Biology subjects

Nguyen, T. K.

Publications and source records attributed to Nguyen, T. K..

8 recordsLinked to original sources

bioRxiv2026

Fatty acid metabolism and dietary lipid composition shape B-cell responses

B-cell activation requires extensive metabolic reprogramming, yet how B cells acquire and utilize extracellular fatty acids and adapt to changes in lipid availability remains poorly understood. Here, we show that B-cell activation and the extracellular lipid environment dynamically regulate B cells. B-cell receptor (BCR) and Toll-like receptor 4 (TLR4) stimulation induced distinct mitochondrial and lipid-handling programs, differentially regulating fatty-acid uptake, cholesterol acquisition, lipid storage and mitochondrial respiration. Disrupting long-chain fatty-acid uptake, acyl-CoA activation, or mitochondrial utilisation impaired B-cell proliferation, demonstrating that multiple steps of fatty-acid metabolism are required for B-cell expansion. However, increasing extracellular fatty-acid availability alone did not enhance proliferation, indicating that fatty-acid acquisition and metabolic utilisation are functionally distinct. B cells also acquired fatty acids directly from adipocytes, identifying the local microenvironment as a potential source of metabolic substrates. In vivo, dietary fatty-acid chain length differentially shaped the germinal-centre response. A long-chain fatty-acid-rich diet increased germinal-centre B cells and T follicular helper cells and induced mitochondrial and transcriptional changes that partially converged with those observed following obesogenic feeding. Circulating lipidomics further revealed shared remodelling of lipid species between long-chain fatty-acid-rich and obesogenic diets, including altered partitioning of stearate-containing lipids. Exogenous fatty acids also modified membrane order in activated B cells, suggesting that lipid availability can influence both metabolic and biophysical properties. Together, these findings establish fatty-acid uptake, activation, and utilization as integral components of B-cell metabolic adaptation and demonstrate that dietary fatty-acid composition can remodel the lipid environment and germinal-centre response.

immunology↗

bioRxiv2026

Apoptotic bodies from patients with Sjogren's disease drive atypical memory B cell and macrophage activation and autoantibody production

The impaired clearance of apoptotic cells has long been associated with systemic autoimmune diseases like Sjogrens disease (SjD), which is characterised by autoantibodies targeting antigens on apoptotic cells. However, most studies analysing human samples have used patient-derived phagocytes and in vitro generated apoptotic cells, which do not reflect the heterogeneity of patient-derived apoptotic bodies (ApoBDs). Here, we molecularly and functionally compare ApoBDs derived from patients with SjD and healthy donors. ApoBDs were increased in the circulation in SjD and induced atypical memory B cell expansion, which was attenuated by blocking B cell receptor (BCR) and Toll-like receptors (TLR) 7-9 signalling. Co-cultures of ApoBDs and B cells drove autoantibody production. Macrophages engulfing SjD ApoBDs had a distinct inflammatory profile compared to macrophages engulfing healthy control ApoBDs. These findings define patient-derived ApoBDs as immunostimulatory substrates capable of driving innate and adaptive immune responses consistent with the pathogenic features observed in SjD, hence opening a new avenue of diagnostic and therapeutic development.

immunology↗

bioRxiv2026

A Long-lived Avatar for Modeling Age-Related Vascular Disease

BackgroundCurrent microphysiological models do not support long-term investigations into the chronic effects of vascular risk factors and the development of vascular diseases. Prolonged culture frequently leads to cellular senescence and loss of functional integrity, resulting in variability and inconsistency in modeling chronic vascular responses. Here we aimed to develop and sustain a long-term multicellular human vascular avatar, addressing the critical need for long-term disease modeling and drug testing. MethodsTo identify the optimal media for longevity, cell identity and function were assessed by morphology, qPCR, beta-gal staining, ELISA, bulk RNA-seq and single cell RNA-seq analysis. After optimizing the culture media, iPSCs-derived ECs and VSMCs from unaffected and Hutchinson-Gilford Progeria Syndrome (HGPS) donors were grown in Gravitational Lumen Patterning (GLP) Vessel- Chips for 1-6 months to generate a long-lived vascular avatar for the study of vascular aging. ResultsGuided by quantitative morphological analyses and bulk RNAseq profiling, we generated a novel optimized culture media VSL (VEGF, SB431542 as a TGF-{beta} inhibitor, low fetal bovine serum) that enhances the long-term health of vascular endothelial cells (ECs). Furthermore, we modified the VSL formulation (mVSL) by modulating 8Br-cAMP, FGF, PDGF, and a cell viability enhancer HMH1015 levels to enhance EC-VSMC (vascular smooth muscle cell) crosstalk and support long-term cellular viability. Subsequently, we maintained and characterized a human vascular avatar with a three-dimensional extracellular matrix environment and 3D vascular architecture for over 180 days. Finally, we demonstrated that this long-lived human vascular avatar enabled modeling vascular aging using iPSC-derived vascular cells from patients with Hutchinson-Gilford Progeria Syndrome (HGPS). ConclusionsWe have successfully engineered and maintained a human vascular avatar for over 180 days. The vascular avatar provides a robust platform for modeling disease-associated vascular aging and for evaluating therapeutic strategies targeting chronic vascular disorders.

bioengineering↗

bioRxiv2025

VN1K: a genome graph-based and function-driven multi-omics and phenomics resource for the Vietnamese population

Vietnam, the 16th most populated nation, remains profoundly underrepresented in global genomic databases. Here, we present VN1K, a first-ever comprehensive and well-curated resource of multi-omics data with a wide-range of phenotypic information of 1,011 unrelated Vietnamese individuals. High-depth short-read whole-genome sequencing data were generated for all samples along with various - omic data, including microarray, long-read whole-genome sequencing, and RNA sequencing. Using a high-sensitivity variant detection pipeline, which included a pangenome graph reference and a deep-learning framework, we identified nearly 40 million variants of which 8.5 million are novel with nearly 900 thousand short insertions/deletions and 39 thousand structural variants. Specifically, VN1K featured a first-ever whole-genome methylation profile based on long read sequencing. A genotype imputation panel was also created with the highest accuracy on the Vietnamese population. Variants with significantly different allele frequencies in the Vietnamese population compared to others were found to be functionally significant, especially in genes associated with immune diseases (HLA-B, KIR3DL3, KIR2DL1, KIR2DL4) or drug responses (CYP2C19, CYP2D6, VKORC1, CYP2B6). We were also able to map various loci related to hepatitis B virus infection as well as six disease traits, including triglyceride levels, LDL-C, serum glucose levels, HbA1c, and levels of two liver enzymes (ALT and AST). VN1K dataset is accessible via genome.vinbigdata.org, an integrated platform with both linear and graph-based genome browser for facilitating data exploration, research, and applications in precision medicine.

genomics↗

bioRxiv2024

Cytotoxic activity against human leukemia cells of Kaempferol-3-O-rhamnoside from Vietnamese Schima wallichii (DC.) Korth: A combination of in vitro and in silico insights

In the investigation of the cytotoxic activity against leukemia cells of Vietnamese medicinal plants, we identified the extract of Schima wallichii (DC.) Korth as capable of inhibiting several leukemia cell lines. In this study, we isolated a main compound as kaempferol-3-O-rhamnoside, marking the first report of this compound being isolated from the stem of Schima wallichii collected in Vietnam. In in vitro experiments, kaempferol-3-O-rhamnoside exhibited cytotoxic effects on three leukemia cell lines, HL-60 and KG-1. Regarding its mechanism of action, the compound effectively inhibited growth of HL-60 and KG-1 leukemia cell lines by activating caspase-3 and caspase-9 in both cell lines. Additionally, kaempferol-3-O-rhamnoside upregulated the pro-apoptotic protein Bax while downregulating the anti-apoptotic protein Bcl-2 in these cell lines. In silico experiments revealed that docking simulations showed kaempferol-3-O-rhamnoside binds to both the allosteric site of procaspase-3 and the active site of PARP1, with binding energies of -7.36 and -10.76 kcal/mol, respectively. Kaempferol-3-O-rhamnoside demonstrated stable binding affinity with PARP1, characterized by significant hydrogen bonding, hydrophobic interactions, and pi-stacking in the molecular dynamic simulations. These results suggest that kaempferol-3-O-rhamnoside has the potential PARP1 inhibitor, making it a promising candidate for targeting leukemia cells. Moreover, it provides evidence for considering this compound in drug discovery and development targeting PARP1-related pathways.

pharmacology and toxicology↗

bioRxiv2024

Emx2 is an essential regulator of ciliated cell development across embryonic tissues

Cilia are hair-like organelles with vital physiological roles, and ciliogenesis defects underlie a range of severe congenital malformations and human diseases. Here, we report that the empty spiracles homeobox gene 2 (emx2) transcription factor is essential for cilia development across multiple embryonic tissues including the ear, neuromasts and Kupffers vesicle (KV), which establishes left/right axial pattern. emx2 deficient embryos manifest altered fluid homeostasis and kidney defects including decreased multiciliated cells (MCCs), revealing that emx2 is essential to properly establish several renal lineages as well. Further, emx2 deficiency disrupted ciliogenesis on renal monociliated cells and MCCs, and led to aberrant basal body positioning in kidney cells. Interestingly, we discovered that emx2 deficiency was associated with reduced expression of key factors which regulate prostaglandin biosynthesis: the transcriptional regulator peroxisome proliferator-activated receptor gamma 1 alpha (ppargc1a) and its downstream target prostaglandin-endoperoxide synthase 1 (ptgs1), which encodes a crucial enzyme for production of the prostanoid ligand prostaglandin E2 (PGE2). Importantly, both ciliogenesis and renal fate changes were rescued when emx2 deficient embryos were provided with PGE2 or transcripts encoding ptgs1 or ppargc1a. Taken together, our findings reveal new essential roles of emx2 in cilia development across several tissues, and identify emx2 as a critical, novel regulator of prostaglandin biosynthesis during renal development and ciliogenesis.

developmental biology↗

bioRxiv2023

A study of genetic variants associated with skin traits in the Vietnamese population

BackgroundMost skin-related traits have been studied from Caucasian genetic background. A comprehensive study on skin-associated genetic effects on under-represented populations like Vietnam is needed to fill the gaps in the field. ObjectivesTo develop a computational pipeline to predict the effect of genetic factors on skin traits using public data (GWAS catalogs and whole genome sequencing (WGS) data of 1000 genomes project-1KGP) and in-house Vietnamese data (WGS and genotyping by SNP array). By using this information we may have a better understanding of the susceptibility of Vietnamese people. MethodsVietnamese cohorts of whole genome sequencing (WGS) of 1008 healthy individuals for the reference and 96 genotyping samples (which do not have any skin cutaneous issues) by Infinium Asian Screening Array-24 v1.0 BeadChip were employed to predict skin-associated genetic variants of 25 skin-related and micronutrients requirement traits in population analysis and correlation analysis. Simultaneously, we compared the landscape of cutaneous issues of Vietnamese people with other populations by assessing their genetic profiles. ResultsThe skin-related genetic profile of Vietnamese cohorts is similar at most with East Asian (JPT: Fst=0.036, CHB: Fst=0.031, CHS: Fst=0.027, CDX: Fst=0.025) in the population study. In addition, we identified pairs of skin traits being at high risk of frequent co-occurrence (such as skin aging and wrinkles (r = 0.45, p =1.50e-5) or collagen degradation and moisturizing (r = 0.35, p = 1.1e-3). ConclusionThis is the first investigation in Vietnam to explore genetic variants of facial skin. These findings could improve inadequate skin-related genetic diversity in the currently published database.

bioinformatics↗

bioRxiv2022

Holographic stimulation of opposing amygdala ensembles bidirectionally modulates valence-specific behavior

The basolateral amygdala (BLA) is an evolutionarily conserved brain region, well known for valence processing. Despite this central role, the relationship between activity of BLA neuronal ensembles in response to appetitive and aversive stimuli and the subsequent expression of valence-specific behavior has remained elusive. Here we leverage 2-photon calcium imaging combined with single cell holographic photostimulation through an endoscopic lens implanted in the deep brain to demonstrate a direct causal role for discrete ensembles of BLA neurons in the control of oppositely valenced behavior. We report that targeted photostimulation of individual groups of appetitive or aversive BLA neurons shifts behavioral responses toward those behaviors which recruited a specific consumption or avoidance ensemble. Here we identify that neuronal encoding of valence in the BLA is graded and relies on the relative proportion of individual BLA neurons recruited in a stable appetitive or aversive ensemble.

neuroscience↗