Biology subjects

Lim, J.-H.

Publications and source records attributed to Lim, J.-H..

4 recordsLinked to original sources

bioRxiv2025

Filling the Spinal Fracture Treatment Gap: An Osteoporotic Rabbit Model of Vertebral Augmentation

Background contextVertebral compression fractures (VCFs) are the most common osteoporotic fracture, yet current vertebral augmentation (VA) approaches rely exclusively on poly(methyl methacrylate) (PMMA), a non-resorbable cement that is associated with significant clinical drawbacks. Preclinical models are essential for evaluating novel injectable, bioactive alternatives, but existing small- and large-animal systems have translational limitations. PurposeThe purpose of this study was to develop and validate a reproducible osteoporotic rabbit model that integrates controlled osteoporosis induction with a surgically accessible, fluoroscopically guided VA procedure suitable for preclinical evaluation of novel injectable biomaterials. Study designThis study employed a basic science, preclinical method-development approach using an adult female New Zealand White rabbit model of osteoporosis combined with lumbar VA. MethodsAdult female New Zealand White rabbits underwent bilateral ovariectomy followed by glucocorticoid treatment to establish osteoporosis as confirmed by qCT-derived reductions in bone mineral density and T-scores [≤] -2.5. A novel open dorsal surgical approach was optimized ex vivo and applied in vivo to access the lumbar vertebrae (L4 - L5) for bilateral cortical decortication and PMMA injection. Structural changes were assessed by quantitative CT before and after VA. ResultsThe induction protocol produced consistent, reversible, and re-inducible osteoporotic phenotypes, with significant reductions in trabecular and cortical density as well as thinning of cortical microarchitecture. The surgical workflow achieved reproducible, fluoroscopically-confirmed cement delivery into the vertebral cancellous compartment while minimizing leakage. Post-VA imaging demonstrated stable trabecular and cortical parameters, with expected reductions in bone surface metrics attributable to surgical access and cement filling. ConclusionThis study establishes the technical feasibility and reproducibility of a combined osteoporotic and VA rabbit model that integrates disease-relevant bone degeneration with a clinically aligned surgical workflow. Clinical significanceThis model bridges a critical translational gap between rodent and large-animal systems and provides a robust preclinical platform for evaluating next-generation injectable, bioactive, and biodegradable materials aimed at improving safety and regenerative outcomes in osteoporotic VCF repair.

bioengineering↗

bioRxiv2021

The cellular characterisation of SARS-CoV-2 spike protein in virus-infected cells using Receptor Binding Domain-binding specific human monoclonal antibodies.

A human monoclonal antibody panel (PD4, PD5, PD7, SC23 and SC29) was isolated from the B cells of convalescent patients and used to examine the S protein in SARS-CoV-2- infected cells. While all five antibodies bound conformational-specific epitopes within SARS-CoV-2 Spike (S) protein, only PD5, PD7, and SC23 were able to bind to the Receptor Binding Domain (RBD). Immunofluorescence microscopy was used to examine the S protein RBD in cells infected with the Singapore isolates SARS-CoV-2/0334 and SARS-CoV-2/1302. The RBD-binders exhibited a distinct cytoplasmic staining pattern that was primarily localised within the Golgi complex and was distinct from the diffuse cytoplasmic staining pattern exhibited by the non-RBD binders (PD4 and SC29). These data indicated that the S protein adopted a conformation in the Golgi complex that enabled the RBD recognition by the RBD-binders. The RBD-binders also recognised the uncleaved S protein indicating that S protein cleavage was not required for RBD recognition. Electron microscopy indicated high levels of cell-associated virus particles, and multiple cycle virus infection using RBD-binder staining provided evidence for direct cell-to-cell transmission for both isolates. Although similar levels of RBD-binder staining was demonstrated for each isolate, the SARS-CoV-2/1302 exhibited slower rates of cell-to-cell transmission. These data suggest that a conformational change in the S protein occurs during its transit through the Golgi complex that enables RBD recognition by the RBD-binders, and suggests that these antibodies can be used to monitor S protein RBD formation during the early stages of infection. ImportanceThe SARS CoV-2 spike (S) protein receptor binding domain (RBD) mediates the attachment of SARS CoV-2 to the host cell. This interaction plays an essential role in initiating virus infection and the S protein RBD is therefore a focus of therapeutic and vaccine interventions. However, new virus variants have emerged with altered biological properties in the RBD that can potentially negate these interventions. Therefore an improved understanding of the biological properties of the RBD in virus-infected cells may offer future therapeutic strategies to mitigate SARS CoV-2 infection. We used physiologically relevant antibodies that were isolated from the B cells of convalescent COVID19 patients to monitor the RBD in cells infected with SARS CoV-2 clinical isolates. These immunological reagents specifically recognise the correctly folded RBD and were used to monitor the appearance of the RBD in SARS CoV-2-infected cells and identified the site where the RDB first appears.

microbiology↗

bioRxiv2021

Eosinophils are dispensable for development of MOG35-55-induced experimental autoimmune encephalomyelitis in mice

Experimental autoimmune encephalomyelitis (EAE) represents the mouse model of multiple sclerosis, a devastating neurological disorder. EAE development and progression involves the infiltration of different immune cells into the brain and spinal cord. However, less is known about a potential role of eosinophil granulocytes for EAE disease pathogenesis. In the present study, we found enhanced eosinophil abundance accompanied by increased concentration of the eosinophil chemoattractant eotaxin-1 in the spinal cord in the course of EAE induced in C57BL/6 mice by immunization with MOG35-55 peptide. However, the absence of eosinophils did not affect neuroinflammation, demyelination and clinical development or severity of EAE, as assessed in {Delta}dblGATA1 eosinophil-deficient mice. Taken together, despite their enhanced abundance in the inflamed spinal cord during disease progression, eosinophils were dispensable for EAE development.

immunology↗

bioRxiv2017

Efficient parameterization of large-scale mechanistic models enables drug response prediction for cancer cell lines

The response of cancer cells to drugs is determined by various factors, including the cells mutations and gene expression levels. These factors can be assessed using next-generation sequencing. Their integration with vast prior knowledge on signaling pathways is, however, limited by the availability of mathematical models and scalable computational methods. Here, we present a computational framework for the parameterization of large-scale mechanistic models and its application to the prediction of drug response of cancer cell lines from exome and transcriptome sequencing data. With this framework, we parameterized a mechanistic model describing major cancer-associated signaling pathways (>1200 species and >2600 reactions) using drug response data. For the parameterized mechanistic model, we found a prediction accuracy, which exceeds that of the considered statistical approaches. Our results demonstrate for the first time the massive integration of heterogeneous datasets using large-scale mechanistic models, and how these models facilitate individualized predictions of drug response. We anticipate our parameterized model to be a starting point for the development of more comprehensive, curated models of signaling pathways, accounting for additional pathways and drugs.

systems biology↗