Lysosomes are ubiquitous acidified organelles that degrade intracellular and extracellular material trafficked via multiple pathways. Lysosomes also sense cellular nutrient levels to regulate target of rapamycin (TOR) kinase, a signaling enzyme that drives growth and suppresses activity of the MiT/TFE family of transcription factors that control biogenesis of lysosomes. In this study, we subjected worms lacking basic helix–loop–helix transcription factor 30 (hlh-30), the Caenorhabditis elegans MiT/TFE ortholog, to starvation followed by refeeding to understand how this pathway regulates survival with variable nutrient supply. Loss of HLH-30 markedly impaired survival in starved larval worms and recovery upon refeeding bacteria. Remarkably, provision of simple nutrients in a completely defined medium (C. elegans maintenance medium [CeMM]), specifically glucose and linoleic acid, restored lysosomal acidification, TOR activation, and survival with refeeding despite the absence of HLH-30. Worms deficient in lysosomal lipase 2 (lipl-2), a lysosomal enzyme that is transcriptionally up-regulated in starvation in an HLH-30–dependent manner, also demonstrated increased mortality with starvation–refeeding that was partially rescued with glucose, suggesting a critical role for LIPL-2 in lipid metabolism under starvation. CeMM induced transcription of vacuolar proton pump subunits in hlh-30 mutant worms, and knockdown of vacuolar H⁺-ATPase 12 (vha-12) and its upstream regulator, nuclear hormone receptor 31 (nhr-31), abolished the rescue with CeMM. Loss of Ras-related GTP binding protein C homolog 1 RAGC-1, the ortholog for mammalian RagC/D GTPases, conferred starvation–refeeding lethality, and RAGC-1 overexpression was sufficient to rescue starved hlh-30 mutant worms, demonstrating a critical need for TOR activation with refeeding. These results show that HLH-30 activation is critical for sustaining survival during starvation–refeeding stress via regulating TOR. Glucose and linoleic acid bypass the requirement for HLH-30 in coupling lysosome nutrient sensing to survival.

This review explores the dual regenerative and antimicrobial properties of platelet- and marrow-derived biologics, including platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), autologous protein solutions, and plasma fractions. These biologics, widely used in regeneration and tissue repair, offer multiplex bioactivity through growth factors, cytokines, and cellular components that promote healing while reducing infection risk. PRP and BMAC demonstrate significant regenerative effects in musculoskeletal conditions, wound healing, and cartilage repair, with platelets and leukocytes contributing antimicrobial peptides and immune modulation for more indirect regenerative mechanisms. Preparation methods, patient factors, and lack of standardization impact clinical outcomes and efficacy. While promising for reducing reliance on chronic pain medications and improving function, these therapies face limitations including inconsistent preparation and utilization protocols, limited long-term safety data, and regulatory challenges. Here, we review the need for consensus-building, standardized procedures, and robust research to optimize clinical integration and realize the full potential of biologic regenerative therapies in pain medicine.

Absorbable Antibacterial Envelope Reduces Surgical Site Infections for Intrathecal Pain Pump Implants: A Retrospective Analysis