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Many urinary tract infections (UTIs) are recurrent because uropathogens persist within the bladder epithelial cells (BECs) for extended periods between bouts of infection. Because persistent uropathogens are intracellular, they are often refractive to antibiotic treatment. The recent discovery of endogenous Lactobacillus spp. in the bladders of healthy humans raised the question of whether these endogenous bacteria directly or indirectly impact intracellular bacterial burden in the bladder. Here, we report that in contrast to healthy women, female patients experiencing recurrent UTIs have a bladder population of Lactobacilli that is markedly reduced. Exposing infected human BECs to L. crispatus in vitro markedly reduced the intracellular uropathogenic Escherichia coli (UPEC) load. The adherence of Lactobacilli to BECs was found to result in increased type I interferon (IFN) production, which in turn enhanced the expression of cathepsin D within lysosomes harboring UPECs. This lysosomal cathepsin D–mediated UPEC killing was diminished in germ-free mice and type I IFN receptor–deficient mice. Secreted metabolites of L. crispatus seemed to be responsible for the increased expression of type I IFN in human BECs. Intravesicular administration of Lactobacilli into UPEC-infected murine bladders markedly reduced their intracellular bacterial load suggesting that components of the endogenous microflora can have therapeutic effects against UTIs.

Obesity increases the risks of metabolic syndromes including nonalcoholic fatty liver disease (NAFLD), diabetic dyslipidemia, and chronic kidney disease. Dietary krill oil (KO) has shown antioxidant and anti-inflammatory properties, thereby being a therapeutic potential for obesity-induced metabolic syndromes. Thus, the effects of KO on lipid metabolic alteration were examined in a high-fat diet (HFD)-fed mice model. The HFD model (n = 10 per group) received an oral gavage with distilled water as a control, metformin at 250 mg/kg, and KO at 400, 200, and 100 mg/kg for 12 weeks. The HFD-induced weight gain and fat deposition were significantly reduced in the KO treatments compared with the control. Blood levels were lower in parameters for NAFLD (e.g., alanine aminotransferase, and triglyceride), type 2 diabetes (e.g., glucose and insulin), and renal dysfunction (e.g., blood urea nitrogen and creatinine) by the KO treatments. The KO inhibited lipid synthesis through the modification of gene expressions in the liver and adipose tissues and adipokine-mediated pathways. Furthermore, KO showed hepatic antioxidant activities and glucose lowering effects. Histopathological analyses revealed that the KO ameliorated the hepatic steatosis, pancreatic endocrine/exocrine alteration, adipose tissue hypertrophy, and renal steatosis. These analyses suggest that KO may be promising for inhibiting obesity and metabolic syndromes.

During severe nuclear power plant (NPP) accidents, a H2/CO mixture can be generated in the reactor pressure vessel by core degradation and in the containment as well by molten corium-concrete interaction. In spite of its importance, a state-of-the-art methodology predicting H2/CO combustion risk relies predominantly on empirical correlations. It is therefore necessary to develop a proper methodology for flammability evaluation of H2/CO mixtures at ex-vessel phases characterized by three factors: CO concentration, high temperature, and diluents. The developed methodology adopted Le Chatelier’s law and a calculated non-adiabatic flame temperature model. The methodology allows the consideration of the individual effect of the heat transfer characteristics of hydrogen and carbon monoxide on low flammability limit prediction. The accuracy of the developed model was verified using experimental data relevant to ex-vessel phase conditions. With the developed model, the prediction accuracy was improved substantially such that the maximum relative prediction error was approximately 25% while the existing methodology showed a 76% error. The developed methodology is expected to be applicable for flammability evaluation in chemical as well as NPP industries.

Acupuncture is a treatment option for dry eye syndrome (DES), but its efficacy remains still controversial. We assessed the effectiveness of this treatment for typical DES without specific aetiologies. Eight databases up through June 2018 were searched for randomized clinical trials (RCTs) comparing treatments of acupuncture with artificial tears. The risk of bias was assessed using Cochrane criteria, and a random effects model was used for meta-analyses on tear-film breakup time (BUT), Schirmer test, corneal fluorescein staining (CFS), ocular surface disease index, visual analogue scale and score of symptoms (SOS). Subgroup and sensitivity analyses were conducted to explore the heterogeneity, and publication bias was assessed by funnel plot using Egger's test. Twenty-one RCTs in 19 studies (n = 1542 eyes) met our eligible criteria. The results demonstrated the superiority of acupuncture in improving the symptoms of BUT, Schirmer test, CFS and SOS, compared to artificial tears acting alone. The BUT and Schirmer test were also more improved in acupuncture combination with artificial tears than artificial tears alone. Further subgroup analyses suggest that acupuncture applied at 2.0-3.0 times per week for 21-30 days may be optimal for treating typical DES. This provides useful information for guiding acupuncture in the clinical trials.

The reproductive performance of lactating sows was investigated by using different feeding methods including conventional feeding (CF, 3 times/d) or free feeding (FF), and different dietary energy level including low energy (LE: 3,300) or high energy (HE: 3,400 kcal/kg) during the hot season. A total of twenty-eight crossbred (Yorkshire × Landrace) sows were distributed into four treatments as a 2 × 2 factorial arrangement. Sows in the FF group showed lower body weight and backfat loss (p < 0.05) compared with the CF group. Backfat loss during lactation was lower (p < 0.05) in sows fed HE diet than in that fed LE diet. There were no significant differences in litter survival rate and weaning to estrus interval, but the litter weight at weaning was improved (p < 0.05) in FF and HE sows. Hence, it is concluded that using the free-feeding system or increased dietary energy density leads to improved sow performance during hot ambient temperature.

Balneotherapy is a common non-pharmacological treatment for osteoarthritis (OA), however, the efficacy is controversial in knee OA. Jeju magma-seawater (JMS) has high contents of various minerals, which has anti-inflammatory and antioxidant properties via an oral route. Thus, we examined the effects of JMS bathing on knee OA and the combination effects with diclofenac sodium as an anti-inflammatory drug. Knee OA was induced by transection of the anterior cruciate ligament and the partial meniscectomy in rat. The rats were administered subcutaneously saline or diclofenac sodium in saline, followed by bathing in thermal distilled water or JMS for 8 weeks. The model represented the characteristic changes of the cartilage degradation, osteophyte formation and synovial inflammation, and the relevant symptoms of the joint swelling and stiffness. However, the JMS bathing reduced the joint thickness and improved the mobility. It also contributed to a well-preserved tissue supported by increases in bone mineral density of the joint and decreases in Mankin scores in the cartilages. The effects involved anti-inflammation, chondroprotection, anti-apoptosis, and chondrogenesis. Overall, the JMS bathing in combination with diclofenac sodium showed a similar trend associated with synergic effects. It suggests that JMS bathing can be promising for a clinical use in knee OA.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), characterized by the gut mucosal ulceration. Growing evidence indicates that dysregulation of immune response to the commensal microbiota involves the pathogenesis of IBD. Previous studies have demonstrated the favorable probiotic effects of fermented rice extracts through triple fermentation with Saccharomyces cerevisiae and Weissella cibaria (FRe). Thus, the therapeutic potential of FRe for UC was examined. Dextran sodium sulfate UC mice model was orally administered distilled water as a control, sulfasalazine, or FRe at 300, 200, and 100 mg/kg, once a day for a week. The UC control exhibited body weight loss, bloody stools, and colonic shortening. However, the FRe, especially at 300 mg/kg, led to a reduction in weight loss, disease activity index scores, and colon weight, and an increase in colorectal length. The histopathological analyses revealed mild changes involved in the colonic crypt and mucosal damages in the FRe groups, along with inhibited inflammation. Indeed, the FRe reduced neutrophil infiltration and production of proinflammatory cytokines (i.e., tumor necrosis factor‐α, interleukin‐6/‐8). This was accompanied by the down‐regulation of nuclear factor‐kappa B. The gene expression responsible for the intestinal barrier integrity (i.e., Zonna occludens‐1/‐2, Claudin‐1, Occludin, Mucin‐1/‐2) was up‐regulated in the FRe groups. In addition, the FRe reduced lipid peroxidation and enhanced antioxidant activity. Interestingly, the microbiota dysbiosis was attenuated in the FRe groups, and the number of beneficial bacteria, Lactobacilli and Bifidobacteria, was increased. It suggests that the FRe potently ameliorate UC as a functional food., Oral treat of FRe ameliorated the UC symptoms by (a) improved dysbiosis as prebiotics, (b) NF‐κB‐mediated anti‐inflammation, (c) enhanced antioxidant activity, (d) restored mucus layer and the tight junction, (e) reduced immunity of CD4+ and CD8+ T cell, and (f) increased serum IgG but decreased IgA.

Currently, there is a growing interest among consumers in selecting healthier meat with a greater proportion of essential fatty acids (FA). This experiment was conducted to evaluate the role of different ratios of dietary n-6:n-3 on growth performance, FA profile of longissimus dorsi (LD), relative gene expression of cytokines, meat quality, and blood parameters in finishing pigs. A total of 108 finishing pigs was randomly allotted to three treatments including a control (basal diet) and low ratios (4:1 and 2:1) of n-6:n-3. The 4:1 and 2:1 diets decreased the overall stearic acid in LD. There were reductions in the content of stearic acid, palmitoleic acid, total saturated acid, and n-6:n-3 ratio of LD in pigs fed 4:1 and 2:1 diet compared with the control diet. The 4:1 and 2:1 diets increased the concentration of α-Linolenic acid and polyunsaturated FA in the LD of pigs. Acetyl-CoA carboxylase enzyme gene was down-regulated in pigs fed 2:1 diet compared with finishing pigs fed the control or 4:1 diets. The relative expression of hormone-sensitive lipase was increased in pigs fed 2:1 and 4:1 ratio diets. Lower total cholesterol of plasma was observed in finishing pigs fed 2:1 and 4:1 diets. The cooking loss ratio of meat was lower in pigs fed the 2:1 and 4:1 diets compared with the control diet. Pigs fed the 4:1 and 2:1 diets had greater final body weight. In conclusion, the 2:1 and 4:1 diets have the potential to increase the meat quality and growth performance of pigs.

Metformin, the first-line drug for type 2 diabetes mellitus (T2DM), has additional effects on improvements of nonalcoholic fatty liver disease (NAFLD); however, there are no treatments for both T2DM and NAFLD. Previous studies have shown hepatoprotective effects of a mixture of lemon balm and dandelion (LD) through its antioxidant and anti-steatosis properties. Thus, combination effects of metformin and LD were examined in a high-fat diet (HFD)-induced metabolic disease mouse model. The model received an oral administration of distilled water, monotherapies of metformin and LD, or a metformin combination with LD for 12 weeks. The HFD-induced weight gain and body fat deposition were reduced more by the combination than either monotherapy. Blood parameters for NAFLD (i.e., alanine aminotransferase and triglyceride), T2DM (i.e., glucose and insulin), and renal functions (i.e., blood urea nitrogen and creatinine) were reduced in the combination. The combination further enhanced hepatic antioxidant activities, and improved insulin resistance via the AMP-activated protein kinase and lipid metabolism pathways. Histopathological analyses revealed that the metformin combination ameliorated the hepatic hypertrophy/steatosis, pancreatic endocrine/exocrine alteration, fat tissue hypertrophy, and renal steatosis, more than either monotherapy. These results suggest that metformin combined with LD can be promising for preventing and treating metabolic diseases involving insulin resistance.

Atopic dermatitis (AD) is a chronic and allergic skin disease, however, there is no cure for the disease. Many studies have shown anti-AD potentials of red ginseng, while red ginseng marc (RGM) remained after the ginseng extraction is discarded as industrial waste. However, it is recently reported that RGM, particularly fermented RGM (fRGM), still contains the bioactive properties. Thus, anti-allergic effects of fRGM were examined in 2,4-dinitrochlorobenzene-induced AD-like mice model. The model was topically treated with distilled water (control), dexamethasone, or fRGM for six weeks. The treatments of fRGM alleviated the skin lesions and reduced serum IgE levels, compared with the control. The fRGM also reduced skin levels of lipid peroxidation and superoxide anion, however, increased glutathione contents, with down-regulated gene expressions for inflammatory mediators. The histopathological analyses demonstrated that fRGM suppressed the epidermal thickening, collagen deposition, and inflammatory cell and mast cell infiltration, which involved the anti-inflammatory, anti-oxidant, and anti-apoptotic effects. Further, fRGM suppressed hypertrophic changes and inflammatory responses in the spleen and lymph node. The beneficial effects were observed in the dexamethasone and fRGM groups, however, the antioxidant effects were evident only in the fRGM treatments. These provide useful information for developing fRGM as therapeutic sources for AD.

Objectives. A powerful analgesic called Morphine causes addiction behaviors and immune suppression as a potential oxidative stressor. Acupuncture showed to inhibit oxidative stress-induced hepatic damage, regulate reactive oxygen species, and attenuate morphine addiction behaviors. Therefore, we investigated the potential effects of acupuncture on morphine-induced immune suppression. Materials and Methods. Rats received morphine intravenously through implanted catheters for 3, 7, or 21 days to determine the optimal condition for morphine-induced immune suppression. Second, we examined whether intravenous (iv.) or intraperitoneal (ip.) administration produced different results. Third, the effects of acupuncture in rats who received morphine for 21 days were investigated. Spleen and submandibular lymph node (S-LN) weights and natural killer (NK) cell activity were measured, and the white pulp diameter, total and cortical spleen thicknesses, and the number of lymphoid follicles in S-LNs were examined. The number of immunoreactive cells was also measured. Results. Decreased organ weights and increased atrophic changes were observed as morphine-induced immune suppression. However, dose-dependent increased immune suppression was not observed between 5.0 mg/kg and 10.0 mg/kg of morphine. And, 3-day withdrawal did not affect. Similar histopathological findings were observed in 5.0 and 10.0 ip. rats when compared to equal dosages of iv., respectively. The morphine induced-immune suppression evidenced by spleen and left S-LN weights, splenic NK cell activities, histopathological findings, and the immunoreactive cell number were normalized by acupuncture. Conclusion. These results indicate that acupuncture inhibits morphine-induced immune suppression, maybe via antioxidative action.

An abnormal hair-growth cycle induces hair loss, which affects psychological distress and impairs life quality. Red ginseng marc (RGM) is usually discarded as a byproduct after extracting red ginseng, but several studies have shown that the RGM still has bioactive components including ginsenosides. Therefore, the hair-growth effects of fermented RGM (fRGM) and traditional polyherb formula (PH) were examined in C57BL/6 mice. The dorsal hairs of mice were depilated, and they were topically treated with fRGM or PH at 400, 200 and 100 mg/kg or the combination of both middle doses (combi) once a day for two weeks. The hair-covering regions were significantly increased with higher doses of fRGM and PH and in combi groups, compared with the control treated with distilled water. Hair length, thickness and weight also increased in the treatment groups. In particular, the fRGM and PH increased the anagen-phased hair follicles, the follicular diameters and the dermal thickness. Immunostains for Ki-67 showed the anagen-phased cell division in the treatment groups. The beneficial effects were greater in the high doses of fRGM and PH and the combi groups. These suggest hair-growth-promoting effects of fRGM, PH and the combination by enhancing the hair-growth cycle.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with 85% of all lung cancer reported as NSCLC. Moreover, there are no effective treatments in advanced NSCLC. This study shows for the first time that oral administration of plasma-treated water (PTW) can cure advanced NSCLC. The cold plasma in water generates a cocktail of reactive species, and oral administration of this cocktail to mice showed no toxicities even at the highest dose of PTW, after a single dose and repeated doses for 28 d in mice. In vivo studies reveal that PTW showed favorable anticancer effects on chemo-resistant lung cancer, similarly to gefitinib treatment as a reference drug in a chemo-resistant NSCLC model. The anticancer activities of PTW seem to be involved in inhibiting proliferation and angiogenesis and enhancing apoptosis in the cancer cells. Interestingly, the PTW contributes to enhanced immune response and improved cachexia in the model.

Acute kidney injury (AKI) is a disease caused by sudden renal dysfunction, which is an important risk factor for chronic renal failure. However, there is no effective treatment for renal impairment. Although some traditional polyherbs are commercially available for renal diseases, their effectiveness has not been reported. Therefore, we examined the nephroprotective effects of polyherbs and their relevant mechanisms in a cisplatin-induced cell injury model. Rat NRK-52E and human HK-2 subjected to cisplatin-induced AKI were treated with four polyherbs, Injinhotang (IJ), Ucha-Shinki-Hwan (US), Yukmijihwang-tang (YJ), and UrofenTM (Uro) similar with Yondansagan-tang, for three days. All polyherbs showed strong free radical scavenging activities, and the treatments prevented cisplatin-induced cell death in both models, especially at 1.2 mg/mL. The protective effects involved antioxidant effects by reducing reactive oxygen species and increasing the activities of superoxide dismutase and catalase. The polyherbs also reduced the number of annexin V-positive apoptotic cells and the expression of cleaved caspase-3, along with inhibited expression of mitogen-activated protein kinase-related proteins. These findings provide evidence for promoting the development of herbal formulas as an alternative therapy for treating AKI.

Acute kidney injury (AKI) is characterized by a rapid loss of renal function. Drug-induced AKI accounts for up to 60% of all cases, resulting in a severe threat particularly to hospitalized patients, but there are no effective treatments. Four polyherbal formulas, Bojungikki-tang (BJ), Palmijihwang-tang (PJ), Oryeong-san (OR), and Wiryeong-tang (WR), have long been used for treatments of symptoms of kidney disease in traditional Korean medicine. Even though they are commercially available, evidences supporting the efficacy on AKI are still lacking. Therefore, the effectiveness of polyherbs on AKI and the underlying mechanisms were examined. Renal cell damage was induced by cisplatin at 20 μM and 16 μM in proximal tubular epithelial cell lines of rat NRK-52E and human HK-2, respectively. The cells were treated with the polyherbal formals for 3 days, and the cell viability, antioxidant activities, and apoptosis were examined. In addition, the proliferative effects were assessed under serum-free conditions. The results were compared with those of the vehicle-treated cells as a control. Three polyherbs BJ, PJ, and WR but not OR showed strong free radical scavenging activities in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The treatments of BJ, PJ, OR, and WR significantly increased the cell viabilities under cisplatin-induced nephrotoxicity. Consistent with the results of the DPPH assay, superoxide dismutase and catalase activities were increased in the cisplatin-induced cell model treated with BJ, PJ, and WR but not with OR. However, annexin-V-positive cells and cleaved caspase 3 expression were significantly reduced in the cell model treated with all of the polyherbs. Cell proliferation was observed in treatment with all of the polyherbs, which was particularly evident in the OR-treated cells. This provides effective complementary evidences to promote the development of traditional herbal formulas to treat AKI.

Prion diseases are fatal neurodegenerative disorders of humans and animals and no effective treatments are currently available. Allogenic transplantation of immortalized human mesenchymal stem cells (MSCs) can prolong the survival of mice infected with prions. However, autologous transplantation is an appropriate model for evaluating the effects of MSCs on prion diseases. Therefore, we isolated and purified MSCs from the femur and tibia of mice as compact bone-derived MSCs (CB-MSCs). Flow cytometric analysis showed that CB-MSCs were negative for myeloid stem cell-derived cell markers CD11b and CD45, but positive for molecules such as Sca-1, CD105 and CD90.2, which are reported to be expressed on MSCs. The ability of CB-MSCs to migrate to brain extracts from prion-infected mice was confirmed by an in vitro migration assay. Intra-hippocampus transplantation of CB-MSCs at 120 days post-inoculation marginally but significantly prolonged the survival of mice infected with the Chandler prion strain. The transplantation of CB-MSCs did not influence the accumulation of disease-specific prion protein. However, the CB-MSC transplantation enhanced microglial activation, which appeared to be polarized to the M2-type activation state. These results suggest that autologous MSC transplantation is a possible treatment for prion diseases, while the modification of microglial activation may be a therapeutic target for neurodegenerative diseases.

Objectives : In our previous study, single co-administration GMODT within 5 min significantly inhibited the oral bioavailability of tamoxifen through variable influences on the absorption and excretion of tamoxifen. Therefore, the object of this study was to elucidate the possible effects on the pha...

The present study investigated the anti-aging effects of pomegranate juice concentrated powder (PCP) in hairless mice following 15 weeks of UVB irradiation (three times a week; 0.18 J/cm2). Skin moisturizing effects were evaluated through skin water, collagen type I and hyaluronan contents, as well as collagen type I and hyaluronan synthesis-related transcript levels. Wrinkle formation and edema scores (skin weights) were also assessed, along with skin matrix metalloproteinase (MMP)-1, MMP-9 and MMP-13 transcript levels. To determine the anti-inflammatory effects of PCP, myeloperoxidase (MPO) activity, interleukin (IL)-1β and IL-10 contents were observed. Caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) were used as an apoptotic index in epidermal keratinocytes. To determine the anti-oxidative effects of PCP, nitrotyrosine and 4-hydroxynonenal immunoreactive cells were detected and glutathione (GSH) content, malondialdehyde levels, superoxide anion production, Nox2, and GSH reductase mRNA expression were all measured. The results indicated that skin wrinkles induced by photoaging were significantly reduced by PCP, whereas skin water contents, collagen type I and hyaluronan contents all increased. Furthermore, IL-1β levels in the PCP-treated groups were lower than those in the UVB-exposed control group. UVB-induced GSH depletion was also inhibited by PCP. Taken together, the results of the current study suggest that PCP has favorable protective effects against UVB-induced photoaging through anti-apoptotic effects, MMP activity inhibition and ECM (COL1 and hyaluronan) synthesis-related moisturizing, anti-inflammatory and anti-oxidative effects.

In the present study, it was evaluated whether east saline groundwater concentration solution (ESGWc) exerted a favorable inhibitory effect on 2,4-dinitrochlorobenzene (DNCB)-induced allergic/atopic-like dermatitis (AD). AD was induced and boosted by sensitization with DNCB via topical application on the dorsal back skins. Mice with DNCB-induced AD were bathed in 100-, 200- and 400-fold diluted ESGWc. After 6 weeks bathing, changes to body weight, clinical skin severity scores, scratching behavior, serum total immunoglobulin (Ig)E levels, submandibular lymph node and spleen weights, splenic cytokine levels, skin cytokine mRNA expressions, antioxidant defense systems and superoxide anion productions were recorded to determine the effects of bathing on the histopathology of dorsal back skin tissues. All DNCB-induced mice demonstrated that the induction of AD through IgE-mediated hypersensitivities, oxidative stresses, activation of MMP and apoptosis of keratinocytes resulted in no significant differences in body weight between the different groups at each time point following initial sensitization. However, markers of DNCB-induced AD were significantly inhibited (P

Green tea is generally considered safe, but there have been concerns regarding side effects relating to the main component, catechins, especially hepatotoxicities. We have previously shown beneficial effects of fermented green tea with Aquilariae Lignum (fGT) via an oral route in diabetic and obese models. Thus, the toxicological safety of fGT was assessed at limited oral doses for a rodent. Mice or rats of both genders were orally administered distilled water as a control and fGT at 2.0, 1.0, and 0.5 g/kg. There were no mortalities or gross abnormalities in the fGT groups for 2 weeks following the single oral dose in mice. No fGT-relevant abnormalities were found in postmortem and histopathological examinations, suggesting LD50of fGT at more than 2.0 g/kg with no specific target organs. There were also no fGT-relevant mortalities or abnormal signs in the repeated oral dose for 13 weeks in rats. In the fGT groups, no body weight changes or daily metabolic changes were found, and hematological and serum biochemical ranges were normal. The postmortem and histopathological examinations revealed few fGT-related abnormalities in most of the organs including the liver, although slight lymphoid cell hyperplasia in the lymph node was observed in a few rats with fGT at 2.0 g/kg. This may be secondary to increased immune response to the highest dose because there were no histopathological lesions or organ weight changes. It suggests nontoxic safety of fGT at up to 2.0 g/kg, which provides useful information for clinical use.

Background Constipation, a common health problem, causes discomfort and affects the quality of life. This study intended to evaluate the potential laxative effect of triple fermented barley (Hordeum vulgare L.) extract (FBe), produced by saccharification, Saccharomyces cerevisiae, and Weissella cibaria, on loperamide (LP)-induced constipation in Sprague-Dawley (SD) rats, a well-established animal model of spastic constipation. Methods Spastic constipation was induced via oral treatment with LP (3 mg/kg) for 6 days 1 h before the administration of each test compound. Similarly, FBe (100, 200 and 300 mg/kg) was orally administered to rats once a day for 6 days. The changes in number, weight, and water content of fecal, motility ratio, colonic mucosa histology, and fecal mucous contents were recorded. The laxative properties of FBe were compared with those of a cathartic stimulant, sodium picosulfate. A total of 48 (8 rats in 6 groups) healthy male rats were selected and following 10 days of acclimatization. Fecal pellets were collected one day before administration of the first dose and starting from immediately after the fourth administration for a duration of 24 h. Charcoal transfer was conducted after the sixth and final administration of the test compounds. Results In the present study, oral administration of 100–300 mg/kg of FBe exhibited promising laxative properties including intestinal charcoal transit ratio, thicknesses and mucous producing goblet cells of colonic mucosa with decreases of fecal pellet numbers and mean diameters remained in the lumen of colon, mediated by increases in gastrointestinal motility. Conclusion Therefore, FBe might act as a promising laxative agent and functional food ingredient to cure spastic constipation, with less toxicity observed at a dose of 100 mg/kg.

Background Hordeum vulgare L (barley) contains numerous phenolic substances with proven anticancer, antioxidant and gastroprotective activities. Saccharification increases the functionality and bioavailability of these compounds thus can aid in the development of a natural product based medicine. This study aimed to investigate the possible gastroprotective effects of saccharification on the indomethacin (IND)-induced gastric ulcers in rats using Weissella cibaria- and Saccharomyces cerevisiae-triple fermented H. vulgare extract (FBe). Methods In total, 60 healthy male 6-week old Sprague-Dawley SD (SPF/VAF Outbred CrljOri:CD1) rats were commercially purchased. The FBe extract (100, 200, and 300 mg kg− 1) was orally administered 30 min before an oral treatment of IND (25 mg kg− 1). Six hours after IND treatment, variations in the histopathology, myeloperoxidase (MPO) activity, gross lesion scores, lipid peroxidation, and antioxidant defense system component (superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)) levels were measured. Results FBe treatment showed significant (p

Persicariae Rhizoma (PR) has been used as an anti-inflammatory and detoxification agent in Korea, and contains the biologically active dyes purple indirubin and blue indigo. Despite synthetic indigo showing genotoxic potential, thorough studies have not been carried out on the genotoxicity of PR. The potential genotoxicity of an aqueous extract of PR containing indigo (0.043%) and indirubin (0.009%) was evaluated using a standard battery of tests for safety assessment. The PR extract did not induce any genotoxic effects under the conditions of this study. The results of a reverse mutation assay in four Salmonella typhimurium strains and one Escherichia coli strain indicated that PR extract did not increase the frequency of revertant colonies in any strain, regardless of whether S9 mix was present or not. The PR extract also did not increase chromosomal aberrations in the presence or absence of S9 mix. Although slight signs of diarrhea were restrictedly detected in the mice treated with 2,000 mg/kg PR extract, no noteworthy changes in the frequency of micronucleated polychromatic erythrocytes were observed at doses ≤2,000 mg/kg in a bone marrow micronucleus test. These results indicate the potential safety of the PR extract, particularly if it is consumed in small amounts compared with the quantities used in the genotoxicity tests.

A simple approach for the preparation of core–shell microstructures with an anisotropic shape is proposed in which an Ag nanowire/polyurethane acrylate (AgNW/PUA) composite produced by inverted layer processing is used as a temporary template for the sequential electroless plating of a Cu metal core and Ni shell. Through careful optimization of the metallization conditions, a Cu@Ni core–shell microstructure with an anisotropic shape (i.e., an aspect ratio greater than five) is obtained, which can be easily detached from the template through simple sonication. This technique is therefore considered to be readily applicable to the fabrication of conductive fillers for use in composite structures. Keywords: Core–shell structure, Microrod, Metal particle, Electroless plating, Silver nanowire (AgNW)

Ultraviolet (UV) B exposure induces DNA damage and production of reactive oxygen species (ROS), which causes skin photoaging through signaling pathways of inflammation and modulation of extracellular matrix remodeling proteins, collagens, and matrix metalloproteinase (MMP). As low molecular-weight fucoidan (LMF) has potential antioxidant and anti-inflammatory properties, we examined the protective effects of LMF against UVB-induced photoaging. A UVB-irradiated mouse model was topically treated with myricetin or LMF at 2.0, 1.0 and 0.2 mg/cm2 (LMF2.0, LMF1.0 and LMF0.2, respectively) once a day for 15 weeks. Wrinkle formation, inflammation, oxidative stress, MMP expression, and apoptosis in the treated regions were compared with those in a distilled water-treated photoaging model (UVB control). LMF treatments, particularly LMF2.0 and LMF1.0, significantly inhibited the wrinkle formation, skin edema, and neutrophil recruitment into the photo-damaged lesions, compared with those in the UVB control. While LMF decreased interleukin (IL)-1&beta, release, it increased IL-10. The LMF treatment inhibited the oxidative stresses (malondialdehyde and superoxide anion) and enhanced endogenous antioxidants (glutathione). Additionally, LMF reduced the mRNA expression of MMP-1, 9, and 13. The histopathological analyses revealed the anti-photoaging effects of LMF exerted via its antioxidant, anti-apoptotic, and MMP-9-inhibiting effects. These suggest that LMF can be used as a skin-protective remedy for photoaging.

Aims.The effects of platycodin D (PD) pretreatment were examined in reflux esophagitis (RE) induced rats.Methods.Sham, control, and omeprazole (OMP) group were pretreated with distilled water or OMP as a reference, respectively, and PD pretreated groups were given 3 different PD doses once a day for 7 days. One hour after last pretreatment, RE was induced by ligation of the forestomach and pylorus. At 8 h after operation, all animals were sacrificed.Results.PD showed significant dose-dependent reduction of gastric secretion, myeloperoxidase activity, and RE lesion areas of esophagus and stomach mucosa. There was a reduction of lipid peroxidation in 2 doses of PD groups and elevation of antioxidant enzyme activity in all PD groups. Gastric hexose and sialic acid were significantly increased in PD groups, while collagen was reduced. Plasma histamine levels were significantly reduced in all PD groups, but not in the OMP group. Total invasive lesion sizes of esophagus and gastric fundus were significantly decreased in all PD groups. Thicknesses in esophagus of all PD groups were significantly decreased and thicknesses of funds were significantly increased except lowest PD dose.Conclusions.Therapeutic effects of PD on the esophageal and gastric lesions were shown in RE induced rats dose-dependently. The PD pretreatment had significant antioxidant effects with regulation of histamine levels. This study provides useful information regarding the effectiveness of the drug for RE and further novel drug discovery using natural herbal products.

This study was designed to observe the possible protective effects of a triple‐fermented barley (Hordeum vulgare L.) extract (FB e) obtained by saccharification and using Saccharomyces cerevisiae and Weissella cibaria in alleviating gastric damage induced by a hydrochloric acid (HC l) and ethanol (EtOH ) mixture in mice. After oral administration of FB e (300, 200, and 100 mg/kg) followed by 1 hr before and after the single treatment of HC l/EtOH (H/E) mixture, the hemorrhagic lesion scores, histopathology of the stomach, gastric nitrate/nitrite content, lipid peroxidation, and antioxidant defense systems including catalase and superoxide dismutase activities were observed. Following a single oral treatment of H/E‐induced gastric damages as measured by hemorrhagic gross lesions and histopathological gastric, ulcerative lesions were significantly and dose‐dependently (p < 0.01 or p < 0.05) inhibited in mice, when all three different doses of FB e were administered as compared to those in H/E control mice. In particular, FB e also increased gastric nitrate/nitrite content and strengthened the antioxidant defense, with a decrease in the level of gastric lipid peroxidation, but increased the activities of CAT and SOD . Moreover, the effects of FB e are comparable to that of ranitidine, a reference drug. The obtained results suggest that this fermented barley extract prevented mice from H/E‐induced gastric mucosal damages through the suppression of inflammatory responses and oxidative stress‐responsive free radicals. Thus, FB e can be useful to treat patients suffering from gastric mucosal disorders as a potent food supplement, and thereby, it would increase the necessity of application in the food industry.

Plants rich in antioxidant substances may be useful for preventing skin aging. Pomegranates, containing flavonoids and other polyphenolic compounds, are widely consumed due to their beneficial properties. We examined the underlying mechanisms of dried pomegranate concentrate powder (PCP) on melanin synthesis in B16F10 melanoma cells. The antioxidant effects of PCP were determined by measuring free radical scavenging capacity and transcript levels of antioxidant enzymes. To explore the inhibitory effects of PCP on melanin synthesis, we measured tyrosinase activity and melanin content in α-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 cells. In addition, the levels of tyrosinase-related protein-1 (TRP-1), TRP-2, tyrosinase, and microphthalmia-associated transcription factor (MITF) expression were determined by Western blotting. Changes in the phosphorylation status of protein kinase A (PKA), cAMP response element-binding protein (CREB), mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), serine/threonine kinase Akt, and glycogen kinase 3β (GSK3β) were also examined. The free radical scavenging activity of PCP increased in a dose-dependent manner. In PCP-treated B16F10 cells, transcript levels of glutathione peroxidase-1 (GPx-1) were increased compared with α-MSH-stimulated cells. In addition, PCP led to the down-regulation of phospho-p38, phospho-PKA, phospho-CREB, phospho-GSK3β, MITF, and TRP-1 compared with α-MSH-stimulated B16F10 cells. We believe this effect may be associated with PCP activity, which leads to the inhibition of melanin production and tyrosinase activity. These results suggest that PCP decreases tyrosinase activity and melanin production via inactivation of the p38 and PKA signaling pathways, and subsequently decreases phosphorylation of CREB, MITF, and melanogenic enzymes. These observations provided new insights on the molecular mechanisms of the skin-whitening property of PCP.

Transparent electrodes based on percolated networks of silver nanowires (AgNWs) are known for their good conductivity, transparency, and flexibility. Owing to these intrinsic properties, AgNWs are gaining much attention and are considered potential electrode materials in large-area and flexible devices. However, a major drawback of the AgNWs—poor adhesion to polymers—is holding back their practical usage. The weak bond of AgNWs to polymers limits their fine-pitch patternability, which is one of the most important requirements in the electronics industry. In the study reported here, we irradiated nanowires, attached to the polymer during photolithography and metal etching, with intense pulsed light to improve the adhesion. As a result, a complicated pattern of nanowires was fabricated without any form of damage. For better flexibility, we transferred the patterned AgNWs to the surface of a colorless polyimide film to produce a highly stable electrode under repeated bending cycles. As a result of these developments, a flexible touch panel based on a capacitive sensor was successfully fabricated.

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency.

We evaluated the preventive effects of four types of seawater collected in Republic of Korea on hairless mice with 2,4-dinitrochlorobenzene- (DNCB-) induced allergic/atopic dermatitis (AD). The anti-inflammatory effects were evaluated by measuring tumor necrosis factor- (TNF-)αand interleukins (ILs). Glutathione (GSH), malondialdehyde (MDA), superoxide anion, and inducible nitric oxide synthase (iNOS) were measured to evaluate the antioxidant effects. Caspase-3 and poly (ADP-ribose) polymerase (PARP) were observed to measure the antiapoptotic effects; matrix metalloproteinase- (MMP-) 9 levels were also evaluated. Mice with AD had markedly higher clinical skin severity scores and scratching behaviors; higher TNF-αand ILs (1β, 10, 4, 5, and 13) levels; higher MDA, superoxide anion, caspase-3, PARP, and MMP-9 levels; and greater iNOS activity. However, the severity of AD was significantly decreased by bathing in seawaters, but it did not influence the dermal collagen depositions and skin tissue antioxidant defense systems. These results suggest that bathing in all four seawaters has protective effects against DNCB-induced AD through their favorable systemic and local immunomodulatory effects, active cytoprotective antiapoptotic effects, inhibitory effects of MMP activity and anti-inflammatory and antioxidative effects.

Chongmyungtang (CMT) is a famous Korean herbal medicine for improving learning and memory, which has been reported to have anti-cholinergic and neuroprotective effects. Therefore, drug-drug interactions were examined between CMT and donepezil as a first screening of combination therapy for cognitive deficits. Rats received oral co-administration of donepezil with distilled water as a control or donepezil with CMT as a combination. The distilled water or CMT was co-administered at intervals within 5min after donepezil or 1.5h intervals. The plasma samples were analyzed for donepezil concentration and its pharmacokinetic parameters of T

Because antioxidants from natural sources may be an effective approach to the treatment and prevention of UV radiation-induced skin damage, the effects of purified exopolymers from Aureobasidium pullulans SM-2001 ('E-AP-SM2001') were evaluated in UVB-induced hairless mice. E-AP-SM2001 consists of 1.7% β-1,3/1,6-glucan, fibrous polysaccharides and other organic materials, such as amino acids, and mono- and di-unsaturated fatty acids (linoleic and linolenic acids) and shows anti-osteoporotic and immunomodulatory effects, through antioxidant and anti-inflammatory mechanisms. Hairless mice were treated topically with vehicle, E-AP-SM2001 stock and two and four times diluted solutions once per day for 15 weeks against UVB irradiation (three times per week at 0.18 J/cm(2) ). The following parameters were evaluated in skin samples: myeloperoxidase (MPO) activity, cytokine levels [interleukin (IL)-1β and IL-10], endogenous antioxidant content (glutathione, GSH), malondialdehyde (MDA) levels, superoxide anion production; matrix metalloproteases (MMP-1, -9 and -13), GSH reductase and Nox2 (gp91phox) mRNA levels, and immunoreactivity for nitrotyrosine (NT), 4-hydroxynonenal (HNE), caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP). Photoageing was induced by UVB irradiation through ROS-mediated inflammation, which was related to the depletion of endogenous antioxidants, activation of MMPs and keratinocyte apoptosis. Topical treatment with all three doses of E-AP-SM2001 and 5 nm myricetin attenuated the UV-induced depletion of GSH, activation of MMPs, production of IL-1β, the decrease in IL-10 and keratinocyte apoptosis. In this study, E-AP-SM2001 showed potent inhibitory effects against UVB-induced skin photoageing. Thus, E-AP-SM2001 may be useful as a functional ingredient in cosmetics, especially as a protective agent against UVB-induced skin photoageing.

Prion diseases are fatal neurodegenerative disorders characterized by accumulation of PrP Sc , vacuolation of neurons and neuropil, astrocytosis, and microglial activation. Upregulation of gene expressions of innate immunity-related factors, including complement factors and CD14, is observed in the brains of mice infected with prions even in the early stage of infections. When CD14 knockout (CD14 −/− ) mice were infected intracerebrally with the Chandler and Obihiro prion strains, the mice survived longer than wild-type (WT) mice, suggesting that CD14 influences the progression of the prion disease. Immunofluorescence staining that can distinguish normal prion protein from the disease-specific form of prion protein (PrP Sc ) revealed that deposition of PrP Sc was delayed in CD14 −/− mice compared with WT mice by the middle stage of the infection. Immunohistochemical staining with Iba1, a marker for activated microglia, showed an increased microglial activation in prion-infected CD14 −/− mice compared to WT mice. Interestingly, accompanied by the increased microglial activation, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor β (TGF-β) appeared to be expressed earlier in prion-infected CD14 −/− mice. In contrast, IL-1β expression appeared to be reduced in the CD14 −/− mice in the early stage of infection. Double immunofluorescence staining demonstrated that CD11b- and Iba1-positive microglia mainly produced the anti-inflammatory cytokines, suggesting anti-inflammatory status of microglia in the CD14 −/− mice in the early stage of infection. These results imply that CD14 plays a role in the disease progression by suppressing anti-inflammatory responses in the brain in the early stage of infection.

A series of green dopants based on 2,2-diphenylvinyl end-capped bithiophene and three different arylamine moieties (9-phenylcarbazole, triphenylamine, and N,N’-di-(p-tolyl)benzeneamine) were successfully synthesized by the Suzuki and Wittig coupling reactions. The photophysical properties of these compounds are reported. The strongest PL emitting compound with the 9-phenylcarbazole moiety has been used for fabricating an OLED device with good overall performance.

The dystonias are comprised of a group of disorders that share common neurological abnormalities of involuntary twisting or repetitive movements and postures. The most common inherited primary dystonia is DYT1 dystonia, which is due to loss of a GAG codon in the TOR1A gene that encodes torsinA. Autopsy studies of brains from patients with DYT1 dystonia have revealed few abnormalities, although recent neuroimaging studies have implied the existence of microstructural defects that might not be detectable with traditional histopathological methods. The current studies took advantage of a knock-in mouse model for DYT1 dystonia to search for subtle anatomical abnormalities in the striatum, a region often implicated in studies of dystonia. Multiple abnormalities were identified using a combination of quantitative stereological measures of immunohistochemical stains for specific neuronal populations, morphometric studies of Golgi-stained neurons, and immuno-electron microscopy of synaptic connectivity. In keeping with other studies, there was no obvious loss of striatal neurons in the DYT1 mutant mice. However, interneurons immunoreactive for choline acetyltransferase or parvalbumin were larger in the mutants than in control mice. In contrast, interneurons immunoreactive for neuronal nitric oxide synthase were smaller in the mutants than in controls. Golgi histochemical studies of medium spiny projection neurons in the mutant mice revealed slightly fewer and thinner dendrites, and a corresponding loss of dendritic spines. Electron microscopic studies showed a reduction in the ratio of axo-spinous to axo-dendritic synaptic inputs from glutamatergic and dopaminergic sources in mutant mice compared with controls. These results suggest specific anatomical substrates for altered signaling in the striatum and potential correlates of the abnormalities implied by human imaging studies of DYT1 dystonia.