Pseudanabaena galeata CCNP1313 : biological activity and peptides production

Even cyanobacteria from ecosystems of low biodiversity, such as the Baltic Sea, can constitute a rich source of bioactive metabolites. Potent toxins, enzyme inhibitors, and anticancer and antifungal agents were detected in both bloom-forming species and less commonly occurring cyanobacteria. In previous work on the Baltic Pseudanabaena galeata CCNP1313, the induction of apoptosis in the breast cancer cell line MCF-7 was documented. Here, the activity of the strain was further explored using human dermal fibroblasts, African green monkey kidney, cancer cell lines (T47D, HCT-8, and A549(ACE2/TMPRSS2)) and viruses (SARS-CoV-2, HCoV-OC43, and WNV). In the tests, extracts, chromatographic fractions, and the main components of the P. galeata CCNP1313 fractions were used. The LC-MS/MS analyses of the tested samples led to the detection of forty-five peptides. For fourteen of the new peptides, putative structures were proposed based on MS/MS spectra. Although the complex samples (i.e., extracts and chromatographic fractions) showed potent cytotoxic and antiviral activities, the effects of the isolated compounds were minor. The study confirmed the significance of P. galeata CCNP1313 as a source of metabolites with potent activity. It also illustrated the difficulties in assigning the observed biological effects to specific metabolites, especially when they are produced in minute amounts

Neutrophil Maturation, Reactivity and Granularity Research Parameters to Characterize and Differentiate Convalescent Patients from Active SARS-CoV-2 Infection

Studying the dynamics changes of neutrophils during innate immune response in coronavirus 2019 (COVID-19) can help understand the pathogenesis of this disease. The aim of the study was to assess the usefulness of new neutrophil activation parameters: Immature Granulocyte (IG), Neutrophil Reactivity Intensity (NEUT-RI), Neutrophil Granularity Intensity (NEUT-GI), and data relating to granularity, activity, and neutrophil volume (NE-WX, NE-WY, NE-WZ) available in hematology analyzers to distinguish convalescent patients from patients with active SARS-CoV-2 infection and healthy controls (HC). The study group consisted of 79 patients with a confirmed positive RT-PCR test for SARS-CoV2 infection, 71 convalescent patients, and 20 HC. We observed leukopenia with neutrophilia in patients with active infection compared to convalescents and HC. The IG median absolute count was higher in convalescent patients than in COVID-19 and HC (respectively, 0.08 vs. 0.03 vs. 0.02, p < 0.0001). The value of the NEUT-RI parameter was the highest in HC and the lowest in convalescents (48.3 vs. 43.7, p < 0.0001). We observed the highest proportion of NE-WX, NE-WY, and NE-WZ parameters in HC, without differences between the COVID-19 and convalescent groups. New neutrophil parameters can be useful tools to assess neutrophils’ activity and functionalities in the immune response during infection and recovery from COVID-19 disease

The Utility of BDNF Detection in Assessing Severity of Huntington’s Disease

Brain-derived neurotrophic factor (BDNF) is involved in the survival and maturation of neurons, and also promotes and controls neurogenesis. Its levels are lowered in many neurodegenerative diseases, including Huntington’s disease (HD). Clinical pictures of HD can be very diverse, which makes it difficult to assess its severity; however, molecular markers may be helpful. The aim of the study was to determine the relationship between HD severity and the plasma BDNF concentration in HD patients. The study recruited 42 patients with diagnosed and genetically confirmed HD and 40 healthy volunteers. BDNF levels were determined in plasma with the enzyme-linked immunosorbent assay (ELISA). Correlations between BDNF levels and clinical profiles and HD severity were also investigated. The BDNF level was significantly lower in HD patients compared to the control. There was no correlation between the BDNF level and motor symptoms and cognitive impairment. In the early disease stages, BDNF levels were associated with a better neurological examination, independence, and functional evaluation, in contrast to later HD stages, where the correlations were inverse. Multidirectional correlations between parameters of saccadic disorders and the BDNF level do not allow for drawing a conclusion, whether or not there is a relationship between the severity of saccadic disorders and the BDNF concentration

Refolding of lid subdomain of SARS-CoV-2 nsp14 upon nsp10 interaction releases exonuclease activity

During RNA replication, coronaviruses require proofreading to maintain the integrity of their large genomes. Nsp14 associates with viral polymerase complex to excise the mismatched nucleotides. Aside from the exonuclease activity, nsp14 methyltransferase domain mediates cap methylation, facilitating translation initiation and protecting viral RNA from recognition by the innate immune sensors. The nsp14 exonuclease activity is modulated by a protein co-factor nsp10. While the nsp10/nsp14 complex structure is available, the mechanistic basis for nsp10-mediated modulation remains unclear in the absence of the nsp14 structure. Here, we provide a crystal structure of nsp14 in an apo-form. Comparative analysis of the apo- and nsp10-bound structures explain the modulatory role of the co-factor protein and reveal the allosteric nsp14 control mechanism essential for drug discovery. Further, the flexibility of the N-terminal lid of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp14 structure presented in this study rationalizes the recently proposed idea of nsp14/nsp10/nsp16 ternary complex