Oxygen-enriched carbon quantum dots from coffee waste: Extremely active organic photocatalyst for sustainable solar-to-H2O2 conversion.

Solar-driven artificial photosynthesis offers a promising avenue for hydrogen peroxide (H2O2) generation, an efficient and economical replacement for current methods. The efficiency and selectivity hurdles of the two-electron oxygen reduction reaction (ORR) in solar-to- H2O2 conversion are substantial barriers to large scale production. In this manuscript, a simple biomass-assisted synthesis was performed to produce oxygen-enriched carbon quantum dots (OE-CQDs) from spent coffee waste, acting as an efficient photocatalyst for solar-powered H2O2 production. OE-CQDs can stabilize and store light-generated electrons effectively, boosting charge separation and enhancing photocatalytic performance with longevity. The maximal photocatalytic H2O2 production was achieved viz the utilization of OE-CQDs with generation rate of 356.86 µmol g-1 h-1 by retaining 80% activity without any external sacrificial donors. The outstanding performance of synthesized OE-CQDs under light exposure at wavelength (λ) of 280 nm has been ensured by the quantum yield value of 9.4% upon H2O2 generation. The combinatorial benefits of OE-CQDs with their authentic crystalline structure and oxygen enrichment, is expected to be enhancing the ORR activity through accelerating charge transfer, and optimizing oxygen diffusion. Consequently, our eco-friendly method holds considerable promise for creating highly efficient, metal-free photocatalysts for artificial H2O2 production.

Impact of essential and optional ingredients on microbial and metabolic profiles of kimchi.

This study aimed to examine the impacts of essential and optional ingredients on the microbial and metabolic profiles of kimchi during 100 days of fermentation, using a mix-omics approach. Kimchi manufactured without essential ingredients (e.g., red pepper, garlic, ginger, green onion, and radish) had lower lactic acid content. The absence of garlic was associated with a higher proportion of Latilactobacillus and Lactococcus, while the absence of red pepper was associated with a greater proportion of Leuconostoc than the control group. In addition, red pepper and garlic served as primary determinants of the levels of organic acids and biogenic amines. Sugar was positively correlated with the levels of melibiose, and anchovy sauce was positively correlated with the levels of amino acids such as methionine, leucine, and glycine. These findings contribute to a fundamental understanding of how ingredients influence kimchi fermentation, offering valuable insights for optimizing kimchi production to meet various preferences.

Dual effects of TGF-ß inhibitor in ALS - inhibit contracture and neurodegeneration.

As persistent elevation of transforming growth factor-ß (TGF-ß) promotes fibrosis of muscles and joints and accelerates disease progression in amyotrophic lateral sclerosis (ALS), we investigated whether inhibition of TGF-ß would be effective against both exacerbations. The effects of TGF-ß and its inhibitor on myoblasts and fibroblasts were tested in vitro and confirmed in vivo, and the dual action of a TGF-ß inhibitor in ameliorating the pathogenic role of TGF-ß in ALS mice was identified. In the peripheral neuromuscular system, fibrosis in the muscles and joint cavities induced by excessive TGF-ß causes joint contracture and muscular degeneration, which leads to motor dysfunction. In an ALS mouse model, an increase in TGF-ß in the central nervous system (CNS), consistent with astrocyte activity, was associated with M1 microglial activity and pro-inflammatory conditions, as well as with neuronal cell death. Treatment with the TGF-ß inhibitor halofuginone could prevent musculoskeletal fibrosis, resulting in the alleviation of joint contracture and delay of motor deterioration in ALS mice. Halofuginone could also reduce glial cell-induced neuroinflammation and neuronal apoptosis. These dual therapeutic effects on both the neuromuscular system and the CNS were observed from the beginning to the end stages of ALS; as a result, treatment with a TGF-ß inhibitor from the early stage of disease delayed the time of symptom exacerbation in ALS mice, which led to prolonged survival.

Effect of Hind- and Fore-Foot Eversion on Positional and Rotational Displacement of the Knee in Standing Posture.

We investigated the effects of hindfoot and forefoot eversion on the knee's positional and rotational displacement, plantar pressure, and foot discomfort in a standing posture, beyond the traditional focus on external knee adduction moments (EKAM) in lateral wedge insoles. Twenty-six healthy participants underwent hindfoot eversion from 0 to 10 degrees in 2-degree increments, and forefoot eversion from 0 degrees to the hindfoot eversion angle in 2-degree increments in a standing posture. At each eversion angle, the knee's medial displacement, EKAM's moment arm decrease, plantar pressure changes, and foot discomfort were obtained and compared across varying angles. Both hindfoot-only and entire-foot eversion led to significant medial knee displacement and the EKAM's moment arm decrease, with more pronounced effects in entire-foot eversion. At each hindfoot eversion angle, increasing forefoot eversion resulted in significant medial knee displacement and EKAM's moment arm decrease. Lower leg rotations were not significantly affected in hindfoot-only eversion but displayed significant medial tilting and internal rotation in entire-foot eversion at specific combinations. Varying eversion angles significantly influenced the forefoot pressure, with heel pressure remaining unaffected. Notably, the lateral forefoot pressure increased significantly as the forefoot eversion angle increased, particularly at higher hindfoot eversion angles. Foot discomfort increased significantly with higher eversion angles, particularly in entire-foot eversion, and also increased significantly as the forefoot eversion angle increased at higher hindfoot eversion angles. Insole configurations incorporating 6-10 degrees of hindfoot eversion and 40-60% forefoot eversion of the hindfoot angle may offer optimized biomechanical support for knee osteoarthritis patients.

Performance enhancement of HfO2-based resistive random-access memory devices using ZnO nanoparticles.

In this study, resistive random-access memory (ReRAM) devices with ZnO nanoparticles (NPs) are suggested to enhance performance and reduce variation in device switching parameters. The ZnO NPs are formed by annealing ZnO prepared via atomic layer deposition on HfO2, which is verified using transmission electron microscopy, x-ray diffraction pattern, and atomic force microscopy. The depth profile analysis of x-ray photoelectron spectroscopy shows that oxygen diffuses from HfO2to ZnO NPs during annealing. This can be explained by the calculation results using density functional theory (DFT) where the formation energy of oxygen vacancies is reduced at the interface of ZnO NPs and HfO2compared to single HfO2. The fabricated ZnO NPs ReRAM demonstrates reduced forming voltage, stable resistive switching behavior, and improved cycle-to-cycle uniformity in a high-resistance state.

Comprehensive elucidation of the terroir of Korean kimchi through the study of recipes, metabolites, microbiota, and sensory characteristics.

The aim of this study was to investigate the differences in characteristics of the fermented food kimchi based on the regions where it is produced. A total of 108 kimchi samples were collected from five different provinces in Korea to analyze the recipes, metabolites, microbes, and sensory characteristics. Overall, 18 ingredients (including salted anchovy and seaweed), 7 quality indicators (such as salinity and moisture content), 14 genera of microorganisms (mainly Tetragenococcus and Weissella belonging to LAB), and 38 metabolites contributed to the characteristics of kimchi by region. Kimchi from the southern and northern regions showed distinct metabolite profile (collected 108 kimchi) and flavor profile differences (kimchi manufactured using the standard regional recipes). This is the first study to investigate the terroir effect of kimchi by identifying differences in ingredients, metabolites, microbes, and sensory characteristics based on the region of production, and the correlations between these factors.

Synthetic colourants in capsule dietary supplements on the Korean market.

This study developed a rapid and easy analytical method for the simultaneous determination of nine synthetic colourants (SCs) in capsule dietary supplements. Sample pretreatment involved thermal treatment to dissolve gelatin, using the enzymes protease and amylase to prevent the gelation of gelatin and fat-soluble substances removal using petroleum ether. The method was linear (r2 ≥0.999), with LOD of 0.009-0.029 µg/mL and LOQ of 0.42-1.40 µg/g. Recovery ranged from 90.9 to 108.9%. The relative expanded measurement uncertainty ranged from 4.1 to 6.3%. Allura Red AC (R40) and Brilliant Blue FCF (B1) were commonly detected in 20 of the 28 samples. Up to six SCs such as Tartrazine (Y4), Sunset yellow (Y5), Amaranth (R2), Erythrosine B (R3), R40 and B1 were detected in a single sample, ranging from 30.5 to 40.2 µg/g. Total content of SCs in various capsule supplements ranged from 0.3 to 73.7 µg/g.

Large-Scale Screening of the Plant Extracts for Antifungal Activity against the Plant Pathogenic Fungi.

Plants produce chemicals of immense diversity that provide great opportunities for development of new antifungal compounds. In search for environment-friendly alternatives to the fungicide of current use, we screened plant extracts obtained from more than eight hundred plant materials collected in Korea for their antifungal activity against the model plant pathogenic fungus, Magnaporthe oryzae. This initial screening identified antifungal activities from the eleven plant extract samples, among which nine showed reproducibility in the follow-up screening. These nine samples were able to suppress not only M. oryzae but also other fungal pathogens. Interestingly, the plant extracts obtained from Actinostemma lobatum comprised five out of eight samples, and were the most effective in their antifungal activity. We found that butanol fraction of the A. lobatum extract is the most potent. Identification and characterization of antifungal substances in the A. lobatum extracts would provide the promising lead compounds for new fungicide.

Bottom-Gated ZnO TFT Pressure Sensor with 1D Nanorods.

In this study, a bottom-gated ZnO thin film transistor (TFT) pressure sensor with nanorods (NRs) is suggested. The NRs are formed on a planar channel of the TFT by hydrothermal synthesis for the mediators of pressure amplification. The fabricated devices show enhanced sensitivity by 16~20 times better than that of the thin film structure because NRs have a small pressure transmission area and causes more strain in the underlayered piezoelectric channel material. When making a sensor with a three-terminal structure, the leakage current in stand-by mode and optimal conductance state for pressure sensor is expected to be controlled by the gate voltage. A scanning electron microscope (SEM) was used to identify the nanorods grown by hydrothermal synthesis. X-ray diffraction (XRD) was used to compare ZnO crystallinity according to device structure and process conditions. To investigate the effect of NRs, channel mobility is also extracted experimentally and the lateral flow of current density is analyzed with simulation (COMSOL) showing that when the piezopotential due to polarization is formed vertically in the channel, the effective mobility is degraded.

ALS-Linked Mutant SOD1 Associates with TIA-1 and Alters Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder caused by motor neuron loss. T-cell intracellular antigen-1 (TIA-1), a cytotoxic T lymphocyte granule-associated RNA binding protein, is a key component of stress granules. However, it remains uncertain whether ALS-causing superoxide dismutase-1 (SOD1) toxicity alters the dynamics of stress granules. Thus, through mouse and cell line models, and human cells and tissues, we showed the subcellular location of TIA-1 and its recruitment by stress granules following mutant SOD1-related stimuli. An overexpression of MTSOD1 resulted in increased TIA-1-positive cytoplasmic inclusions in the spinal cord tissue of SOD1G93A transgenic mouse and the SOD1G86S familial ALS patient. Moreover, we demonstrated the stages of ALS-like disease-dependent increase in TIA-1 in the spinal cord of transgenic mice. A similar increase of TIA-1 was found in the spinal cord of the SOD1G86S patient and induced pluripotent stem cell-derived neural stem cells from the SOD1G17S patient. By using immunoprecipitation assays in wild type (WT) human SOD1 (hSOD1) or mutant (MT) hSOD1-transfected motor neuronal cell lines and SOD1G93A transgenic mouse model, we observed that MTSOD1 interacts with TIA-1. In WT or MT hSOD1-transfected HEK293 and NSC-34 cells, the formation of TIA-1-positive stress granules was delayed in MTSOD1 by sodium arsenite treatment. These findings suggest that MTSOD1 could affect the dynamics of stress granules through the abnormal MTSOD1-TIA-1 interaction. Consequently, the resulting pathological TIA-1 may be involved in RNA metabolism found in ALS.

Utility of CPR Machine Power and Change in Right Atrial Pressure for Estimating CPR Quality.

When a cardiac arrest occurs, it is necessary to perform cardiopulmonary resuscitation (CPR) as soon as possible. This requires maintaining the pressure depth at 5 cm at a rate of 100 cpm. For CPR machines, which are frequently used in ambulances, the return of spontaneous circulation (ROSC) is not superior to that of manual CPR, although CPR machines can maintain the compression rate and reciprocal distance of the compression plate more accurately. When the thoracic cavity is deformed due to repeated chest compressions, CPR machines must be adjusted. It is necessary to develop a method for measuring whether adequate CPR is achieved using CPR machines. CPR was performed on two pigs with a CPR machine, commencing 1 minute after the heart was stopped. Four CPR modes were used, with compression rates of 60 or 100 cpm and compression depths of 3 or 5 cm. The CPR machine was equipped with a load cell for measuring compression force, and a potentiometer for measuring compression depth. The measurement results obtained from the sensor were used to calculate the frequency components. The compression force and depth data were used to calculate the mechanical power of the CPR machine and mechanical impedance of the thoracic cavity. Changes in end-tidal carbon dioxide (ETCO2), coronary perfusion pressure (CPP), carotid blood flow (CBF), and right atrial pressure (RAP) were measured during performance of CPR; change in RAP refers to variation therein with chest compressions. Continuous CPR in both animals resulted in deformation of the chest cavity and a steady decline in impedance. The correlation between CPR power and change in RAP was 0.78, and that between compression force and CBF was 0.64. Impedance was not correlated with blood pressure or CBF. When the condition of the animal deteriorated due to cardiac arrest, the CPP decreased and ETCO2 increased. The CPR power and RAP varied according to the CPR mode rather than the condition of the animal. Measuring the CPR machine power does not require a separate procedure, such as catheter intubation, so should be suitable as an index of the quality of CPR in emergency situations.

Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.

Inhibitory effect of Carnosol on UVB-induced inflammation via inhibition of STAT3.

Ultraviolet B (UVB) irradiation causes sunburn, inflammatory responses, dysregulation of immune function, oxidative stress, DNA damage and photocarcinogenesis on skin. Rosemary (Rosmarinus officinalis L.) has been reported to inhibit inflammation. Carnosol, a major component of Rosemary, has prominent anti-inflammatory effects. However, its protective effect on UVB-induced inflammatory skin responses has not yet been reported. Here, we investigated the effectiveness of carnosol on UVB-induced inflammation. We examined the anti-inflammation effect of topical application of carnosol (0.05 µg/cm2) on UVB (540 mJ/cm2, for 3 successive days)-induced skin inflammation in HR1 mice. Topical application of carnosol inhibited UVB-induced erythema, epidermal thickness, inflammatory responses in HR1 mice. Carnosol reduced the level of Immunoglobulin-E and IL-1ß in blood serum of UVB-induced mice. Carnosol also significantly inhibited the UVB-induced expression of inflammatory marker protein (iNOS and COX-2) in back skin of mice. In addition, carnosol treated skin decreased activation of STAT3, a transcriptional factor regulating inflammatory genes. Our study suggested that carnosol has protective effects on skin inflammatory skin damages by UVB.

Estimation of the variations in mechanical impedance between the actuator and the chest, and the power delivered to the chest during cardiopulmonary resuscitation using machine-embedded sensors.

BACKGROUND: To reduce the risk of patient damage and complications during the cardiopulmonary resuscitation (CPR) process in emergency situations, it is necessary to monitor the status of the patient and the quality of CPR while CPR processing without additional bio-signal measurement devices. In this study, an algorithm is proposed to estimate the mechanical impedance (MI) between an actuator of the CPR machine and the chest of the patient, and to estimate the power delivered to the chest of the patient during the CPR process. METHODS: Two sensors for force and depth measurement were embedded into a custom-made CPR machine and the algorithm for MI and power estimation was implemented. The performance of the algorithm was evaluated by comparing the results from the kinetic model, the conventional discrete Fourier transform (DFT), and the proposed method. RESULTS: The estimations of the proposed method showed similar increasing/decreasing trends with the calculations from the kinetic model. In addition, the proposed method showed statistically equivalent performance in the MI estimation, and at the same time, showed statistically superior performance in the power estimation compared with the calculations from the conventional DFT. Furthermore, the MI and power estimation could be performed almost in real-time during the CPR process without excessive hands-off periods, and the intensity of random noise contained in the input signals did not seriously affect the MI and power estimations of the proposed method. CONCLUSION: We expect that the proposed algorithm can reduce various CPR-related complications and improve patient safety.

Neuropeptide Y mitigates ER stress-induced neuronal cell death by activating the PI3K-XBP1 pathway.

The unfolded protein response (UPR) is an evolutionarily conserved adaptive reaction that increases cell survival under endoplasmic reticulum (ER) stress conditions. ER stress-associated neuronal cell death pathways play roles in the pathogenesis of neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's disease. Neuropeptide Y (NPY) has an important role in neuroprotection against neurodegenerative diseases. In this study, we investigated whether NPY has a protective role in ER stress-induced neuronal cell death in SK-N-SH human neuroblastoma cells. An ER stress-inducing chemical, tunicamycin, increased the activities of caspase-3 and -4, whereas pretreatment with NPY decreased caspase-3 and -4 activities during the ER stress response. In addition, NPY suppressed the activation of three major ER stress sensors during the tunicamycin-induced ER stress response. NPY-mediated activation of PI3K increased nuclear translocation of XBP1s, which in turn induced expression of Grp78/BiP. Taken together, our data indicated that NPY plays a protective role in ER stress-induced neuronal cell death through activation of the PI3K-XBP1 pathway, and that NPY signaling can serve as therapeutic target for ER stress-mediated neurodegenerative diseases.

Regulation of SIRT3 signal related metabolic reprogramming in gastric cancer by Helicobacter pylori oncoprotein CagA.

Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α). However, it is unclear whether increased ROS production by H. pylori is regulated by SIRT3 followed by HIF-1α regulation and whether intracellular CagA acts as a regulator thereof. In this study, we investigated correlations among SIRT3, ROS, and HIF-1α in H. pylori-infected gastric epithelial cells. We observed that SIRT3-deficient AGS cells induce HIF-1α protein stabilization and augmented transcriptional activity under hypoxic conditions. In CagA +H. pylori infected cells, CagA protein localized to mitochondria where it subsequently suppressed SIRT3 proteins. CagA +H. pylori infection also increased HIF-1α activity through the ROS production induced by the downregulated SIRT3 activity, which is similar to the hypoxic condition in gastric epithelial cells. In contrast, overexpression of SIRT3 inhibited the HIF-1α protein stabilization and attenuated the increase in HIF-1α transcriptional activity under hypoxic conditions. Moreover, CagA +H. pylori attenuated HIF-1α stability and decreased transcriptional activity in SIRT3-overexpressing gastric epithelial cells. Taken together, these findings provide valuable insights into the potential role of SIRT3 in CagA +H. pylori-mediated gastric carcinogenesis and a possible target for cancer prevention via inhibition of HIF-1α.

(E)-2-Methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) Phenol Ameliorates LPS-Mediated Memory Impairment by Inhibition of STAT3 Pathway.

Alzheimer's disease (AD) is pathologically characterized by an excessive accumulation of amyloid-beta (Aß) fibrils within the brain. We tested the anti-inflammatory and anti-amyloidogenic effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP), a selective signal transducer and activator of transcription 3 (STAT3) inhibitor. We examined whether MMPP (5 mg/kg in drinking water for 1 month) prevents amyloidogenesis and cognitive impairment on AD model mice induced by intraperitoneal LPS (250 µg/kg daily 7 times) injections. Additionally, we investigated the anti-neuroinflammatory and anti-amyloidogenic effect of MMPP (1, 5, and 10 µg/mL) in LPS (1 µg/mL)-treated cultured astrocytes and microglial BV-2 cells. MMPP treatment reduced LPS-induced memory loss. This memory recovery effect was associated with the reduction of LPS-induced inflammatory proteins; cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as activation of microglial cells and astrocytes in the brain. Furthermore, MMPP reduced LPS-induced ß-secretase and Aß generation. In in vitro study, LPS-induced expression of inflammatory proteins and amyloidogenic proteins was decreased in microglial BV-2 cells and cultured astrocytes by MMPP treatment. Moreover, MMPP treatment suppressed DNA binding activities of the activation of STAT3 in in vivo and in vitro. These results indicated that MMPP inhibits LPS-induced amyloidogenesis and neuroinflammation via inhibition of STAT3.

KRICT-9 inhibits neuroinflammation, amyloidogenesis and memory loss in Alzheimer's disease models.

Alzheimer's disease (AD) is one of the most common forms of dementia and is characterized by neuroinflammation and amyloidogenesis. Here we investigated the effects of KRICT-9 on neuroinflammation and amyloidogenesis in in vitro and in vivo AD models. We found that KRICT-9 decreased lipopolysaccharide (LPS)-induced inflammation in microglial BV-2 cells and astrocytes while reducing nitric oxide generation and expression of inflammatory marker proteins (iNOS and COX-2) as well as APP, BACE1, C99, Iba-1, and GFAP. KRICT-9 also inhibited ß-secretase. Pull-down assays and docking model analyses indicated that KRICT-9 binds to the DNA binding domain of signal transducer and activator of transcription 3 (STAT3). KRICT-9 also decreased ß-secretase activity and Aß levels in tissues from LPS-induced mice brains, and it reversed memory impairment in mice. These experiments demonstrated that KRICT-9 protects against LPS-induced neuroinflammation and amyloidogenesis by inhibiting STAT3 activity. This suggests KRICT-9 or KRICT-9-inspired reagents could be used as therapeutic agents to treat AD.

Comparison of the response using ICR mice derived from three different sources to multiple low-dose streptozotocin-induced diabetes mellitus.

This study was conducted to compare the multiple low-dose streptozotocin (MLDS)-induced diabetic patterns of Korl:ICR, A:ICR, and B:ICR mice obtained from three different sources. Six-week-old male ICR mice were obtained from three difference sources. Korl:ICR mice were kindly provided by the National Institute of Food and Drug Safety Evaluation (NIFDS). The other two groups of ICR mice were purchased from different vendors located in the United States (A:ICR) and Japan (B:ICR). All ICR mice that received MLDS exhibited overt diabetic symptoms throughout the study, and the incidence and development of diabetes mellitus were similar among the three ICR groups. The diabetic mice exhibited hyperglycemia, loss of body weight gain, decreased plasma insulin levels, impaired glucose tolerance, decreased number of insulin-positive cells, and decreased size of ß-cells in the pancreas. The diabetes symptoms increased as the blood glucose level increased in the three ICR groups. In particular, the level of blood glucose in the STZ-treated group was higher in Korl:ICR and A:ICR mice than in B:ICR mice. The plasma insulin levels, glucose tolerance, blood chemistry, and morphological appearance of the pancreas were very similar in the ICR groups obtained from the three different sources. In conclusion, our results suggest that Korl:ICR, A:ICR, and B:ICR mice from different sources had similar overall responses to multiple low-dose STZ to induce diabetes mellitus.

Inhibitory Effect of Carnosol on Phthalic Anhydride-Induced Atopic Dermatitis via Inhibition of STAT3.

Carnosol is a phenolic antioxidant present in rosemary (Rosmarinus officinalis). It is known for anti-inflammatory effects, analgesic activity and anti-cancer effects. However, no study has been dedicated yet to its effect on atopic dermatitis (AD). Here, we show that carnosol effectively inhibited LPS-induced nitric oxide (NO) generation and expression of inflammatory marker proteins (iNOS and COX-2) in RAW 264.7 cells. In addition, carnosol effectively inhibits the phosphorylation of STAT3 and DNA binding activity in RAW 264.7 cells. Pull down assay and docking model analysis showed that carnosol directly binds to the DNA binding domain (DBD) of STAT3. We next examined the anti-atopic activity of carnosol (0.05 µg/cm2) using 5% Phthalic anhydride (PA)-induced AD model in HR1 mice. Carnosol treatment significantly reduced 5% PA-induced AD like skin inflammation in skin tissues compared with control mice. Moreover, carnosol treatment inhibits the expression of iNOS and COX-2 in skin tissue. In addition, the levels of TNF-α, IL-1ß, and Immunoglobulin-E in blood serum was significantly decreased in carnosol treated mice compared with those of 5% PA treated group. Furthermore, the activation of STAT3 in skin tissue was decreased in carnosol treated mice compared with control mice. In conclusion, these findings suggest that carnosol exhibited a potential anti-AD activity by inhibiting pro-inflammatory mediators through suppression of STAT3 activation via direct binding to DBD of STAT3.