bioRxiv Science⌕ Search

Biology subjects

Mumtaz, M.

Publications and source records attributed to Mumtaz, M..

2 recordsLinked to original sources

Biomechanical Implications of Spinopelvic Alignment on Femoral Head Cartilage and the Proximal Femoral Physis in Slipped Capital Femoral Epiphysis: A Theoretical Finite Element Analysis

BackgroundSlipped capital femoral epiphysis (SCFE) is a prevalent pediatric hip disorder. Recent studies suggest the spines sagittal profile may influence the proximal femoral growth plates slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how different spinopelvic alignments affect shear stress and potential slippage at the growth plate. MethodsA finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through rotational boundary conditions. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum Tresca (shear) stress on the growth plate. FindingsPosterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear stress. InterpretationOur findings suggest that posterior pelvic tilt and high pelvic incidence can lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially causing slippage.

bioengineering↗

Large pan-cancer cell screen coupled to (phospho-) proteomics underscores high-dose vitamin C as a potent anti-cancer agent

Increasing preclinical and clinical evidence has positioned high-dose vitamin C as a promising anti-cancer treatment that merits more clinical attention. Multiple cytotoxicity mechanisms have been described, including pro-oxidant effects. To contribute to the preclinical understanding of the broad pan-cancer effects of high-dose vitamin C in a global manner, we determined the IC50 of a large panel of cancer cell lines (n=51) representing 7 solid tumour types and generated proteome data. The majority of cell lines were highly sensitive (IC50 range 0.036-10mM, mean 1.7 {+/-} 0.4 mM), well below a clinically achievable dose. The proteome data (>5000 proteins per sample), showed that high sensitivity is associated with proliferation, as indicated by functional enrichment of cell cycle, RNA splicing and chromatin organization, while lower sensitivity is linked to extracellular vesicles, glycolysis, fatty acid metabolism and mitochondria. Moreover, (phospho-)proteome analysis of on-treatment vitamin C effects on four pancreatic ductal adenocarcinoma (PDAC) cells dosed at a range of IC50 values (Hs766 T, 2 mM; Capan-2, 0.6 mM; PANC-1, 0.14 mM and Suit-2, 0.1 mM) revealed, next to cell line specific effects, down-modulation of AKT-MTOR signalling and immune suppressive signalling, while IFN- response was enhanced upon vitamin C. Altogether, our comprehensive pharmacological and (phospho-)proteome analysis is the first to assess cancer vulnerabilities and effects of vitamin C on a large cancer cell line panel and underscores the potential of high-dose vitamin C as an anti-cancer agent.

cancer biology↗