Biology subjects

Chuang, C.-H.

Publications and source records attributed to Chuang, C.-H..

11 recordsLinked to original sources

bioRxiv2026

Deficiency of miR130a leads to fat hypertrophy, hepatic steatosis, insulin resistance and glucose intolerance in mice

Insulin resistance, excessive and ectopic fat accumulation, chronic low-grade inflammation, and pancreatic beta-cell failure are pathological features of type 2 diabetes mellitus.MiR-130a has been demonstrated to suppress the mRNA levels of PPAR{gamma}, NF-{kappa}B, and TNF- in vitro. PPAR{gamma} is a master regulator of systemic fat and glucose metabolism. NF-{kappa}B and TNF- are pivotal modulators of inflammation. Therefore, we aimed to examine the systemic effect of miR130a on fat metabolism, glucose/insulin homeostasis, and inflammation in mice. We found that mirR130a-deficient mice exhibited larger white fat mass with hypertrophic adipocytes, increased lipogenic gene expression in fat, and elevated serum leptin levels than controls. The white fat pads of mirR130a-deficient mice showed significant macrophage infiltration with enhanced expression of pro-inflammatory genes. In addition, mirR130a-deficient mice had more severe hepatic steatosis and higher hepatic triglycerides content than controls. Similarly, mirR130a-deficient mice had increased macrophage infiltration and lipogenic and inflammatory gene expression in the liver. Consistently, we found that Lepob/ob mice expressed markedly decreased miR130a expression in the liver and white fat compared to controls. Importantly, mirR130a-deficient mice displayed impaired glucose tolerance and worsened insulin resistance, accompanied with reduced serum adiponectin levels. Furthermore, insulin secretion is reduced in mirR130a-deficient mice compared to controls. In conclusion, knockout of miR130a in mice results in fat hypertrophy, hepatic steatosis, increased macrophage infiltration in liver and fat, glucose intolerance, and insulin resistance. These data indicate miR130a exert systemic anti-diabetic effects.

molecular biology↗

bioRxiv2024

Centella asiatica Tissue Culture-Derived Extracellular Vesicles: A Multifaceted Approach to Skincare Applications

BackgroundCentella asiatica has long been used as a medicinal herb in traditional Asian medicine. Its wound healing, skin improvement, and neuroprotective properties have been widely studied. Extracellular vesicles (EVs) are secreted by cells and contain bioactive components with therapeutic properties. ObjectivesThis study aims to characterize EVs isolated from C. asiatica tissue culture and investigate their therapeutic properties using in vitro assays and a UVB-induced damage mouse model. MethodsEVs were isolated from C. asiatica tissue culture and characterized by nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM). Cytotoxicity, anti-oxidation, anti-melanin, and anti-inflammation of the EVs were evaluated by MTT assay, tyrosinase assay and RT-qPCR in chemical or in vitro assays. A UVB-induced photodamage mouse model was established to assess the anti-inflammation effect of EVs in vivo. Gels with or without EVs were applied to the damaged site and skin appearance was observed daily and skin histopathology was analyzed on day 7 by H&E and immunohistochemical staining. ResultsC. asiatica EVs were found to contain high levels of polyphenols and mitigate hydrogen peroxide-induced intracellular ROS. The EVs were further able to reduce intracellular melanin content and tyrosinase activity, and exhibited anti-inflammatory effects by downregulating the expression of pro-inflammatory genes COX2 as well as nitric oxide production. In mice with UVB-induced skin damage, daily application of C. asiatica EV gel reduced skin epidermis thickness and inflammation compared to UVB-only or blank gel at seven days after UV irradiation. ConclusionsThe beneficial effects of C. asiatica EVs on skin quality warrant further studies as promising agents in skin care applications.

pharmacology and toxicology↗

bioRxiv2023

Cortical microtubules oppose actomyosin-driven membrane ingression during C. elegans meiosis I polar body extrusion

During C. elegans oocyte meiosis I, cortical actomyosin is locally remodeled to assemble a contractile ring near the spindle. In contrast to mitosis, when most cortical actomyosin converges into a contractile ring, the small oocyte ring forms within and remains part of a much larger and actively contractile cortical actomyosin network. This network both mediates contractile ring dynamics and generates shallow ingressions throughout the oocyte cortex during polar body extrusion. Based on our analysis of requirements for CLS-2, a member of the CLASP family of proteins that stabilize microtubules, we recently proposed that a balance of actomyosin-mediated tension and microtubule-mediated stiffness are required for contractile ring assembly within the oocyte cortical actomyosin network. Here, using live cell imaging and fluorescent protein fusions, we show that CLS-2 is part of a complex of kinetochore proteins, including the scaffold KNL-1 and the kinase BUB-1, that also co-localize to patches distributed throughout the oocyte cortex during meiosis I. By reducing their function, we further show that KNL-1 and BUB-1, like CLS-2, are required for cortical microtubule stability, to limit membrane ingression throughout the oocyte, and for meiotic contractile ring assembly and polar body extrusion. Moreover, nocodazole or taxol treatment to destabilize or stabilize oocyte microtubules, respectively, leads to excess or decreased membrane ingression throughout the oocyte and defective polar body extrusion. Finally, genetic backgrounds that elevate cortical microtubule levels suppress the excess membrane ingression in cls-2 mutant oocytes. These results support our hypothesis that CLS-2, as part of a sub-complex of kinetochore proteins that also co-localize to patches throughout the oocyte cortex, stabilizes microtubules to stiffen the oocyte cortex and limit membrane ingression throughout the oocyte, thereby facilitating contractile ring dynamics and the successful completion of polar body extrusion during meiosis I.

cell biology↗

bioRxiv2022

Allosteric inhibitors of Zika virus NS2B-NS3 protease targeting protease in super-open conformation

Zika virus (ZIKV) is a member of the Flaviviridae family and is considered a major health threat causing cases of microcephaly in newborns and Guillain-Barre syndrome in adults. Here we targeted a transient deep and hydrophobic pocket of the super-open conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the orthosteric inhibitors. After virtual docking screening of approximately 7 million compounds against the novel allosteric site we selected the top seven candidates and tested them in an enzymatic assay. Six out of seven top candidates selected by the docking screen inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations, as well as suppressing viral replication. These six compounds, targeting the selected protease pocket conserved in ZIKV as well as several other Flaviviruses, have opened an opportunity for a new kind of drug candidate that might be useful to treat several flaviviral infections.

pharmacology and toxicology↗

bioRxiv2021

Near-Zero Phase-Lag Hyperscanning in a Novel Wireless EEG System

Hyperscanning is an emerging technology that concurrently scans the neural dynamics of multiple individuals to study interpersonal interactions. In particular, hyperscanning with wireless electroencephalography (EEG) is increasingly popular owing to its mobility and ability to decipher social interactions in natural settings at the millisecond scale. To align multiple EEG time series with sophisticated event markers in a single time domain, a precise and unified timestamp is required for stream synchronization. This study proposed a clock-synchronized method using a custom-made RJ45 cable to coordinate the sampling between wireless EEG amplifiers to prevent incorrect estimation of interbrain connectivity due to asynchronous sampling. In this method, analog-to-digital converters are driven by the same sampling clock. Additionally, two clock-synchronized amplifiers leverage additional RF channels to keep the counter of their receiving dongles updated, guaranteeing that binding event markers received by the dongle with the EEG time series have the correct timestamp. The results of two simulation experiments and one video gaming experiment revealed that the proposed method ensures synchronous sampling in a system with multiple EEG devices, achieving near-zero phase-lag and negligible amplitude difference between signals. According to all of the signal-similarity metrics, the suggested method is a promising option for wireless EEG hyperscanning and can be utilized to precisely assess the interbrain couplings underlying social-interaction behaviors.

bioengineering↗

bioRxiv2021

Mindfulness Training Alters Resting-State EEG Dynamics in Novice Practitioners via Mindful Breathing and Body-scan

Mindfulness-based stress reduction (MBSR) has been proven to improve mental health and quality of life. This study examined how mindfulness training and various types of mindfulness practices altered brain activity. Specifically, the spectral powers of scalp electroencephalography (EEG) of the MBSR group who underwent an 8-week mindfulness training--including mindful breathing and body-scan--were evaluated and compared with those of the waitlist controls. Empirical results indicated that the long-term mindfulness intervention effect significantly elevated the resting-state beta powers and reduced resting-state delta powers in both practices; such changes were not observed in the waitlist control. Compared with mindful breathing, body-scanning resulted in an overall decline in EEG spectral powers at both delta and gamma bands among trained participants. Together with our preliminary data of expert mediators, the aforementioned spectral changes were salient after intervention, but mitigated along with expertise. Additionally, after receiving training, the MBSR groups mindfulness and emotion regulation levels improved significantly, which were correlated with the EEG spectral changes in the theta, alpha, and low-beta bands. This study elaborated the neurophysiological correlates of mindfulness practices, suggesting that MBSR might function as a unique internal processing that involves increased vigilant capability and induces alterations similar to other cognitive training.

neuroscience↗

bioRxiv2020

miR-200 deficiency promotes lung cancer metastasis by activating cancer-associated fibroblasts

Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the KrasLSL-G12D/+; Trp53flox/flox lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential.

cancer biology↗

bioRxiv2020

A Genome-based Model to Predict the Virulence of Pseudomonas aeruginosa Isolates

Variation in the genome of Pseudomonas aeruginosa, an important pathogen, can have dramatic impacts on the bacteriums ability to cause disease. We therefore asked whether it was possible to predict the virulence of P. aeruginosa isolates based upon their genomic content. We applied a machine learning approach to a genetically and phenotypically diverse collection of 115 clinical P. aeruginosa isolates using genomic information and corresponding virulence phenotypes in a mouse model of bacteremia. We defined the accessory genome of these isolates through the presence or absence of accessory genomic elements (AGEs), sequences present in some strains but not others. Machine learning models trained using AGEs were predictive of virulence, with a mean nested cross-validation accuracy of 75% using the random forest algorithm. However, individual AGEs did not have a large influence on the algorithms performance, suggesting instead that the virulence prediction derives from a diffuse genomic signature. These results were validated with an independent test set of 25 P. aeruginosa isolates whose virulence was predicted with 72% accuracy. Machine learning models trained using core genome single nucleotide variants and whole genome k-mers also predicted virulence. Our findings are a proof of concept for the use of bacterial genomes to predict pathogenicity in P. aeruginosa and highlight the potential of this approach for predicting patient outcomes. IMPORTANCEPseudomonas aeruginosa is a clinically important gram-negative opportunistic pathogen. As a species, P. aeruginosa has a large degree of heterogeneity both through variation in sequences found throughout the species (core genome) and the presence or absence of sequences in different isolates (accessory genome). P. aeruginosa isolates also differ markedly in their ability to cause disease. In this study, we used machine learning to predict the virulence level of P. aeruginosa isolates in a mouse bacteremia model based on genomic content. We show that both the accessory and core genome are predictive of virulence. This study provides a machine learning framework to investigate relationships between bacterial genomes and complex phenotypes such as virulence.

genomics↗

bioRxiv2020

Microtubule Assembly and Pole Coalescence: Early Steps in C. elegans Oocyte Meiosis I Spindle Assembly

How oocytes assemble bipolar meiotic spindles in the absence of centrosomes as microtubule organizing centers remains poorly understood. We have used live cell imaging in C. elegans to investigate requirements for the nuclear lamina and for conserved regulators of microtubule dynamics during oocyte meiosis I spindle assembly, assessing these requirements with respect to recently identified spindle assembly steps. We show that the nuclear lamina is required for microtubule bundles to form a cage-like structure that appears shortly after oocyte nuclear envelope breakdown and surrounds the oocyte chromosomes, although bipolar spindles still assembled in its absence. Although two conserved regulators of microtubule nucleation, RAN-1 and {gamma}-tubulin, are not required for bipolar spindle assembly, both contribute to normal levels of spindle-associated microtubules and spindle assembly dynamics. Finally, the XMAP215 ortholog ZYG-9 and the nearly identical minus-end directed kinesins KLP-15/16 are required for proper assembly of the early cage-like structure of microtubule bundles, and for early spindle pole foci to coalesce into a bipolar structure. Our results provide a framework for assigning molecular mechanisms to recently described steps in C. elegans oocyte meiosis I spindle assembly.

cell biology↗

bioRxiv2019

Axon-like protrusions promote small cell lung cancer migration and metastasis

Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic types of human cancer. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.

cancer biology↗

bioRxiv2018

Female-biased embryonic death from genomic instability-induced inflammation

Genomic instability (GIN) can trigger cellular responses including checkpoint activation, senescence, and inflammation. Though extensively studied in cell culture and cancer paradigms, little is known about the impact of GIN during embryonic development, a period of rapid cellular proliferation. We report that GIN-causing mutations in the MCM2-7 DNA replicative helicase render female mouse embryos to be dramatically more susceptible than males to embryonic lethality. This bias was not attributable to X-inactivation defects, differential replication licensing, or X vs Y chromosome size, but rather \"maleness,\" since XX embryos could be rescued by transgene-mediated sex reversal or testosterone (T) administration. The ability of exogenous or endogenous T to protect embryos was related to its anti-inflammatory properties. The NSAID ibuprofen rescued female embryos containing mutations not only in MCM genes but also Fancm, which have elevated GIN from compromised replication fork repair. Additionally, deficiency for the anti-inflammatory IL10 receptor was synthetically lethal with the GIN-causing Mcm4Chaos3 helicase mutant. Our experiments indicate that embryonic and maternal GIN arising from DNA replication-associated DNA damage induces embryonic inflammation likely via the cGAS-STING response, preferentially killing female embryos while male embryos are protected by high levels of intrinsic T.

genetics↗