Peripheral nerve injury (PNI) leads to a series of cellular and molecular events necessary for axon regeneration and reinnervation of target tissues, among which inflammation is crucial for the orchestration of all these processes. Macrophage activation underlies the pathogenesis of PNI and is characterized by morphological/phenotype transformation from proinflammatory (M1) to an anti-inflammatory (M2) type with different functions in the inflammatory and reparative process. The aim of this study was to evaluate influence of the vitamin B (B1, B2, B3, B5, B6, and B12) complex on the process of neuroinflammation that is in part regulated by l-type Ca_V1.2 calcium channels. A controlled transection of the motor branch of the femoral peripheral nerve was used as an experimental model. Animals were sacrificed after 1, 3, 7, and 14 injections of vitamin B complex. Isolated nerves were used for immunofluorescence analysis. Treatment with vitamin B complex decreased expression of proinflammatory and increased expression of anti-inflammatory cytokines, thus contributing to the resolution of neuroinflammation. In parallel, B vitamins decreased the number of M1 macrophages that expressed the Ca_V1.2 channel, and increased the number of M2 macrophages that expressed this channel, suggesting their role in M1/M2 transition after PNI. In conclusion, B vitamins had the potential for treatment of neuroinflammation and neuroregeneration and thereby might be an effective therapy for PNI in humans.

Peripheral nerve injury (PNI) triggers a complex multi-cellular response involving the injured neurons, Schwann cells (SCs), and immune cells, often resulting in poor functional recovery. The aim of this study was to investigate the effects of the treatment with vitamin B (B1, B2, B3, B5, B6, and B12) complex on the interaction between macrophages and SCs during the recovery period after PNI. Transection of the motor branch of the femoral nerve followed by reconstruction by termino-terminal anastomosis was used as an experimental model. Isolated nerves from the sham (S), operated (O), and operated groups treated with the B vitamins (OT group) were used for immunofluorescence analysis. The obtained data indicated that PNI modulates interactions between macrophages and SCs in a time-dependent manner. The treatment with B vitamins complex promoted the M1-to M2-macrophage polarization and accelerated the transition from the non-myelin to myelin-forming SCs, an indicative of SCs maturation. The effect of B vitamins complex on both cell types was accompanied with an increase in macrophage/SC interactions, all of which correlated with the regeneration of the injured nerve. Clearly, the capacity of B vitamins to modulate macrophages-SCs interaction may be promising for the treatment of PNI.

CRISPR/Cas is an adaptive bacterial immune system, whose CRISPR array can actively change in response to viral infections. However, Type I-E CRISPR/Cas in E. coli (an established model system), appears not to exhibit such active adaptation, which suggests that it might have functions other than immune response. Through computational analysis, we address the involvement of the system in non-canonical functions. To assess targets of CRISPR spacers, we align them against both E. coli genome and an exhaustive (~230) set of E. coli viruses. We systematically investigate the obtained alignments, such as hit distribution with respect to genome annotation, propensity to target mRNA, the target functional enrichment, conservation of CRISPR spacers and putative targets in related bacterial genomes. We find that CRISPR spacers have a statistically highly significant tendency to target (i) host compared to phage genomes, (ii) one of the two DNA strands, (iii) genomic dsDNA rather than mRNA, (iv) transcriptionally active regions, and (v) sequences (cis-regulatory elements) with slower turn-over rate compared to CRISPR spacers (trans-factors). The results suggest that the Type I-E CRISPR/Cas system has a major role in transcription regulation of endogenous genes, with a potential to rapidly rewire these regulatory interactions, with targets being selected through naïve adaptation.

The dietary habits of fruit flies profoundly influence their fitness, morphology, and physiology yet the mechanisms underlying these effects remain incompletely understood. To address this gap, the relationship between dietary regimens and the composition and function of adult Drosophila melanogaster microbiota was investigated in the present study. The adult fly microbiota communities that were reared for long time on five different diets were characterized by means of 16S rRNA sequencing. Obtained results revealed distinct community structures associated with each dietary regimen, which was additionally corroborated through machine learning-based analysis. In general, sugar-rich diets correlate with microbial ecosystems of higher richness/diversity. Dominance of the phyla Proteobacteria and Firmicutes in the microbiota was confirmed irrespective of diet, with the varying proportions of the most abundant families: Acetobacteraceae, Lactobacillaceae, Moraxellaceae, Bradyrhizobiaceae, and Leucostonocaceae. Bacterial families of lower abundance also emerged as differentially present among the studied fly groups. Additionally, functional prediction provided initial clues into how nutrient availability might modulate the metabolic traits of adult fly microbiota in a sex-specific manner to meet host metabolic needs. Overall, the presented findings highlight the intricate interplay between diet, microbiota composition, and host phenotype in fruit flies, underscoring the importance of diet as a determinant of host-microbiota interactions.

Background/Objectives: In heart failure with preserved ejection fraction (HFpEF), the gut–heart axis has emerged as a potential contributor to inflammation and cardiometabolic stress. We characterised gut microbiota composition, diversity, and predicted metabolic potential in HFpEF to assess their associations with disease status and clinical heterogeneity. Methods and Results: Faecal samples from 30 HFpEF patients and 28 healthy controls were profiled by means of bacterial ribosomal RNA gene sequencing. The groups were comparable in age (74 years in both groups) and sex (female: 60% vs. 60.7%). HFpEF patients exhibited lower community evenness (p = 0.04) and a trend toward lower diversity (p = 0.08), but no detectable shift in global community structure. The tested clinical and demographic variables explained only a modest proportion of the observed variation in community structure, with substantial residual variation across the beta-diversity analyses. No taxa were differentially abundant between groups at the predefined thresholds. Among clinical stratifications, New York Heart Association (NYHA) class showed the most consistent family-level associations, including stepwise depletion of Lachnospiraceae, Butyricicoccaceae, and Ruminococcaceae and enrichment of Akkermansiaceae; Enterobacteriaceae peaked in milder disease. These severity-associated taxonomic trajectories were accompanied by predicted functional shifts consistent with microbial adaptation to increasing metabolic constraints, including enrichment of stress-adaptation traits and, with increasing functional limitation, depletion of core metabolic and fermentative pathways and relative enrichment of oxidative stress-response pathways. Conclusions: HFpEF is associated with subtle gut microbiota alterations that appear to reflect severity- and context-dependent ecological reorganisation rather than uniform dysbiosis. These findings support severity-informed approaches targeting microbial metabolic function and ecological context rather than broad compositional changes.