Jai Narain Vyas University

Duchenne Muscular Dystrophy (DMD) is a severe X-linked genetic disorder caused by a mutation in the dystrophin gene. Current treatments primarily rely on symptomatic management of DMD pathophysiology by corticosteroid treatment, as exon skipping drugs are inaccessible to the majority of the DMD population due to their high treatment cost. However, long-term corticosteroid treatment is associated with a range of adverse effects. To address this, we developed a peptide library derived from a myogenesis-promoting micropeptide and identified M.P-2 as a lead candidate for promoting myogenesis. M.P-2 was further engineered to E.M.P-2, a mitochondrial-targeted peptide to address DMD's secondary pathologies. E.M.P-2 promotes myogenic differentiation by upregulating MyHC and MyoD at a nanomolar dose (0.156 μM) while suppressing fibrosis. It effectively chelates calcium ions to reduce mitochondrial reactive oxygen species (ROS), and maintain mitochondrial membrane potential. E.M.P-2 also demonstrates significant potential in modulating inflammation via inhibiting the expression of IL-6 and TGFβ. Mechanistically, E.M.P-2 functions through inhibition of mitoROS-driven activation of the NF-κB pathway, which collectively promotes myogenesis, suppresses fibrosis, and manages inflammation. Overall, E.M.P-2 holds potential for addressing DMD pathophysiology as the first peptide-based therapeutic providing a safer alternative to corticosteroids.

The global surge in plastic production and inadequate waste management have resulted in widespread environmental contamination with microplastics (MPs). Derived either as primary particles from consumer products or as secondary fragments from the degradation of larger plastics, MPs are now omnipresent in terrestrial, aquatic, and atmospheric ecosystems. Their small size, durability, and surface reactivity enable biofilm formation, heavy metal adsorption, and easy entry into food chains, ultimately posing significant risks to human health. This review outlines the sources, types, human exposure, including dietary intake, inhalation, and dermal contact, and their toxicological impacts on multiple organ systems. MPs can cross biological barriers, including the gastrointestinal epithelium, blood-brain barrier, and placenta, leading to distribution and bioaccumulation. Mechanistically, they induce oxidative stress, inflammation, immune dysregulation, and disruption of the gut microbiota. In the digestive system, MPs impair intestinal integrity, inhibit digestive enzymes, and promote hepatic inflammation. Inhalation alters pulmonary surfactant function, triggers cytokine release, and is implicated in asthma, fibrosis, and chronic obstructive pulmonary disease. MPs also function as endocrine-disrupting chemicals, interfering with hypothalamic-pituitary axes and reproductive hormones, thereby affecting fertility and development. Neurological consequences include oxidative stress-mediated neurotoxicity, neuroinflammation, and potential links to neurodegenerative disorders. Additionally, chronic exposure to MPs and associated additives may promote carcinogenesis by inducing DNA damage, persistent inflammation, and immune evasion. Collectively, these findings highlight MPs as emerging environmental toxins with wide-ranging adverse effects on human health. Further mechanistic studies and regulatory interventions are essential to mitigate exposure and address this growing global health threat.

Diabetes often leads to neurodegenerative complications that complicate treatment. Exploring dietary components with neuroprotective properties could offer new therapeutic avenues. This study aimed to evaluate the neuroprotective potential of β-sitosterol against diabetes-associated neurodegenerative complications using a combined in silico and in vivo approach. β-Sitosterol exhibited significant neuroprotective effects in a diabetic neuropathy model. Compared to sitagliptin, β-sitosterol demonstrated stronger binding affinities to DPP4, acetylcholinesterase, and butyrylcholinesterase, along with more stable molecular dynamics profiles. In vivo, β-sitosterol treatment markedly improved glucose tolerance, insulin sensitivity, lipid profiles, and antioxidant capacity. Histological analysis revealed reduced neurodegenerative changes and enhanced neuronal integrity in the cortex and hippocampus. These findings suggest β-sitosterol as a promising therapeutic agent for managing diabetic neurodegeneration, warranting further research and potential clinical application.