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Background Increasing evidence suggests a double-faceted role of alpha-synuclein (α-syn) following infection by a variety of viruses, including SARS-CoV-2. Although α-syn accumulation is known to contribute to cell toxicity and the development and/or exacerbation of neuropathological manifestations, it is also a key to sustaining anti-viral innate immunity. Consistently with α-syn aggregation as a hallmark of Parkinson's disease, most studies investigating the biological function of α-syn focused on neural cells, while reports on the role of α-syn in periphery are limited, especially in SARS-CoV-2 infection. Results Results herein obtained by real time qPCR, immunofluorescence and western blot indicate that α-syn upregulation in peripheral cells occurs as a Type-I Interferon (IFN)-related response against SARS-CoV-2 infection. Noteworthy, this effect mostly involves α-syn multimers, and the dynamic α-syn multimer:monomer ratio. Administration of excess α-syn monomers promoted SARS-CoV-2 replication along with downregulation of IFN-Stimulated Genes (ISGs) in epithelial lung cells, which was associated with reduced α-syn multimers and α-syn multimer:monomer ratio. These effects were prevented by combined administration of IFN-β, which hindered virus replication and upregulated ISGs, meanwhile increasing both α-syn multimers and α-syn multimer:monomer ratio in the absence of cell toxicity. Finally, in endothelial cells displaying abortive SARS-CoV-2 replication, α-syn multimers, and multimer:monomer ratio were not reduced following exposure to the virus and exogenous α-syn, suggesting that only productive viral infection impairs α-syn multimerization and multimer:monomer equilibrium. Conclusions Our study provides novel insights into the biology of α-syn, showing that its dynamic conformations are implicated in the innate immune response against SARS-CoV-2 infection in peripheral cells. In particular, our results suggest that promotion of non-toxic α-syn multimers likely occurs as a Type-I IFN-related biological response which partakes in the suppression of viral replication. Further studies are needed to replicate our findings in neuronal cells as well as animal models, and to ascertain the nature of such α-syn conformations.

Background: Although more than four years have passed since the pandemic began, SARS-CoV-2 continues to be of concern. Therefore, research into the underlying mechanisms that contribute to the development of the disease, especially in more severe forms, remains a priority. Sustained activation of the complement (CS), contact (CAS), and fibrinolytic and kinin–kallikrein systems (KKS) has been shown to play a central role in the pathogenesis of the disease. Since the C1 esterase inhibitor (C1-INH) is a potent inhibitor of all these systems, its role in the disease has been investigated, but some issues remained unresolved. Methods: We evaluated the impact of C1-INH and KKS on disease progression in a cohort of 45 COVID-19 patients divided into groups according to disease severity. We measured plasma levels of total and functional C1-INH and its complexes with kallikrein (PKa), reflecting KKS activation and kallikrein spontaneous activity. Results: We observed increased total and functional plasma concentrations of C1-INH in COVID-19 patients. A direct correlation (positive Spearman’s r) was observed between C1-INH levels, especially functional C1-INH, and the severity of the disease. Moreover, a significant reduction in the ratio of functional over total C1-INH was evident in patients exhibiting mild to intermediate clinical severity but not in critically ill patients. Accordingly, activation of the KKS, assessed as an increase in PKa:C1-INH complexes, was explicitly observed in the mild categories. Conclusions: Our study’s findings on the consumption of C1-INH and the activation of the KKS in the less severe stages of COVID-19 but not in the critical stage suggest a potential role for C1-INH in containing disease severity. These results underscore the importance of C1-INH in the early phases of the disease and its potential implications in COVID-19 progression and/or long-term effects.

Background Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare disease. Few states in developing countries have an adequate management of HAE, but none of them belongs to the former USSR area. This study analyses data from C1-INH-HAE patients from Belarus. Methods Data about clinical characteristics, genetics, access to diagnosis and treatment were collected from 2010 by the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology in Minsk. A questionnaire about attacks, prophylactic (LTP) and on-demand therapy (ODT) was administered to patients. Results We identified 64 C1-INH-HAE patients belonging to 26 families, 27 (42.2%) of which were diagnosed in the last 3 years. The estimated minimal prevalence was 1:148,000. Median age at diagnosis was 29 years, with diagnostic delay of 19 years. Thirty-eight patients answered a questionnaire about therapy. Eleven patients did not use any treatment to resolve HAE attacks. Twenty-seven patients underwent ODT: 9 with appropriate treatments, and 18 with inappropriate treatments. Nine patients used LTP with attenuated androgens and 1 with tranexamic acid. Thirty-two patients answered a questionnaire about attacks and triggers: 368 angioedema attacks were reported, with an average of 10 attacks per year. We found 24 different SERPING1 variants: 9 missenses, 6 in splice sites, 6 small deletions, 2 nonsense, 1 large deletion; 7 have not been previously described. De novo variants were found in 11 patients. Conclusions C1-INH-HAE diagnosis and management in Belarus is improved as seen from the high number of new diagnosis in the last 3 years. Next steps will be to reduce the diagnostic delay and to promote the LTP and ODT.

Avobenzone (AVO) is a sunscreen with high global production and is constantly released into the environment. Incorporating sewage biosolids for fertilization purposes, the leaching from cultivated soils, and the use of wastewater for irrigation explain its presence in the soil. There is a lack of information about the impact of this sunscreen on plants. In the present study, the ecotoxicity of AVO was tested at concentrations 1, 10, 100, and 1,000 ng/L. All concentrations caused a reduction in root growth of Allium cepa , Cucumis sativus, and Lycopersicum esculentum seeds, as well as a mitodepressive effect, changes in the mitotic spindle and a reduction in root growth of A. cepa bulbs. The cell cycle was disturbed because AVO disarmed the enzymatic defense system of root meristems, leading to an accumulation of hydroxyl radicals and superoxides, besides lipid peroxidation in cells. Therefore, AVO shows a high potential to cause damage to plants and can negatively affect agricultural production and the growth of non-cultivated plants.