the ability to induce non-apoptotic regulated cell death (RCD) pathways such as ferroptosis, necroptosis, and pyroptosis. Our analysis indicates that pesticides are implicated in driving liver diseases by inducing ferroptosis, necroptosis, and pyroptosis. Non-apoptotic RCDs mediate pesticide-induced liver steatosis and fibrosis. Furthermore, these cell death modalities fuel inflammation through the promotion of pro-inflammatory cytokine production and the generation of damage-associated molecular patterns. Understanding of deeper mechanisms of pesticide-induced effects on the non-apoptotic cell death machinery and subsequent immunogenic effects in liver pathology might help develop novel preventive strategies to reduce liver damage.

Introduction: Post-COVID syndrome, also known as long COVID, has emerged as a major public health concern, affecting a substantial proportion of individuals recovering from SARS-CoV-2 infection. This condition is characterized by persistent symptoms lasting at least 2 months after acute infection, significantly impacting quality of life and increasing healthcare burdens. In Kazakhstan, the recognition of post- COVID syndrome in national clinical protocols highlights the need for effective prevention and management strategies. Vaccination has been suggested as a key intervention to reduce the severity and prevalence of long COVID symptoms, yet data on its effectiveness, particularly for the domestic QazVac vaccine, remain limited. The aim of this study is to investigate the impact of vaccination with the domestic QazVac vaccine on the features of humoral and cellular immunity in patients with post-COVID conditions and to identify the leading clinical variants of the course.Methods: We analyzed data from 90 vaccinated and 217 non-vaccinated patients, examining sex, age, smoking status, BMI, comorbidities, and clinical manifestations.Results: There were no significant differences between the groups with regard to sex, age, and smoking status. However, the characteristics of the subjects indicated that vaccination was correlated with a lower prevalence of diabetes mellitus (2.2% vs. 11.1%, p = 0.011) and cardiovascular diseases (0.0% vs. 10.1%, p = 0.047), and a higher prevalence of hypertension among non-vaccinated subjects. With regard to clinical symptoms, vaccinated individuals presented a significantly decreased frequency of neurological (51.1% vs. 74.2%, p = 0.001), gastrointestinal (4.4% vs. 15.2%, p = 0.008), respiratory (21.1% vs. 36.4%, p = 0.009), rheumatological symptoms (26.7% vs. 38.7%, p = 0.044), and kidney symptoms (2.2% vs. 9.7%, p = 0.024). In contrast, unvaccinated participants had more memory loss (49.8% vs. 22.2%, p < 0.001), depression (31.3% vs. 6.7%, p < 0.001), joint pain (33.2% vs. 14.4%, p = 0.001), and other psychopathological symptoms.Discussion: A sharp decrease in the frequency of neurological, gastrointestinal, respiratory, and rheumatological symptoms was recorded in vaccinated patients, advocating for the protective role of vaccination against long COVID-19 sequelae. These findings highlight the potential for vaccination to mitigate the burden of post-COVID complications across various organ systems.

Chronic hepatitis B virus (HBV) infection is a significant cause of progressive liver disease and cirrhosis, often accompanied by hematological complications, including anemia. Evidence increasingly indicates that eryptosis—the programmed death of erythrocytes—may play a role in disrupting red blood cell balance in chronic liver conditions. Eryptosis is characterized by phosphatidylserine externalization, intracellular calcium accumulation, oxidative stress, and ceramide-dependent signaling pathways. Entecavir, a highly effective antiviral medication, is used to consistently suppress HBV replication in patients with chronic hepatitis B and HBV-related cirrhosis. Entecavir-induced viral suppression is associated with improved hepatic function, biochemical markers, and clinical outcomes. However, direct evidence on the effects of HBV suppression on red blood cell survival, eryptosis, and anemia is lacking. In this review, we summarize current knowledge of eryptosis in HBV-related liver cirrhosis, focusing on its molecular mechanisms, biomarkers, and potential role in anemia. We also review the documented effects of entecavir on virological, biochemical, and hematologic parameters, and discuss possible indirect links between viral suppression, restored hepatic function, and erythrocyte homeostasis. Direct evidence linking entecavir therapy to changes in eryptosis remains scarce, underscoring the need for prospective clinical and experimental studies.