Biology subjects

Tran, T.-A.

Publications and source records attributed to Tran, T.-A..

2 recordsLinked to original sources

bioRxiv2024

Masitinib Limits Neuronal Damage, as Measured by Serum Neurofilament Light Chain Concentration, in a Model of Neuroimmune-Driven Neurodegenerative Disease

BackgroundMasitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the innate neuroimmune system. We have studied the neuroprotective action of masitinib on the manifestations of experimental autoimmune encephalitis (EAE) induced axonal and neuronal damage. EAE is a model of neuroimmune-driven chronic neuroinflammation and therefore highly relevant to masitinibs mechanism of action in neurodegenerative diseases. Importantly, neuronal damage, or prevention thereof, can be rapidly assessed by measuring serum neurofilament light chain (NfL) concentration in EAE-induced mice. MethodsEAE induction was performed in healthy female C57BL/6 mice via active MOG35-55 peptide immunization. Treatments were initiated 14 days post EAE induction. On day-0, 39 mice with established EAE symptoms were randomly assigned to 3 treatment groups (n=13): EAE control, masitinib 50 mg/kg/day (M50), and masitinib 100 mg/kg/day (M100). Treatment started on day-1 and ended on day-15. Blood samples were collected at day-1, day-8 (via tail vein sampling) and day-15 (via intracardiac puncture). Assessments included quantification of serum NfL levels along the disease duration, cytokine quantification at day-15, and clinical assessments. ResultsMasitinib treatment significantly (p<0.0001) limited NfL production with respect to control; specifically, relative change in serum NfL concentration at day-8 was 43% and 60% lower for the M50 and M100 groups, respectively. Likewise, for the assessment of absolute serum NfL at day-8 and day-15, there was a significantly lower NfL concentration for masitinib treatment as compared with control. Furthermore, EAE mice treated with masitinib showed significantly lower concentrations of several well-established pro-inflammatory cytokines relative to control at day-15. A beneficial effect of masitinib on functional performance was also observed, with both M50 and M100 groups showing significantly less relative deterioration in grip strength at day-15 as compared with control (p<0.001). ConclusionThis study is the first demonstration that masitinib, a drug that targets the innate as opposed to the adaptive neuroimmune system, can lower serum NfL levels, and by extension therefore, neuronal damage, in a neuroimmune-driven neurodegenerative disease model. Overall, findings indicate that masitinib has a neuroprotective effect under conditions of chronic neuroinflammation and therefore plausible disease-modifying activity across a broad range of neurodegenerative diseases.

neuroscience↗

bioRxiv2021

Exploring the genomic diversity and antimicrobial susceptibility of Bifidobacterium pseudocatenulatum in the Vietnamese population to aid probiotic design

Bifidobacterium pseudocatenulatum is a member of the human gut microbiota, and has previously been used as a probiotic to improve gut integrity and reduce inflammatory responses. We showed previously that B. pseudocatenulatum was significantly depleted during dysenteric diarrhea, suggesting the organism may aid in recovery from diarrhea. Here, in order to investigate its probiotic potential, we aimed to assess the genomic diversity and predicted metabolic profiles of B. pseudocatenulatum found colonizing the gut of healthy Vietnamese adults and children. We found that the population of B. pseudocatenulatum from each individual was distinct and highly diverse, with intra-clonal variation attributed to gain or loss of carbohydrate utilizing enzymes. The B. pseudocatenulatum genomes were enriched with glycosyl hydrolases that target plant-based non-digestible carbohydrates (GH13, GH43), but not host-derived glycans. Notably, the exopolysaccharide biosynthesis region from organisms isolated from healthy children showed greater genetic diversity, and was subject to a high degree of genetic modification. Antimicrobial susceptibility testing revealed that the Vietnamese B. pseudocatenulatum were uniformly susceptible to beta-lactams, but exhibited variable resistance to azithromycin, tetracycline, ciprofloxacin and metronidazole. The genomic presence of ermX and tet variants conferred resistance against azithromycin and tetracycline, respectively; ciprofloxacin resistance was associated with mutation(s) in the quinolone resistance determining region (GyrA, S115 and/or D119). Our work provides the first detailed genomic and antimicrobial resistance characterization of B. pseudocatenulatum found in the Vietnamese population, which could inform the next phase of rational probiotic design. ImportanceBifidobacterium pseudocatenulatum is a probiotic candidate with potential applications in several health conditions, but its efficacy is largely strain-dependent and associated with distinct genomic and biochemical features. However, most commercial probiotics have been developed by Western institutions, which may not have ideal efficacy when administered in developing countries. This study taps into the underexplored diversity of the organism in Vietnam, and provides more understanding to its lifestyles and antimicrobial susceptibility. These data are key for selecting an optimal probiotic candidate, from our established collection, for downstream investigations and validation. Thus, our work represents a model in identifying and characterizing bespoke probiotics from an indigenous population in a developing setting.

microbiology↗