Linking gut microbiota dysbiosis to molecular pathways in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and synaptic dysfunction. Emerging evidence suggests a significant relationship between gut microbiota and brain health, mediated through the gut-brain axis. Alterations in gut microbiota composition may influence AD progression by affecting molecular pathways and miRNA interactions. METHODS: We retrieved and analyzed microarray data from 34 tissue samples of AD patients and controls (GEO accession number GSE110298). Differentially expressed genes (DEGs) with the GCS score package in R, considering a p-value < 0.05 and logFC<-1 and logFC>1 to isolate significant gene clusters. Enrichment analysis of signaling pathways and gene ontology was conducted using Enrichr, KEGG, Panther, DAVID, and shiny GO databases. Protein-protein interactions were visualized with Networkanalyst and CytoScape. Gut microbiota in 200 CE patients was analyzed using next-generation sequencing (NGS) data from gutMDisorder and GMrepo databases. miRNA interactions were evaluated using miEAA, Targetscan, MienTurnet, and miRnet databases. RESULTS: Significant reductions in microbial taxa, including Clostridia (LDA score -4.878208), Firmicutes (LDA score -4.817032), and Faecalibacterium (LDA score -4.40714), were observed in AD patients. Pathway analysis highlighted the involvement of Axon guidance, ErbB, and MAPK signaling pathways in AD. Venn diagram analysis identified 619 intersecting genes in brain and gut tissues, emphasizing pathways such as Axon Guidance and Cell Cycle. miRNA analysis revealed important regulatory miRNAs, including hsa-let-7c, hsa-mir-125b-2, and hsa-mir-145, which target key transcription factors involved in AD pathology. CONCLUSION: The study demonstrates significant dysbiosis in the gut microbiota of AD patients and underscores the potential role of gut microbiota in AD progression through altered signaling pathways and miRNA interactions. These findings highlight the need for further research into microbiota-based interventions as potential therapeutic strategies for AD.

A review of the advances, insights, and prospects of gene therapy for Alzheimer's disease: A novel target for therapeutic medicine.

Neurodegenerative diseases such as Alzheimer's disease (AD) are still an important issue for scientists because it is difficult to cure with the available molecular medications and conventional treatments. Due to the complex nature of the brain structures and heterogeneous morphological and physiological properties of neuronal cells, interventions for cerebral-related disorders using surgical approaches, and classical and ongoing treatments remain hard for physicians. Furthermore, the development of newly designed medications attempts to target AD are not successful in improving AD, because abnormalities of tau protein, aggregation of amyloid ß (Aß) peptide, inflammatory responses, etc lead to advanced neurodegeneration processes that conventional treatments cannot stop them. In recent years, novel diagnostic strategies and therapeutic approaches have been developed to identify and cure early pathological events of AD. Accordingly, many gene-based therapies have been developed and introduce the therapeutic potential to prevent and cure AD. On the other hand, genetic investigations and postmortem assessments have detected a large number of factors associated with AD pathology. Also, genetically diverse animal models of AD help us to detect and prioritize novel resilience mechanisms. Hence, gene therapy can be considered an effective and powerful tool to identify and treat human diseases. Ultimately, gene study and gene-based therapy with a critical role in the detection and cure of various human disorders will have a fundamental role in our lives forever. This scientific review paper discusses the present status of different therapeutic strategies, particularly gene-based therapy in treating AD, along with its challenges.

Enhancing the biodesulphurization capacity of Rhodococcus sp. FUM94 in a biphasic system through optimization of operational factors.

The biodesulfurization activity of bacteria through the 4S pathway in aqueous-oil emulsions is affected by various operational factors. These factors also demonstrate interacting effects that influence the potential for field applications of biodesulfurization technology and can solely be deciphered through multi-variable experiments. In this study, the effects of the influential factors and their interactions on the desulfurizing activity of a newly identified desulfurizing bacterium, Rhodococcus sp, FUM94 were quantitatively investigated. The capacity improvement achieved through optimized values obtained in this study is significant due to its simple implementation to large scale processes. This is the most simple and the most cost-effective way to scale-up a biodesulfurization process.Using response surface methodology (RSM). Optimum values of the factors were identified with the objective of maximizing biodesulfurization activity. Results revealed that the desulfurization activity of the biocatalyst increased from 0.323 ± 0.072 to 46.57 ± 4.556 mmol 2-Hydroxybiphenyl (kg dry cell weight)-1 h-1 at the optimized conditions of 6 h reaction time, 2 g.L-1 biocatalyst concentration, 0.54 mM (100 ppm) dibenzothiophene (DBT) concentration (sulfur source), and 25% oil phase fraction. Desirability analysis proved that the selected conditions are the most desirable combination of factors (desirability value = 0.896) to achieve the highest biodesulfurization activity of the biocatalyst. A comparison between the biodesulfurization capacity achieved in this study and the capacities reported in similar studies published in the past two decades revealed that biodesulfurization under optimized operational conditions outperforms previously proposed techniques.