Multi-System-Level Analysis with RNA-Seq on Pterygium Inflammation Discovers Association between Inflammatory Responses, Oxidative Stress, and Oxidative Phosphorylation.

A pterygium is a common conjunctival degeneration and inflammatory condition. It grows onto the corneal surface or limbus, causing blurred vision and cosmetic issues. Ultraviolet is a well-known risk factor for the development of a pterygium, although its pathogenesis remains unclear, with only limited understanding of its hereditary basis. In this study, we collected RNA-seq from both pterygial tissues and conjunctival tissues (as controls) from six patients (a total of twelve biological samples) and retrieved publicly available data, including eight pterygium samples and eight controls. We investigated the intrinsic gene regulatory mechanisms closely linked to the inflammatory reactions of pterygiums and compared Asian (Korea) and the European (Germany) pterygiums using multiple analysis approaches from different perspectives. The increased expression of antioxidant genes in response to oxidative stress and DNA damage implies an association between these factors and pterygium development. Also, our comparative analysis revealed both similarities and differences between Asian and European pterygiums. The decrease in gene expressions involved in the three primary inflammatory signaling pathways-JAK/STAT, MAPK, and NF-kappa B signaling-suggests a connection between pathway dysfunction and pterygium development. We also observed relatively higher activity of autophagy and antioxidants in the Asian group, while the European group exhibited more pronounced stress responses against oxidative stress. These differences could potentially be necessitated by energy-associated pathways, specifically oxidative phosphorylation.

Multi-System-Level Analysis Reveals Differential Expression of Stress Response-Associated Genes in Inflammatory Solar Lentigo.

Although the pathogenesis of solar lentigo (SL) involves chronic ultraviolet (UV) exposure, cellular senescence, and upregulated melanogenesis, underlying molecular-level mechanisms associated with SL remain unclear. The aim of this study was to investigate the gene regulatory mechanisms intimately linked to inflammation in SL. Skin samples from patients with SL with or without histological inflammatory features were obtained. RNA-seq data from the samples were analyzed via multiple analysis approaches, including exploration of core inflammatory gene alterations, identifying functional pathways at both transcription and protein levels, comparison of inflammatory module (gene clusters) activation levels, and analyzing correlations between modules. These analyses disclosed specific core genes implicated in oxidative stress, especially the upregulation of nuclear factor kappa B in the inflammatory SLs, while genes associated with protective mechanisms, such as SLC6A9, were highly expressed in the non-inflammatory SLs. For inflammatory modules, Extracellular Immunity and Mitochondrial Innate Immunity were exclusively upregulated in the inflammatory SL. Analysis of protein-protein interactions revealed the significance of CXCR3 upregulation in the pathogenesis of inflammatory SL. In conclusion, the upregulation of stress response-associated genes and inflammatory pathways in response to UV-induced oxidative stress implies their involvement in the pathogenesis of inflammatory SL.

A Methodological Approach for Motor Selection in Dental Impression Material Dispensers Using Experimental and Image Analysis Techniques.

This study presents a methodology to prevent the overdesign of electric dispensers for dental impression materials by analyzing the necessary load and determining the appropriate pressurization speed and drive motor capacity. We derived an equation to calculate the required torque and rotational speed of the motor based on the extrusion load and the speed of the impression material. A specialized load measurement system was developed to measure the load necessary to extrude the impression material. Through experiments and image processing, we measured the radius of curvature of the trajectory of the impression material and correlated it with the pressurization speed. Techniques such as position coordinate plotting, curve fitting, and circle fitting were employed to determine the pressurization speed that aligns with the manufacturer's recommended curvature radius. These findings led to a substantial decrease in the necessary motor torque and rotational speed compared with the current standards. This research provides a systematic approach to sizing drive motors using extrusion load and pressurization speed, aiming to reduce overdesign, power consumption, and the weight and size of the motor and battery, thereby contributing to the development of more efficient and compact dental impression material dispensers.

Recyclable Curcumin-Based Bioepoxy Resin with On-Demand Chemical Cleavability.

We synthesized a novel curcumin-based bioepoxy resin by introducing epichlorohydrin (ECH) into the hydroxyl groups of curcumin and analyzed it using Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). The epoxy equivalent weight (EEW) was determined based on a reaction with sodium hydroxide (NaOH) through titration, and the actual curing process was conducted after exploring the optimal conditions using an amine-based curing agent through dynamic scanning in differential scanning calorimetry (DSC) and isotherm analysis. The cured epoxy resin had a tensile strength, Young's modulus, and glass transition temperature (Tg) of 33 MPa, 1.4 GPa, and 86 °C, respectively. Interestingly, the diunsaturated ketone contained in the epoxy resin showed on-demand chemical cleavability, in that it had been decomposed into an aldehyde and ketone only after having been converted to a hydroxyl ketone through an oxidation reaction. The results of this study can significantly contribute to improving the eco-friendliness and recyclability of epoxy resins used in fields requiring long-term stability and chemical resistance.

RNA-Sequencing Analysis Reveals the Role of Mitochondrial Energy Metabolism Alterations and Immune Cell Activation in Form-Deprivation and Lens-Induced Myopia in Mice.

Myopia is a substantial global public health concern primarily linked to the elongation of the axial length of the eyeball. While numerous animal models have been employed to investigate myopia, the specific contributions of genetic factors and the intricate signaling pathways involved remain incompletely understood. In this study, we conducted RNA-seq analysis to explore genes and pathways in two distinct myopia-inducing mouse models: form-deprivation myopia (FDM) and lens-induced myopia (LIM). Comparative analysis with a control group revealed significant differential expression of 2362 genes in FDM and 503 genes in LIM. Gene Set Enrichment Analysis (GSEA) identified a common immune-associated pathway between LIM and FDM, with LIM exhibiting more extensive interactions. Notably, downregulation was observed in OxPhos complex III of FDM and complex IV of LIM. Subunit A of complex I was downregulated in LIM but upregulated in FDM. Additionally, complex V was upregulated in LIM but downregulated in FDM. These findings suggest a connection between alterations in energy metabolism and immune cell activation, shedding light on a novel avenue for understanding myopia's pathophysiology. Our research underscores the necessity for a comprehensive approach to comprehending myopia development, which integrates insights from energy metabolism, oxidative stress, and immune response pathways.

Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy.

In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (Tg), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug-polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of Tg. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of Tg and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC-bisacodyl at a 1:4 ratio (w/w) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug-polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes.

Semi-conductive micellar networks of all-conjugated diblock and triblock copolymer blends.

The crystallization-driven self-assembly of the blends of the all-conjugated block copolymers of poly(3-hexylthiophene) (P3HT) and poly(3-ethylhexylthiophene) (P3EHT) results in the cross-linking of the one-dimensional nanowires of P3HT-b-P3EHT, which is achieved by intercalating P3HT-b-P3EHT-b-P3HT into the nanowire cores. The micellar networks constitute flexible and porous materials that conduct electricity upon doping.

Combination Effect of Cilengitide with Erlotinib on TGF-ß1-Induced Epithelial-to-Mesenchymal Transition in Human Non-Small Cell Lung Cancer Cells.

The epithelial-to-mesenchymal transition (EMT) is important for morphogenesis during development and is mainly induced by transforming growth factor (TGF)-ß. In lung cancer, EMT is characterized by the transformation of cancer cells into a mobile, invasive form that can transit to other organs. Here, using a non-small cell lung cancer (NSCLC) cell line, we evaluated the EMT-related effects of the epidermal growth factor receptor inhibitor erlotinib alone and in combination with cilengitide, a cyclic RGD-based integrin antagonist. Erlotinib showed anti-proliferative and inhibitory effects against the TGF-ß1-induced EMT phenotype in NSCLC cells. Compared with erlotinib alone, combination treatment with cilengitide led to an enhanced inhibitory effect on TGF-ß1-induced expression of mesenchymal markers and invasion in non-small cell lung cancer A549 cells. These results suggest that cilengitide could improve anticancer drug efficacy and contribute to improved treatment strategies to inhibit and prevent EMT-based cancer progression.

Soluble RAGE attenuates Ang II-induced arterial calcification via inhibiting AT1R-HMGB1-RAGE axis.

BACKGROUND AND AIMS: Arterial calcification (AC), which is an important process in the pathogenesis of atherosclerosis, is accelerated by angiotensin II (Ang II), a critical effector of the renin-angiotensin system (RAS). Receptor for advanced glycation end-product (RAGE) is an important pattern recognition receptor downstream of Ang II. Although recent studies have suggested an association between RAGE-mediated signaling and RAS in AC, the detailed mechanism, particularly in relation to Ang II, remains unclear. METHODS: Therefore, we investigated the role of RAGE-mediated signaling pathways and the therapeutic efficacy of soluble RAGE (sRAGE) in Ang II-induced AC, using both a human aortic smooth muscle cell (HAoSMC) model, and an in vivo apolipoprotein E knockout (ApoE KO) mouse model. RESULTS: According to our data, Ang II significantly increased the calcification of HAoSMCs, and the associated activation of RAGE was mediated by subsequent HMGB1 release through Angiotensin II type 1 receptor activation. Both HMGB1 neutralizing antibody and sRAGE inhibited Ang II-induced calcium deposition. Furthermore, sRAGE attenuated HMGB1 secretion and the activation of RAGE-mediated signaling. The in vivo study indicated that Ang II significantly induced calcium deposition in the aorta, and this was significantly attenuated by sRAGE. CONCLUSIONS: Our findings strongly suggest that blockade of RAGE, using sRAGE, effectively attenuates Ang II-induced arterial calcification.

Liquefaction of Lignin Using Chemical Decomposition and Its Application to Polyurethane Foam.

To utilize the chemical application of lignin (LN), a decomposition reaction was carried out to cleave chemical bonds. Indeed, a liquefaction process is essential for the chemical use of lignin to achieve a uniform reaction and maximize the chemical utility of lignin. To this end, hydroxyl radicals were adopted as a powerful oxidation agent, and FT-IR results confirmed the cleavage of the ether linkages. Additionally, the water solubility of LN significantly increased after decomposition, and dissolution levels up to 0.5 g·mL-1 were obtained. Using these high solubility properties in water, NMR and DLS analyses were performed. In particular, an average particle diameter of 300 ± 240 nm was found, corresponding to the size of polydisperse l-LN. By controlling size uniformity and using high water-solubility levels, polyurethane foams were manufactured using l-LN.

Cyclic RGD Pentapeptide Cilengitide Enhances Efficacy of Gefitinib on TGF-ß1-Induced Epithelial-to-Mesenchymal Transition and Invasion in Human Non-Small Cell Lung Cancer Cells.

During non-small cell lung cancer (NSCLC) progression, transforming growth factor (TGF)-ß mediated epithelial-to-mesenchymal transition (EMT) is an important process leading to high mortality and poor prognosis. The EMT is a fundamental process for morphogenesis characterized by the transformation of cancer cells into invasive forms that can be transferred to other organs during human lung cancer progression. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, has shown anti-proliferative effects in EGFR-mutated NSCLC cells and an inhibitory effect on migration and invasion of NSCLC cells to other organs. In this study, we evaluated the combinatorial treatment effect of cilengitide, a cyclic RGD pentapeptide, on TGF-ß1-induced EMT phenotype and invasion. Gefitinib suppressed the expression of TGF-ß1-induced mesenchymal markers by inhibiting Smad and non-Smad signaling pathways. Cilengitide enhanced the inhibitory effect of gefitinib on TGF-ß1-induced expression of mesenchymal markers, phosphorylation of Smad2/3, and invasion of NSCLC A549 cells. We suggested that the use of cilengitide can improve the efficacy of anti-cancer drugs in combination drug-based chemotherapy. These results provide an improved therapeutic strategy for treating and preventing EMT-related disorders, such as NSCLC, lung fibrosis, cancer metastasis, and relapse.

Pure Trans-Resveratrol Nanoparticles Prepared by A Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats.

The aim of this study was to prepare pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) using a supercritical antisolvent (SAS) process with alcohol (methanol or ethanol) and dichloromethane mixtures. In addition, in order to investigate the effect of particle size on the dissolution and oral bioavailability of the trans-resveratrol, two microparticles with different sizes (1.94 µm and 18.75 µm) were prepared using two different milling processes, and compared to trans-resveratrol nanoparticles prepared by the SAS process. The solid-state properties of pure trans-resveratrol particles were characterized. By increasing the percentage of dichloromethane in the solvent mixtures, the mean particle size of trans-resveratrol was decreased, whereas its specific surface area was increased. The particle size could thus be controlled by solvent composition. Trans-resveratrol nanoparticle with a mean particle size of 0.17 µm was prepared by the SAS process using the ethanol/dichloromethane mixture at a ratio of 25/75 (w/w). The in vitro dissolution rate of trans-resveratrol in fasted state-simulated gastric fluid was significantly improved by the reduction of particle size, resulting in enhanced oral bioavailability in rats. The absolute bioavailability of trans-resveratrol nanoparticles was 25.2%. The maximum plasma concentration values were well correlated with the in vitro dissolution rate. These findings clearly indicate that the oral bioavailability of trans-resveratrol can be enhanced by preparing pure trans-resveratrol nanoparticles without additives (surfactants, polymers, and sugars) by the SAS process. These pure trans-resveratrol nanoparticles can be applied as an active ingredient for the development of health supplements, pharmaceutical products, and cosmetic products.

Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach.

The purpose of this study was to develop a resveratrol nanosuspension with enhanced oral bioavailability, based on an understanding of the formulation and process parameters of nanosuspensions and using a quality by design (QbD) approach. Particularly, the antisolvent method, which requires no solvent removal and no heating, is newly applied to prepare resveratrol nanosuspension. To ensure the quality of the resveratrol nanosuspensions, a quality target product profile (QTPP) was defined. The particle size (z-average, d90), zeta potential, and drug content parameters affecting the QTPP were selected as critical quality attributes (CQAs). The optimum composition obtained using a 3-factor, 3-level Box-Behnken design was as follows: polyvinylpyrrolidone vinyl acetate (10 mg/mL), polyvinylpyrrolidone K12 (5 mg/mL), sodium lauryl sulfate (1 mg/mL), and diethylene glycol monoethyl ether (DEGEE, 5% v/v) at a resveratrol concentration of 5 mg/mL. The initial particle size (z-average) was 46.3 nm and the zeta potential was -38.02 mV. The robustness of the antisolvent process using the optimized composition conditions was ensured by a full factorial design. The dissolution rate of the optimized resveratrol nanosuspension was significantly greater than that of the resveratrol raw material. An in vivo pharmacokinetic study in rats showed that the area under the plasma concentration versus time curve (AUC0-12h) and the maximum plasma concentration (Cmax) respectively, than those of the resveratrol raw material. Therefore, the prepara values of the resveratrol nanosuspension were approximately 1.6- and 5.7-fold higher,tion of a resveratrol nanosuspension using the QbD approach may be an effective strategy for the development of a new dosage form of resveratrol, with enhanced oral bioavailability.

Preparation and Evaluation of Resveratrol-Loaded Composite Nanoparticles Using a Supercritical Fluid Technology for Enhanced Oral and Skin Delivery.

We created composite nanoparticles containing hydrophilic additives using a supercritical antisolvent (SAS) process to increase the solubility and dissolution properties of trans-resveratrol for application in oral and skin delivery. Physicochemical properties of trans-resveratrol-loaded composite nanoparticles were characterized. In addition, an in vitro dissolution-permeation study, an in vivo pharmacokinetic study in rats, and an ex vivo skin permeation study in rats were performed. The mean particle size of all the composite nanoparticles produced was less than 300 nm. Compared to micronized trans-resveratrol, the trans-resveratrol/hydroxylpropylmethyl cellulose (HPMC)/poloxamer 407 (1:4:1) nanoparticles with the highest flux (0.792 µg/min/cm2) exhibited rapid absorption and showed significantly higher exposure 4 h after oral administration. Good correlations were observed between in vitro flux and in vivo pharmacokinetic data. The increased solubility and flux of trans-resveratrol generated by the HPMC/surfactant nanoparticles increased the driving force on the gastrointestinal epithelial membrane and rat skin, resulting in enhanced oral and skin delivery of trans-resveratrol. HPMC/surfactant nanoparticles produced by an SAS process are, thus, a promising formulation method for trans-resveratrol for healthcare products (owing to their enhanced absorption via oral administration) and for skin application with cosmetic products.

Soluble RAGE attenuates AngII-induced endothelial hyperpermeability by disrupting HMGB1-mediated crosstalk between AT1R and RAGE.

Increased endothelial permeability, one of the earliest signs of endothelial dysfunction, is associated with the development of cardiovascular diseases such as hypertension and atherosclerosis. Recent studies suggest that the receptor for advanced glycation end products (RAGE) regulates endothelial permeability in inflammation. In the present study, we investigated the regulatory mechanism of RAGE in endothelial hyperpermeability induced by angiotensin II (Ang II), a well-known inflammatory mediator, and the potential therapeutic effect of soluble RAGE (sRAGE), a decoy receptor for RAGE ligands. For in vitro studies, Ang II-treated human umbilical vein endothelial cells (HUVECs) were treated with siRNA specific to either RAGE or sRAGE to disrupt RAGE-mediated signaling. Endothelial permeability was estimated using FITC-labeled dextran 40 and a resistance meter. To evaluate intercellular junction disruption, VE-cadherin expression was examined by western blotting and immunocytochemistry. Ang II increased the expression of the Ang II type 1 receptor (AT1R) and RAGE, and this increase was inhibited by sRAGE. sRAGE prevented Ang II-induced VE-cadherin disruption in HUVECs. For in vivo studies, Ang II-infused, atherosclerosis-prone apolipoprotein E knockout mice were utilized. Endothelial permeability was assessed by Evans blue staining of the aorta. Ang II increased endothelial barrier permeability, and this effect was significantly attenuated by sRAGE. Our data demonstrate that blockade of RAGE signaling using sRAGE attenuates Ang II-induced endothelial barrier permeability in vitro and in vivo and indicate the therapeutic potential of sRAGE in controlling vascular permeability under pathological conditions.

Radiological assessment of effectiveness of soluble RAGE in attenuating Angiotensin II-induced LVH mouse model using in vivo 9.4T MRI.

We investigated the effectiveness of soluble Receptor for Advanced Glycation Endproducts (sRAGE) in attenuating angiotensin II (AngII)-induced left ventricular hypertrophy (LVH) using in vivo 9.4T cine-magnetic resonance imaging (CINE-MRI). Mice were divided into four groups: AngII (n = 9), saline (n = 10), sRAGE (n = 10), and AngII + sRAGE (n = 10). CINE-MRI was performed in each group after administration of the AngII or sRAGE, and CINE-MR images were analyzed to obtain parameters indicating cardiac anatomical and functional changes including end-diastolic and end-systolic blood volume, end-diastolic and end-systolic myocardial volume, ejection fraction, end-diastolic and end-systolic myocardial mass, and LV wall thickness. LVH observed in AngII group was significantly attenuated by sRAGE. These trends were also observed in histological analysis, demonstrating that cardiac function tracking using in vivo and real-time 9.4T MR imaging provides valuable information about the cardiac remodeling induced by AngII and sRAGE in an AngII-induced LV hypertrophy mice model.

Understanding the multifaceted roles of the phosphoenolpyruvate: Phosphotransferase system in regulation of Salmonella virulence using a mutant defective in ptsI and crr expression.

The phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) catalyzes the translocation of sugar substrates with their concomitant phosphorylation in bacteria. In addition to its intrinsic role in sugar transport and metabolism, numerous recent studies report the versatility of the PTS to interconnect energy and signal transduction in response to sugar availability. In this study, the role of PTS in Salmonella virulence regulation was explored. To decipher the regulatory network coordinated by the PTS during Salmonella infection, a transcriptomic approach was applied to a transposon insertion mutant with defective expression of ptsI and crr, which encode enzyme I and enzyme IIAGlc of the PTS, respectively. There were 114 differentially expressed genes (DEGs) exhibiting two-fold or higher expression changes in the transposon mutant strain, with 13 up-regulated genes versus 101 down-regulated genes. One-third of the DEGs were associated with energy production and carbohydrate/amino acid metabolism pathways, implicating the prominent role of the PTS in carbohydrate transport. With regard to regulation of virulence, the tested mutant decreased the expression of genes associated with quorum sensing, Salmonella pathogenicity islands, flagella, and the PhoPQ regulon. We investigated the possibility of PTS-mediated regulation of virulence determinants identified in the transcriptomic analysis and proposed a regulatory circuit orchestrated by the PTS in Salmonella infection of host cells. These results suggest that Salmonella divergently controls virulence attributes in accordance with the availability of carbohydrates in the environment.

Nelumbo nucifera Receptaculum Extract Suppresses Angiotensin II-Induced Cardiomyocyte Hypertrophy.

Nelumbo nucifera Gaertn. (lotus) is an important medicinal plant, and many parts of the plant have been investigated for their therapeutic effects. However, the therapeutic effect of receptacles of lotuses on pathological cardiomyocyte hypertrophy has not been investigated yet. Therefore, the current study aimed to determine the protective effect of lotus against angiotensin II (Ang II)-induced cardiomyocyte hypertrophy in vitro. Ang II was used to induce hypertrophy of H9c2 cells. The lotus receptacle powder (MeOH extract of receptaculum Nelumbinis; MRN) used in the experiments was prepared by MeOH extraction and subsequent evaporation. To evaluate the effect of MRN on cardiomyocyte hypertrophy, cell size, protein synthesis, and hypertrophic marker expressions were examined. The antioxidant ability of MRN was determined by using CM-H2DCFDA, a general oxidative stress indicator. Ang II-induced cardiomyocyte hypertrophy was significantly attenuated by 5 µg/mL of MRN, as confirmed by the reductions in cell size, protein synthesis, and hypertrophic marker expression. MRN also attenuated Ang II-induced excessive intracellular reactive oxygen species (ROS) production through the suppression of protein kinase C (PKC), extracellular-signal-regulated kinase (ERK), and NF-κB activation and subsequent type I angiotensin receptor (AT1R), receptor for advanced glycation end products (RAGE), and NADPH oxidase (NOX) expression. MRN exerted a significant protective effect against Ang II-induced cardiomyocyte hypertrophy through suppression of PKC-ERK signaling, and this subsequently led to attenuation of intracellular ROS production.

sRAGE attenuates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting RAGE-NFκB-NLRP3 activation.

OBJECTIVE AND DESIGN: The receptor for advanced glycation endproducts (RAGE) is an innate immunity receptor that has been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, the possibility that RAGE-mediated signaling is involved in angiotensin II (Ang II)-induced cardiac left ventricular hypertrophy has yet to be investigated. We therefore determined whether RAGE has a role in regulating pathological cardiac hypertrophy. MATERIALS AND SUBJECTS: Protein abundance was estimated using Western blotting and intracellular ROS level and phospho-p65 were detected using fluorescence microscopy. Enzyme-linked immunosorbent assay was used to detect HMGB1 and IL-1ß. All in vitro experiments were performed using H9C2 cells. TREATMENTS: To induce cardiomyocyte hypertrophy, 300 nM Ang II was treated for 48 h and 2 µg/ml sRAGE was treated 1 h prior to addition of Ang II. RESULTS: sRAGE attenuated Ang II-induced cardiomyocyte hypertrophy by downregulating RAGE and angiotensin II type 1 receptor expression. Secretion levels of high motility group box 1 and interleukin-1ß, estimated from a cell culture medium, were significantly reduced by sRAGE. Activated PKCs and ERK1/2, important signals in left ventricular hypertrophy (LVH) development, were downregulated by sRAGE treatment. Furthermore, we found that nuclear factor-κB and NOD-like receptor protein 3 (NLRP3) were associated with RAGE-mediated cardiomyocyte hypertrophy. CONCLUSIONS: In the context of these results, we conclude that RAGE induces cardiac hypertrophy through the activation of the PKCs-ERK1/2 and NF-κB-NLRP3-IL1ß signaling pathway, and suggest that RAGE-NLRP3 may be an important mediator of Ang II-induced cardiomyocyte hypertrophy. In addition, we determined that inhibition of RAGE activation with soluble RAGE (sRAGE) has a protective effect on Ang II-induced cardiomyocyte hypertrophy.

Development of an integrated process to produce d-mannose and bioethanol from coffee residue waste.

A novel, integrated process for economical high-yield production of d-mannose and ethanol from coffee residue waste (CRW), which is abundant and widely available, was reported. The process involves pretreatment, enzymatic hydrolysis, fermentation, color removal, and pervaporation, which can be performed using environmentally friendly technologies. The CRW was pretreated with ethanol at high temperature and then hydrolyzed with enzymes produced in-house to yield sugars. Key points of the process are: manipulations of the fermentation step that allowing bioethanol-producing yeasts to use almost glucose and galactose to produce ethanol, while retaining large amounts of d-mannose in the fermented broth; removal of colored compounds and other components from the fermented broth; and separation of ethanol and d-mannose through pervaporation. Under optimized conditions, approximately 15.7g dry weight (DW) of d-mannose (approximately 46% of the mannose) and approximately 11.3g DW of ethanol from 150g DW of ethanol-pretreated CRW, were recovered.