Biology subjects

Hong, J. M.

Publications and source records attributed to Hong, J. M..

4 recordsLinked to original sources

bioRxiv2026

Vibration's frequency and intensity for optimal setup for enhancement bone response in small rodents: A systematic review and Bayesian network meta-analysis

Low-intensity vibration (LIV) is a non-invasive mechanical stimulus capable of regulating skeletal adaptation and cellular signaling pathways involved in bone remodeling. Despite growing interest in LIV, substantial methodological heterogeneity persists in the selection of experimental vibration parameters such as frequency, expressed in Hertz (Hz) and intensity, defined as earths gravitational field (g) (9.81 m/s2). Focusing on micro-computed tomography ({micro}CT) derived trabecular bone volume fraction (BV/TV) as the main outcome mesure, this study sought to synthesize the effects of different LIV frequency and intensity on BV/TV in small rodents (mice and rats) as they remain as the most studied pre-clinical model. To accomplish this, we performed a systematic review searching for publications in English on PubMed, Web of Science, CINAHL, and Embase databases. Two independent investigators followed inclusion criteria to select only peer-reviewed studies with mature mice, using whole-body vibration experiments without other co-variables. We further restricted to include studies that analyzed non-fractured bones and compared pre- and post-intervention or control values. In addition to these core criteria, a detailed hierarchical screening framework was applied during full-text review. The two independent investigators extracted data independently and considered the characteristics of the study, animals characteristics, intervention characteristics, and results. For this study we considered load-bearing hindlims, femur and tibia, separately but did not include vertebrae in the analysis. A Bayesian network meta-analysis and a revised SYRCLE risk of bias (RoB) tool were used to evaluate the risk of bias across included studies. Seven studies met the inclusion criteria. Results showed that an LIV regime applied at 45Hz at 2g presented higher chances to increase trabecular BV/TV of the mouse tibia (estimated effect 3.22 [CrI 1.98, 4.45]), while LIV regimes applied to the femur at 90Hz and 1.4g (estimated effect 3.08 [CrI -1.99, 7.97]) present better chances to increase trabecular BV/TV results compared to other interventions but with no significant differences. Finally, we applied 45Hz at 0.2g LIV to 5 month old male C57BL/6 for 5 weeks (n=10/group) which showed significantly increased Trabecular Thickness (Tb.Th) for both the tibia (10%, p<0.01) and femur (17%, p<0.001), with the femur showing further increaseses in trabecular BV/TV (32%, p<0.05) compared to non-LIV controls. We conclude that changes in the microarchitectures of the tibia and femur respond differently to the same application of LIV (45Hz, 0.2g) in mice and rats.

bioengineering↗

bioRxiv2023

RNF213 variant and autophagic impairment: A pivotal link to endothelial dysfunction in Moyamoya disease

BackgroundMoyamoya disease (MMD) is closely associated with the Ring Finger Protein 213 (RNF213), a susceptibility gene for this disease. However, its biological function remains unclear. We aimed to elucidate the role of RNF213 in the damage incurred by human endothelial cells under oxygen-glucose deprivation (OGD), a condition that mimics intracranial ischemia in patients with MMD. MethodsWe analyzed autophagy in peripheral blood mononuclear cells (PBMCs) derived from patients carrying either RNF213 wild-type (WT) or variant (R4810K). Subsequently, human umbilical vein endothelial cells (HUVECs) were transfected with RNF213 WT (HUVECWT) or R4810K (HUVECR4810K) and exposed to OGD for 2 h to determine the role of the RNF213 variant in such a setting. Immunoblotting was used to analyze autophagy marker proteins, and tube formation assays were performed to examine endothelial function. Autophagic vesicles were observed using transmission electron microscopy. Post-OGD exposure, we administered autophagy modulators such as rapamycin and cilostazol. ResultsThe RNF213 variant group during post-OGD exposure (vs. pre-OGD exposure) showed autophagy inhibition, increased protein expression of SQSTM1/p62 (p < 0.0001) and LC3-II (p = 0.0039), and impaired endothelial function (p = 0.0252). HUVECR4810K during post-OGD exposure (versus pre-OGD exposure) showed a remarkable increase in autophagic vesicles. Administration of autophagy modulators notably restored the function of HUVECR4810K and cellular autophagy. ConclusionsOur findings support the pivotal role of autophagy impaired by the RNF213 variant in MMD-induced endothelial cell dysfunction and underscore the critical mechanism of autophagy leading to progressive endothelial dysfunction and MMD pathogenesis under relative ischemia within the intracranial portion.

neuroscience↗

bioRxiv2023

MMPs and NETs are detrimental in human CNS-tuberculosis and MMP inhibition in a mouse model improves survival

Despite anti-tuberculous treatment (ATT), central nervous system tuberculosis (CNS-TB) still cause permanent neurological deficits and death. To identify prognostic factors, we profiled a prospective cohort of tuberculous meningitis (TBM) and non-TBM patients. We determined significantly increased cerebrospinal fluid (CSF) matrix metalloproteinases (MMPs) and neutrophil extracellular traps (NETs) are up-regulated in TBM patients with neuroradiological abnormalities and poor outcomes. To dissect mechanisms, we created a CNS-TB murine model which show neutrophil-rich necrotizing pyogranulomas with MMP-9 and NETs colocalizing, resembling human CNS-TB. Spatial transcriptomic analysis of both human and murine CNS-TB demonstrates a highly-inflamed and neutrophil-rich microenvironment of inflammatory immune responses, extracellular matrix degradation and angiogenesis within CNS-TB granulomas. Murine CNS-TB treated with ATT and MMP inhibitors SB-3CT or doxycycline show significantly suppressed NETs with improved survival. MMP inhibition arms show attenuated inflammation and well-formed blood vessels within granulomas. Adjunctive doxycycline is highly promising to improve CNS-TB outcomes and survival.

pathology↗

bioRxiv2021

Nos2-/- mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis

BackgroundUnderstanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. MethodsWe injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. ResultsIntra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. ConclusionsIntra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

microbiology↗