Chronic infrared-A irradiation-induced photoaging of human dermal fibroblasts from different donors at physiological temperature.

BACKGROUND: In this study, we examined cellular responses to acute and chronic IRA irradiation at mild and natural levels of exposure in two types of human fibroblasts, each isolated from a different donor, at physiological temperature (34°C). METHOD: Two types of human dermal fibroblasts (derived from a 20- and 50-year-old women, respectively) were exposed to different repeat numbers of IRA exposure (3, 6, 10, and 14 times; 42 mW/cm2 ) at a frequency of 3-4 times per week (4 h per irradiation). Cellular responses to acute and chronic IRA irradiation were examined by reactive oxygen species (ROS) level, apoptotic signals, cellular morphology, and collagen level. RESULTS: We demonstrated that chronic IRA irradiation-induced severe cellular damage, including prolonged cell proliferation, increased intracellular ROS levels, activated cellular apoptosis, and elongated cell morphology, whereas acute IRA irradiation had negligible effects at 34°C. In addition, it was evident that the degree of cellular damage due to IRA irradiation differed according to the type of fibroblasts. CONCLUSIONS: Considering the severe cellular damage induced by chronic IRA irradiation without heat, continuous exposure of skin to IRA irradiation during daily life may be harmful enough to induce photoaging.

Formulation of Glycyrrhizic Acid-based Nanocomplexes for Enhanced Anti-cancer and Anti-inflammatory Effects of Curcumin.

In this study, nanocomplexes composed of glycyrrhizic acid (GA) derived from the root of the licorice plant (Glycyrrhiza glabra) were formulated for the delivery of curcumin (CUR). Sonication of amphiphilic GA solution with hydrophobic CUR resulted in the production of nanosized complexes with a size of 164.8 ± 51.7 nm, which greatly enhanced the solubility of CUR in aqueous solution. A majority of the CURs were released from these GA/ CUR nanocomplexes within 12 h. GA/CUR nanocomplexes exhibited excellent intracellular uptake in human breast cancer cells (Michigan cancer foundation-7/multi-drug resistant cells), indicating enhanced anti-cancer effects compared to that of free CUR. In addition, GA/CUR nanocomplexes demonstrated high intracellular uptake into macrophages (RAW264.7 cells), consequently reducing the release of the pro-inflammatory cytokine tumor necrosis factor-α. Furthermore, GA/CUR nanocomplexes successfully reduced the levels of serum pro-inflammatory cytokines and splenomegaly in a rheumatoid arthritis model.

Effective toluene oxidation under ozone over mesoporous MnOx/γ-Al2O3 catalyst prepared by solvent deficient method: Effect of Mn precursors on catalytic activity.

In this study, the role of manganese precursors in mesoporous (meso) MnOx/γ-Al2O3 catalysts was examined systematically for toluene oxidation under ozone at ambient temperature (20 °C). The meso MnOx/γ-Al2O3 catalysts developed with Mn(CH3COO)2, MnCl2, Mn(NO3)2.4H2O and MnSO4 were prepared by an innovative single step solvent-deficient method (SDM); the catalysts were labeled as MnOx/Al2O3(A), MnOx/Al2O3(C), MnOx/Al2O3(N), and MnOx/Al2O3(S), respectively. Among all, MnOx/Al2O3(C) showed superior performance both in toluene removal (95%) as well as ozone decomposition (88%) followed by acetate, nitrate and sulphated precursor MnOx/Al2O3. The superior performance of MnOx/Al2O3(C) in the oxidation of toluene to COx is associated with the ozone decomposition over highly dispersed MnOx in which extremely active oxygen radicals (O2-, O22- and O-) are generated to enhance the oxidation ability of the catalysts greatly. In addition, toluene adsorption over acid support played a vital role in this reaction. Hence, the properties such as optimum Mn3+/Mn4+ ratio, acidic sites, and smaller particle size (≤2 nm) examined by XPS, TPD of NH3, and TEM results are playing vital role in the present study. In summary, the MnOx/Al2O3 (C) catalyst has great potential in environmental applications particularly for the elimination of volatile organic compounds with low loading of manganese developed by SDM.

Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation Through LPA Receptor.

Heat stress can be caused by various environmental factors. When exposed to heat stress, oxidative stress and inflammatory reaction occur due to an increase of reactive oxygen species (ROS) in the body. In particular, inflammatory responses induced by heat stress are common in muscle cells, which are the most exposed to heat stress and directly affected. Gintonin-Enriched Fraction (GEF) is a non-saponin component of ginseng, a glycolipoprotein. It is known that it has excellent neuroprotective effects, therefore, we aimed to confirm the protective effect against heat stress by using GEF. C2C12 cells were exposed to high temperature stress for 1, 12 and 15 h, and the expression of signals was analyzed over time. Changes in the expression of the factors that were observed under heat stress were confirmed at the protein level. Exposure to heat stress increases phosphorylation of p38 and extracellular signal-regulated kinase (ERK) and increases expression of inflammatory factors such as NLRP3 inflammasome through lysophosphatidic acid (LPA) receptor. Activated inflammatory signals also increase the secretion of inflammatory cytokines such as interleukin 6 (IL-6) and interleukin 18 (IL-18). Also, expression of glutathione reductase (GR) and catalase related to oxidative stress is increased. However, it was confirmed that the changes due to the heat stress were suppressed by the GEF treatment. Therefore, we suggest that GEF helps to protect heat stress in muscle cell and prevent tissue damage by oxidative stress and inflammation.

PLGA Microspheres Coated with Cancer Cell-Derived Vesicles for Improved Internalization into Antigen-Presenting Cells and Immune Stimulation.

Microspheres (MS; 1-3 µm) with different degrees of surface roughness were prepared to assess the effects of surface topology on internalization into antigen-presenting cells (APCs; macrophages and dendritic cells). In this study, we demonstrated that the intracellular uptake of MS is readily enhanced by surface modification with nanoparticles or cancer cell-derived vesicles (VE) to modulate their surface topology. MS coated with nanovesicles (MS-VE) with high surface roughness was more successfully and efficiently engulfed by APCs, compared with bare MS and those with low surface roughness. Incorporated MPLA within MS-VEs (M/MS-VE) triggered greatly elevated release of immune stimulating cytokines, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), from macrophages and dendritic cells, compared to free MPLA. Taken together, this MS-VE could serve as a platform system for the delivery of immune stimulators and antigens to APCs with negligible toxicity.

Enhanced intracellular uptake and stability of umbelliferone in compound mixtures from Angelica gigas in vitro.

Understanding how natural compounds work together for disease treatments can improve their clinical efficacy and therapeutic effects. To elucidate the mechanisms of synergistic biological effects in natural compound mixtures, umbelliferone (UMB, 7-hydroxycoumarin), derived from Angelica (A.) gigas, was selected as active compound with fluorescent characteristic to examine bioactivities in vitro in the presence of other compounds from Angelica gigas. Antioxidant effects of UMB in biochemical assays and cellular reactive oxygen species (ROS) levels in RAW264.7 cells were not significantly improved by addition of other compounds. However, intracellular uptake, inhibition of the efflux pump P-glycoprotein (P-gp), and physiological stability of UMB were greatly enhanced by the addition of other compounds, specifically Angelicin (ANG) and Byakangelicin (BYN). Taken together, enhanced intracellular localization and enzymatic stability in compound mixtures might lead to superior synergistic bioactivity of UMBs in compound mixtures.

Removal of toluene using ozone at room temperature over mesoporous Mn/Al2O3 catalysts.

The catalytic oxidation of toluene with ozone at room temperature was carried out over hierarchically ordered mesoporous catalysts (CeO2 (meso), Mn2O3 (meso), ZrO2 (meso), and γ-Al2O3 (meso)) and Al2O3 with various textural properties and phases (γ-Al2O3 (meso), γ-Al2O3 (13 nm), and α-Al2O3) to examine the effects of the nature of the catalyst on the catalytic activity. The catalysts were characterized by N2-physisorption measurements, powder X-ray diffraction, temperature programmed reduction, X-ray photoelectron spectroscopy and scanning transmission electron microscopy with energy dispersive spectroscopy. Among the ordered mesoporous catalysts, γ-Al2O3 (meso) had the highest toluene removal efficiency because of its highest surface area and pore volume, which in turn was selected for further investigation. Manganese (Mn) was introduced to various Al2O3 to improve the toluene removal efficiency. Comparing the Mn-loaded catalysts supported on various Al2O3 with different crystalline phases or pore structures, Mn/γ-Al2O3 (meso), had the highest catalytic activity as well as the highest CO2/CO ratio. The higher activity was attributed to the larger surface area, weaker interaction between Mn and Al2O3, and larger portion of Mn2O3 phase. The increase in ozone concentration led to an improvement in the carbon balance but this enhancement was insufficient due to the deposition of by-products on the catalyst. After long term tests at room temperature, the reaction intermediates and carbonaceous deposits of the used catalysts were identified.

Acetaldehyde removal and increased H2/CO gas yield from biomass gasification over metal-loaded Kraft lignin char catalyst.

Acetaldehyde removal tests were performed to compare the catalytic activity of the Kraft lignin char (KC), KOH-treated Kraft lignin char (KKC), and activated carbon (AC) along with their impregnation with Mn in a plasma reactor. The gasification characteristics (syngas content, and H2/CO ratio) of yellow poplar were investigated using nickel catalysts supported on KC, KKC, AC, and γ-Al2O3 in a U-type quartz reactor. KKC and Mn/KKC improved significantly the surface area and contents of O and N functional groups over the raw char. In particular, Mn/KKC showed the highest acetaldehyde-removal efficiency. The catalytic activity of Ni-impregnated KC, KKC, AC, and γ-Al2O3 decreased in the order of Ni/KKC > Ni/AC > Ni/KC > Ni/γ-Al2O3 for the gas yield and Ni/γ-Al2O3 >Ni/KC > Ni/AC >Ni/KKC for the oil yield, respectively. The Ni/KKC provides a more conducive environment for gasification, resulting in larger amounts of syngas (H2 and CO) in the product gases. Moreover, Ni impregnated with char may be the most inexpensive and effective solution for achieving maximum tar reduction and syngas generation.

Simultaneous removal of hydrogen sulfide and ammonia using a combined system with absorption and electrochemical oxidation.

Hydrogen sulfide (H2S) and ammonia (NH3), common impurities in biogas, need to be removed before utilizing it. In this study, a combined system, which consisted of an absorption column and an electrochemical oxidation reactor, was tested to simultaneously remove these impurities. The effects of the current density and the chemical loading rate on the system performance were investigated. Firstly, the mass transfer coefficients for the absorption column were determined at various gas flow rates. More mass of NH3 was transferred, compared with that of H2S, because of its higher solubility. In the electro-oxidation reactor, reactive chlorine species (RCSs) were generated and oxidized both H2S and NH3; however, NH3 started to degrade only after H2S was completely eliminated. At a current density of 400 A/m2, the current efficiencies of H2S and NH3 were 23.1% and 5.9%, respectively. In the combined system, the removal efficiency of H2S was closely related to the mass ratio of the H2S transferred and the RCSs generated. The removal efficiency of H2S was greater than 99% when the ratio was less than 1. The mass transfer potential and the oxidation kinetics should be balanced to improve the system performance for the simultaneous removal of H2S and NH3.

Spirulina maxima Extract Ameliorates Learning and Memory Impairments via Inhibiting GSK-3ß Phosphorylation Induced by Intracerebroventricular Injection of Amyloid-ß 1-42 in Mice.

Spirulina maxima, a microalga containing high levels of protein and many polyphenols, including chlorophyll a and C-phycocyanin, has antioxidant and anti-inflammatory therapeutic effects. However, the mechanisms where by Spirulina maxima ameliorates cognitive disorders induced by amyloid-ß 1-42 (Aß1-42) are not fully understood. In this study, we investigated whether a 70% ethanol extract of Spirulina maxima (SM70EE) ameliorated cognitive impairments induced by an intracerebroventricular injection of Aß1-42 in mice. SM70EE increased the step-through latency time in the passive avoidance test and decreased the escape latency time in the Morris water maze test in Aß1-42-injected mice. SM70EE reduced hippocampal Aß1-42 levels and inhibited amyloid precursor protein processing-associated factors in Aß1-42-injected mice. Additionally, acetylcholinesterase activity was suppressed by SM70EE in Aß1-42-injected mice. Hippocampal glutathione levels were examined to determine the effects of SM70EE on oxidative stress in Aß1-42-injected mice. SM70EE increased the levels of glutathione and its associated factors that were reduced in Aß1-42-injected mice. SM70EE also promoted activation of the brain-derived neurotrophic factor/phosphatidylinositol-3 kinase/serine/threonine protein kinase signaling pathway and inhibited glycogen synthase kinase-3ß phosphorylation. These findings suggested that SM70EE ameliorated Aß1-42-induced cognitive impairments by inhibiting the increased phosphorylation of glycogen synthase kinase-3ß caused by intracerebroventricular injection of Aß1-42 in mice.

Protective role of ginseng in endometriosis during covid-19.

The coronavirus disease 2019 (COVID) pandemic began in December 2019. Many countries have implemented restrictions such as mandatory mask wearing and social distancing. These measures have caused diverse and complex health problems, particularly in women's health, anxiety, and depression. This review examines an alternative approach to the treatment of endometriosis during the COVID pandemic. The efficacy of ginseng with anti-inflammatory activity and ability to relieve or prevent symptoms of endometriosis is discussed and reviewed.

Multiresponsive 3D Structured PVDF Cube Switches for Security Systems Using Piezoelectric Anisotropy.

Advancements in flexible electronics using piezoelectric materials have paved the way for numerous applications. In this study, we suggest a three-dimensional (3D) structured poly(vinylidene fluoride) (PVDF) film cube switch to maximize piezoelectric anisotropy and flexibility. Unlike piezoelectric material-based flexible electronics, PVDF cube switches have a simple design and easy fabrication process. Each side of the cube switch demonstrates independent voltage signals with pressing displacements and corresponding directions. With cutting angle variations and planar figure designs, derived cube switches respond with various combinations of voltage waveforms. PVDF switches can endure more than 1000 cycles of 70% vertical strain in terms of both electrical responses and mechanical operations. As an application, we establish a security system with multiresponsibility of a cube switch. This security system can protect users from potential threats owing to its multiresponsibility and user-dependent operability.

Protection of Skin Fibroblasts from Infrared-A-Induced Photo-Damage Using Ginsenoside Rg3(S)-Incorporated Soybean Lecithin Liposomes.

Protection of skin cells from chronic infrared-A (IRA) irradiation is crucial for anti-photoaging of the skin. In this study, we investigated the protective activity of Rg3(S) and Rg3(S)-incorporated anionic soybean lecithin liposomes (Rg3/Lipo) with a size of approximately 150 nm against IRA-induced photodamage in human fibroblasts. The formulated Rg3/Lipo showed increased solubility in aqueous solution up to a concentration of 200 µg/ml, compared to free Rg3(S). In addition, Rg3/Lipo exhibited superior colloidal stability in aqueous solutions and biocompatibility for normal human dermal fibroblasts (NHDFs). After repeated IRA irradiation on NHDFs, elevated levels of cellular and mitochondrial reactive oxygen species (ROS) were greatly reduced by Rg3(S) and Rg3/Lipo. In addition, cells treated with Rg3/Lipo exhibited noticeably reduced apoptotic signals following IRA irradiation compared to untreated cells. Thus, considering aqueous solubility and cellular responses, Rg3/Lipo could serve as a promising infrared protector for healthy aging of skin cells.

Tunable hybrid hydrogels with multicellular spheroids for modeling desmoplastic pancreatic cancer.

The tumor microenvironment consists of diverse, complex etiological factors. The matrix component of pancreatic ductal adenocarcinoma (PDAC) plays an important role not only in physical properties such as tissue rigidity but also in cancer progression and therapeutic responsiveness. Although significant efforts have been made to model desmoplastic PDAC, existing models could not fully recapitulate the etiology to mimic and understand the progression of PDAC. Here, two major components in desmoplastic pancreatic matrices, hyaluronic acid- and gelatin-based hydrogels, are engineered to provide matrices for tumor spheroids composed of PDAC and cancer-associated fibroblasts (CAF). Shape analysis profiles reveals that incorporating CAF contributes to a more compact tissue formation. Higher expression levels of markers associated with proliferation, epithelial to mesenchymal transition, mechanotransduction, and progression are observed for cancer-CAF spheroids cultured in hyper desmoplastic matrix-mimicking hydrogels, while the trend can be observed when those are cultured in desmoplastic matrix-mimicking hydrogels with the presence of transforming growth factor-ß1 (TGF-ß1). The proposed multicellular pancreatic tumor model, in combination with proper mechanical properties and TGF-ß1 supplement, makes strides in developing advanced pancreatic models for resembling and monitoring the progression of pancreatic tumors, which could be potentially applicable for realizing personalized medicine and drug testing applications.

Unlearned adaptive responses to heterospecific referential alarm calls in two bird species from separate evolutionary lineages.

The interspecific responses to alarm signals may be based on unlearned mechanisms but research is often constrained by the difficulties in differentiating between unlearned and learned responses in natural situations. In a field study of two Paridae species, Parus minor and Sittiparus varius, who originated from a common ancestor 8 million years ago, we found a considerable degree of between-species overlap in acoustic properties of referential snake-alarm calls. Playback of these calls triggered unlearned adaptive fledging behavior in conspecific and heterospecific naive nestlings, suggesting a between-species overlap in the hypothetical unlearned neural templates involved in nestlings' reactions to alarm calls in both species. This suggests that similar calls and similar unlearned sensitivity might have been present in the common ancestor of the two species, and possibly in the ancestor of the whole family Paridae that originated 10-15 million years ago in Asian regions rich in snakes.

Kinetics and simulations of substrate interactions during the biodegradation of benzene, toluene, p-xylene and styrene.

Air streams commonly emitted from industrial sources generally contain various mixtures of volatile organic compounds (VOCs), and these complex mixtures can present challenges with respect to bioreactor design and applications. In this study, therefore, a modified Monod-type model using interaction parameters was employed to describe the biodegradation kinetics of mixtures of aromatic compounds by a Pseudomonas isolate. In addition, the model and estimated parameters were utilized to predict the performance of a bubble-column bioreactor for the treatment of mixtures of benzene, toluene, p-xylene, and styrene (BTXS). Benzene, toluene and styrene, as individual substrates, were actively degraded by the bacterial culture, whereas p-xylene was not degraded as a single substrate. Relative to the single substrate experiments, the degradation of benzene and toluene was inhibited by the other compounds, while the degradation of styrene was significantly stimulated in the presence of the other BTXS compounds. The cometabolic degradation of p-xylene was observed in the presence of benzene and toluene. The estimated interaction parameters indicated that the degradation of benzene was substantially inhibited in the presence of styrene, whereas the degradation of styrene was strongly stimulated by toluene. The kinetic coefficients and interaction parameters were used to successfully predict the biodegradation kinetics and performance of a bioreactor subjected to the quaternary mixture. Overall, the model was able to provide reasonable predictions when substrate interactions, including inhibition, stimulation, and cometabolism, play significant roles in biodegradation processes.

Improved performance of stretchable piezoelectric energy harvester based on stress rearrangement.

With the development of wearable devices and soft electronics, the demand for stretchable piezoelectric energy harvesters (SPEHs) has increased. Energy harvesting can provide energy when large batteries or power sources cannot be employed, and stretchability provides a user-friendly experience. However, the performance of SPEHs remains low, which limits their application. In this study, a wearable SPEH is developed by adopting a kirigami structure on a polyvinylidene fluoride film. The performance of the SPEH is improved by rearranging the stress distribution throughout the film. This is conducted using two approaches: topological depolarization, which eliminates the opposite charge generation by thermal treatment, and optimization of the neutral axis, which maximizes the stress applied at the surface of the piezoelectric film. The SPEH performance is experimentally measured and compared with that of existing SPEHs. Using these two approaches, the stress was rearranged in both the x-y plane and z-direction, and the output voltage increased by 21.57% compared with that of the original film with the same stretching motion. The generated energy harvester was successfully applied to smart transmittance-changing contact lenses.

Exosome-mediated delivery of transforming growth factor-ß receptor 1 kinase inhibitors and toll-like receptor 7/8 agonists for combination therapy of tumors.

In this study, combination therapy with the transforming growth factor-ß receptor I (TGFßRI) kinase inhibitor SD-208 and a toll-like receptor (TLR)-7/8 agonist resiquimod (R848) was examined along with serum-derived exosomes (EXOs) as versatile carriers. SD-208-encapsulated EXOs (SD-208/EXOs) and R848-encapsulated EXOs (R848/EXOs) were successfully prepared with a size of 87 ± 8 nm and 51 ± 4 nm, respectively, which were stable in aqueous solution at pH 7.4. SD-208/EXOs and R848/EXOs reduced the migration of cancer cells (B16F10 and PC-3) and triggered the release of proinflammatory cytokines from stimulated macrophages and dendritic cells, respectively. The fluorescent dye-labeled EXOs showed significantly improved penetration through the PC-3/fibroblast co-culture spheroids and enhanced accumulation in the B16F10 mouse tumor model compared with the free fluorescent dye. In addition, the combination therapy of R848/EXOs (R848 dose of 0.36 mg/kg) and SD-208/EXOs (SD-208 dose of 0.75 mg/kg) reduced tumor growth and improved survival rate at low doses in the B16F10 tumor xenograft model. Taken together, the combination therapy using the TGFßRI kinase inhibitor and TLR 7/8 agonist with EXOs may serve as a promising strategy to treat melanoma and prostate cancer. STATEMENT OF SIGNIFICANCE: Owing to the prevalence of several non-responding cancers that resist treatment, it is necessary to identify a novel combined treatment strategy with biomaterials to maximize therapeutic efficacy and minimize the undesirable side effects. In this study, we aimed to examine the use of the TGFßRI kinase inhibitor SD-208 and the TLR7/8 agonist resiquimod (R848) encapsulated within serum-derived EXOs for their synergistic antitumor effects. We first demonstrated that combined treatment with SD-208 and R848 can be a convincing strategy to circumvent tumor growth in vivo using serum-derived exosomes as promising carriers. Therefore, we believe this manuscript would be of great interest to the biomaterial communities especially who are studying immunotherapy.

Machine learning-based quantitative prediction of drug exposure in drug-drug interactions using drug label information.

Many machine learning techniques provide a simple prediction for drug-drug interactions (DDIs). However, a systematically constructed database with pharmacokinetic (PK) DDI information does not exist, nor is there a machine learning model that numerically predicts PK fold change (FC) with it. Therefore, we propose a PK DDI prediction (PK-DDIP) model for quantitative DDI prediction with high accuracy, while constructing a highly reliable PK-DDI database. Reliable information of 3,627 PK DDIs was constructed from 3,587 drugs using 38,711 Food and Drug Administration (FDA) drug labels. This PK-DDIP model predicted the FC of the area under the time-concentration curve (AUC) within ± 0.5959. The prediction proportions within 0.8-1.25-fold, 0.67-1.5-fold, and 0.5-2-fold of the AUC were 75.77, 86.68, and 94.76%, respectively. Two external validations confirmed good prediction performance for newly updated FDA labels and FC from patients'. This model enables potential DDI evaluation before clinical trials, which will save time and cost.

Removal of formaldehyde over amine functionalized SBA-15.

Amine-functionalized SBA-15 materials were synthesized by a post synthesis method. Surface area and pore size decreased by attaching functional groups to the pore surface. Furthermore, pore volume was reduced with functionalization. The carbon and nitrogen content gradually increased with the number of amine groups in the silane precursors. Among the amine-functionalized SBA-15 materials, the SBA-15/TMSPDETA showed the highest removal activity given its high reactivity with formaldehyde.