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The aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosomabrucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles’ interaction with arginine kinase of T. brucei led to a >70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nM and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.

Neurodegenerative diseases (NDs) like Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a “killer factor” or a “protective factor” depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer’s disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

Background Scleroderma is a multisystem disease, characterized by fibrosis of skin and internal organs, immune dysregulation, and vasculopathy. The etiology of the disease remains unknown, but it is likely multifactorial. However, the genetic basis for this condition is defined by multiple genes that have only modest effect on disease susceptibility. Methods Three Moroccan siblings, born from non-consanguineous Moroccan healthy parents were referred for genetic evaluation of familial scleroderma. Whole Exome Sequencing was performed in the proband and his parents, in addition to Sanger sequencing that was carried out to confirm the results obtained. Results Mutation analysis showed two compound heterozygous mutations c.196C>T in exon 4 and c.635_636delTT in exon 9 of GNPTG gene. Sanger sequencing confirmed these mutations in the affected patient and demonstrated that their parents are heterozygous carriers. Conclusion Our findings expand the mutation spectrum of the GNPTG gene and extend the knowledge of the phenotype–genotype correlation of Mucolipidosis Type III gamma. This report also highlights the diagnostic utility of Next Generation Sequencing particularly when the clinical presentation did not point to specific genes.

Proteases are critical enzymes in cellular processes which regulate intricate events like cellular proliferation, differentiation and apoptosis. This review highlights the multifaceted roles of the serine proteases FAM111A and FAM111B, exploring their impact on cellular functions and diseases. FAM111A is implicated in DNA replication and replication fork protection, thereby maintaining genome integrity. Additionally, FAM111A functions as an antiviral factor against DNA and RNA viruses. Apart from being involved in DNA repair, FAM111B, a paralog of FAM111A, participates in cell cycle regulation and apoptosis. It influences the apoptotic pathway by upregulating anti-apoptotic proteins and modulating cell cycle-related proteins. Furthermore, FAM111B’s association with nucleoporins suggests its involvement in nucleo-cytoplasmic trafficking and plays a role in maintaining normal telomere length. FAM111A and FAM111B also exhibit some interconnectedness and functional similarity despite their distinct roles in cellular processes and associated diseases resulting from their dysfunction. FAM111A and FAM111B dysregulation are linked to genetic disorders: Kenny–Caffey Syndrome type 2 and Gracile Bone Dysplasia for FAM111A and POIKTMP, respectively, and cancers. Therefore, the dysregulation of these proteases in diseases emphasizes their potential as diagnostic markers and therapeutic targets. Future research is essential to unravel the intricate mechanisms governing FAM111A and FAM111B and explore their therapeutic implications comprehensively.

Metabolic dysfunction-associated steatotic liver disease (MASLD), which affects a significant portion of the global population, is linked to high-fat diets (HFD) and characterized by abnormal lipid accumulation and activation of inflammatory pathways in hepatocytes. The precise mechanisms underlying MASLD, especially the involvement of inflammatory cytokines in its pathophysiology, remain unclear. This study evaluated the changes and interactions of steatotic liver and inflammatory markers in an animal model of MASLD by feeding male Wistar rats a high-fat diet (HFD) for 17 weeks. After this period, the serum lipid profiles were assessed, along with liver enzymes, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The changes in liver morphology and triglyceride levels were determined by histology and a colorimetric assay, respectively. Steatotic liver and inflammatory markers were measured using a RT Profiler PCRArray and validated with quantitative real-time PCR (qRT-PCR). Histological evaluations indicated that HFD livers exhibited macrovesicular steatosis and lobular inflammation. The HFD-fed group had significantly higher hepatic triglyceride levels than the controls (383 ± 23 mg/dL vs. 100 ± 9 mg/dL) and elevated serum lipid levels (p < 0.0001), along with increased liver aminotransferase levels. Gene expression analysis showed decreased adiponectin signaling (AdipoR2, p < 0.001) and upregulated de novo lipogenesis (Srebf1, p < 0.05). Notably, pro-inflammatory cytokines (Cxcl10, Ccl2, Ilβ, p < 0.001; TNF-α, p < 0.01) were significantly elevated, correlating with reduced hepatic glucose transporter Glut2 expression (p < 0.05), as confirmed by STRING analysis. These findings demonstrate that HFD consumption alters key genes and pathways involved in adiponectin and insulin signalling, lipogenesis, and inflammatory responses, thereby contributing to the pathogenesis of MASLD. Additionally, it identifies a comprehensive chemokine expression profile, highlighting potential therapeutic targets for MASLD.

Poikiloderma with tendon contracture, myopathy and pulmonary fibrosis (POIKTMP) is a rare hereditary disorder caused by mutations in the FAM111B gene, characterised by multi‐organ fibrosis, particularly affecting the lungs. This study investigates the molecular mechanisms of fibrosis in POIKTMP through genotyping and gene expression profiling of FAM111B and associated fibrotic pathways. Post‐mortem formalin‐fixed paraffin‐embedded (FFPE) tissues from a POIKTMP patient and healthy controls were analysed. Genomic DNA was extracted, confirming the FAM111B Y621D mutation via Sanger sequencing. RT‐qPCR and the RT2 Profiler PCR Array were used to evaluate fibrosis‐related gene expression in lung and skin tissues. Disease and pathway enrichment analyses were conducted using Metascape, GeneMANIA and Enrichr tools. The FAM111B Y621D mutation was validated, and gene expression profiling revealed significant upregulation of fibrotic markers, such as TGFβ‐3, PDGFA, ITGB1, MMP3, MMP13 and CCN2 in the lungs, and COL3A1 and THBS2 in the skin. Pathway enrichment analysis linked FAM111B to extracellular matrix remodelling, cell adhesion, and cancer. These findings suggest that FAM111B mutations drive fibrosis through dysregulated gene networks, highlighting potential therapeutic targets for POIKTMP and related fibrotic diseases. Further research is required to understand FAM111B's role in fibrosis fully.

Ageing contributes to the onset of various diseases. It is accompanied by malfunctioning and deterioration of the body systems. Identifying the biomarkers for the prediction, diagnosis, management, or prognosis of ageing and biological ageing was the aim of this study. The peptide identification was done by analysing the conserved sequences in a comprehensive multiple alignment and domain annotation of the small peptide of methyl jasmonate esterase 1 ( ) present in the (wine grape). The discovery of biomarkers was done by annotating the RNA-Seq dataset that comprehensively sequenced the human Achilles tendon transcriptome in young and older people to identify differentially expressed genes. Followed by molecular docking, ADMET and protein-protein interactions studies. The molecular docking was performed by docking the active peptide of with the human complement factor H ( ) identified in the RNA-Seq data analysis. The sequenced alignment analysis indicated high similarity (~99%) of protein in the (wine grape), as well as some other set of plant species that also encode a gene for . The pharmacokinetics and ADMET properties of MJE1 revealed a molecular weight of 224.30 g/mol and polar surface area measured at 43.37 Å , suggesting its adherence to Lipinski's rules of for drug likeliness; moreover, data supported MJE1 interactions with mostly nuclear receptors. Of all the annotated biomarkers in the RNA-Seq dataset analysed in this study, we prioritised the for the robust data supporting its activities in ageing research and the availability of its crystalline structured. The molecular docking of MJE1 selected peptide with surface identified conformational changes enacted by the surface and orientation interactions with four amino acid residues (CYS 1167, THR 1227, TRP 2 and PHE 10) of the protein. By using computational techniques to investigate the plausible anti-ageing potential of the small peptide of present in the we identified a complex interaction between and . This finding necessitates further investigation in mouse, zebrafish or non-human primate model towards the understanding of anti-ageing therapy.

Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with a 50% increase in subsequent risk for type 2 diabetes. There is increasing interest in identifying biomarkers that may facilitate the stratification of subsequent type 2 diabetes risk among women with GDM. In this study, we considered the choline acetyltransferase ( ) gene. CHAT plays a critical role in acetylcholine synthesis and regulates insulin secretion from the pancreatic islet to maintain glucose homeostasis. We screened for deleterious variants in the gene in 12 GDM patients and 10 ethnically matched controls from a South African cohort. We isolated DNA from the placental samples of these patients and performed DNA sequencing of the protein-coding region of the gene. Sequence alignments and variant annotations were done using UGENE software and Ensembl VEP. A novel heterozygous missense variant in exon 8 of the gene was identified. The plausible phenotypic impact of the variant (NM_020549.5):c.1213C>G (p.Leu405Val) can be explained by haploinsufficiency, changing protein activities, strong transcription activity, and epigenetic repression activities of the variant. Also, structurally, the variant is located 18bp in-frame to a stop-gained variant (p.Gly411Ter). The RegulomeDB DNase expression data clearly show the identified variant in a peak expression in the spleen and placenta. This observation corroborates that the gene may play an essential role in GDM. Taken together, the metric scores for this variant show that it could affect the functions of the gene, but more functional studies are necessary to validate these effects. Consequently, this study sets the stage for the future screening of a larger cohort and functional validation of deleterious variants to underpin the gene and GDM association.

Mutations of the human FAM111B gene are associated with hereditary fibrosing poikiloderma with tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP), a rare and autosomal dominant multi-systemic fibrosing disease. To date, a total of 36 cases are documented, with eleven associated mutations identified and confirmed by Whole-Exome Sequencing and Sanger sequencing. However, these methods require a certain level of expertise. The FAM111B gene was annotated using the SNAPGENE tool to identify various restriction enzymes. The enzymes that cut at the positions where mutations of interest have been reported were selected. The method was implemented using the DNA samples extracted from the skin fibroblast collected from an affected South African family and unrelated control. The findings showed that of the eleven FAM111B mutational sites investigated with this method, ten mutations can be identified including the known mutation FAM111B NM_198947.4: c.1861T>G (pTyr621Asp) associated with the POIKTMP in South Africa. Limited access to molecular diagnosis contributes to why POIKTMP is rarely diagnosed. Our study describes an inexpensive PCR-RFLP method to screen for POIKTMP FAM111B gene mutations. The PCR-RFLP can be used as a cost-effective method for diagnosing FAM111B mutations in POIKTMP, and it does not require having robust experience in molecular biology.