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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.

Drug repositioning is used to discover drug candidates to treat human diseases, through the application of drugs or compounds that are approved for the treatment of other diseases. This method can significantly reduce the time required and cost of discovering new drug candidates for human diseases. Previous studies have reported pro‐inflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti‐inflammatory responses and mechanisms of methylthiouracil (MTU), which is an antithyroid drug, and its effects on PolyP‐induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behaviour of human neutrophils and vascular permeability were determined in PolyP‐activated HUVECs and mice. MTU suppressed the PolyP‐mediated vascular barrier permeability, up‐regulation of inflammatory biomarkers, adhesion/migration of leucocytes, and activation and/or production of nuclear factor‐κB, tumour necrosis factor‐α and interleukin‐6. Furthermore, MTU demonstrated protective effects on PolyP‐mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of MTU on various systemic inflammatory diseases, such as sepsis or septic shock.

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.

Endocan is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. The aim of this study was to evaluate the effects of endocan on proinflammatory responses and on septic mice and underlying mechanisms. Human umbilical vein endothelial cells (HUVECs) or mice were exposed to lipopolysaccharide (LPS) or endocan with or without neutralizing endocan antibody. Mice were subjected to cecal ligation and puncture (CLP) surgery with or without neutralizing endocan antibody. Endocan was highly released by LPS and it enhanced proinflammatory responses. In a CLP-induced sepsis model, endocan was also highly released, but this release was prevented by administration of neutralizing endocan antibody. Circulating levels of endocan measured in patients admitted to the intensive care unit with sepsis were significantly elevated compared with control donors. Furthermore, the administration of endocan antibody reduced CLP-induced sepsis mortality. This study shows endocan can elicit severe inflammatory responses and inhibiting endocan release offers a potential strategy for treating sepsis. J. Cell. Physiol. 229: 620–630, 2014. © 2013 Wiley Periodicals, Inc.

The main purpose of this study was to evaluate whether donepezil, acetylcholinesterase inhibitor, shown to play a protective role through inhibiting glycogen synthesis kinase-3β (GSK-3β) activity, could also exert neuroprotective effects by stimulating protein phosphatase 2A (PP2A) activity in the amyloid-beta (Aβ)42-induced neuronal toxicity model of Alzheimer's disease. In Aβ42-induced toxic conditions, each PP2A and GSK-3β activity measured at different times showed time-dependent reverse pattern toward the direction of accelerating neuronal deaths with the passage of time. In addition, donepezil pre-treatment showed dose-dependent stepwise increase of neuronal viability and stimulation of PP2A activity. However, such effects on them were significantly reduced through the depletion of PP2A activity with either okadaic acid or PP2Ac siRNA. In spite of blocked PP2A activity in this Aβ42 insult, however, donepezil pretreatment showed additional significant recovering effect on neuronal viability when compared to the value without donepezil. Moreover, donepezil partially recovered its dephosphorylating effect on hyperphosphorylated tau induced by Aβ42. This observation led us to assume that additional mechanisms of donepezil, including its inhibitory effect on GSK-3β activity and/or the activation role of nicotinic acetylcholine receptors (nAChRs), might be involved. Taken together, our results suggest that the neuroprotective effects of donepezil against Aβ42-induced neurotoxicity are mediated through activation of PP2A, but its additional mechanisms including regulation of GSK-3β and nAChRs activity would partially contribute to its effects. We investigated neuroprotective mechanisms of donepezil against Aβ42 toxicity: Donepezil increased neuronal viability with reduced p-tau by enhancing PP2A activity. Despite of blocked PP2A activity, donepezil showed additional recovering effect on neuronal viability, which findings led us to assume that additional mechanisms of donepezil including its inhibitory effect on GSK-3β activity and activating role of nicotinic AChRs might be involved.

Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, three (1-3) of diketopiperazines were isolated from two strains of marine-derived bacteria. The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses in vitro and in vivo. From 1 μM, 1-3 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer and in mice in a dose-dependent manner suggesting that 1-3 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.

Kim YS, Kang SJ, Kim JW, Cho HR, Moon SB, Kim KY, Lee HS, Han CH, Ku SK, Lee YJ. Effects of Polycan, a β-glucan, on experimental periodontitis and alveolar bone loss in Sprague-Dawley rats. J Periodont Res 2012; 47: 800–810. © 2012 John Wiley & Sons A/S Background and Objective: Polycan is a promising candidate for the treatment of periodontal disease. This study was undertaken to examine whether Polycan, a type of β-glucan, has a protective effect on ligature-induced experimental periodontitis and related alveolar bone loss in Sprague-Dawley rats. Material and Methods: Polycan was orally administered, daily, for 10 d, at 21.25, 42.5 or 85 mg/kg, beginning 1 d after ligation. Changes in body weight and alveolar bone loss were monitored, and the anti-inflammatory effects of Polycan were determined by measuring the levels of myeloperoxidase (MPO), interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in gingival tissue. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentrations as a measure of the antioxidant effect. Results: Ligature placement led to a marked decrease in body weight, increased alveolar bone loss and increased concentrations of MPO, IL-1β, TNF-α and MDA, as well as increased iNOS activity and inflammatory cell infiltration and decreased collagen-fiber content. Histological examination revealed increases in the number and activity of osteoclast cells, decreases in alveolar bone volume and elevated percentages of osteclasts on the alveolar bone surface. Daily oral treatment with 42.5 or 85 mg/kg of Polycan for 10 d led to significant, dose-dependent inhibition of the effect of ligature placement. Conclusion: Taken together, these results suggest that 10 d of oral treatment with Polycan effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via an antioxidant effect.

Silicone-based formulations are extensively used for the management of hypertrophic scars. Although the exact mechanism of action is still unknown, it has been postulated that some occlusion and hydration of the stratum corneum with subsequent cytokine-mediated signaling from keratinocytes to dermal fibroblasts is involved in its antiscarring effects. In this study, the effectiveness of silicone-based gels containing allantoin, dexpanthenol, and heparin was evaluated for improving the healing of hypertrophic scars. It was found that silicone-based gels showed remarkable improvements in hypertrophic scar healing and low amounts of skin pigmentation in the rabbit ear model compared with the nontreated control or base alone. Furthermore, the histopathological and histomorphometrical profiles of three different formulations containing 1%, 5%, and 20% silicone contents exhibited marked or significant decreases in the scar elevation index, anterior skin and epithelial thicknesses, inflammatory cells, vessels, collagen disorganization, and fibroblasts compared with nontreated control hypertrophic scars. Therefore, these results indicate that silicone-based gels containing heparin, allantoin, and dexpanthenol could be promising formulations for the healing of hypertrophic scars.

The distributions and frequencies of some endocrine cells in the eight portions of the gastrointestinal (GI) tract - fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum of the ddN mouse, were studied with immunohistochemical method using seven types of antisera against chromogranin (Cg) A serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP). In the GI tract of ddN mice, CgA, serotonin, somatostatin, glucagon, gastrin, CCK-8 immunoreactive (IR) cells were identified with various frequencies, but hPP-IR cells were not observed in this study. Most of IR cells in the intestinal portion were generally spherical or spindle in shape (open type cell) whereas cells showing round in shape (close type cell) were found in the intestinal gland and stomach regions occasionally. They showed the highest frequency in the pylorus or colon. CgA-IR cells were observed from the pylorus to ileum. Serotonin-IR cells were detected throughout the whole GI tract except for the fundus. Somatostatin-IR cells were demonstrated throughout the whole GI tract except for the cecum and colon. Gastrin and CCK-8-IR cells were restricted to the pylorus and duodenum. In addition, a few glucagon-IR cells were restricted to the fundus and rectum. In conclusion, the general distribution patterns and relative frequency of GI endocrine cells of the ddN mouse was similar to that of other strains of mice. However, some strain and/or species-dependent unique distributions and frequencies of endocrine cells were also observed in the present study.

The regional distribution and relative frequency of neurohormonal peptides-producing cells were demonstrated in the gut of the stomachless teleost, Zacco platypus (Temminck et Schegel), using 10 types of specific antisera raised against mammalian regulatory peptides. The gut of Z. platypus was divided into five portions from proximal to distal (segment I-V). Most of immunoreactive cells in the epithelial lining portion, between epithelial cells, were generally spherical or spindle shape having long cytoplasmic process that was reached via the lumen while cells round in shape were found in the basal portions of epithelial lining occasionally. Serotonin-, somatostatin-, glucagon-, cholecystokinin (CCK)-8 and pancreatic polypeptide (PP)-immunoreactive cells were observed in this study. However, no chromogranin A-, secretin-, vasoactive intestinal peptide (VIP)-, substance P- and bombesin-immunoreactive cells were found. Serotonin-immunoreactive cells were demonstrated throughout the entire gut tract and occurred more frequently than other cells. Somatostatin-immunoreactive cells were restricted to proximal segments of the gut (segment I-III) with rare frequencies, and glucagon-immunoreactive cells were demonstrated in the proximal segments of the gut (segment I, II) with moderate to few occurrences. CCK-8-immunoreactive cells were found throughout the whole intestinal tract except for most proximal segment (segment I) with moderate to few frequencies and PP-immunoreactive cells were demonstrated in the proximal to middle segments, segment I-III, with a few, rare and rare frequencies, respectively.

The regional distribution and relative frequency of endocrine cells in the alimentary tract of the red-eared slider, Trachemys scripta elegans, were investigated by immunohistochemical methods using 10 antisera. Most of the immunoreactive cells in the intestine were spherical or spindle-like in shape (open-type cells), while round cells (closed-type cells) were occasionally found in the stomach. These immunoreactive cells were located in the basal portion of the intestine, including the oesophagus, and in the gastric glands of the stomach. Cg A-immunoreactive cells were restricted to the pylorus and duodenum and were few in number. Serotonin-immunoreactive cells, which were most commonly found in the pylorus, were found in the epithelia throughout the alimentary tract at various frequencies. Gastrin-immunoreactive cells were found in the pylorus, duodenum and jejunum at moderate, low and very low frequencies, respectively. Somatostatin-immunoreactive cells were found throughout the alimentary tract except for the rectum, at various frequencies. Glucagon-immunoreactive cells were detected in the fundus, pylorus, jejunum and ileum at low or very low frequencies. CCK-8-immunoreactive cells were found in the pylorus, fundus and duodenum at very low, low and moderate frequencies, respectively. Bombesin-immunoreactive cells were restricted to the fundus and pylorus at low frequencies. No secretin-, BPP- or VIP-immunoreactive cells were found in this study.