Nouf Saeed Al-Abbas

Perturbation of oral and gut microbiomes has been implicated in alzheimer’s disease (AD) along the oral-gut-brain axis; however, the extent of global community restructuring may differ between niches. The present work constitutes a computational interrogation of 16S rRNA profiles from eight-month-old APP/PS1 and wild-type mice, characterizing oral and gut community structure and predicted functional capacity through PICRUSt-driven, KEGG-anchored pathway inference. Comparative taxonomic interrogation disclosed patterns consistent with ectopic occurrence, whereby classically oral genera ( Fusobacterium , Streptococcus ) were preferentially enriched within intestinal assemblages and gut-typical genera ( Muribaculum , Paramuribaculum ) emerged as prominent constituents of the oral microbiota in APP/PS1 mice. These cross-niche enrichment patterns, together with significant oral community separation but non-significant gut beta-diversity separation by ANOSIM, were accompanied by predicted decrements in 85 orally enriched enzymes distributed across 25 KEGG pathways, approximately 40 % of which were associated with the biosynthesis of metabolites with reported neuroprotective properties, including glutathione, acetyl-CoA, succinate, malate, formate, lactate, acetate, and monoterpenoids. Systems-level synthesis of these predictions indicated convergent perturbation of antioxidant defenses, bioenergetic circuitry, and one-carbon metabolism, plausibly reflecting metabolic choke points that may favor cognitive deterioration. Although the oral microbiome showed significant inter-cohort separation, the gut microbiome did not, indicating that gut changes are best viewed as taxon-specific shifts within an otherwise stable community. These observations support a hypothesis-generating framework in which oral dysbiosis, selective gut alterations, and cross-niche enrichment patterns are linked to computationally inferred neuroprotective metabolite insufficiency, highlighting specific taxa, enzymes, and pathways as candidates for biomarker and microbiome-targeted therapeutic development in AD.

Introduction: For many years, 5-fluorouracil (5-FU) has been utilized as a chemotherapeutic treatment for a variety of malignancies. Unfortunately, 5-FU causes cardiotoxicity, which restricts its clinical use. Nifuroxazide (NFX) is a STAT-3 inhibitor with antioxidant and anti-inflammatory effects. Methods: Cardiotoxicity was induced by 5-FU (30 mg/kg) once daily for 5 days. NFX was administered in two doses, 25 and 50 mg. Results: Compared to 5-FU-control rats, NFX significantly attenuates cardiotoxicity induced by 5-FU, as indicated by decreasing creatine kinase (CK)-MB, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) serum levels. Histopathological examinations confirmed the protective effects of NFX against histological abrasions induced by 5-FU. NFX attenuated the oxidative damage induced by 5-FU mediated by peroxisome proliferator-activated receptor gamma (PPAR-γ) signal activation. Moreover, NFX mitigated 5-FU-induced inflammation by suppressing nucleotide-binding domain, leucine-rich repeat-containing protein 3/signal transducer and activator of transcription 3 (NLRP3/STAT3) signal activation. Notably, these protective effects are dose-dependent. Additionally, NFX mitigated 5-FU-induced apoptosis by downregulating Bax, while upregulating Bcl-2. Conclusions: Collectively, NFX attenuated 5-FU-induced cardiac intoxication by regulating NLRP3/STAT-3, PPAR-γ, and Bax/Bcl-2 signals.

Background: This study explores how gut metabolites, produced through bacterial metabolism in the gut, influence neurological conditions like Alzheimer's disease (AD). Key metabolites such as succinate and short-chain fatty acids signal through the autonomic nervous system and can cross the blood-brain barrier, impacting central nervous system functions. Objective: The aim is to examine the role of the gut microbiota in compensating for metabolic deficiencies in AD. By analyzing wild-type (WT) and APP/PS1 mice, the study investigates how the microbiome affects key metabolic processes and whether it can slow AD progression. Methods: High-throughput sequencing data from the gut microbiomes of APP/PS1 transgenic AD model mice and age-matched WT C57BL/6 male mice were analyzed for microbial and metabolite profiles. Results: Alpha and beta diversity analyses showed differences in microbial composition between groups. Partial least squares discriminant analysis and Anosim confirmed distinct microbiome profiles in WT and APP/PS1 mice. At the genus level, Vescimonas was more abundant in WT mice, while Odoribacter, Lacrimispora, Helicobacter, Bacteroides, and Alloprevotella were more prevalent in APP/PS1 mice. Conclusions: While taxonomic differences did not directly link specific microorganisms to AD, functional analysis identified key metabolites—acetyl-CoA, glucose, succinate, lipids, choline, and acetylcholine—that may alleviate energy deficits and synaptic dysfunction. This study suggests that the microbiome may help compensate for AD-related impairments, opening avenues for microbiome-based therapies.

Despite advancements in cancer therapy, hepatocellular carcinoma (HCC) remains a major health concern due to late-stage diagnosis and poor prognosis. In this study, the expression of Glypican-3 (GPC3), a cell surface protein encoded by the GPC3 gene was analyzed at both Messenger RNA and protein levels. The goal was to advance understandings into the role of GPC3 in HCC progression and design a fusion protein as a potential therapy targeting cancer cells expressing this oncogene. Expression analysis of GPC3 in liver hepatocellular carcinoma (LIHC) was performed using GEPIA 2 and OncoDB servers. The analysis revealed a significantly high expression level of GPC3 in cancerous tissues of HCC, with a p-value of p = 1.07e-37. This finding indicates the potential involvement of GPC3 in HCC development. To construct the chimeric proteins (CPs), rituximab, a linker, and an approved Anti-Ogawa O-antigen monoclonal antibody S-20-4 penetrating peptide were combined using trRosetta. The peptide sequence of the Anti-Ogawa O-antigen monoclonal antibody S-20-4, namely, NHNYPPLSLLTF, SHDWRLMLSHLQ, QHDRLLMLSYLV, HHILPPKALLFG, SHTFPPSWLLVR and YSVKPPLPYLPP was obtained from the Immunet BDB database. The HDock scoring algorithms were employed to assess the degree of connection between the CP and the GPC3 gene expressed in HCC. The analysis showed a strong binding affinity of -258.53 KJ/mol between the CP and GPC3, indicating a favorable interaction. Simulations and toxicity analysis further supported the therapeutic potential of the constructed CP for treating LIHC. These findings highlight the potential of the CP as a targeted therapy against HCC, leveraging the high expression of GPC3 in cancerous tissues.

Several microRNAs (miRNAs) are known to participate in adipogenesis. However, their role in this process, especially in the differentiation of bovine preadipocytes, remains to be elucidated. This study was intended to clarify the effect of microRNA-33a (miR-33a) on the differentiation of bovine preadipocytes by cell culture, real-time fluorescent quantitative PCR (qPCR), Oil Red staining, BODIPY staining, and Western blotting. The results indicate that overexpression of miR-33a significantly inhibited lipid droplet accumulation and decreased the mRNA and protein expression of adipocyte differentiation marker genes such as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), and fatty acid-binding protein 4 (FABP4). In contrast, the interference expression of miR-33a promoted lipid droplet accumulation and increased the expression of marker genes. Additionally, miR-33a directly targeted insulin receptor substrate 2 (IRS2) and regulated the phosphorylation level of serine/threonine kinase (Akt). Furthermore, miR-33a inhibition could rescue defects in the differentiation of bovine preadipocytes and the Akt phosphorylation level caused by small interfering IRS2 (si-IRS2). Collectively, these results indicate that miR-33a could inhibit the differentiation of bovine preadipocytes, possibly through the IRS2–Akt pathway. These findings might help develop practical means to improve the quality of beef.

Metagenomic approach was used to detect microbial gene abundance and relative abundance in the rhizosphere of Moringa oleifera and surrounding bulk soil and to detect the response of soil microbes to watering. Expectedly, the number and abundance of non-redundant genes were extremely higher in bacteria followed by archaea, eukaryota and viruses. Results demonstrated unexpected high abundance of some microbes (ex., endophyte genus Nocardioides) in the rhizosphere that are supposed to exist mainly in other rhizocompartments. We suggest this differential distribution of microbes is due to the specific pattern of host-microbe interaction. Other endosymbiont microbes, ex., fungi Mucoromycota and Ascomycota, were highly abundant in the bulk soil possibly because they are phytopathogens where plant exudates might inhibit their growth or force these fungi to approach reverse chemotaxis. Our data indicated high abundance of other symbiont microbes in the rhizosphere of M. oleifera at phylum (ex., Actinobacteria) and genus (ex., Streptomyces) levels. Watering experiment indicated that phylum Actinobacteria and the descending genus Streptomyces are among the highest. Rhizobiome of M. oleifera seems to harbor a wealth of new species of the genus Streptomyces that are required to be deciphered for function in order to be eventually utilized in pharmaceutical and agricultural applications.

Pumpkin has received significant attention due to its nutritional compounds that have antioxidant, antifatigue, and anti‐inflammatory effects. This study is aimed at assessing the antidepressant‐like effect of L. Cucurbita pepo, sweet pumpkin, in an animal model of chronic unpredictable mild stress (CUMS) and investigating its effect on the histological structure of hippocampus compared to fluoxetine. Forty male albino rats assigned into the negative control, positive control (CUMS), and Flu‐treated and pumpkin‐treated groups (n = 10) were utilized in this study. Exposing rats to CUMS continued for 28 days, and treatments used were applied during the last 14 days of exposure. Behavioral, biochemical, and histopathological changes were assessed after 28 days. In this study, pumpkin significantly reduced the immobility time (p = 0.02), corticosterone (p < 0.001), TNF‐α, IL‐6 (p < 0.001), and malondialdehyde (p = 0.003), whereas it significantly increased the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in the serum of rats exposed to CUMS. Pumpkin markedly relieved the degenerative and atrophic changes observed in the CA3 region and the dentate gyrus of the hippocampus. It significantly reduced caspase‐3 and increased glial fibrillary acidic protein (GFAP) immunoexpression in the CA3 and DG. In conclusion, administration of pumpkin extract improved the behavioral, biochemical, and hippocampal pathological alternations induced in rats after exposure to CUMS in a comparable pattern to fluoxetine. This study highlighted the potential efficacy of pumpkin in alleviating depression disorder either alone or in conjugation with conventional antidepressant therapy.