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Biology subjects

Lee, J.-C.

Publications and source records attributed to Lee, J.-C..

6 recordsLinked to original sources

Supplemental deinoxanthin ameliorates bone marrow microenvironmental impairments and recovers functional damage of bone marrow-retained cells in total body irradiation-exposed mice

Total body irradiation (TBI) can impair the bone marrow (BM) microenvironment and dysregulate the fates of BM-residing cells by overproducing reactive oxygen species (ROS) and inflammatory mediators. This study aims to investigate the potency and mechanism of Deinococcus radiodurans-derived deinoxanthin (DEIX) in mitigating TBI-mediated injuries in the BM microenvironment and BM-resident cells. C57BL/6 mice were divided into control, TBI, TBI+DEIX, and/or DEIX groups, in which the mice were exposed to sub-lethal TBI (5 Gy) or in combination with oral DEIX supplementation (25 mg/kg body weight). While the DEIXs effect on BM and BM-resident cells was determined after five weeks of TBI, RNA sequence profiling on the mouse group-derived BM cells was performed after two weeks of TBI. Supplementation with DEIX protected mice against TBI-mediated decrease in bone mineral density of trabecular bones. Supplemental DEIX suppressed BM microenvironmental impairment and the induction of oxidative stress and senescence in BM cells of TBI-exposed mice. That suppression was orchestrated by the DEIX-induced restoration of TBI-stimulated disorders in osteogenic, osteoclastogenic, and adipogenic activation in the BM. Ex vivo assays using BM cells supported the notion that DEIX restores TBI-mediated defects in BM cell function, including colony formation, migration, and differentiation. RNA sequence profiling demonstrated DEIXs potency to modulate the expression of genes that regulate cellular and systemic immune responses, cell proliferation and differentiation, and bone metabolism. Collectively, our results highlight the roles and associated mechanisms of DEIX in mitigating TBI-mediated microenvironmental impairment and in regulating BM-resident cells.

cell biology↗

Maternal age modulates progeny social behavior via a small RNA-neuropeptide axis

Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in C. elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of old mothers display reduced neuronal responses and weaker repulsion. We identify an ERI-1-microRNA-neuropeptide signaling axis operating in peptidergic AVH interneurons that modulates ADL circuit responsiveness. ERI-1 promotes expression of the neuropeptide gene flp-26 by repressing mir-8207, and signaling from AVH to ADL establishes pheromone sensitivity. Maternal aging is associated with reduced ERI-1 expression in progeny AVH neurons and dampening this signaling pathway. Consequently, progeny of young mothers, though developmentally less robust, disperse more readily from crowded, pheromone-rich environments, offsetting their early-life disadvantages. Our findings reveal a molecular and circuit-level mechanism by which maternal physiology adaptively configures offspring neural computation and behavioral strategy across generations.

neuroscience↗

Novel naphthyridones targeting Pannexin 1 for colitis management

Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 is proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, we performed hit-to-lead optimization and identified a naphthyridone, compound 12, as a new PANX1 inhibitor with an IC50 of 0.73 M that does not affect pannexin-homologous LRRC8/SWELL1 channels. Using structure-activity relationship analysis, mutagenesis, cell thermal shift assays, and molecular docking, we revealed that compound 12 directly engages PANX1 Trp74 residue. Using a dextran sodium sulfate mouse model of IBD, we found that compound 12 markedly reduced colitis severity, highlighting new PANX1 inhibitors as a proof-of-concept treatment for IBD. These data describe the mechanism of action for a new PANX1 inhibitor, identify the binding site for future drug design, and present a targeted strategy for treating IBD. TeaserA specific PANX1 inhibitor presents a proof-of-concept treatment for inflammatory bowel disease.

molecular biology↗

In-situ microscopy-assisted meniscus-guided coating for highly sensitive reduced graphene oxide-based nanocomposite biosensor

Meniscus-guided coating provides great potential for fabricating the nanomaterial-based thin film into high-performance biomedical devices due to the strong relationship between its experimental parameters and the resulting structural properties. However, the complex leverages of various fluid dynamics phenomena hamper optimization of structural properties and device performances. This is due to the absence of in-depth analytical techniques to observe, interpret, and control the solidification process. In this work, we propose an analytical strategy based on the rheological properties of a rGO-based solution using computational fluid dynamics modeling and in situ high-speed microscopy. Through this, we reveal the principles of the solidification mechanism that creates a rGO-based nanocomposite in the form of highly- and evenly-wrinkled thin film and the experimental condition at which this mechanism occurs. The optimized thin film presents high electroconductivity, low chip-to-chip signal variation, and multiplexed electrochemical biosensing performance for three classes of antibodies related to the excessive enrichment of endoplasmic reticulum stress, with detection limits of picomolar levels. This optimizing technique can be universally applied to understanding various solution-based coating systems, and can streamline the production of large-area and high-quality nanocomposite biosensors.

bioengineering↗

Consequences of the Nyquist-Shannon sampling criterion in Mesoscopic Multiphoton Microscopy to avail full-field sub-micron resolution resolvability

With a limited effective voxel rate, to date, each laser-scanning mesoscopic multiphoton microscope (MPM), despite securing an ultra-large field of view (FOV) and an ultra-high optical resolution simultaneously, experiences a fundamental issue with digitization; i.e., inability to satisfy the Nyquist-Shannon sampling criterion to resolve the optics-limited sub-micron resolution over the whole FOV. Such a system either neglects the criterion degrading the digital resolution to twice the pixel size, or significantly reduces the imaging area and/or the imaging speed to respect the digitization. Here we introduce a Nyquist figure of merit parameter to assess this issue, further to comprehend a maximum aliasing-free FOV and a cross-over excitation wavelength for a laser scanning MPM system. Based on our findings we demonstrate an ultra-high voxel rate acquisition in a custom-built mesoscopic MPM system to exceed the Nyquist-rate for a >3800 FOV-resolution ratio while not compromising the imaging speed as well as the photon-budget.

bioengineering↗

Causes of death among hospitalized adults with dengue fever in Tainan, 2015: emphasis on cardiac events and bacterial infections

IntroductionThe 2015 dengue outbreak in southern Taiwan caused substantial mortality rates in the elderly. We analyzed here the causes of death among adults with dengue.\n\nMethodsThe retrospective study was conducted at a medical center in Tainan from the 1st of August to 31th of December in the year 2015. The detection of the dengue NS1 antigen IgM or viral RNA in patients blood were used to diagnose dengue. Clinical courses and causes of death were retrieved from chart reviews by two intensivists.\n\nResultsThere were 4,488 cases of dengue diagnosed in the study hospital, and these cases had an in-hospital case fatality rate of 1.34% (60 cases). Of these, the mean age was 73 years and gender did not predict outcome. Twenty-eight (46.7%) cases died of severe dengue, and 29 (48.3%) deaths were possibly caused by dengue-related complications, which were mostly secondary infections (24 cases). Most of the families of fatal case (70%) signed do-not-resuscitate (DNR) orders prior to the patients death. When the dengue epidemic peaked, 13 cardiac arrest events, including out-of-hospital (5 events) and in-hospital (8) cardiac arrests at the emergency department, occurred within four weeks of the dengue epidemic. Notably, in half (7) of these cases, the patients did not search for medical aid prior to experiencing cardiac arrest. Of the 40 cases that had early death (occurring within one week after hospitalization), 60% died of severe dengue. In contrast, 50% of the 20 deaths that occurred later than one week after hospitalization were related to hospital-acquired infections, mainly pneumonia.\n\nConclusionThe elderly that experience dengue fever may die of severe dengue early or die of secondary infections later. Cardiac arrests can also occur unpredictably at the first aids, which highlight the need of professional and patient education regarding the danger signs that are related to severe dengue in an epidemic setting.\n\nAuthor summaryThe 2015 dengue outbreak in Tainan City caused substantial deaths among the elderly. The main causes of death were severe dengue and its complications. We here highlight the deaths caused by heart complications of dengue that the elderly has underlying cardiovascular comorbidities is more prone to be involved. The presentations of heart complications vary, ranging from arrythmia to myocarditis and to unexpected cardiac arrest. Clinicians should carefully evaluate and monitor the heart function of patients with severe dengue and provide timing intervention. Secondary infections or healthcare-associated infections may occur throughout the whole hospitalized course. They were also the leading causes of death during the late or recovery phase of dengue in the study. Judicious application of antimicrobial agents and early elimination of infection source may be beneficial. Overall, the substantial deaths during this outbreak may be related to low public awareness of dengue, emergency department overclouding, and lack of clinical experience. Professional and public education regarding the danger signs that are related to severe dengue is necessary in an epidemic setting.

epidemiology↗