Biology subjects

Nguyen, T.-A.

Publications and source records attributed to Nguyen, T.-A..

8 recordsLinked to original sources

bioRxiv2026

Increasing plasma bile salt levels with Bulevirtide alleviates DSS-induced colitis and LPS-induced inflammation

Background & AimsBulevirtide, a viral entry inhibitor used to treat chronic hepatitis delta virus (HDV) infection, targets the hepatic bile salt transporter Na+-Taurocholate Co-transporting Polypeptide (NTCP). As Bulevirtide displays preclinical potential to mitigate cholestatic liver injury, NTCP inhibition is currently explored as treatment for primary sclerosing cholangitis (PSC), a condition frequently associated with colitis. Here, we investigated the immunomodulatory effects of Bulevirtide in lipopolysaccharide (LPS)-induced inflammation and dextran sodium sulfate (DSS)-induced colitis in mice. MethodsThe immunomodulatory properties of the bile salt taurochenodeoxycholic acid (TCDC) were investigated in LPS-challenged mouse bone marrow-derived macrophages (BMDM) and human BLaER1 macrophages. The therapeutic efficacy of Bulevirtide against LPS-induced inflammation and DSS-induced colitis was evaluated in Slco1a/1b-/- FVB and C57BL/6J mice, which recapitulate human bile salt dynamics. ResultsIn BMDMs, TCDC reduced pro-inflammatory tumor necrosis factor alpha (TNF), increased anti-inflammatory interleukin (IL)-10, and suppressed inflammasome activation, as evidenced by reduced IL-1{beta}, IL-18 and cleaved-IL-1{beta} levels. Consistently, TCDC also reduced TNF and IL1B expression in human BLaER1 macrophages. In both FVB and C57BL/6J Slco1a/1b-/- mice, Bulevirtide increased plasma bile salt levels at least 30-fold. This systemic elevation of bile salts reduced plasma TNF and increased IL-10 in LPS-treated mice. Moreover, Bulevirtide attenuated DSS-induced colitis, evidenced by reduced disease scores and reduced intestinal Tnf expression. ConclusionThese findings highlight the anti-inflammatory effects of bile salts in preclinical models of colitis and support NTCP inhibition as a future therapeutic strategy to ameliorate both cholestasis and colitis in PSC. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=173 SRC="FIGDIR/small/719641v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@38efbeorg.highwire.dtl.DTLVardef@3e09borg.highwire.dtl.DTLVardef@8f1262org.highwire.dtl.DTLVardef@100179c_HPS_FORMAT_FIGEXP M_FIG C_FIG SynopsisInhibition of the Na+-Taurocholate Co-transporting Polypeptide using Bulevirtide induces systemic bile salt elevation and mitigates acute inflammation and colitis in mice. These findings support clinical evaluation of Bulevirtide in primary sclerosing cholangitis with protective effects against cholestasis and colitis.

immunology↗

bioRxiv2025

A Modular Genetic Code Expansion Approach to Site-Specific Lysine Acylations

Lysine acylations are a diverse class of post-translational modifications (PTMs) that dynamically regulate protein function. Access to homogenous, site-specifically modified proteins is essential for dissecting their molecular roles, yet remains challenging with traditional methods. Here we present a modular strategy that combines genetic code expansion (GCE) with a chemoselective amide bond-forming reaction to install a wide range of lysine acylations directly onto folded proteins. Key to this approach is the genetic encoding of N{varepsilon}-methoxylysine, which reacts efficiently with N-methyliminodiacetyl (MIDA) acylboronates to generate diverse acyl lysine modifications from a single protein precursor, including several acyl PTMs not previously accessible through GCE. This mild and broadly applicable methodology enables systematic studies of lysine acylation on multiple target proteins. We demonstrate its utility by probing the effects of defined acyl modifications on enzymatic activity, protein-RNA interactions and deacylase-mediated regulation. Together, this platform establishes a versatile strategy to interrogate the functional consequences of this wide-spread class of PTMs.

synthetic biology↗

bioRxiv2025

Loss of age-associated increase in m6A-modified RNA contributes to GABAergic dysregulation in Alzheimer's disease

Dysregulated RNA metabolism is a significant feature of Alzheimers disease (AD), yet how post-transcriptional RNA modifications like N6-methyladenosine (m6A) are altered in AD is unknown. Here, we performed deamination adjacent to RNA modification targets (DART-seq) on human dorsolateral prefrontal cortices to assess changes in m6A with nucleotide resolution. In non-AD brains, m6A sites increased with age, predominantly within the 3'UTR of transcripts encoding tripartite synapse proteins. In contrast, AD brains lost the age-associated m6A site increase and exhibited global hypomethylation of transcripts, including MAPT and APP. Hypomethylated genes involved with GABAergic signaling, glutamate transport, and ubiquitin-mediated proteolysis exhibited reduced expression, connecting m6A to synaptic excitotoxicity and disrupted proteostasis in AD. Site-specific m6A levels were linked with GABRA1 expression and protein levels, but this relationship was abolished in AD. Our findings provide insight into post-transcriptional mechanisms of dysregulated RNA metabolism in AD that are related to aging and GABAergic regulation. HIGHLIGHTSO_LIWith age, the number of m6A sites increases among Control cases (lacking AD pathology) but remains unchanged in AD cases. C_LIO_LITranscripts are globally hypomethylated in AD cases. C_LIO_LIHypomethylation is linked to decreased mRNA expression of transcripts related to synaptic and proteostatic function in AD. C_LIO_LI3UTR-localized m6A sites lack typical association with transcript metabolism of GABRA1 in AD. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/651974v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@995c55org.highwire.dtl.DTLVardef@7d0619org.highwire.dtl.DTLVardef@1b6a20org.highwire.dtl.DTLVardef@1d47dce_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Targeted Protein Degradation of NUDT5 Reveals an Unexpected Non-Enzymatic Role in 6-Thioguanine-Mediated Toxicity

6-Thioguanine (6-TG), an FDA-approved antimetabolite drug, is widely used in the treatment of leukemia. Its cellular effects require metabolic activation and are regulated through interactions with various proteins such as NUDT15, which catalyzes the hydrolysis of the active 6-TG metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP. Recent genome-wide CRISPR loss-of-function studies have identified another NUDIX hydrolase, NUDT5, as a crucial mediator of 6-TG toxicity. Here, we present the development and characterization of potent and selective NUDT5 degraders, guided by a cell-based assay screening strategy. These degraders, in conjunction with orthogonal CRISPR knock-out and reconstitution experiments, reveal a novel and unexpected, non-enzymatic role for NUDT5 in modulating the cellular response to 6-TG. Depletion of NUDT5 protein is antagonistic to NUDT15 inhibition, suggesting a distinct mode-of-action with potential implications for patient therapy.

cell biology↗

bioRxiv2025

Functional profiling reveals a non-enzymatic role of NUDT5 in repressing purine de novo synthesis

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. Here, we investigate the chemical and genetic dependencies caused by mutations in the folate enzyme MTHFD1 and discover a key role for Nudix hydrolase 5 (NUDT5) in regulating purine de novo synthesis. Through genetic knockout and development of a selective chemical NUDT5 degrader, we uncover an unprecedented scaffolding role rather than NUDT5 enzymatic activity is responsible for this phenotype. We find that NUDT5 interacts with the rate-limiting enzyme of purine de novo synthesis, PPAT, to repress the pathway in response to elevated purine levels. Our findings establish NUDT5 as an important regulator of purine de novo synthesis and elucidate its role in mediating sensitivities to 6-thioguanine in cancer treatment and to adenosine in MTHFD1 deficiency.

molecular biology↗

bioRxiv2020

Identification of Acinetobacter baumannii and detection of beta - lactam antibiotic resistance genes in clinical samples by multiplex PCR

Acinetobacter baumannii is the leading cause of hospital-acquired infection in Vietnam. Of note, antibiotic resistance genes are significantly popular in clinical isolates of A. baumannii. Therefore, rapid identification of A. baumannii and determination of antibiotic resistance genes will help to make effective clinical decisions related to antibiotic use. This paper proposes a multiplex PCR to identify Acinetobacter baumannii and detect their {beta}-lactam antibiotic resistance genes in clinical isolates. Multiplex PCR was applied to amplified recA gene and region ITS 16S - 23S rDNA for Rapid detection of A. baumannii. The two antibiotic resistance genes - blaOXA-51-like, ampC gene - were detected by multiplex PCR and three genes coding Extended-spectrum beta-lactamases - blaCTX-M, blaTEM, blaSHV genes - were subjected to PCR. 49 bacteria strains were subjected to colony PCR. The result showed that 46 strains were A. baumannii and 3 strains belonged to the genus Acinetobacter. The multiplex PCR showed that all of 46 A. baumannii containing the blaOXA-51-like gene and the AmpC gene; 34 strains possess the gene blaTEM and none of them has blaCTX-M and blaSHV genes. The results of the multiplex PCR are the same as those of the in vitro antibiotic sensitivity testing of A. baumannii. However, applying the multiplex PCR directly from the bacteria colony, we can proceed simultaneously with the bacterial identification and the antibiotic resistance gene detection. Highlights O_LI100% of isolates of A. baumannii contains the blaOXA-51-like gene and the AmpC gene. C_LIO_LI34/46 isolates possess the gene blaTEM, however, do not contain blaCTX-M and blaSHV genes. C_LIO_LICombined disc test with cefotaxime/clavulanic acid/boronic acid is an excellent method to analyse ESBL phenotype. C_LI

microbiology↗

bioRxiv2020

Fluorescence Microscopy Datasets for Training Deep Neural Networks

BackgroundFluorescence microscopy is an important technique in many areas of biological research. Two factors which limit the usefulness and performance of fluorescence microscopy are photobleaching of fluorescent probes during imaging, and, when imaging live cells, phototoxicity caused by light exposure. Recently developed methods in machine learning are able to greatly improve the signal to noise ratio of acquired images. This allows researchers to record images with much shorter exposure times, which in turn minimizes photobleaching and phototoxicity by reducing the dose of light reaching the sample. FindingsTo employ deep learning methods, a large amount of data is needed to train the underlying convolutional neural network. One way to do this involves use of pairs of fluorescence microscopy images acquired with long and short exposure times. We provide high quality data sets which can be used to train and evaluate deep learning methods under development. ConclusionThe availability of high quality data is vital for training convolutional neural networks which are used in current machine learning approaches.

bioinformatics↗

bioRxiv2019

Antioxidant and antimicrobial activites on uropathogenic bacteria of Asteraceae medicinal plants

Asteraceae species were widely applied in traditional medicines in Asia countries as sources of natural antioxidants and antimicrobial agents. This study aimed to evaluate DPPH-scavenging capacities and antimicrobial activities of nine Asteraceae species collected from Southern Vietnam. Antioxidant and antimicrobial activities were determined by standard protocols. Essential oils from Ageratum conyzoides, Helianthus annuus, Artemisia vulgaris indicated significant inhibitory effects on Staphyloccocus aureus and Candida spp.. Crude extracts and fractions from Taraxacum officinale, Chrysanthemum morifolium, Ageratum conyzoides, Tagetes erecta showed inhibitory ability on at least one testing bacterial strains including S. aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa. Study on clinical isolates, ethyl acetate fraction from A. conyzoides displayed the most potent effect on uropathogenic E. coli and K. pneumoniae with MIC at 1.25-10 mg/ml and 5-12.5 mg/ml, respectively. DPPH scavenging assay indicated that Tagetes erecta extract had the lowest IC50 (17.280 g/ml) and 2.5 times higher than vitamin C (7.321 g/ml). This study revealed that A. conyzoides has good potential against uropathogenic E. coli and K. pneumoniae, and could, therefore, apply to prophylactic urinary tract infection.

microbiology↗