Human Gut Microbiota and Parkinson\u27s Disease in an Egyptian Population

Multiple lines of evidence suggest the role of the gut microbiome in the predisposition and progression of Parkinson’s disease. This present cross-sectional study was performed to compare the composition of the gastrointestinal microbiota in patients with Parkinson\u27s disease to their counterparts. Stringent inclusion criteria were followed to reliably identify our target population. Parkinson’s patients (n = 40) along with reference subjects (n = 39) were recruited from November 2021 to August 2022. Detailed demographic and clinical data were obtained at baseline using a set of questionnaires and clinical assessment tools. Fecal specimens were collected from all participants, and gut commensals were characterized using 16S rRNA gene amplicon sequencing. The endpoint was to discern the disparities in the gut microbiota structure. Our results demonstrate no significant difference at the taxonomic level between Parkinson\u27s patients and the reference group. However, marginally significant species associated with intestinal inflammation, gut permeability, and mitochondrial dysfunction were reported. These recent findings create an opportunity for further studies comprising a bigger sample size and using higher resolution sequencing techniques in aims to better understand whether and to what extent gut microbiota alterations play a role in the disease pathogenesis

Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these neurotoxicants has been linked to neurodegeneration, particularly Parkinson’s disease. However, their mechanisms of action have not been fully elucidated, nor has the relative vulnerability of neuronal subtypes to their exposures. To address this, the current study investigated the cytotoxic effects of PQ, RO, and MPTP and their relative effects on cellular bioenergetics and oxidative stress on undifferentiated human neuroblastoma (SH-SY5Y) cells and those differentiated to dopaminergic (DA) or cholinergic (CH) phenotypes. The tested neurotoxicants were all cytotoxic to the three cell phenotypes that correlated with both concentration and exposure duration. At half-maximal effective concentrations (EC50s), there were significant reductions in cellular ATP levels and reduced activity of the mitochondrial complexes I and III, with a parallel increase in lactate production. PQ at 10 µM significantly decreased ATP production and mitochondrial complex III activity only in DA cells. RO was the most potent inhibitor of mitochondrial complex 1 and did not inhibit mitochondrial complex III even at concentrations that induced a 50% loss of cell viability. MPTP was the most potent toxicant in undifferentiated cells. All neurotoxicants significantly increased reactive oxygen species, lipid peroxidation, and nuclear expression of Nrf2, with a corresponding inhibition of the antioxidant enzymes catalase and superoxide dismutase. At a 10 µM exposure to PQ or RO, oxidative stress biomarkers were significant in DA cells. Collectively, this study underscores the importance of mitochondrial dysfunction and oxidative stress in PQ, RO, and MPTP-induced cytotoxicity and that neuronal phenotypes display differential vulnerability to these neurotoxicants

The Role of an Altered Gut Microbiome in Parkinson’s Disease: A Narrative Review

Parkinson’s disease is a debilitating multisystemic disorder affecting both the central and peripheral nervous systems. Accumulating evidence suggests a potential interaction between gut microbiota and the pathophysiology of the disease. As a result of the degradation of dopaminergic neurons, PD patients develop motor impairments such as tremors, rigidity, and slowness of movement. These motor features are preceded by gastrointestinal issues, including constipation. Given these gastrointestinal issues, the gut has emerged as a potential modulator of the neurodegenerative cascade of PD. Several studies have been carried out to broaden our understanding of the gut–microbiota–brain axis in PD. As a result, a decrease in short-chain fatty acid synthesizing bacteria has been observed in multiple studies. Some studies, on the other hand, have shown an enrichment of mucin- and levodopa-degrading microbes. In this review, we compiled the available evidence from the literature on the bidirectional communication between the gut microbiome system and the brain in PD. We also addressed the association between dysbiosis and the clinical symptoms of PD and host–drug metabolism. Finally, we touched on some of the therapeutic interventions that may restore eubiosis and modulate the gut structure to restrain disease progression

Using 6-CIT, P300 encephalography, and pro-inflammation assessments for screening age-related cognitive decline and exploring associated risk factors in Egyptian elderly

Abstract Background The elderly population is suffering from many mental health problems that are aggravated as a matter of age and cognitive decline is a serious one of them. The aim of the present work is to screen the cognitive performance among a sample of Egyptian elderly volunteers and to investigate the associated risk factors. Results A sample of 88 elderly volunteers from both genders was enrolled in the study according to the specified eligibility criteria after signing the approval consent. Medical history and socio-demographic data were collected from all participants in addition to basic clinical examination. Cognitive performance was assessed using the 6-Item Cognitive Impairment Test (6-CIT) while the endogenous event-related potentials (ERP) was measured using P300. The inflammatory biomarkers; TNF-α and COX-2 levels were assessed in serum using ELISA technique in addition to gene expression of TNF-α, PPAR-γ and CD-36 exploration using qRT-PCR. About half (51%) of the sample under investigation showed cognitive problems with scores on the 6-CIT exceeding the normal level. TNF-α serum levels showed positive correlation with P300 latency and correlated negatively with P300 reaction time. Furthermore, serum COX-2 levels correlated positively with P300 reaction time and negatively with P300 amplitude. Conclusion The study population is showing early signs of cognitive decline that invites attention to the importance of spreading preventive measures against further deterioration. Inflammatory biomarkers under investigation and 6-CIT are suggested to be used in prediction of early stages of cognitive decline among the elderly population

Additional file 1 of Using 6-CIT, P300 encephalography, and pro-inflammation assessments for screening age-related cognitive decline and exploring associated risk factors in Egyptian elderly

Additional file 1: S1. Testing the correlation between P300 variables, 6-CIT scores and cognitive decline risk factors; Fold Change TNF-α, Fold Change PPAR-γ, & Fold Change CD-36

Genome-wide association study for systemic lupus erythematosus in an egyptian population

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis