Sphingosine-1-phosphate-cathelicidin axis plays a pivotal role in the development of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, caused by mutagenesis resulting from excess ultraviolet radiation or other types of oxidative stress. These stressors also upregulate production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), via endoplasmic reticulum (ER) stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. While CAMP has beneficial antimicrobial activities, it also can be pro-inflammatory and pro-carcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that: 1) CAMP expression is increased in cSCC cells and skin from cSCC patients; 2) S1P levels are elevated in cSCC cells, while inhibition of S1P production attenuates CAMP-stimulated cSCC growth; 3) exogenous CAMP stimulates cSCC, but not normal human keratinocyte growth; 4) blockade of formyl peptide receptor-like (FPRL) 1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; 5) Foxp3+ regulatory T cell (which decreases anti-tumor immunity) levels increase in cSCC skin; and 6) CAMP induces ER stress in cSCC cells. Together, the ER stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, i.e., cSCC growth and invasion impedes anti-cancer immunity.

Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

A Review of Recent Advancements in Sensor-Integrated Medical Tools.

A medical tool is a general instrument intended for use in the prevention, diagnosis, and treatment of diseases in humans or other animals. Nowadays, sensors are widely employed in medical tools to analyze or quantify disease-related parameters for the diagnosis and monitoring of patients' diseases. Recent explosive advancements in sensor technologies have extended the integration and application of sensors in medical tools by providing more versatile in vivo sensing capabilities. These unique sensing capabilities, especially for medical tools for surgery or medical treatment, are getting more attention owing to the rapid growth of minimally invasive surgery. In this review, recent advancements in sensor-integrated medical tools are presented, and their necessity, use, and examples are comprehensively introduced. Specifically, medical tools often utilized for medical surgery or treatment, for example, medical needles, catheters, robotic surgery, sutures, endoscopes, and tubes, are covered, and in-depth discussions about the working mechanism used for each sensor-integrated medical tool are provided.

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (Pgc1α), and downregulated adipogenic/lipogenic genes (Pparγ and C/ebpα) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (il-6, Tnf-α, Cox-2, and inos), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders.

Nanowatt-Level Photoactivated Gas Sensor Based on Fully-Integrated Visible MicroLED and Plasmonic Nanomaterials.

Photoactivated gas sensors that are fully integrated with micro light-emitting diodes (µLED) have shown great potential to substitute conventional micro/nano-electromechanical (M/NEMS) gas sensors owing to their low power consumption, high mechanical stability, and mass-producibility. Previous photoactivated gas sensors mostly have utilized ultra-violet (UV) light (250-400 nm) for activating high-bandgap metal oxides, although energy conversion efficiencies of gallium nitride (GaN) LEDs are maximized in the blue range (430-470 nm). This study presents a more advanced monolithic photoactivated gas sensor based on a nanowatt-level, ultra-low-power blue (λpeak  = 435 nm) µLED platform (µLP). To promote the blue light absorbance of the sensing material, plasmonic silver (Ag) nanoparticles (NPs) are uniformly coated on porous indium oxide (In2 O3 ) thin films. By the plasmonic effect, Ag NPs absorb the blue light and spontaneously transfer excited hot electrons to the surface of In2 O3 . Consequently, high external quantum efficiency (EQE, ≈17.3%) and sensor response (ΔR/R0 (%) = 1319%) to 1 ppm NO2 gas can be achieved with a small power consumption of 63 nW. Therefore, it is highly expected to realize various practical applications of mobile gas sensors such as personal environmental monitoring devices, smart factories, farms, and home appliances.

Dnmt1/Tet2-mediated changes in Cmip methylation regulate the development of nonalcoholic fatty liver disease by controlling the Gbp2-Pparγ-CD36 axis.

Dynamic alteration of DNA methylation leads to various human diseases, including nonalcoholic fatty liver disease (NAFLD). Although C-Maf-inducing protein (Cmip) has been reported to be associated with NAFLD, its exact underlying mechanism remains unclear. Here, we aimed to elucidate this mechanism in NAFLD in vitro and in vivo. We first identified alterations in the methylation status of the Cmip intron 1 region in mouse liver tissues with high-fat high-sucrose diet-induced NAFLD. Knockdown of DNA methyltransferase (Dnmt) 1 significantly increased Cmip expression. Chromatin immunoprecipitation assays of AML12 cells treated with oleic and palmitic acid (OPA) revealed that Dnmt1 was dissociated and that methylation of H3K27me3 was significantly decreased in the Cmip intron 1 region. Conversely, the knockdown of Tet methylcytosine dioxygenase 2 (Tet2) decreased Cmip expression. Following OPA treatment, the CCCTC-binding factor (Ctcf) was recruited, and H3K4me3 was significantly hypermethylated. Intravenous Cmip siRNA injection ameliorated NAFLD pathogenic features in ob/ob mice. Additionally, Pparγ and Cd36 expression levels were dramatically decreased in the livers of ob/ob mice administered siCmip, and RNA sequencing revealed that Gbp2 was involved. Gbp2 knockdown also induced a decrease in Pparγ and Cd36 expression, resulting in the abrogation of fatty acid uptake into cells. Our data demonstrate that Cmip and Gbp2 expression levels are enhanced in human liver tissues bearing NAFLD features. We also show that Dnmt1-Trt2/Ctcf-mediated reversible modulation of Cmip methylation regulates the Gbp2-Pparγ-Cd36 signaling pathway, indicating the potential of Cmip as a novel therapeutic target for NAFLD.

Nypa fruticans Wurmb inhibits melanogenesis in isobutylmethylxanthine­treated melanoma via the PI3K/AKT/mTOR/CREB and MAPK signaling pathways.

Malignant melanoma is responsible for 3.0 and 1.7% of cases of tumor incidence and tumor-associated mortality, respectively, in the Caucasian population. Melanoma is a type of skin cancer that occurs when melanocytes mutate and divide uncontrollably. Nypa fruticans Wurmb (NF) is abundant in phytochemicals (polyphenols and flavonoids) and is traditionally used to treat diseases of the respiratory tract. The present study investigated the inhibitory effect of the ethyl acetate fraction of NF (ENF) on melanogenesis-related factors in isobutylmethylxanthine-treated B16F10 melanoma cells. Phenolics and flavonoids (caffeic acid, catechin, epicatechin and hirsutine) in ENF were analyzed via liquid chromatography-mass spectrometry. In addition, the main factors involved in melanogenesis were identified using immunoblotting, reverse transcription-polymerase chain reaction (RT-PCR), RT-quantitative PCR and immunofluorescence. ENF significantly suppressed the expression of tyrosinase (TYR) and TYR-related proteins 1 and 2 (TYRP-1/2), which are the main factors involved in melanogenesis. ENF also inhibited the expression of microphthalmia-associated transcription factor (MITF) by phosphorylating the related cell signaling proteins (protein kinase B, mammalian target of rapamycin, phosphoinositide 3-kinase and cAMP response element-binding protein). Furthermore, ENF inhibited the phosphorylation of extracellular signal-regulated kinase and thereby downregulated melanogenesis. In conclusion, ENF inhibited melanogenesis by suppressing MITF, which controls TYRP-1/2 and TYR. These results suggested that ENF may be a natural resource that can inhibit excessive melanin expression by regulating various melanogenesis pathways.

Optimization of the clinically approved mg-Zn alloy system through the addition of ca.

BACKGROUND: Although several studies on the Mg-Zn-Ca system have focused on alloy compositions that are restricted to solid solutions, the influence of the solid solution component of Ca on Mg-Zn alloys is unknown. Therefore, to broaden its utility in orthopedic applications, studies on the influence of the addition of Ca on the microstructural, mechanical, and corrosion properties of Mg-Zn alloys should be conducted. In this study, an in-depth investigation of the effect of Ca on the mechanical and bio-corrosion characteristics of the Mg-Zn alloy was performed for the optimization of a clinically approved Mg alloy system comprising Ca and Zn. METHODS: The Mg alloy was fabricated by gravitational melting of high purity Mg, Ca, and Zn metal grains under an Ar gas environment. The surface and cross-section were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to analyze their crystallographic structures. Electrochemical and immersion tests in Hank's balanced salt solution were used to analyze their corrosion resistance. Tensile testing was performed with universal testing equipment to investigate the impact of Ca addition. The examination of cytotoxicity for biometric determination was in line with the ISO10993 standard. RESULTS: In this study, the 0.1% Ca alloy had significantly retarded grain growth due to the formation of the tiny and well-dispersed Ca2Mg6Zn3 phase. In addition, the yield strength and elongation of the 0.1% Ca alloy were more than 50% greater than the 2% Zn alloy. The limited cell viability of the 0.3% Ca alloy could be attributed to its high corrosion rate, whereas the 0.1% Ca alloy demonstrated cell viability of greater than 80% during the entire experimental period. CONCLUSION: The effect of the addition of Ca on the microstructure, mechanical, and corrosion characteristics of Mg-Zn alloys was analyzed in this work. The findings imply that the Mg-Zn alloy system could be optimized by adding a small amount of Ca, improving mechanical properties while maintaining corrosion rate, thus opening the door to a wide range of applications in orthopedic surgery.

High Accuracy Real-Time Multi-Gas Identification by a Batch-Uniform Gas Sensor Array and Deep Learning Algorithm.

Semiconductor metal oxide (SMO) gas sensors are attracting great attention as next-generation environmental monitoring sensors. However, there are limitations to the actual application of SMO gas sensors due to their low selectivity. Although the electronic nose (E-nose) systems based on a sensor array are regarded as a solution for the selectivity issue, poor accuracy caused by the nonuniformity of the fabricated gas sensors and difficulty of real-time gas detection have yet to be resolved. In this study, these problems have been solved by fabricating uniform gas sensor arrays and applying the deep learning algorithm to the data from the sensor arrays. Nanocolumnar films of metal oxides (SnO2, In2O3, WO3, and CuO) with a high batch uniformity deposited through glancing angle deposition were used as the sensing materials. The convolutional neural network (CNN) using the input data as a matrix form was adopted as a learning algorithm, which could conduct pattern recognition of the sensor responses. Finally, real-time selective gas detection for CO, NH3, NO2, CH4, and acetone (C3H6O) gas was achieved (minimum response time of 1, 8, 5, 19, and 2 s, respectively) with an accuracy of 98% by applying preprocessed response data to the CNN.

Discovery of Orphan Olfactory Receptor 6M1 as a New Anticancer Target in MCF-7 Cells by a Combination of Surface Plasmon Resonance-Based and Cell-Based Systems.

Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.

Chemo-Mechanically Operating Palladium-Polymer Nanograting Film for a Self-Powered H2 Gas Sensor.

This study proposes a reliable and self-powered hydrogen (H2) gas sensor composed of a chemo-mechanically operating nanostructured film and photovoltaic cell. Specifically, the nanostructured film has a configuration in which an asymmetrically coated palladium (Pd) film is coated on a periodic polyurethane acrylate (PUA) nanograting. The asymmetric Pd nanostructures, optimized by a finite element method simulation, swell upon reacting with H2 and thereby bend the PUA nanograting, changing the amount of transmitted light and the current output of the photovoltaic cell. Since the degree of warping is determined by the concentration of H2 gas, a wide concentration range of H2 (0.1-4.0%) can be detected by measuring the self-generated electrical current of the photovoltaic cell without external power. The normalized output current changes are ∼1.5%, ∼2.8%, ∼3.5%, ∼5.0%, ∼21.5%, and 25.3% when the concentrations of H2 gas are 0.1%, 0.5%, 1.0%, 1.6%, 2%, and 4%, respectively. Moreover, because Pd is highly chemically reactive to H2 and also because there is no electrical current applied through Pd, the proposed sensor can avoid device failure due to the breakage of the Pd sensing material, resulting in high reliability, and can show high selectivity against various gases such as carbon monoxide, hydrogen sulfide, nitrogen dioxide, and water vapor. Finally, using only ambient visible light, the sensor was modularized to produce an alarm in the presence of H2 gas, verifying a potential always-on H2 gas monitoring application.

Lubricant-infused directly engraved nano-microstructures for mechanically durable endoscope lens with anti-biofouling and anti-fogging properties.

While a clear operating field during endoscopy is essential for accurate diagnosis and effective surgery, fogging or biofouling of the lens can cause loss of visibility during these procedures. Conventional cleaning methods such as the use of an irrigation unit, anti-fogging surfactant, or particle-based porous coatings infused with lubricants have been used but proven insufficient to prevent loss of visibility. Herein, a mechanically robust anti-fogging and anti-biofouling endoscope lens was developed by forming a lubricant-infused directly engraved nano-/micro-structured surface (LIDENS) on the lens. This structure was directly engraved onto the lens via line-by-line ablation with a femtosecond laser. This directly engraved nano/microstructure provides LIDENS lenses with superior mechanical robustness compared to lenses with conventional particle-based coatings, enabling the maintenance of clear visibility throughout typical procedures. The LIDENS lens was chemically modified with a fluorinated self-assembled monolayer (F-SAM) followed by infusion of medical-grade perfluorocarbon lubricants. This provides the lens with high transparency (> 70%) along with superior and long-lasting repellency towards various liquids. This excellent liquid repellency was also shown to be maintained during blood dipping, spraying, and droplet condensation experiments. We believe that endoscopic lenses with the LIDENS offer excellent benefits to endoscopic surgery by securing clear visibility for stable operation.

Femtosecond laser induced nano-textured micropatterning to regulate cell functions on implanted biomaterials.

Posterior capsular opacification (PCO) is the most common complication of cataract surgery. PCO is due to the proliferation, migration, and epithelial-to-mesenchymal transition of the residual lens epithelial cells (LECs) within the lens capsule. As surface topography influences cellular response, we investigated the effect of modulating the dimensions of periodic nano-textured patterns on the surface of an intraocular lens material to regulate lens epithelial cell functions such as cell adhesion, migration, orientation, and proliferation. Patterned poly(HEMA) samples were prepared by a femtosecond laser microfabrication, and the behaviors of human B-3 LECs were observed on groove/ridge patterns with widths varying from 5 to 40 µm. In the presence of ridge and groove patterns, the adherent cells elongated along the direction of the patterns, and f-actin of the cells was spread to a lesser extent on the nano-textured groove surfaces. Both single and collective cell migrations were significantly inhibited in the perpendicular direction of the patterns on the nano-textured micro-patterned samples. We also fabricated the patterns on the curved surface of a commercially available intraocular lens for in vivo evaluation. In vivo results showed that a patterned IOL could help suppress the progression of PCO by inhibiting cell migration from the edge to the center of the IOL. Our reports demonstrate that nano- and microscale topographical patterns on a biomaterial surface can regulate cellular behavior when it is implanted into animals.

Butein Synergizes with Statin to Upregulate Low-Density Lipoprotein Receptor Through HNF1α-Mediated PCSK9 Inhibition in HepG2 Cells.

Downregulation of the low-density lipoprotein (LDL) receptor (LDLR) can lead to hypercholesterolemia and related conditions, including cardiovascular diseases. Statins are a class of LDL cholesterol-lowering agents and are best-selling medications for patients at high risk of developing cardiovascular diseases. Indeed, statins upregulate LDLR and proprotein convertase subtilisin/kexin type 9a (PCSK9), leading to LDLR lysosomal degradation, which interferes with the attenuation of hypercholesterolemia. In the present study, butein was found to decrease extracellular PCSK9 levels by reducing its mRNA expression, which was attributable to butein-mediated downregulation of HNF1α in HepG2 cells. Butein-mediated PCSK9 inhibition further reversed LDLR protein synthesis inhibition, which possibly occurred through butein-mediated inhibition of LDLR degradation. When treated as a combination of butein and a statin, butein reduced statin-mediated enhancement of PCSK9 protein expression. This resulted in a synergistic enhancement of LDLR protein expression, whereas butein alone marginally increased LDLR protein expression. These findings suggest that butein, a novel PCSK9 inhibitor, may be a potential alternative or adjunct to statin treatment.

Self-Powered Gas Sensor Based on a Photovoltaic Cell and a Colorimetric Film with Hierarchical Micro/Nanostructures.

We report a new type of self-powered gas sensors based on the combination of a colorimetric film with hierarchical micro/nanostructures and organic photovoltaic cells. The transmittance of the colorimetric film with micro/nanostructures coated with N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) changes by reacting with NO2 gas, and it is measured as a current output of the photovoltaic cell. For this purpose, materials for the organic photovoltaic cells were carefully chosen to match the working wavelength of the TMPD. Micropost arrays and nanowires increase the surface area for the gas reaction and thus improve the transmittance changes by NO2 gas (6.7% change for the plain film vs 27.7% change for the film with hierarchical micro/nanostructures to 20 ppm of NO2). Accordingly, the colorimetric device with the hierarchical structures showed a response of ΔI/I0 = 0.27-20 ppm of NO2, which is a 71% improvement compared to that of the plain sensing film. Furthermore, it showed a high selectivity against other gases such as H2S and CO with almost negligible responses. Since the current output change of the photovoltaic cell is utilized as a sensor signal, no extra electrical power is required for the operation of gas sensors. We also integrated the sensor device with an electrical module and demonstrated a self-powered gas alarm system.

Microscale Biosensor Array Based on Flexible Polymeric Platform toward Lab-on-a-Needle: Real-Time Multiparameter Biomedical Assays on Curved Needle Surfaces.

In vivo sensing of various physical/chemical parameters is gaining increased attention for early prediction and management of various diseases. However, there are major limitations on the fabrication method of multiparameter needle-based in vivo sensing devices, particularly concerning the uniformity between sensors. To address these challenges, we developed a microscale biosensor array for the measurement of electrical conductivity, pH, glucose, and lactate concentrations on a flexible polymeric polyimide platform with electrodeposited electrochemically active layers. The biosensor array was then transferred to a medical needle toward multiparametric in vivo sensing. The flexibility of the sensor platform allowed an easy integration to the curved surface (φ = 1.2 mm) of the needle. Furthermore, the electrodeposition process was used to localize various active materials for corresponding electrochemical sensors on the microscale electrodes with a high precision (patterning area = 150 µm × 2 mm). The biosensor array-modified needle was aimed to discriminate cancer from normal tissues by providing real-time discrimination of glucose, lactate concentration, pH, and electrical conductivity changes associated with the cancer-specific metabolic processes. The sensor performance was thus evaluated using solution samples, covering the physiological concentrations for cancer discrimination. Finally, the possibility of in vivo electrochemical biosensing during needle insertion was confirmed by utilizing the needle in a hydrogel phantom that mimicked the normal and cancer microenvironments.

Biopsy needle integrated with multi-modal physical/chemical sensor array.

A biopsy needle integrated with a multi-modal physical/chemical sensor array for electrical conductivity, pH, and glucose concentration measurement was developed. A flexible device with an electrical conductivity sensor, a pH sensor, and a glucose sensor was fabricated on a flexible polyimide substrate with thickness less than 20 µm. Then, the sensor was directly integrated onto the surface of biopsy needle by attaching with a pressure sensitive adhesive. The performance factors of the sensor were examined, showing that it could properly measure the parameters in the ranges of human body conditions (conductivity = 0.0265 S/m - 1.027 S/m, pH = 6.6-7.4, and glucose concentration = 2 mM-13 mM). The capabilities of dual-modal and multi-modal sensing were demonstrated by tests with a liver cancer mimicking hydrogel phantom, a solution sample, and porcine liver tissue with exchanged parameters by perfusion of the phosphate buffer saline. Based on these results, we expect that the biopsy needle integrated with the multi-modal sensor array could help to increase the accuracy of the image-guided biopsy process by providing the information of tissue types at the needle tip.

Ethanol Extract of Ligularia fischeri Inhibits the Lipopolysaccharide-Induced Inflammatory Response by Exerting Anti-Histone Acetyltransferase Activity to Negatively Regulate p65.

Histone acetyltransferase (HAT) activity is well established to regulate inflammatory responses. In contrast, the mechanisms by which natural nutritional extracts influence epigenetic mechanisms to regulate inflammation have not yet been thoroughly investigated. Thus, in the present study, we observed that the anti-HAT activity exerted by an ethanol extract of Ligularia fischeri (ELF) inhibited inflammation. Specifically, we used a cell-free system to show that ELF attenuates HAT activity. We also demonstrated that ELF decreases lipopolysaccharide (LPS)-induced HAT mRNA and protein expression levels in Raw 264.7 cells, and thereby attenuates inflammation-induced patterns of hyperacetylation at nonhistone and histone-H4 proteins. Interestingly, we found that ELF blocked p65 translocation in LPS-stimulated Raw 264.7 cells by attenuating acetylation at lysine residue 310 of p65. Finally, we investigated whether ELF reduces the inflammatory cytokines, IL-6, IL-1ß, and TNFα, using its HAT inhibitor activity. Taken together, these results suggest that ELF negatively regulates inflammatory responses by inhibiting HATs and HAT activity.

Genome-wide analysis of DNA methylation identifies novel differentially methylated regions associated with lipid accumulation improved by ethanol extracts of Allium tubersosum and Capsella bursa-pastoris in a cell model.

Hepatic steatosis is the most common chronic liver disease in Western countries. Both genetic and environmental factors are known as causes of the disease although their underlying mechanisms have not been fully understood. This study investigated the association of DNA methylation with oleic acid-induced hepatic steatosis. It also examined effects of food components on DNA methylation in hepatic steatosis. Genome-wide DNA methylation of oleic acid (OA)-induced lipid accumulation in vitro cell model was investigated using reduced representation bisulfite sequencing. Changes of DNA methylation were also analyzed after treatment with food components decreasing OA-induced lipid accumulation in the model. We identified total 81 regions that were hypermethylated by OA but hypomethylated by food components or vice versa. We determined the expression of seven genes proximally located at the selected differentially methylated regions. Expression levels of WDR27, GNAS, DOK7, MCF2L, PRKG1, and CMYA5 were significantly different between control vs OA and OA vs treatment with food components. We demonstrated that DNA methylation was associated with expression of genes in the model of hepatic steatosis. We also found that food components reversely changed DNA methylation induced by OA and alleviated lipid accumulation. These results suggest that DNA methylation is one of the mechanisms causing the hepatic steatosis and its regulation by food components provides insights that may prevent or alleviate lipid accumulation.