Extracts of the leaves of Pyrus ussuriensis Maxim. Alleviate itch sensation via TSLP-dependent manner in mouse models of atopic dermatitis

2019 ◽  
Vol 210 ◽  
pp. 112624
Author(s):  
Bo Hyun Kim ◽  
Wook-Joo Lee ◽  
Babina Sanjel ◽  
Kyohee Cho ◽  
Youn Kyoung Son ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mouse Models ◽  
Dependent Manner ◽  
Itch Sensation ◽  
Pyrus Ussuriensis Maxim

scholarly journals Protective Effect of Pyrus ussuriensis Maxim. Extract against Ethanol-Induced Gastritis in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 439
Author(s):  
Naila Boby ◽  
Muhammad Aleem Abbas ◽  
Eon-Bee Lee ◽  
Zi-Eum Im ◽  
Walter H. Hsu ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
Adenosine Monophosphate ◽  
Ethanol Ingestion ◽  
Dependent Manner ◽  
Protective Effects ◽  
Gastric Mucosal Lesions ◽  
Cellular Degeneration ◽  
Mucosal Lesions ◽  
Pyrus Ussuriensis Maxim

Pyrus ussuriensis Maxim (Korean pear) has been used for hundreds of years as a traditional herbal medicine for asthma, cough, and atopic dermatitis in Korea and China. Although it was originally shown to possess anti-inflammatory, antioxidant, and antiatopic properties, its gastroprotective effects have not been investigated. In the present study, we evaluated the protective effects of Pyrus ussuriensis Maxim extract (PUE) against ethanol-induced gastritis in rats. The bioactive compound profile of PUE was determined by gas chromatography mass spectroscopy (GC-MS) and high-performance liquid chromatography (HPLC). The gastroprotection of PUE at different doses (250 and 500 mg/kg body weight) prior to ethanol ingestion was evaluated using an in vivo gastritis rat model. Several endpoints were evaluated, including gastric mucosal lesions, cellular degeneration, intracellular damage, and immunohistochemical localization of leucocyte common antigen. The gastric mucosal injury and ulcer score were determined by evaluating the inflamed gastric mucosa and by histological examination. To identify the mechanisms of gastroprotection by PUE, antisecretory action and plasma prostaglandin E2 (PGE2), gastric mucosal cyclic adenosine monophosphate (cAMP), and histamine levels were measured. PUE exhibited significant antioxidant effects with IC50 values of 56.18 and 22.49 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′- azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) inhibition (%), respectively. In addition, GC/MS and HPLC analyses revealed several bioactive compounds of PUE. Pretreatment with PUE significantly (P < 0.05) decreased the ulcer index by preventing gastric mucosal lesions, erosion, and cellular degeneration. An immunohistochemical analysis revealed that PUE markedly attenuated leucocyte infiltration in a dose-dependent manner. The enhancement of PGE2 levels and attenuation of cAMP levels along with the inhibition of histamine release following PUE pretreatment was associated with the cytoprotective and healing effects of PUE. In contrast, the downregulation of the H+/K+ ATPase pathway as well as muscarinic receptor (M3R) and histamine receptor (H2R) inhibition was also involved in the gastroprotective effects of PUE; however, the expression of cholecystokinin-2 receptors (CCK2R) was unchanged. Finally, no signs of toxicity were observed following PUE treatment. Based on our results, we conclude that PUE represents an effective therapeutic option to reduce the risk of gastritis and warrants further study.

scholarly journals Advanced glycation end products induce a prothrombotic phenotype in mice via interaction with platelet CD36

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6136-6144 ◽  
Author(s):  
Weifei Zhu ◽  
Wei Li ◽  
Roy L. Silverstein
Keyword(s):  
Diabetes Mellitus ◽  
Mouse Models ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Drug Induced ◽  
Glycation End Products ◽  
End Products

Abstract Diabetes mellitus has been associated with platelet hyperreactivity, which plays a central role in the hyperglycemia-related prothrombotic phenotype. The mechanisms responsible for this phenomenon are not established. In the present study, we investigated the role of CD36, a class-B scavenger receptor, in this process. Using both in vitro and in vivo mouse models, we demonstrated direct and specific interactions of platelet CD36 with advanced glycation end products (AGEs) generated under hyperglycemic conditions. AGEs bound to platelet CD36 in a specific and dose-dependent manner, and binding was inhibited by the high-affinity CD36 ligand NO2LDL. Cd36-null platelets did not bind AGE. Using diet- and drug-induced mouse models of diabetes, we have shown that cd36-null mice had a delayed time to the formation of occlusive thrombi compared with wild-type (WT) in a FeCl3-induced carotid artery injury model. Cd36-null mice had a similar level of hyperglycemia and a similar level of plasma AGEs compared with WT mice under this condition, but WT mice had more AGEs incorporated into thrombi. Mechanistic studies revealed that CD36-dependent JNK2 activation is involved in this prothrombotic pathway. Therefore, the results of the present study couple vascular complications in diabetes mellitus with AGE-CD36–mediated platelet signaling and hyperreactivity.

scholarly journals Neuronal and synaptic plasticity in the visual thalamus in mouse models of glaucoma

2020 ◽  
Author(s):  
Matthew J. Van Hook ◽  
Corrine Monaco ◽  
Jennie C. Smith
Keyword(s):  
Mouse Models ◽  
Ganglion Cells ◽  
Brain Regions ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Intrinsic Excitability ◽  
Dependent Manner ◽  
Functional Changes ◽  
Genetic Mouse Model

AbstractHomeostatic plasticity plays important roles in regulating synaptic and intrinsic neuronal function to stabilize output following perturbations to circuit activity. In glaucoma, a neurodegenerative disease of the visual system commonly associated with elevated intraocular pressure (IOP), early disease is associated with altered synaptic inputs to retinal ganglion cells (RGCs), changes in RGC intrinsic excitability, and deficits in optic nerve transport and energy metabolism. These early functional changes can precede RGC degeneration and are likely to alter RGC outputs to their target structures in the brain and thereby trigger homeostatic changes in synaptic and neuronal properties in those brain regions. In this study, we sought to determine whether and how neuronal and synaptic function is altered in the dorsal lateral geniculate nucleus (dLGN), an important RGC projection target in the thalamus, and how functional changes relate to IOP. We accomplished this using patch-clamp recordings from thalamocortical (TC) relay neurons in the dLGN in two established mouse models of glaucoma – the DBA/2J (D2) genetic mouse model and an inducible glaucoma model with intracameral microbead injections to elevate IOP. We found that the intrinsic excitability of TC neurons was enhanced in D2 mice and these functional changes were mirrored in recordings of TC neurons from microbead-injected mice. Notably, many neuronal properties were correlated with IOP in older D2 mice, but not younger D2 mice or microbead-injected mice. The frequency of miniature excitatory synaptic currents (mEPSCs) was reduced in both ages of D2 mice, and vGlut2 staining of RGC synaptic terminals was reduced in an IOP-dependent manner in older D2 mice. Among D2 mice, functional changes observed in younger mice without elevated IOP were distinct from those observed in older mice with elevated IOP and RGC degeneration, suggesting that glaucoma-associated changes to neurons in the dLGN might represent a combination of stabilizing/homeostatic plasticity at earlier stages and pathological dysfunction at later stages.

scholarly journals Immunomodulatory Effects of a Low-Molecular Weight Polysaccharide from Enteromorpha prolifera on RAW 264.7 Macrophages and Cyclophosphamide- Induced Immunosuppression Mouse Models

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 340
Author(s):  
Yingjuan Liu ◽  
Xiaolin Wu ◽  
Weihua Jin ◽  
Yunliang Guo
Keyword(s):  
Mouse Models ◽  
The Body ◽  
Water Soluble ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Enteromorpha Prolifera ◽  
Immunomodulatory Effects ◽  
Raw 264.7 Macrophages ◽  
Cell Counts ◽  
Tnf Α

The water-soluble polysaccharide EP2, from Enteromorpha prolifera, belongs to the group of polysaccharides known as glucuronoxylorhamnan, which mainly contains glucuronic acid (GlcA), xylose (Xyl), and rhamnose (Rha). The aim of this study was to detect the immunomodulatory effects of EP2 on RAW 264.7 macrophages and cyclophosphamide (CYP)-induced immunosuppression mouse models. The cells were treated with EP2 for different time periods (0, 0.5, 1, 3, and 6 h). The results showed that EP2 promoted nitric oxide production and up-regulated the expression of pro-inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, in a time-dependent manner. Furthermore, we found that EP2-activated iNOS, COX2, and NLRP3 inflammasomes, and the TLR4/MAPK/NF-κB signaling pathway played an important role. Moreover, EP2 significantly increased the body weight, spleen index, thymus index, inflammatory cell counts, and the levels of IL-1β, IL-6, and TNF-α in CYP-induced immunosuppression mouse models. These results indicate that EP2 might be a potential immunomodulatory drug and provide the scientific basis for the comprehensive utilization and evaluation of E. prolifera in future applications.

scholarly journals Inhibitory Effect of Centella asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 411 ◽  
Author(s):  
Yonghyeon Lee ◽  
Hyeon Kyeong Choi ◽  
Kaudjhis Patrick Ulrich N’deh ◽  
Young-Jin Choi ◽  
Meiqi Fan ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Allergic Inflammation ◽  
Centella Asiatica ◽  
Ethanol Extract ◽  
Inhibitory Effect ◽  
Interferon Γ ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Signaling Mechanism ◽  
Tnf Α

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the Centella asiatica ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm2, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.

Mouse models of atopic dermatitis: a critical reappraisal

2020 ◽  
Author(s):  
Amos Gilhar ◽  
Kristian Reich ◽  
Aviad Keren ◽  
Kenji Kabashima ◽  
Martin Steinhoff ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mouse Models

scholarly journals Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1/PD-L1 blockade-sensitive mouse models

2020 ◽  
Vol 8 (1) ◽  
pp. e000400 ◽  
Author(s):  
Taiki Kurino ◽  
Reiko Matsuda ◽  
Ayu Terui ◽  
Hiroyuki Suzuki ◽  
Tomomi Kokubo ◽  
...  
Keyword(s):  
Mouse Models ◽  
Pharmacological Activity ◽  
Tumor Model ◽  
High Dose ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Poor Outcome ◽  
Liver And Kidney ◽  
High Doses

BackgroundRecently, antiprogrammed cell death protein 1 (aPD-1) and antiprogrammed death-ligand 1 (aPD-L1) monoclonal antibodies (mAbs) have been approved. Even though aPD-1 and aPD-L1 mAbs target the same PD-1/PD-L1 axis, it is still unclear whether both mAbs exert equivalent pharmacological activity in patients who are sensitive to PD-1/PD-L1 blockade therapy, as there is no direct comparison of their pharmacokinetics (PK) and antitumor effects. Therefore, we evaluated the differences between both mAbs in PK and therapeutic effects in PD-1/PD-L1 blockade-sensitive mouse models.MethodsHerein, murine breast MM48 and colon MC38 xenografts were used to analyze the pharmacological activity of aPD-1 and aPD-L1 mAbs. The PK of the mAbs in the tumor-bearing mice was investigated at low and high doses using two radioisotopes (Indium-111 and Iodine-125) to evaluate the accumulation and degradation of the mAbs.ResultsaPD-1 mAb showed antitumor effect in a dose-dependent manner, indicating that the tumor model was sensitive to PD-1/PD-L1 blockade therapy, whereas aPD-L1 mAb failed to suppress tumor growth. The PK study showed that aPD-L1 mAb was accumulated largely in normal organs such as the spleen, liver, and kidney, resulting in low blood concentration and low distributions to tumors at a low dose, even though the tumors expressed PD-L1. Sufficient accumulation of aPD-L1 mAb in tumors was achieved by administration at a high dose owing to the saturation of target-mediated binding in healthy organs. However, degradation of aPD-L1 mAb in tumors was greater than that of aPD-1 mAb, which resulted in poor outcome presumably due to less inhibition of PD-L1 by aPD-L1 mAb than that of PD-1 by aPD-1 mAb.ConclusionAccording to the PK studies, aPD-1 mAb showed linear PK, whereas aPD-L1 mAb showed non-linear PK between low and high doses. Collectively, the poor PK characteristics of aPD-L1 mAb caused lower antitumor activity than of aPD-1 mAb. These results clearly indicated that aPD-L1 mAb required higher doses than aPD-1 mAb in clinical setting. Thus, targeting of PD-1 would be more advantageous than PD-L1 in terms of PK.

scholarly journals Insights into atopic dermatitis gained from genetically defined mouse models

2019 ◽  
Vol 143 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Saeko Nakajima ◽  
Takashi Nomura ◽  
John Common ◽  
Kenji Kabashima
Keyword(s):  
Atopic Dermatitis ◽  
Mouse Models

The New CXCR4 Inhibitor MDX-1338 Exerts Anti-Tumor Activity in Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1844-1844 ◽  
Author(s):  
Aldo M Roccaro ◽  
Antonio Sacco ◽  
Michelle Kuhne ◽  
AbdelKareem Azab ◽  
Patricia Maiso ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Tumor Cells ◽  
Mouse Models ◽  
Research Funding ◽  
Therapeutic Agents ◽  
Dependent Manner ◽  
Apoptotic Pathways ◽  
Dose Dependent

Abstract Abstract 1844 Background. We have previously shown the SDF1/CXCR4 axis plays a major role in homing and trafficking of multiple myeloma (MM) to the bone marrow (BM), and disruption of the interaction of tumor cells with the BM leads to enhanced sensitivity to therapeutic agents. We hypothesize that the novel anti-CXCR4 antibody, BMS936564/MDX-1338, may prevent the homing and adhesion of MM cells to the BM and will sensitize them to therapeutic agents. Methods. Primary MM cells (CD138+); MM cell lines (MM.1S, RPMI.8226); and primary MM bone marrow stromal cells (BMSCs) were used. Migration towards SDF-1 and BMSCs has been evaluated. Cytotoxicity and DNA synthesis were measured by MTT and thymidine uptake, respectively. Cell signaling and apoptotic pathways were studied by Western Blot. Synergism was calculated using the Chou-Talalay method. In vivo MM tumor growth was evaluated with xenograft mouse models. Results. MDX-1338 inhibited migration of MM cells toward SDF-1a and primary MM BMSCs, in a dose-dependent manner. Adhesion of primary MM cells to BMSCs was also inhibited by BMS936564/MDX-1338 in a dose-dependent manner, while also inducing cytotoxicity on primary BM-derived CD138+ cells. BMS936564/MDX-1338 targeted MM cells in the context of BM milieu by overcoming BMSC-induced proliferation of tumor cells. In addition, BMS936564/MDX-1338 synergistically enhanced bortezomib-induced cytotoxicity in MM cells. BMS936564/MDX-1338-dependent activation of apoptotic pathways in MM cells was documented, as shown by cleavage of caspase-9 and PARP. SDF-1a-induced ERK-, Akt-, and Src-phosphorilation was inhibited by BMS936564/MDX-1338 in a dose-dependent manner. Importantly, BMS936564/MDX-1338 inhibited MM cell proliferation in vivo in xenograft mouse models. Conclusion. These studies therefore show that targeting CXCR-4 in MM by using BMS936564/MDX-1338 represents a valid therapeutic strategy in this disease. Disclosures: Roccaro: Roche:. Kuhne:BMS: Employment. Pan:Bristol-Myers Squibb: Employment. Cardarelli:Bristol-Myers Squibb: Employment. Ghobrial:Noxxon: Research Funding; Bristol-Myers Squibb: Research Funding; Millennium: Research Funding; Noxxon:; Millennium:; Celegene:; Novartis:.

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