Background: Red marine algae have shown the potential to reduce inflammation, influence microbiota, and provide neuroprotection. Objective: To examine the prebiotic properties of Palmaria palmata aqueous extract (Palmaria p.) and its potential as a neuroprotective agent in multiple sclerosis (MS). Methods: eighty-eight adult Swiss mice were divided into four male and four female groups, including a control group (distilled water), Palmaria p.-treated group (600 mg/kg b.w.), cuprizone (CPZ)-treated group (mixed chow 0.2%), and a group treated with both CPZ and Palmaria p. The experiment continued for seven weeks. CPZ treatment terminated at the end of the 5th week, with half of the mice sacrificed to assess the demyelination stage. To examine the spontaneous recovery, the rest of the mice continued until the end of week seven. Behavioral (grip strength (GS) and open field tests (OFT)), microbiome, and histological assessments for general morphology of corpus callous (CC) were all conducted at the end of week five and week 7. Results: Palmaria p. can potentially protect against CPZ-induced MS with variable degrees in male and female Swiss mice. This protection was demonstrated through three key findings: (1) increased F/B ratio and expansion of the beneficial Lactobacillus, Proteobacteria, and Bactriodia communities. (2) Protection against the decline in GS induced by CPZ and prevented CPZ-induced anxiety in OFT. (3) Preservation of structural integrity. Conclusions: Because of its propensity to promote microbiota alterations, its antioxidant activity, and its content of −3 fatty acids, Palmaria p. could be a promising option for MS patients and could be beneficial as a potential probiotic for the at-risk groups as a preventive measure against MS.

Background: The Signal Transducer and Activator of Transcription 1 (STAT1) gene is an essential component of the JAK-STAT signaling pathway. This pathway plays a pivotal role in the regulation of different cellular processes, including immune responses, cell growth, and apoptosis. Mutations in the STAT1 gene contribute to a variety of immune system dysfunctions. Objectives: We aim to identify disease-susceptible single-nucleotide polymorphisms (SNPs) in STAT1 gene and predict structural changes associated with the mutations that disrupt normal protein–protein interactions using different computational algorithms. Methods: Several in silico tools, such as SIFT, Polyphen v2, PROVEAN, SNAP2, PhD-SNP, SNPs&GO, Pmut, and PANTHER, were used to determine the deleterious nsSNPs of the STAT1. Further, we evaluated the potentially deleterious SNPs for their effect on protein stability using I-Mutant, MUpro, and DDMUT. Additionally, we predicted the functional and structural effects of the nsSNPs using MutPred. We used Alpha-Missense to predict missense variant pathogenicity. Moreover, we predicted the 3D structure of STAT1 using an artificial intelligence system, alphafold, and the visualization of the 3D structures of the wild-type amino acids and the mutant residues was performed using ChimeraX 1.9 software. Furthermore, we analyzed the structural and conformational variations that have resulted from SNPs using Project Hope, while changes in the biological interactions between wild type, mutant amino acids, and neighborhood residues was studied using DDMUT. Conservational analysis and surface accessibility prediction of STAT1 was performed using ConSurf. We predicted the protein–protein interaction using STRING database. Results: In the current study, we identified six deleterious nsSNPs (R602W, I648T, V642D, L600P, I578N, and W504C) and their effect on protein structure, function, and stability. Conclusions: These findings highlight the potential of approaches to pinpoint pathogenic SNPs, providing a time- and cost-effective alternative to experimental approaches. To the best of our knowledge, this is the first comprehensive study in which we analyze STAT1 gene variants using both bioinformatics and artificial-intelligence-based model tools.

The Signal Transducer and Activator of Transcription 1 (STAT1) gene is an essential component of the JAK-STAT signalling pathway. This pathway has a pivotal role in regulating different cellular processes, including immune responses, cell growth, and apoptosis. Mutations in the STAT1 gene contribute to various body pathologies [OMIM #600555], including immune system dysfunction. In the current study, we used eighteen online computational approaches. Six pathogenic variants (R602W, I648T, V642D, L600P, I578N, and W504C) were predicted to significantly disrupt protein stability and function. These findings highlight the potential of approaches to pinpoint pathogenic single nucleotide polymorphisms, providing a time and cost effective alternative to experimental approaches. Up to the best of our knowledge, this is the original inclusive study, where we analyze STAT1 gene variants using both bioinformatics and artificial intelligence based model tools.