Effect of Silica Nanoparticle Treatment on Adhesion between Tissue-like Substrates and In Vivo Skin Wound Sealing.

Silica nanoparticles are innovative solutions of surgical glue that can readily adhere to various tissue-like substrates without the need for time-consuming chemical reactions or ultraviolet irradiation. Herein, 10 nm-sized silica nanoparticle (SiNP10) treatment exhibited maximum adhesion strength in the porcine heart tissue model, which was approximately 7.15 times higher than that of the control group of non-treatment. We assessed the effects of silica nanoparticle treatment on in vivo skin wounds by scoring tissue adhesion and inflammation using histological images. Compared to the commercial cyanoacrylate skin adhesive (Dermabond), suppression of inflammatory cytokine levels in the incision wound skin was observed. We further quantified the expression of angiogenic growth factors and connective tissue formation-related proteins. On day 5 after wound closing treatment, the expression levels of PDGF-BB growth factor were significantly higher in SiNP10 treatment (0.64 ± 0.03) compared to Dermabond (0.07 ± 0.05). This stimulated angiogenesis and connective tissue formation in the skin of the incision wound may be associated with the promoting effects of SiNP10 treatment on wound closure and tissue adhesion.

Novel Role of the ALPI Gene Associated with Constipation Caused by Complement Component 3 Deficiency.

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

Novel Therapeutic Effects of Euphorbia heterophylla L. Methanol Extracts in Macular Degeneration Caused by Blue Light in A2E-Laden ARPE-19 Cells and Retina of BALB/c Mice.

Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.

Identification of acrolein as a novel diagnostic odor biomarker for 1,2,3-trichloropropane-induced hepatotoxicity in Sprague Dawley rats.

Body odor is considered a diagnostic indicator of various infectious and chronic diseases. But, few studies have examined the odor markers for various toxic effects in the mammalian system. This study attempted to identify the novel diagnostic odor biomarkers for chemical-induced hepatotoxicity in animals. The changes in the concentration of odors were analyzed in the urine of Sprague Dawley (SD) rats treated with two dosages (100 or 200 mg/kg) of 1,2,3-trichloropropane (TCP) using gas chromatography-mass spectrometry (GC-MS). The TCP treatment induced significant toxicity, including a decrease in body weight, an increase in serum biochemical factors, and histopathological changes in the liver of SD rats. During this hepatotoxicity, the concentrations of six odors (ethyl alcohol, acrolein (2-propenal), methanesulfonyl chloride, methyl ethyl ketone, cyclotrisiloxane, and 2-heptanone) in urine changed significantly after the TCP treatment. Among them, acrolein, an acrid and pungent compound, showed the highest rate of increase in the TCP-treated group compared to the Vehicle-treated group. In addition, this increase in acrolein was accompanied by enhanced spermine oxidase (SMOX) expression, an acrolein metabolic enzyme, and the increased level of IL-6 transcription as a regulator factor that induces SMOX production. The correlation between acrolein and other parameters was conformed using correlagram analyses. These results provide scientific evidence that acrolein have potential as a novel diagnostic odor biomarker for TCP-induced hepatotoxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00253-0.

Association Between Cytokeratin 19-Specific IgG and Neutrophil Activation in Asthma.

PURPOSE: Patients with non-eosinophilic asthma (NEA) are less responsive to anti-inflammatory drugs and suffer from frequent asthma exacerbations. The pathogenic mechanism of NEA is not fully understood; however, the roles of monocytes and autoimmune mechanisms targeting airway epithelial cell (AEC) antigens have been proposed. METHODS: The effects of monocyte extracellular traps (MoETs) on cytokeratin 19 (CK19) production in AECs, as well as the impact of CK19-specific immunoglobulin (Ig) G on neutrophil and monocyte activation, were investigated both in vivo and in vitro. Sixty asthmatic patients and 15 healthy controls (HCs) were enrolled, and the levels of serum immune complexes containing CK19-specific IgG and neutrophil extracellular trap (NET)-specific IgG were measured using enzyme-linked immunoassay. RESULTS: MoETs induced CK19 and CK19-specific IgG production. Furthermore, the levels of serum CK19-specific IgG were significantly higher in the NEA group than in the eosinophilic asthma group. Among patients with NEA, asthmatics with high levels of CK19-specific IgG had higher levels of myeloperoxidase and NET-specific IgG than those with low levels of CK19-specific IgG (P = 0.020 and P = 0.017; respectively). Moreover, the immune complexes from asthmatics with high CK19-specific IgG enhanced NET formation and reactive oxygen species production (neutrophil activation), which were suppressed by N-acetylcysteine and anti-CD16 antibody treatment. CONCLUSIONS: These findings suggest that circulating CK19 and CK19-specific IgG may contribute to NET formation, leading to airway inflammation and steroid resistance in NEA.

Citrullus mucosospermus Extract Exerts Protective Effects against Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Steatohepatitis in Mice.

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

Retraction Notice to: Decreased Lung Tumor Development in SwAPP Mice through the Downregulation of CHI3L1 and STAT 3 Activity via the Upregulation of miRNA342-3p.

[This retracts the article DOI: 10.1016/j.omtn.2019.02.007.].

Citrullus mucosospermus Extract Reduces Weight Gain in Mice Fed a High-Fat Diet.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines' mRNA levels (TNF-α, IL-1ß and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

N-benzyl-N-methyldecan-1-amine, derived from garlic, and its derivative alleviate 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically applying N-benzyl-N-methyldecan-1-amine (BMDA), derived from garlic, and its derivative [decyl-(4-methoxy-benzyl)-methyl-1-amine] (DMMA) could effectively alleviate AD-like skin lesions in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Administering these compounds to the irritated skin of DNCB-treated mice significantly reduced swelling, rash, and excoriation severity, alongside a corresponding decrease in inflamed epidermis and dermis. Moreover, they inhibited spleen and lymph node enlargement and showed fewer infiltrated mast cells in the epidermis and dermis through toluidine-blue staining. Additionally, they led to a lower IgE titer in mouse sera as determined by ELISA, compared to vehicle treatment. Analyzing skin tissue from the mice revealed decreased transcript levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6), IL-4, iNOS, and COX-2, compared to control mice. Simultaneously, the compounds impeded the activation of inflammation-related signaling molecules such as JNK, p38 MAPK, and NF-κB in the mouse skin. In summary, these findings suggest that BMDA and DMMA hold the potential to be developed as a novel treatment for healing inflammatory AD.

Antiadhesive Hyaluronic Acid-Based Wound Dressings Promote Wound Healing by Preventing Re-Injury: An In Vivo Investigation.

Wound dressings are widely used to protect wounds and promote healing. The water absorption and antifriction properties of dressings are important for regulating the moisture balance and reducing secondary damages during dressing changes. Herein, we developed a hyaluronic acid (HA)-based foam dressing prepared via the lyophilization of photocrosslinked HA hydrogels with high water absorption and antiadhesion properties. To fabricate the HA-based foam dressing (HA foam), the hydroxyl groups of the HA were modified with methacrylate groups, enabling rapid photocuring. The resulting photocured HA solution was freeze-dried to form a porous structure, enhancing its exudate absorption capacity. Compared with conventional biopolymer-based foam dressings, this HA foam exhibited superior water absorption and antifriction properties. To assess the wound-healing potential of HA foam, animal experiments involving SD rats were conducted. Full-thickness defects measuring 2 × 2 cm2 were created on the skin of 36 rats, divided into four groups with 9 individuals each. The groups were treated with gauze, HA foam, CollaDerm®, and CollaHeal® Plus, respectively. The rats were closely monitored for a period of 24 days. In vivo testing demonstrated that the HA foam facilitated wound healing without causing inflammatory reactions and minimized secondary damages during dressing changes. This research presents a promising biocompatible foam wound dressing based on modified HA, which offers enhanced wound-healing capabilities and improved patient comfort and addresses the challenges associated with conventional dressings.

Compositional changes in fecal microbiota in a new Parkinson's disease model: C57BL/6-Tg(NSE-haSyn) mice.

BACKGROUND: The gut-brain axis (GBA) in Parkinson's disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. RESULTS: The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSE-hαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. CONCLUSIONS: The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Chemosensitivity to doxorubicin in primary cells derived from tumor of FVB/N-Trp53tm1Hw1 with TALEN-mediated Trp53 mutant gene.

BACKGROUND: To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. RESULTS: The primary tumor cells showed a significant (P < 0.05) defect for UV-induced upregulation of the Trp53 protein, and consisted of different ratios of leukocytes, fibroblasts, epithelial cells and mesenchymal cells. The IC50 level to DOX was lower in both primary cells (IC50 = 0.12 µM and 0.20 µM) as compared to the CT26 cells (IC50 = 0.32 µM), although the solid tumor was more sensitive. Also, the number of cells arrested at the G0/G1 stage was significantly decreased (24.7-23.1% in primary tumor cells treated with DOX, P < 0.05) while arrest at the G2 stage was enhanced to 296.8-254.3% in DOX-treated primary tumor cells compared with DOX-treated CT26 cells. Furthermore, apoptotic cells of early and late stage were greatly increased in the two primary cell-lines treated with DOX when compared to same conditions for CT26 cells. However, the Bax/Bcl-2 expression level was maintained constant in the primary tumor and CT26 cells. CONCLUSIONS: To the best of our knowledge, these results are the first to successfully detect an alteration in chemosensitivity to DOX in solid tumor cells and ascetic tumor cells derived from tumor of FVB/N-Trp53tm1Hw1 mice TALEN-mediated Trp53 mutant gene.

Adiposity Reduction by Cucumis melo var. gaettongchamoe Extract in High-Fat Diet-Induced Obese Mice.

This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.

Visualizing mast cell migration to tumor sites using sodium iodide symporter of nuclear medicine reporter gene.

PURPOSE: Owing to the close relationship between mast cells and cancer progression, an imaging technique that can be applied in a clinical setting to explore the biological behavior of mast cells in the tumor microenvironment is needed. In this study, we visualized mast cell migration to lung tumor lesions in live mice using sodium iodide symporter (NIS) as a nuclear medicine reporter gene. EXPERIMENTAL DESIGN: The murine mast cell line MC-9 was infected with retrovirus including NIS, luciferase (as a surrogate marker for NIS), and Thy1.1 to generate MC-9/NFT cells. Radioiodine uptake was measured in MC-9/NFT cells, and an inhibition assay of radioiodine uptake using KCLO4 was also performed. Cell proliferation and FcεRI expression was examined in MC-9 and MC-9/NFT cells. The effect of mast cell-conditioned media (CM) on the proliferation of Lewis lung cancer (LLC) cells was examined. The migration level of MC-9/NFT cells was confirmed in the presence of serum-free media (SFM) and CM of cancer cells. After intravenous injection of MC-9/NFT cells into mice with an LLC tumor, I-124 PET/CT and biodistribution analysis was performed. RESULTS: MC-9/NFT cells exhibited higher radioiodine avidity compared to parental MC-9 cells; this increased radioiodine avidity in MC-9/NFT cells was reduced to basal level by KCLO4. Levels of FcεRI expression and cell proliferation were not different in parental MC-9 cell and MC-9/ NFT cells. The CM of MC-9/NFT cells increased cancer cell proliferation relative to that of the SFM. The migration level of MC-9/NFT cells was higher in the CM than the SFM of LLC cells. PET/CT imaging with I-124 clearly showed infiltration of reporter mast cells in lung tumor at 24 h after transfer, which was consistent with the findings of the biodistribution examination. CONCLUSION: These findings suggest that the sodium iodide symporter can serve as a reliable nuclear medicine reporter gene for non-invasively imaging the biological activity of mast cells in mice with lung tumors. Visualizing mast cells in the tumor microenvironment via a nuclear medicine reporter gene would provide valuable insights into their biological functions.

Characterisation of changes in global genes expression in the lung of ICR mice in response to the inflammation and fibrosis induced by polystyrene nanoplastics inhalation.

This study characterised the changes in global gene expression in the lung of ICR mice in response to the inflammation and fibrosis induced by the inhalation of 0.5 µm polystyrene (PS)-nanoplastics (NPs) at various concentrations (4, 8, and 16 µg/mL) for 2 weeks. The total RNA extracted from the lung tissue of NPs-inhaled mice was hybridised into oligonucleotide microarrays. Significant upregulation was detected in several inflammatory responses, including the number of immune cells in bronchoalveolar lavage fluid (BALF), the expression level of inflammatory cytokines, mucin secretion, and histopathological changes, while they accumulated average of 13.38 ± 1.0 µg/g in the lungs of the inhaled ICR mice. Similar responses were observed regarding the levels of fibrosis-related factors in the NPs-inhaled lung of ICR mice, such as pulmonary parenchymal area, expression of pro-fibrotic marker genes, and TGF-ß1 downstream signalling without any significant hepatotoxicity and nephrotoxicity. In microarray analyses, 60 genes were upregulated, and 55 genes were downregulated in the lung of ICR mice during inflammation and fibrosis induced by NPs inhalation compared to the Vehicle-inhaled mice. Among these genes, many were categorised into several ontology categories, including the anatomical structure, binding, membrane, and metabolic process. Furthermore, the major genes in the upregulated categories included Igkv14-126000, Egr1, Scel, Lamb3, and Upk3b. In contrast, the major genes in the down-regulated categories were Olfr417, Olfr519, Rps16, Rap2b, and Vmn1r193. These results suggest several gene functional groups and individual genes as specific biomarkers respond to inflammation and fibrosis induced by PS-NPs inhalation in ICR mice. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00188-y.

Dipterocarpus tuberculatus as a promising anti-obesity treatment in Lep knockout mice.

Introduction: The therapeutic effects and mechanisms of Dipterocarpus tuberculatus (D. tuberculatus) extracts have been examined concerning inflammation, photoaging, and gastritis; however, their effect on obesity is still being investigated. Methods: We administered a methanol extract of D. tuberculatus (MED) orally to Lep knockout (KO) mice for 4 weeks to investigate the therapeutic effects on obesity, weight gain, fat accumulation, lipid metabolism, inflammatory response, and ß-oxidation. Results: In Lep KO mice, MED significantly reduced weight gains, food intake, and total cholesterol and glyceride levels. Similar reductions in fat weights and adipocyte sizes were also observed. Furthermore, MED treatment reduced liver weight, lipid droplet numbers, the expressions of adipogenesis and lipogenesis-related genes, and the expressions of lipolysis regulators in liver tissues. Moreover, the iNOS-mediated COX-2 induction pathway, the inflammasome pathway, and inflammatory cytokine levels were reduced, but ß-oxidation was increased, in the livers of MED-treated Lep KO mice. Conclusion: The results of this study suggest that MED ameliorates obesity and has considerable potential as an anti-obesity treatment.

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

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

Anti­tumor effects of an aqueous extract of Ecklonia cava in BALB/cKorl syngeneic mice using colon carcinoma CT26 cells.

Ecklonia cava (E. cava) is well known as one of edible alga that contains various unique polyphenols. The anti­tumor activity of an aqueous extract of E. cava (AEC) against colon carcinoma was evaluated by analyzing the alterations in tumor growth, histopathological structure and molecular mechanisms in CT26 tumor­bearing BALB/cKorl syngeneic mice after administrating AEC for five weeks. AEC contained high total phenolic contents and demonstrated significant scavenging activity against 2,2­diphenyl­1­picrylhydrazyl radicals. Marked anti­tumor effects were demonstrated in the AEC­treated CT26 cells. In the in vivo syngeneic model, the AEC treatment decreased the volume and weight of CT26 tumors, and expanded the necrotic region in the hematoxylin and eosin stained tumor sections. The inhibitory effects of AEC on tumor growth were reflected by the increased level of apoptotic proteins, inhibition of cell proliferation, suppression of metastasis ability and increase in tumor­suppressing activity in CT26 tumor­bearing BALB/cKorl syngeneic mice. The potential function of phlorotannin (PT), one of the primary active compounds in AEC, was demonstrated by the increased cytotoxicity, apoptosis and suppression of cell proliferation in PT­treated CT26 cells. Overall, the results of the present study provide novel scientific evidence that AEC can suppress the growth of CT26 colon cancer by activating apoptosis, suppressing cell proliferation, inhibiting cell migration and enhancing the tumor­suppressing activity.

Anti-Atopic Dermatitis Effects of Abietic Acid Isolated from Rosin under Condition Optimized by Response Surface Methodology in DNCB-Spread BALB/c Mice.

Abietic acid (AA) is known to have beneficial effects on inflammation, photoaging, osteoporosis, cancer, and obesity; however, its efficacy on atopic dermatitis (AD) has not been reported. We investigated the anti-AD effects of AA, which was newly isolated from rosin, in an AD model. To achieve this, AA was isolated from rosin under conditions optimized by response surface methodology (RSM), and its effects on cell death, iNOS-induced COX-2 mediated pathway, inflammatory cytokine transcription, and the histopathological skin structure were analyzed in 2,4-dinitrochlorobenzene (DNCB)-treated BALB/c mice after treatment with AA for 4 weeks. AA was isolated and purified through isomerization and reaction-crystallization under the condition (HCl, 2.49 mL; reflux extraction time, 61.7 min; ethanolamine, 7.35 mL) established by RSM, resulting in AA with a purity and extraction yield of 99.33% and 58.61%, respectively. AA exhibited high scavenging activity against DPPH, ABTS, and NO radicals as well as hyaluronidase activity in a dose-dependent manner. The anti-inflammatory effects of AA were verified in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages through amelioration of the inflammatory response, including NO production, iNOS-induced COX-2 mediated pathway activation, and cytokine transcription. In the DNCB-treated AD model, the skin phenotypes, dermatitis score, immune organ weight, and IgE concentration were significantly ameliorated in the AA cream (AAC)-spread groups compared to the vehicle-spread group. In addition, AAC spread ameliorated DNCB-induced deterioration of skin histopathological structure through the recovery of the thickness of the dermis and epidermis and the number of mast cells. Furthermore, activation of the iNOS-induced COX-2 mediated pathway and increased inflammatory cytokine transcription were ameliorated in the skin of the DNCB+AAC-treated group. Taken together, these results indicate that AA, newly isolated from rosin, exhibits anti-AD effects in DNCB-treated AD models, and has the potential to be developed as a treatment option for AD-related diseases.