Facile and cost-effective fabrication of wearable alpha-naphtholphthalein-based halochromic sensor for wound pH monitoring.

The sensor, designed to be worn directly on the skin, is suitable for real-time monitoring of the recovery level of not only general wounds, but also difficult-to-heal wounds, such as those with chronic inflammation. Notably, healthy skin has a pH range of 4-6. When a wound occurs, the pH is known to be approximately 7.4. In this study, alpha-naphtholphthalein (Naph) was immersed in a cotton-blended textile to produce a wearable halochromic sensor that clearly changed color depending on the pH of the skin in the range 6-9, including pH 7.4, which is the skin infection state. The coating was performed without using an organic solvent by dissolving it in micelle form using cetyltrimethylammonium bromide, a surfactant, in water. Naph-based halochromic sensor shows light yellow, which is the dye's own color, at pH 6, which is a healthy skin condition, and gradually showed a clear color change to light green-green-blue as pH increased. Even after washing and drying by rubbing with regular tap water, the color change due to pH was maintained more than 10 times. Naph-based halochromic sensors use a simple solution production and coating method and are not only reusable sensors that can be washed with water but also use environmentally friendly water, making them very suitable for developing commercial products for wound pH monitoring. In addition, it can be easily applied to medical supplies, such as medical gauze, patient clothes, and compression bandages, as well as everyday wear, such as clothing, gloves, and socks. Therefore, it is expected to be widely used as a wound pH sensor, allowing real-time monitoring of the skin condition of individuals with chronic skin inflammation, including patients requiring wound recovery.

Reversible thermochromic fibers with excellent elasticity and hydrophobicity for wearable temperature sensors.

Color-changing fibers, which can intuitively convey information to the human eye, can be used to facilely add functionality to various types of clothing. However, they are often expensive and complex, and can suffer from low durability. Therefore, in this study, we developed highly elastic and hydrophobic thermochromic fibers as wearable temperature sensors using a simple method that does not require an electric current. A thermochromic pigment was embedded inside and outside hydrophobic silica aerogel particles, following which the thermochromic aerogel was fixed to highly elastic spandex fibers using polydimethylsiloxane as a flexible binder. In particular, multi-strand spandex fibers were used instead of single strands, resulting in the thermochromic aerogels penetrating the inside of the strands upon their expansion by solvent swelling. During drying, the thermochromic aerogel adhered more tightly to the fibers by compressing the strands. The thermochromic fiber was purple at room temperature (25 °C), but exhibited a two-stage color change to blue and then white as the temperature increased to 37 °C. In addition, even after 100 cycles of tension-contraction at 200%, the thermochromic aerogel did not detach and was strongly attached to the fiber. Additionally, it was confirmed that color change due to temperature was stable even after exposure to 1 wt% NaCl (artificial sweat) and 0.1 wt% detergent solutions. The developed thermochromic fiber therefore exhibited excellent elasticity and hydrophobicity, and is expected to be widely utilized as an economical wearable temperature sensor as it does not require electrical devices.

Cesium tungsten oxide-carbon nanotube-hydroxypropyl cellulose thermoresponsive display.

Among different heat-responsive polymers, hydroxypropyl cellulose (HPC) is biodegradable and is widely used in products that are harmless to the human body, such as food and pharmaceuticals. When the temperature of the hydrogel-type HPC increases, the hydrophilic bonds between the HPC molecules break, and the HPC molecules aggregate owing to the hydrophobic bonds. Therefore, light transmittance may vary because the aggregated HPC molecules scatter light. This study investigated the implementation of a display using the thermoreversible phase transition of HPC. Herein, a near-infrared (NIR) laser was irradiated only to a local area to control the surface temperature and enable the effective operation of the thermoreversible phase transition of HPC. For this, cesium tungsten oxide (CTO), which absorbs NIR light and generates heat, was mixed with the HPC hydrogel to improve the photothermal effect. Moreover, by additionally mixing carbon nanotubes (CNTs) with high thermal conductivity, the heat generated from the CTO is quickly transferred to the HPC hydrogel, and the heat of the HPC hydrogel is quickly cooled through the CNTs after stopping the NIR laser irradiation. The produced NIR-writing CTO-CNT-HPC (CCH) thermoresponsive display exhibited a fast thermoresponsive time. The CCH thermoresponsive display developed in this study can be applied in situations that require fast display response times, such as interactive advertising, property exhibitions, navigation systems for car, schedule information, event information, and public announcements.

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis.

As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1ß production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA.

Chloroquine prevents hypoxic accumulation of HIF-1α by inhibiting ATR kinase: implication in chloroquine-mediated chemosensitization of colon carcinoma cells under hypoxia.

BACKGROUND: Chloroquine (CQ) is an effective and safe antimalarial drug that is also used as a disease-modifying antirheumatic drug. Recent studies have shown that CQ can sensitize cancer cells to anti-cancer therapies. METHODS: In this study, we investigated the molecular mechanisms underlying CQ-mediated chemosensitization in human colon carcinoma cells. RESULTS: CQ prevented hypoxia-inducible factor (HIF)-1α protein induction in human colon carcinoma cells. CQ also suppressed HIF-1 activity, as represented by CQ inhibition of HIF-1-dependent luciferase activity and reduced induction of vascular endothelial growth factor. Under hypoxia, CQ restricted HIF-1α synthesis but did not affect HIF-1α transcription and protein stability. The hypoxic state activated ataxia telangiectasia and Rad3-related (ATR) kinase and increased the level of phosphorylated checkpoint kinase 1, a substrate of ATR kinase; however, this was prevented by CQ. An ATR kinase inhibitor suppressed the hypoxic induction of HIF-1α protein and was as effective as CQ. The cytotoxicity of 5-fluorouracil (5-FU), the first choice for the treatment of colorectal cancer, was attenuated under hypoxia. CQ enhanced the cytotoxicity of 5-FU treatment, which was mimicked by the transient transfection with HIF-1α siRNA. CONCLUSIONS: Under hypoxia, CQ-mediated sensitization of colon carcinoma HCT116 cells to 5-FU involves HIF-1 inhibition via ATR kinase suppression.

N-Acetylserotonin is an oxidation-responsive activator of Nrf2 ameliorating colitis in rats.

N-Acetylserotonin (NAS) is an intermediate in the melatonin biosynthetic pathway. We investigated the anti-inflammatory activity of NAS by focusing on its chemical feature oxidizable to an electrophile. NAS was readily oxidized by reaction with HOCl, an oxidant produced in the inflammatory state. HOCl-reacted NAS (Oxi-NAS), but not NAS, activated the anti-inflammatory nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase (HO)-1 pathway in cells. Chromatographic and mass analyses demonstrated that Oxi-NAS was the iminoquinone form of NAS and could react with N-acetylcysteine possessing a nucleophilic thiol to form a covalent adduct. Oxi-NAS bound to Kelch-like ECH-associated protein 1, resulting in Nrf2 dissociation. Moreover, rectally administered NAS increased the levels of nuclear Nrf2 and HO-1 proteins in the inflamed colon of rats. Simultaneously, NAS was converted to Oxi-NAS in the inflamed colon. Rectal NAS mitigated colonic damage and inflammation. The anticolitic effects were significantly compromised by the coadministration of an HO-1 inhibitor.

Washable and stretchable fiber with heat and ultraviolet color conversion.

Wearable fabric-type color conversion sensors are very effective in quickly expressing danger or warnings to people. In particular, they can visually show information regarding the external environment, such as its temperature or ultraviolet (UV) intensity. However, a wearable sensor worn on the human body should maintain its sensing performance without deterioration even when exposed to various external stimuli, such as the repeated movements caused by human activity, sweat, and washing. In this study, thermochromic and UV photochromic fibers were fabricated to maintain stable color conversion functionality in response to temperature and UV irradiation even after continuous tensile-shrinkage, exposure to sweat and detergent solution. The thermochromic or UV photochromic materials were coated on the inside and outside of strands constituting a highly elastic spandex fiber. By adding polydimethylsiloxane to the color-changing material, the physical and chemical stability of the color-conversion thin film coated on the strand increased. The fabricated thermochromic fiber had a blue-green color and changed to white as the temperature increased, whereas the fabricated UV photochromic fiber was white and changed to purple as the UV intensity increased. In addition, the color conversion coating film was not lost even when exposed to repeated stretching and sweat/washing solutions, and a stable color-change reactivity was maintained. The thermochromic and UV photochromic fibers introduced in this study are expected to contribute to the commercialization of wearable colorimetric sensors by solving the problems regarding the physical stimulation and washing stability of existing coating-type color conversion fibers and textiles.

A Colon-Targeted Prodrug of Riluzole Improves Therapeutic Effectiveness and Safety upon Drug Repositioning of Riluzole to an Anti-Colitic Drug.

Riluzole (RLZ) is a neuroprotective drug indicated for amyotrophic lateral sclerosis. To examine the feasibility of RLZ for repositioning as an anti-inflammatory bowel disease (IBD) drug, RLZ (2, 5, and 10 mg/kg) was administered orally to rats with colitis induced by 2,4-dinitrobenzenesulfonic acid. Oral RLZ was effective against rat colitis in a dose-dependent manner, which was statistically significant at doses over 5 mg/kg. To address safety issues upon repositioning and further improve anti-colitic effectiveness, RLZ was coupled with salicylic acid (SA) via an azo-bond to yield RLZ-azo-SA (RAS) for the targeted colonic delivery of RLZ. Upon oral gavage, RAS (oral RAS) was efficiently delivered to and activated to RLZ in the large intestine, and systemic absorption of RLZ was substantially reduced. Oral RAS ameliorated colonic damage and inflammation in rat colitis and was more effective than oral RLZ and sulfasalazine, a current anti-IBD drug. Moreover, oral RAS potently inhibited glycogen synthase kinase 3ß (GSK3ß) in the inflamed distal colon, leading to the suppression of NFκB activity and an increase in the level of the anti-inflammatory cytokine interleukin-10. Taken together, RAS, which enables RLZ to be delivered to and inhibit GSK3ß in the inflamed colon, may facilitate repositioning of RLZ as an anti-IBD drug.

Dapsone Azo-Linked with Two Mesalazine Moieties Is a "Me-Better" Alternative to Sulfasalazine.

Dapsone (DpS) is an antimicrobial and antiprotozoal agent, especially used to treat leprosy. The drug shares a similar mode of action with sulfonamides. Additionally, it possesses anti-inflammatory activity, useful for treating autoimmune diseases. Here, we developed a "me-better" alternative to sulfasalazine (SSZ), a colon-specific prodrug of mesalazine (5-ASA) used as an anti-inflammatory bowel diseases drug; DpS azo-linked with two molecules of 5-ASA (AS-DpS-AS) was designed and synthesized, and its colon specificity and anti-colitic activity were evaluated. AS-DpS-AS was converted to DpS and the two molecules of 5-ASA (up to approximately 87% conversion) within 24 h after incubation in the cecal contents. Compared to SSZ, AS-DpS-AS showed greater efficiency in colonic drug delivery following oral gavage. Simultaneously, AS-DpS-AS substantially limited the systemic absorption of DpS. In a dinitrobenzene sulfonic acid-induced rat colitis model, oral AS-DpS-AS elicited better efficacy against rat colitis than oral SSZ. Moreover, intracolonic treatment with DpS and/or 5-ASA clearly showed that combined treatment with DpS and 5-ASA was more effective against rat colitis than the single treatment with either DpS or 5-ASA. These results suggest that AS-DpS-AS may be a "me-better" drug of SSZ with higher therapeutic efficacy, owing to the combined anti-colitic effects of 5-ASA and DpS.

Colon-Targeted Trans-Cinnamic Acid Ameliorates Rat Colitis by Activating GPR109A.

We designed colon-targeted trans-cinnamic acid (tCA) and synthesized its conjugates with glutamic acid (tCA-GA) and aspartic acid (tCA-AA). We evaluated the anti-colitic activity of colon-targeted tCA using a dinitrobenzenesulfonic acid-induced rat colitis model. The conjugates lowered the distribution coefficient and Caco-2 cell permeability of tCA and converted to tCA in the cecum, with higher rates and percentages with tCA-GA than with tCA-AA. Following oral gavage, tCA-GA delivered a higher amount of tCA to the cecum and exhibited better anti-colitic effects than tCA and sulfasalazine (SSZ), which is the current treatment for inflammatory bowel disease. In the cellular assay, tCA acted as a full agonist of GPR109A (EC50: 530 µM). The anti-colitic effects of tCA-GA were significantly compromised by the co-administration of the GPR109A antagonist, mepenzolate. Collectively, colon-targeted tCA potentiated the anti-colitic activity of tCA by effectively activating GPR109A in the inflamed colon, enabling tCA to elicit therapeutic superiority over SSZ.

Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation.

Tranilast (TRL), a synthetic derivative of a tryptophan metabolite, is an anti-allergic drug used to treat bronchial asthma. We investigated how TRL activated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1) pathway based on the electrophilic chemistry of the drug and whether TRL activity contributed to the treatment of rat colitis. In human colon carcinoma cells, TRL activated Nrf2, as represented by an increase in nuclear Nrf2 and induction of Nrf2-dependent luciferase and, subsequently, HO-1, a target gene product of Nrf2. TRL activation of Nrf2 and induction of HO-1 were completely prevented by chemical reduction of the electrophilic functional group (α, ß-unsaturated carbonyl group) in the drug. In parallel, TRL was reactive with the nucleophilic thiol group in N-acetylcysteine, forming a covalent adduct. Moreover, TRL, but not reduced TRL, binds to Kelch-like ECH-associated protein 1 (KEAP1), releasing Nrf2. TRL administration ameliorated colonic damage and inflammation in rats with dinitrobenzene sulfonic acid-induced colitis, which was partly compromised by the chemical reduction of TRL or co-treatment with an HO-1 inhibitor. Our results suggest that TRL activated the Nrf2-HO-1 pathway via covalent binding to KEAP1, partly contributing to TRL amelioration in rat colitis.

Design and evaluation of IKK-activated GSK3ß inhibitory peptide as an inflammation-responsive anti-colitic therapeutic.

Glycogen synthase kinase-3ß (GSK3ß), a multi-functional kinase, is a promising therapeutic target for the treatment of inflammation. Inhibitory κB kinase (IKK)-activated GSK3ß inhibitory peptide (IAGIP) was designed as an inflammation-responsive anti-colitic therapeutic. To optimize therapeutic efficiency, IAGIP was tested using two different drug delivery techniques: colon-targeted delivery and cell-permeable peptide modification. In cell-based experiments, in response to tumor necrosis factor (TNF)- and lipopolysaccharide (LPS)-mediated activation of IKK, cell-permeable IAGIP (CTP-IAGIP) inhibited GSK3ß, leading to increased production of anti-inflammatory cytokine interleukin-10 (IL-10) and suppression of TNF- and LPS-induced NFκB activity. Oral gavage of CTP-IAGIP loaded in the colon-targeted capsule attenuated 2,4,6-trinitrobenzene sulfonic acid-induced rat colitis and lowered the expression levels of NFκB-regulated proteins in the inflamed colons. CTP-IAGIP further induced IL-10 production in the inflamed colonic tissues; however, the levels of IL-10 were not affected in the normal colonic tissue or colonic tissue in which inflammation had subsided. Collectively, our data suggest that IAGIP administered using the aforementioned drug delivery techniques is an orally active anti-colitic drug selectively responding to inflammation.

Real-Time Information-Variable Invisible Barcode Comprising Freely Deformable Infrared-Emitting Yarns.

Barcodes are utilized for product information management in shops, offices, hospitals, passenger facilities, and factories because they enable substantial amounts of data to be processed quickly and accurately. However, a limited amount of information can be loaded on the currently used monochrome barcodes that are based on thin-film coatings. Therefore, these barcodes require constant replacement with new barcodes to update the information; furthermore, they cannot be applied to textile products. This study demonstrated the performance of wearable invisible infrared (IR)-emitting barcodes by using twisted yarns that comprised five highly elastic/conductive spandex fibers. The barcode information can be actively updated via the selective IR emission from specific yarns of the barcode by controlling the applied voltage to the IR-emitting yarns. Therefore, the IR barcode required a relatively small number of bars to express a higher volume of information compared to the existing monochrome barcodes. Because the emitted IR light from the yarns was invisible to the human eye and was only recognized by an IR camera, the information-variable IR-emitting yarn-based barcode exhibited an aesthetic design and was composed of a sustainable fabric-type material that could be easily applied to clothes, bags, and shoes. It is expected that the fabricated barcode will be widely utilized as wearable invisible barcodes, whose information will remain invisible to humans and can be updated in real time to ensure information fluidity.

Information-Providing Flexible and Transparent Smart Window Display.

A smart window, which can easily adjust light transmittance, can provide barrier functions, such as improvement in energy efficiency, glare prevention, and privacy protection. However, a smart window that can selectively provide real-time information and display various colorful characters and images at a desired location has not been developed. In this study, a novel smart window capable of real-time information conversion is developed by advancing the light transmittance control of the existing smart windows. A transparent and flexible window display is fabricated by synthesizing poly(N-isopropylacrylamide) (pNIPAM)-N,N-methylenebisacrylamide-crosslinked hydrogels (NBcH) and near-infrared (NIR) absorption-heating films sandwiched between two plastic substrates. When the NIR laser irradiates the window display panel surface, the temperature rises rapidly, as the NIR absorption-heating film absorbs the NIR wavelength. The generated heat is transferred to pNIPAM in contact with the NIR absorption-heating film, and an image forms in real time. In addition, if the NIR laser and projector simultaneously irradiate the window display panel surface, various colorful images can be displayed. The smart window for real-time information provision proposed in this study acts like a glass curtain that can selectively make a desired location transparent or opaque by controlling the transmittance of light and acts as a display that can present various colorful characters and images in real time. Therefore, it is expected to be highly convenient for users.

Preparation and Evaluation of Colon-Targeted Prodrugs of the Microbial Metabolite 3-Indolepropionic Acid as an Anticolitic Agent.

Microbial metabolites play a critical role in mucosal homeostasis by mediating physiological communication between the host and colonic microbes, whose perturbation may lead to gut inflammation. The microbial metabolite 3-indolepropionic acid (3-IPA) is one such communication mediator with potent antioxidative and anti-inflammatory activity. To apply the metabolite for the treatment of colitis, 3-IPA was coupled with acidic amino acids to yield colon-targeted 3-IPA, 3-IPA-aspartic acid (IPA-AA) and 3-IPA-glutamic acid (IPA-GA). Both conjugates were activated to 3-IPA in the cecal contents, which occurred faster for IPA-AA. Oral gavage of IPA-AA (oral IPA-AA) delivered a millimolar concentration of IPA-AA to the cecum, liberating 3-IPA. In a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced rat colitis model, oral IPA-AA ameliorated rat colitis and was less effective than sulfasalazine (SSZ), a current anti-inflammatory bowel disease drug. To enhance the anticolitic activity of 3-IPA, it was azo-linked with the GPR109 agonist 5-aminonicotinic acid (5-ANA) to yield IPA-azo-ANA, expecting a mutual anticolitic action. IPA-azo-ANA (activated to 5-ANA and 2-amino-3-IPA) exhibited colon specificity in in vitro and in vivo experiments. Oral IPA-azo-ANA mitigated colonic damage and inflammation and was more effective than SSZ. These results suggest that colon-targeted 3-IPA ameliorated rat colitis and its anticolitic activity could be enhanced by codelivery of the GPR109A agonist 5-ANA.

Dipping-Press Coating Method for Retaining Transparency and Imparting Hydrophobicity Regardless of Plastic Substrate Type.

Plastics are used in cover substrates for billboards, windows, large LED signboards, lighting devices, and solar panels because they are transparent and can be colored and shaped as desired. However, when plastic cover substrates installed in outdoor environments are constantly exposed to harsh conditions such as snow, rain, dust, and wind, their transparency deteriorates owing to watermarks and dust contamination. Herein, we investigated a simple dipping-press coating method that can impart hydrophobicity while maintaining the transparency, regardless of the plastic substrate type. A highly transparent and hydrophobic coating film was formed on a plastic substrate by a two-step process, as follows: (1) application of a polydimethylsiloxane-octadecylamine coating by a dipping process, and (2) embedding (1H,1H,2H,2H-heptadecafluorodec-1-yl) phosphonic acid-aluminum oxide nanoparticles by a thermal press process. The plastic substrates on which the highly transparent and hydrophobic coating film was formed showed 150° or higher hydrophobicity and 80% or higher visible light transparency. The coating method proposed herein can easily impart hydrophobicity and is compatible with any plastic substrate that must maintain prolonged transparency without contamination when exposed to adverse conditions.

Enhancing Functionality of Epoxy-TiO2-Embedded High-Strength Lightweight Aggregates.

With the increasing trend of high-rise, large-scale, and functional modern architectural structures, lightweight aggregate (LWA) concrete that exhibits excellent strength and high functionality has garnered active research attention. In particular, as the properties of concrete vary considerably with the raw materials and the proportions of aggregates in the mix, in-depth research on weight reduction, strength improvement, and functional enhancements of aggregates is crucial. This study used the negative pressure coating of a mixed solution comprising epoxy (mixture of epoxy resin and crosslinker), hyper-crosslinked polymer, and titanium oxide (TiO2) nanoparticles on the LWA, and achieved an improvement in the strength of the LWA as well as a reduction in air pollutants such as NOx and SOx. Compared to a normal LWA with an aggregate impact value (AIV) of 38.7%, the AIV of the proposed epoxy-TiO2-embedded high-strength functional LWA was reduced by approximately half to 21.1%. In addition, the reduction rates of NOx and SOx gases resulting from the photocatalytic properties of TiO2 nanoparticles coated with epoxy were approximately 90.9% and 92.8%, respectively. Epoxy-TiO2, embedded in LWAs through a mixture, exhibited stability, high strength, and a reduction in air pollutant characteristics, despite repeated water washing. The LWA proposed herein offers excellent structural and functional properties and is expected to be used in functional lightweight concrete that can be practically applied in high-rise and large-scale architectural structures.

A Colon-Targeted Prodrug, 4-Phenylbutyric Acid-Glutamic Acid Conjugate, Ameliorates 2,4-Dinitrobenzenesulfonic Acid-Induced Colitis in Rats.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER-stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield 4-PBA-glutamic acid (PBA-GA) and 4-PBA-aspartic acid (PBA-AA) conjugates. The PBA derivatives were converted to 4-PBA in the cecal contents, and the conversion was greater with PBA-GA than that with PBA-AA. After oral administration of PBA-GA (oral PBA-GA), up to 2.7 mM PBA was detected in the cecum, whereas 4-PBA was not detected in the blood, indicating that PBA-GA predominantly targeted the large intestine. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon and substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was found to be as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably via the attenuation of ER stress in the inflamed colon.

Superhydrophobic, Elastic, and Conducting Polyurethane-Carbon Nanotube-Silane-Aerogel Composite Microfiber.

Flexible fibers composed of a conductive material mixed with a polymer matrix are useful in wearable electronic devices. However, the presence of the conductive material often reduces the flexibility of the fiber, while the conductivity may be affected by environmental factors such as water and moisture. To address these issues, we developed a new conductive fiber by mixing carbon nanotubes (CNT) with a polyurethane (PU) matrix. A silane ((heptadecafluoro-1,1,2,2-tetra-hydrodecyl)trichlorosilane) was added to improve the strain value of the fiber from 155% to 228%. Moreover, silica aerogel particles were embedded on the fiber surface to increase the water contact angle (WCA) and minimize the effect of water on the conductivity of the fiber. As a result, the fabricated PU-CNT-silane-aerogel composite microfiber maintained a WCA of ~140° even after heating at 250 °C for 30 min. We expect this method of incorporating silane and aerogel to help the development of conductive fibers with high flexibility that are capable of stable operation in wet or humid environments.

5-Aminosalicylic Acid Azo-Coupled with a GPR109A Agonist Is a Colon-Targeted Anticolitic Codrug with a Reduced Risk of Skin Toxicity.

To develop a 5-aminosalicylic acid (5-ASA)-based anticolitic drug with enhanced therapeutic activity, a colon-targeted codrug constituting 5-ASA and a GPR109A agonist was designed. 5-ASA azo-coupled with nicotinic acid (ASA-azo-NA) was synthesized, and the colon specificity and anticolitic effects were evaluated. Approximately 89% of ASA-azo-NA was converted to 5-aminonicotinic acid (5-ANA) and 5-ASA after 24 h of incubation in the cecal contents. 5-ANA was identified as a GPR109A agonist (concentration that gives half-maximal response (EC50): 18 µM) in a cell-based assay. Upon oral gavage of ASA-azo-NA (oral ASA-azo-NA) and sulfasalazine (oral SSZ), a colon-targeted 5-ASA prodrug, cecal accumulation of 5-ASA was comparable, and 5-ANA was barely detectable in the blood, while it was detected up to 62.7 µM with oral 5-ANA. In parallel, oral ASA-azo-NA did not elicit an adverse skin response. In murine macrophage and human colon carcinoma cells, activation of GPR109A by 5-ANA elevated the level of the anti-inflammatory cytokine IL-10, suppressed NF-κB activation, and potentiated the inhibitory activity of 5-ASA on NF-κB. Oral ASA-azo-NA ameliorated rat colitis and was more effective than oral SSZ, which were substantially blunted following cotreatment with the GPR109A antagonist, mepenzolate. In conclusion, ASA-azo-NA is a colon-targeted anticolitic codrug with a reduced risk of skin toxicity induced by the GPR109A agonist, therapeutically surpassing a current 5-ASA-based anti-inflammatory bowel disease drug in a rat colitis model.