Biology subjects

Huang, L.-M.

Publications and source records attributed to Huang, L.-M..

4 recordsLinked to original sources

bioRxiv2025

Targeting Wnt Signaling and DNAJB6/MRJ-L as a Dual Anti-RSV Strategy: Insights into a Positive Regulatory Loop

Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections, yet effective treatments are lacking. We found that the molecular chaperon DNAJB6/MRJ plays an essential role in RSV replication. Depletion of the long isoform of MRJ (MRJ-L) suppresses RSV replication. Transcriptomic analysis revealed that MRJ-L depletion downregulates Wnt signaling pathways. A pharmacological inhibitor of Wnt signaling suppressed RSV propagation and unexpectedly reduced MRJ-L expression, suggesting a positive regulatory loop between Wnt signaling and MRJ-L expression. Notably, simultaneous inhibition of Wnt signaling and MRJ-L additively suppressed RSV replication, suggesting that the Wnt-MRJ-L axis may serve as a new therapeutic target. This study provides insights into host-RSV interactions and potential antiviral strategies. Author SummaryThe molecular chaperone DNAJB6/MRJ has been implicated in the replication of respiratory syncytial virus (RSV), although the precise mechanisms remain unclear. In this study, we discovered that MRJ may influence RSV replication via Wnt signaling pathways. Specifically, we demonstrated that Wnt signaling inhibitor Wnt-C59 significantly reduced RSV replication by suppressing the synthesis of viral mRNA and genome/antigenome. Moreover, a positive feedback loop of the Wnt-MRJ axis may play a critical role in regulating RSV replication. Importantly, RSV replication was suppressed additively by inhibition of Wnt signaling and depletion of MRJ-L. Thus, a dual-targeted therapeutic approach may be effective in combating RSV infections.

pathology↗

bioRxiv2024

Cytokinin-inducible DIRIGENT13 involved in lignan synthesis and ROS accumulation promotes root growth and abiotic stress tolerance in Arabidopsis

Dirigent (DIR) proteins mediate regio- and stereoselectivity of phenoxy radical coupling of monolignols for (neo)lignan or lignin synthesis. However, the role of DIR proteins and lignans in plant development and response to environmental stresses remains elusive. Here, we provide a functional characterization of the cytokinin-responsive DIRIGENT13 (DIR13) in Arabidopsis thaliana. DIR13 was localized to the root endodermis and at the margins of lateral root primordia and lateral roots. While not necessary for Casparian strip formation, DIR13 promoted both main and lateral root growth. Untargeted metabolomics and imaging mass spectrometry analyses unveiled the role of DIR13 in facilitating (neo)lignan synthesis in primary and lateral roots. Interestingly, DIR13 activated the production of putative oxomatairesinol and matairesinol-cysteine which are oxidative derivatives of the lignan matairesinol. Our data also identified DIR13 as an enhancer of salt and drought tolerance. Particularly, DIR13 attenuated salt stress-mediated inhibition of germination and root growth. Moreover, DIR13 activated reactive oxygen species (ROS) accumulation both under control and salt stress conditions, and cytokinin further enhanced the salt-induced ROS production specifically in the DIR13 overexpressing line. Our results uncover a role for DIR13-produced lignans in the priming of ROS accumulation, mediating both abiotic stress tolerance and the control of root architecture.

plant biology↗

bioRxiv2020

Inhibition of Severe Acute Respiratory Syndrome Coronavirus 2 main protease by tafenoquine in vitro

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the current pandemic, coronavirus disease 2019 (COVID-19), has taken a huge toll on human lives and the global economy. Therefore, effective treatments against this disease are urgently needed. Here, we established a fluorescence resonance energy transfer (FRET)-based high-throughput screening platform to screen compound libraries to identify drugs targeting the SARS-CoV-2 main protease (Mpro), in particular those which are FDA-approved, to be used immediately to treat patients with COVID-19. Mpro has been shown to be one of the most important drug targets among SARS-related coronaviruses as impairment of Mpro blocks processing of viral polyproteins which halts viral replication in host cells. Our findings indicate that the anti-malarial drug tafenoquine (TFQ) induces significant conformational change in SARS-CoV-2 Mpro and diminishes its protease activity. Specifically, TFQ reduces the -helical content of Mpro, which converts it into an inactive form. Moreover, TFQ greatly inhibits SARS-CoV-2 infection in cell culture system. Hence, the current study provides a mechanistic insight into the mode of action of TFQ against SARS-CoV-2 Mpro. Moreover, the low clinical toxicity of TFQ and its strong antiviral activity against SARS-CoV-2 should warrant further testing in clinical trials.

biochemistry↗

bioRxiv2018

Association of Prevotella enterotype with polysomnographic data in obstructive sleep apnea/hypopnea syndrome patients

Intermittent hypoxia and sleep fragmentation are critical pathophysiological processes involved in obstructive sleep apnea/hypopnea syndrome (OSAHS). These manifestation independently affect similar brain regions and contribute to OSAHS-related comorbidities that are known to be related to the host gut alteration microbiota. We hypothesized that microbiota disruption influences the pathophysiological processes of OSAHS through a microbiota-gut-brain axis. Thus, we aim to survey enterotypes and polysomnographic data of OSAHS patients. Subjects were diagnosed by polysomnography, from whom fecal samples were obtained and analyzed for the microbiome composition by variable regions 3-4 of 16S rRNA pyrosequencing and bioinformatic analyses. We examined blood cytokines level of all subjects. Three enterotypes Bacteroides (n=73), Ruminococcus (n=14), and Prevotella (n=26) were identified. Central apnea indices, mixed apnea indices, N1 sleep stage, mean apnea-hypopnea duration, and arousal indices were increased in apnea-hypopnea indices (AHI) [≥]15 patients with the Prevotella enterotype. However, for AHI<15 subjects, obstructive apnea indices and systolic blood pressure were significantly observed in Ruminococcus and Prevotella enterotypes, respectively. The present study indicates the possibility of pathophysiological interplay between enterotypes and sleep structure disruption in sleep apnea through a microbiota-gut-brain axis and offers some new insight toward the pathogenesis of OSAHS.\n\nImportanceIntermittent hypoxia (IH) and sleep fragmentation (SF) are hallmarks of are the predominant mechanism underlying obstructive sleep apnea/hypopnea syndrome (OSAHS). Moreover, IH and SF of pathophysiological roles in the gut microbiota dysbiosis in OSAHS have been demonstrated. We hypothesized that gut microbiota disruption may cross-talk the brain function via microbiota-gut-brain axis. Indeed, we observed central apnea indices and other parameters of disturbances during sleep were significantly elevated in AHI[≥]15 patients with the Prevotella enterotype. This enterotype prone to endotoxin production, driving systemic inflammation, ultimately contributes to OSAHS-linked comorbidities. Vice versa, increasing the arousal index leads to systemic inflammatory changes and accompanies metabolic dysfunction. We highlight that the possibility that the microbiota-gut-brain axis operates a bidirectional effect on the development of OSAHS pathology.

microbiology↗