Biology subjects

Garg, B.

Publications and source records attributed to Garg, B..

4 recordsLinked to original sources

bioRxiv2026

Biomechanical effects of load-carrying in adolescent idiopathic scoliosis: a subject-specific musculoskeletal modelling study

Load carrying is a common activity during adolescence, yet its biomechanical consequences for the structurally asymmetric spine in adolescent idiopathic scoliosis (AIS) remain poorly understood. This study investigated how load magnitude, carrying height, and side of application influence spinal loading and paraspinal muscle forces in AIS. A subject-specific musculoskeletal model of a 16-year-old female with a 59{degrees} right-convex thoracic curve was used to simulate bilateral and unilateral load carrying at the hand, chest, and above-shoulder levels, with loads corresponding to 5%, 10%, and 15% of body weight. Intervertebral compressive and lateral forces and erector spinae (ES) and multifidus (MF) muscle forces were evaluated. Spinal loading increased progressively with load magnitude and carrying height. At 15% body weight, compressive forces at the curve apex increased from 511-566 N at hand level to 721-831 N above the shoulder. Unilateral carrying produced distinct side-dependent responses: convex-side carrying generated greater compressive forces, whereas concave-side carrying generated greater lateral forces, which were concentrated around the curve apex. Paraspinal muscles also exhibited muscle-specific responses. ES forces primarily reflected the imposed external asymmetry, with unilateral carrying eliciting predominantly contralateral recruitment, whereas MF maintained a characteristic convex-side dominance concentrated around the curve apex. These findings demonstrate that load carrying in AIS produces a coupled biomechanical response governed by both the external loading configuration and the pre-existing structural asymmetry of the spine, highlighting the importance of considering loading direction and muscular adaptation alongside load magnitude when evaluating everyday carrying activities in AIS.

bioengineering↗

bioRxiv2026

Influence of trunk posture on spinal loading and paraspinal muscle forces in adolescent idiopathic scoliosis: a subject-specific musculoskeletal modelling study

Adolescent idiopathic scoliosis (AIS) alters spinal geometry and may influence the biomechanical response of the spine during functional postures. However, posture-dependent changes in spinal loading and paraspinal muscle forces in AIS remain poorly understood. This study investigated the effects of trunk posture on intervertebral loading and paraspinal muscle forces using a subject-specific musculoskeletal model of an adolescent with AIS. The spinal deformity was reconstructed from biplanar radiographs and incorporated into a full-body musculoskeletal model. Flexion, extension, lateral bending, and axial rotation were simulated at three incremental magnitudes, with motion distributed across the thoracolumbar spine. Intervertebral compressive and lateral forces around the curve apex and forces in the erector spinae (ES) and multifidus (MF) muscles were evaluated. Trunk flexion produced the greatest compressive loading, reaching 337 N at the curve apex and 372 N two levels below the apex at 30{degrees} flexion. Lateral bending produced pronounced direction-dependent loading: concave-side bending increased lateral forces, whereas convex-side bending increased compressive forces. Axial rotation produced similar but smaller direction-dependent changes. Paraspinal muscle forces were consistently asymmetric, with concave-side dominance of the ES and convex-side dominance of the MF. Flexion and convex-sided movements generally produced greater muscle imbalance, while increasing posture magnitude amplified spinal loading and muscle forces. These findings demonstrate that trunk posture, movement direction, and magnitude substantially influence the biomechanical environment of the scoliotic spine and should be considered when evaluating spinal mechanics in AIS.

bioengineering↗

bioRxiv2026

Vitamin D mitigates Inflammatory Bone Loss in Postmenopausal Osteoporosis via modulating the Gut-Immune-Bone axis

Osteoporosis is a prevalent skeletal disorder characterized by deterioration of bone microarchitecture and loss of bone mineral density, leading to increased fracture risk and substantial health and economic burdens, particularly among older adults. Bone remodeling is orchestrated by a complex interplay of systemic and local regulators, among which vitamin D plays a central role in maintaining skeletal homeostasis. Although numerous studies have examined the effects of vitamin D on bone metabolism, outcomes have been inconsistent across populations, dosing regimens, and experimental models. To clarify the net skeletal impact of vitamin D, we investigated its effects in postmenopausal osteoporosis (PMO). Vitamin D (1,25-dihydroxyvitamin D3- active form of vitamin D) supplementation effectively prevented bone loss in ovariectomized mice, at both lower and higher concentrations. Mechanistically, vitamin D promoted osteoclast differentiation in vitro, consistent with its RANKL-dependent pro-osteoclastogenic activity, yet paradoxically conferred bone protection in vivo. This discrepancy was explained by vitamin Ds profound immunomodulatory effects, which reshaped both innate and adaptive immune responses to suppress osteoclast formation and function. Concurrently, vitamin D improved intestinal barrier integrity and restored gut microbial composition, thereby stabilizing the gut-immune-bone axis and reducing pro-resorptive inflammatory signaling. Together, these findings demonstrate that vitamin D prevents bone loss through the coordinated regulation of immune and gut homeostasis, reconciling its apparent pro-resorptive effects in vitro with its overall anti-resorptive outcomes in vivo. This integrated mechanism highlights immune-gut microbial modulation as a key mediator of vitamin D-induced bone preservation and supports the development of vitamin D as an immunotherapeutic adjunct for the prevention and management of PMO. Altogether, our findings for the first time dissect the paradox surrounding the osteoprotective property of vitamin D supplementation. O_FIG O_LINKSMALLFIG WIDTH=186 HEIGHT=200 SRC="FIGDIR/small/735433v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@1550497org.highwire.dtl.DTLVardef@a06ab4org.highwire.dtl.DTLVardef@1bd55e5org.highwire.dtl.DTLVardef@1526acd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Vitamin D strengthens intestinal barrier integrity and restores gut microbial composition, which stabilizes the gut-bone axis and suppresses pro-resorptive inflammatory signaling. Vitamin D enhances osteoclastogenesis both directly and through ILC3- and Th17-mediated pathways, while inhibiting osteoclastogenesis via Treg- and Breg-dependent mechanisms. In circulation, vitamin D maintains the homeostasis between IL-10 and IL-17 cytokines. Collectively, these results indicate that vitamin D helps prevent bone loss by orchestrating the immune system and maintaining gut homeostasis. C_FIG

immunology↗

bioRxiv2024

MICAL2 Is a Super Enhancer Associated Gene that Promotes Pancreatic Cancer Growth and Metastasis

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid cancers and thus identifying more effective therapies is a major unmet need. In this study we characterized the super enhancer (SE) landscape of human PDAC to identify novel, potentially targetable, drivers of the disease. Our analysis revealed that MICAL2 is a super enhancer-associated gene in human PDAC. MICAL2 is a flavin monooxygenase that induces actin depolymerization and indirectly promotes SRF transcription by modulating the availability of serum response factor coactivators myocardin related transcription factors (MRTF-A and MRTF-B). We found that MICAL2 is overexpressed in PDAC and correlates with poor patient prognosis. Transcriptional analysis revealed that MICAL2 upregulates KRAS and EMT signaling pathways, contributing to tumor growth and metastasis. In loss and gain of function experiments in human and mouse PDAC cells, we observed that MICAL2 promotes both ERK1/2 and AKT activation. Consistent with its role in actin depolymerization and KRAS signaling, loss of MICAL2 expression also inhibited macropinocytosis. Through in vitro phenotypic analyses, we show that MICAL2, MRTF-A and MRTF-B influence PDAC cell proliferation, migration and promote cell cycle progression. Importantly, we demonstrate that MICAL2 is essential for in vivo tumor growth and metastasis. Interestingly, we find that MRTF-B, but not MRTF-A, phenocopies MICAL2-driven phenotypes in vivo. This study highlights the multiple ways in which MICAL2 impacts PDAC biology and suggests that its inhibition may impede PDAC progression. Our results provide a foundation for future investigations into the role of MICAL2 in PDAC and its potential as a target for therapeutic intervention.

cancer biology↗