T cell large granular lymphocyte (T-LGL) leukemia features a clonal expansion of antigen-primed, competent, cytotoxic T lymphocytes (CTL). To systematically understand signaling components that ...determine the survival of CTL in T-LGL leukemia, we constructed a T-LGL survival signaling network by integrating the signaling pathways involved in normal CTL activation and the known deregulations of survival signaling in leukemic T-LGL. This network was subsequently translated into a predictive, discrete, dynamic model. Our model suggests that the persistence of IL-15 and PDGF is sufficient to reproduce all known deregulations in leukemic T-LGL. This finding leads to the following predictions: (i) Inhibiting PDGF signaling induces apoptosis in leukemic T-LGL. (ii) Sphingosine kinase 1 and NFκB are essential for the long-term survival of CTL in T-LGL leukemia. (iii) NFκB functions downstream of PI3K and prevents apoptosis through maintaining the expression of myeloid cell leukemia sequence 1. (iv) T box expressed in T cells (T-bet) should be constitutively activated concurrently with NFκB activation to reproduce the leukemic T-LGL phenotype. We validated these predictions experimentally. Our study provides a model describing the signaling network involved in maintaining the long-term survival of competent CTL in humans. The model will be useful in identifying potential therapeutic targets for T-LGL leukemia and generating long-term competent CTL necessary for tumor and cancer vaccine development.
Recently, enzymatic quorum quenching has proven its potential as an innovative approach for biofouling control in the membrane bioreactor (MBR) for advanced wastewater treatment. However, practical ...issues on the cost and stability of enzymes are yet to be solved, which requires more effective quorum quenching methods. In this study, a novel quorum quenching strategy, interspecies quorum quenching by bacterial cell, was elaborated and proved to be efficient and economically feasible biofouling control in MBR. A recombinant Escherichia coli which producing N-acyl homoserine lactonase or quorum quenching Rhodococcus sp. isolated from a real MBR plant was encapsulated inside the lumen of microporous hollow fiber membrane, respectively. The porous membrane containing these functional bacteria (i.e., “microbial-vessel”) was put into the submerged MBR to alleviate biofouling on the surface of filtration membrane. The effect of biofouling inhibition by the microbial-vessel was evaluated over 80 days of MBR operation. Successful control of biofouling in a laboratory scale MBR suggests that the biofouling control through the interspecies quorum quenching could be expanded to the plant scale of MBR and various environmental engineering systems with economic feasibility.
Severe xerostomia (dry mouth) compromises the quality of life in patients with Sjögren's syndrome or radiation therapy for head and neck cancer. A clinical management of xerostomia is often ...unsatisfactory as most interventions are palliative with limited efficacy. Following up our previous study demonstrating that mouse BM-MSCs are capable of differentiating into salivary epithelial cells in a co-culture system, we further explored the molecular basis that governs the MSC reprogramming by utilizing high-throughput iTRAQ-2D-LC-MS/MS-based proteomics. Our data revealed the novel induction of pancreas-specific transcription factor 1a (PTF1α), muscle, intestine and stomach expression-1 (MIST-1), and achaete-scute complex homolog 3 (ASCL3) in 7 day co-cultured MSCs but not in control MSCs. More importantly, a common notion of pancreatic-specific expression of PTF1 α was challenged for the first time by our verification of PTF1 α expression in the mouse salivary glands. Furthermore, a molecular network simulation of our selected putative MSC reprogramming factors demonstrated evidence for their perspective roles in salivary gland development. In conclusion, quantitative proteomics with extensive data analyses narrowed down a set of MSC reprograming factors potentially contributing to salivary gland regeneration. Identification of their differential/synergistic impact on MSC conversion warrants further investigation.
Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a ...promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.
To compare axial length (AL) measurements between a swept-source optical coherence tomography (SS-OCT) biometer (IOLMaster 700) and a partial coherence interferometry (PCI) biometer (IOLMaster, ...version 5.4) in myopic eyes.
Severance Hospital, Yonsei University, Seoul, South Korea.
Prospective evaluation of a diagnostic test.
This study enrolled patients with a diagnosis of myopia in their medical records. Two consecutive AL measurements were performed in each eye in random order using the 2 biometers. Subanalysis was performed according to lens status, fixation status, degree of myopia, and the presence of posterior staphyloma. The interdevice agreement was evaluated with Bland-Altman analyses and paired t tests.
This study comprised 219 eyes of 117 patients. During a fixation check using SS-OCT, 19.6% of eyes showed fixation loss. Overall, the SS-OCT biometer showed a longer AL than the PCI biometer. (P < .001) In a subanalysis that categorized eyes according to lens status, fixation status, degree of myopia, and the presence of posterior staphyloma, the SS-OCT biometer also showed longer ALs than the PCI biometer. Of eyes with good fixation, significant differences in AL measurements between devices were detected for those with posterior staphyloma (P < .001) but not for those without posterior staphyloma (P = .104).
The 2 devices showed differences in AL measurements in myopic eyes. Fixation status and the presence of posterior staphyloma were important factors in these differences. For myopic eyes with posterior staphyloma, the SS-OCT biometer is expected to produce more precise AL measurements because it allows evaluation of the fixation status.
Silicon carbide (SiC) fibers can act not only as a load-bearing component, but also as a piezoresistive and microwave lossy material when embedded in fiber-reinforced polymer composites. By ...leveraging these multifunctional characteristics, we propose simultaneous self-sensing and microwave-absorbing composite structures based on embedded SiC fiber networks. A SiC fiber network consists of SiC fiber yarns embedded in each interlaminar of the host composite at regular intervals. The SiC fiber yarns, which do not come into contact with other SiC fiber yarns, act as independent sensing elements using their piezoresistivity. By positioning the SiC fiber yarns at regular intervals within the wavelength of the targeted microwave-absorption bandwidth, the SiC fiber network functions as a microwave lossy material. In this study, specific focus has been placed on designing a multi-functional composite that senses external impacts and also absorbs microwaves in the X-band (8.2–12.4 GHz). The simultaneous self-sensing and microwave-absorbing performance of the fabricated SiC-embedded composite was experimentally verified through microwave return loss measurements and dynamic signal acquisition tests. The proposed SiC fiber network-embedded composite structure has great potential for use in future aerospace structures.
To assess incidence and risk factors of postoperative progressive nasal inner nuclear layer (INL) thickening after epiretinal membrane (ERM) surgery. Progressive nasal INL thickening was defined as ...1.5-fold increase in thickness of nasal INL after ERM surgery compared to preoperative examination. Kaplan-Meier survival analysis was done to compare the cumulative risk ratio between groups stratified by presence of progressive nasal INL thickening. Logistic regression was performed to identify possible risk factors. Progressive nasal INL thickening occurred in 13.0% of ERM removal patients. Patients without progressive nasal INL thickening showed better visual acuity recovery compared to patients with nasal INL thickening (p = 0.029). Presence of cystoid space in inner retinal layer before surgery (odds ratio OR = 0.143, 95% confidence interval CI 0.028-0.736; p = 0.020), older age (OR = 0.896, 95% CI 0.817-0.982, p = 0.020), and thicker preoperative central macular thickness (OR = 0.994, 95% CI 0.988-1.000, p = 0.039) were correlated inversely with thickening of nasal INL. Correlation between nasal INL thickness and postoperative visual outcome was significant. Absence of cystoid space before ERM surgery, younger age, and thinner central macular thickness were risk factors for progressive postoperative nasal INL thickening. Progressive nasal INL thickening may serve as a new biomarker for worsened visual symptom after ERM surgery.
Postmenopausal women experience several symptoms, including inflammation and a sharp rise in oxidative stress caused by estrogen deprivation. Although estrogen replacement therapy (ERT) is generally ...regarded as an effective treatment for menopause, it has been used less frequently due to some adverse effects and high costs. Therefore, there is an immediate need to develop an effective herbal-based treatment that is affordable for low-income populations. Acordingly, this study explored the estrogen-like properties of methanol extracts from
(CW) and
(PM), two important medicinal plants in Republic of Korea, Japan, and China. Due to the similar names and morphologies of these two radixes, they are frequently confused in the marketplace. Our previous colleagues discriminated between these two plants. In this study, we investigated the estrogenic activity of PM and CW using several in vitro assays with their possible mechanism of action. First, their phytochemical contents, such as gallic acid, 2,3,5,4'-tetrahydroxystilbene-2-O-glucoside (TSG) and emodin, were quantified using high-performance liquid chromatography (HPLC). Secondly, estrogen-like activity was assessed utilizing the well-known E-screen test and gene expression analysis in estrogen receptor (ER)-positive MCF7 cells. ROS inhibition and anti-inflammatory effects were analyzed using HaCaT and Raw 264.7 cells, respectively. Our findings demonstrate that PM extracts significantly increased the expression of the estrogen-dependent genes (ERα, ERβ, pS2) and boosted MCF7 cell proliferation in comparison to CW extracts. Additionally, PM extract demonstrated a significant reduction in reactive oxygen species (ROS) production as well as an enhanced antioxidant profile compared to the CW extract. Further, the PM extract treatment significantly reduced the generation of nitric oxide (NO) in RAW 264.7 cells, a murine macrophage cell line, demonstrating the anti-inflammatory properties of the extract. Finally, this research offers an experimental foundation for the use of PM as a phytoestrogen to minimize menopausal symptoms.
•The chemistry of uranium ions in deep eutectic solvents (DES) systems is unknown.•DESs may aid uranium recycling processes as they are biodegradable and non-toxic.•Understanding uranium speciation ...aids development of eco-friendly nuclear fuel cycle
Deep eutectic solvents (DESs) could make uranium recycling processes greener than using conventional solvents, owing to their inherent advantages such as being biodegradable and non-toxic. However, the chemistry of uranium ions in DES systems, particularly the mechanism of direct anodic dissolution of uranium metal, remains unclear. The anodic dissolution of uranium metal in choline chloride (ChCl)–ethylene glycol (EG) DES was conducted by applying a constant current. The oxidation state of uranium in ChCl-EG DES was uranium(IV) when compared to concentration and applied charge. Absorption spectra showed 8 coordinated U(IV) centered complexes formed in the ChCl-EG DES, regardless of the uranium source (i.e. uranium chloride or metallic uranium anodic dissolution). The in situ spectroelectrochemistry during potentiostatic electrolysis, cyclic voltammograms, and absorption spectra of different times of potentiostatic electrolysis showed U(IV) oxidized to U(V), and then the U(V) disproportionated into U(IV) and U(VI) species. Understanding fundamental uranium speciation in DES systems and electrochemical properties could facilitate the development of an eco-friendly nuclear fuel cycle and nuclear uranium recycling process using green DESs.
Dendropanax morbifera is a versatile plant that has been used as a herbal medicine due to its various useful medicinal effects. To protect its active component from biological stress and increase its ...drug efficacy as well as drug bioavailability, nanoemulsion was prepared. Dendropanax morbifera zinc oxide nanoparticles (DM-ZnO NPs) were synthesized using the plant extract via the co-precipitation method and loaded with active indole-3-carbinol for nanoemulsion formulation using the ultrasonication process. Field emission transmission electron microscope revealed the flower shape of the Dendropanax morbifera indole-3-carbinol zinc oxide nanoemulsion (DM-ZnO-I3C-NE). In contrast, DM-ZnO NPs showed a spheroid shape that coincides agreeably with field emission electron scanning microscope. The hydrodynamic sizes by dynamic light scattering are about 65 ± 3 nm and 239.6 ± 6 nm and the crystallite sizes from X-ray diffraction are 11.52 nm and 16.07 nm for DM-ZnO NPs and DM-ZnO-I3C-NE, respectively. In vitro analysis revealed the cytotoxicity of DM-ZnO-I3C-NE against a human lung cancer cell line (A549) at 12.5 µg/mL as well as reactive oxygen species (ROS) production. The DM-ZnO-I3C-NE-induced ROS generation level was higher than that of DM-ZnO NPs and free indole-3-carbinol. The synergistic effect of DM-ZnO and indole-3-carbinol indicates DM-ZnO-I3C-NE as a potential candidate for future lung cancer drug and could be scope for functional food.
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