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https://www.readbyqxmd.com/read/28107775/beta-caryophyllene-protects-against-alcoholic-steatohepatitis-by-attenuating-inflammation-and-metabolic-dysregulation-in-mice
#1
Zoltan V Varga, Csaba Matyas, Katalin Erdelyi, Resat Cinar, Daniela Nieri, Andrea Chicca, Balazs Tamas Nemeth, Janos Paloczi, Tamas Lajtos, Lukas Corey, Gyorgy Hasko, Bin Gao, George Kunos, Jürg Gertsch, Pal Pacher
BACKGROUND AND AIMS: Beta-caryophyllene (BCP) is a plant-derived FDA approved food additive with anti-inflammatory properties. Some of its beneficial effects in vivo reported to involve activation of cannabinoid 2 receptors (CB2) that are predominantly expressed in immune cells. Herein, we evaluated the translational potential of BCP using a well-established model of chronic and binge alcohol-induced liver injury. METHODS: In this study we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real-time PCR and histology analyses...
January 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28107769/the-transcriptional-modulator-ifrd1-controls-pgc-1%C3%AE-expression-under-short-term-adrenergic-stimulation-in-brown-adipocytes
#2
Gyujin Park, Tetsuhiro Horie, Takashi Kanayama, Kazuya Fukasawa, Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Yukari Nakamura, Yukio Yoneda, Takeshi Takarada, Eiichi Hinoi
Sympathetic tone activates the function of classical brown adipocytes, which constitutively exist in the brown adipose tissue, and inducible brown adipocytes (so-called beige adipocytes), which sporadically reside within the white adipose tissue. Here we identified the transcriptional modulator interferon-related developmental regulator 1 (Ifrd1) as a negative regulator of thermogenic and mitochondrial gene expression in brown adipocytes. Ifrd1 expression was markedly induced by cold exposure and administration of CL-316243 (a β3 adrenergic agonist) in interscapular brown adipose and inguinal subcutaneous white adipose tissues, but not in epididymal visceral white adipose tissue, in vivo...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107754/hyperoside-attenuates-ova-induced-allergic-airway-inflammation-by-activating-nrf2
#3
Peng Ye, Xi-Liang Yang, Xing Chen, Cai Shi
Allergic airways disease (AAD) is one of the most common medical illnesses that is associated with an increased allergic airway inflammation. Hyperoside, an active compound isolated from Rhododendron brachycarpum G. Don, has been reported to have anti-inflammatory effect. The aim of this study was to analyze the protective effect of hyperoside on OVA-induced allergic airway inflammation in mice. In the present study, the mouse asthma model was induced by given OVA and hyperoside was administrated 1h before OVA challenge...
January 17, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28107750/effect-of-clinically-approved-hdac-inhibitors-on-plasmodium-leishmania-and-schistosoma-parasite-growth
#4
Ming Jang Chua, Megan S J Arnold, Weijun Xu, Julien Lancelot, Suzanne Lamotte, Gerald F Späth, Eric Prina, Raymond J Pierce, David P Fairlie, Tina S Skinner-Adams, Katherine T Andrews
Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study, four clinically approved anti-cancer drugs (Vorinostat, Belinostat, Panobinostat and Romidepsin) that target histone/lysine deacetylase enzymes were examined for in vitro activity against Plasmodium knowlesi, Schistosoma mansoni, Leishmania amazonensis and L...
December 23, 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28107707/uremia-modulates-the-phenotype-of-aortic-smooth-muscle-cells
#5
Marie Madsen, Annemarie Aarup, Sebastian Albinsson, Karsten Hartvigsen, Charlotte M Sørensen, Karolina Turczynska, Lars B Nielsen, Tanja Xenia Pedersen
BACKGROUND AND AIMS: Chronic kidney disease leads to uremia and markedly accelerates atherosclerosis. Phenotypic modulation of smooth muscle cells (SMCs) in the arterial media plays a key role in accelerating atherogenesis. The aim of this study was to investigate whether uremia per se modulates the phenotype of aortic SMCs in vivo. METHODS: Moderate uremia was induced by 5/6 nephrectomy in apolipoprotein E knockout (ApoE(-/-)) and wildtype C57Bl/6 mice. Plasma analysis, gene expression, histology, and myography were used to determine uremia-mediated changes in the arterial wall...
December 23, 2016: Atherosclerosis
https://www.readbyqxmd.com/read/28107697/egcg-a-tea-polyphenol-as-a-potential-mitigator-of-hematopoietic-radiation-injury-in-mice
#6
Mrinalini Tiwari, Bhakti Dixit, Suhel Parvez, Paban K Agrawala
Agents capable of providing protection, mitigation or therapy against radiation injuries have long been of interest of radiation biologists owing to the ever expanding application of radiation in our day to day life despite the well reported ill effects of exposure. The current study investigates radiomitigating potential of EGCG (epigallocatechin gallate), a tea polyphenol with known DNMT inhibitory property, in C57 Bl/6 mice model. Treatment with 0.1833mg/kg body weight EGCG, 1.5h post-irradiation to lethally whole body irradiated mice rendered 45% survival for 30days and also helped restoring the body weight of the animals...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28107678/nobiletin-and-its-colonic-metabolites-suppress-colitis-associated-colon-carcinogenesis-by-down-regulating-inos-inducing-antioxidative-enzymes-and-arresting-cell-cycle-progression
#7
Xian Wu, Mingyue Song, Zili Gao, Yue Sun, Minqi Wang, Fang Li, Jinkai Zheng, Hang Xiao
Nobiletin (NOB) is a major citrus polymethoxyflavone (PMF) with various beneficial biological activities. We reported previously that dietary NOB significantly inhibited colitis-associated colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice, and the chemopreventive effects were associated with NOB metabolites found in the mouse colonic tissues. In this study, to better understand the role of colonic metabolites of NOB, we determined the anti-inflammation and anticancer effects of a mixture of NOB and its major metabolites (NOB-Met) at the concentrations equivalent to those found in colonic tissues of NOB-fed mice...
January 11, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28107661/targeting-nf-kb-signaling-with-polymeric-hybrid-micelles-that-co-deliver-sirna-and-dexamethasone-for-arthritis-therapy
#8
Qin Wang, Hao Jiang, Yan Li, Wenfei Chen, Hanmei Li, Ke Peng, Zhirong Zhang, Xun Sun
The transcription factor NF-kB plays a pivotal role in the pathogenesis of rheumatoid arthritis. Here we attempt to slow arthritis progression by co-delivering the glucocorticoid dexamethasone (Dex) and small-interfering RNA targeting NF-kB p65 using our previously developed polymeric hybrid micelle system. These micelles contain two similar amphiphilic copolymers: polycaprolactone-polyethylenimine (PCL-PEI) and polycaprolactone-polyethyleneglycol (PCL-PEG). The hybrid micelles loaded with Dex and siRNA effectively inhibited NF-kB signaling in murine macrophages more efficiently than micelles containing either Dex or siRNA on their own...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28107636/visceral-white-adipose-tissue-following-chronic-intermittent-and-sustained-hypoxia-in-mice
#9
David Gozal, Alex Gileles-Hillel, Rene Cortese, Yan Li, Isaac Almendros, Zhuanhong Qiao, Ahamed A Khalyfa, Jorge Andrade, Abdelnaby Khalyfa
BACKGROUND: Angiogenesis, a process induced by hypoxia in visceral white adipose tissue (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of differing magnitude, suggesting different HIF-1α-related activity. METHODS: 8-week old male C57BL/6J mice (n=10-12/group) were exposed to either IH, SH,or room air (RA)...
January 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28107623/dna-advanced-glycation-end-products-dna-ages-are-elevated-in-urine-and-tissue-in-an-animal-model-of-type-2-diabetes
#10
Richard Jaramillo, Sarah C Shuck, Yin S Chan, Xueli Liu, Steven E Bates, Punnajit P Lim, Daniel Tamae, Sandrine Lacoste, Timothy R O'Connor, John Stephen Termini
More precise identification and treatment monitoring of prediabetic/diabetic individuals will require additional biomarkers to complement existing diagnostic tests. Candidates include hyperglycemia-induced adducts such as advanced glycation end products (AGEs) of proteins, lipids, and DNA. The potential for DNA-AGEs as diabetic biomarkers was examined in a longitudinal study using the Leprdb/db animal model of metabolic syndrome. The DNA-AGE, N2-(1-carboxyethyl)-2´-deoxyguanosine (CEdG) was quantified by mass spectrometry using isotope dilution from urine and tissue of hyperglycemic and normoglycemic mice...
January 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28107620/chemical-interaction-of-protein-cysteine-residues-with-reactive-metabolites-of-methyleugenol
#11
Yukun Feng, Hui Wang, Qian Wang, Wenlin Huang, Ying Peng, Jiang Zheng
Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME...
January 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28107610/tonsil-derived-mesenchymal-stem-cells-t-mscs-prevent-th17-mediated-autoimmune-response-via-regulation-of-the-programmed-death-1-programmed-death-ligand-1-pd-1-pd-l1-pathway
#12
Ji-Yon Kim, Minhwa Park, Yu-Hee Kim, Kyung-Ha Ryu, Kyung Ho Lee, Kyung-Ah Cho, So-Youn Woo
Our knowledge of the immunomodulatory role of mesenchymal stem cells (MSCs) in both the innate and adaptive immune systems has dramatically expanded, providing great promise for treating various autoimmune diseases. However, the contribution of MSCs to Th17 dominant immune disease, such as psoriasis and its underlying mechanism remains elusive. In this study, we demonstrated that human palatine tonsil-derived MSCs (T-MSCs) constitutively express both the membrane-bound and soluble forms of programmed death-ligand 1 (PD-L1), which enables T-MSCs to be distinguished from MSCs originating from other organs (i...
January 20, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28107584/targeting-of-tumor-growth-and-angiogenesis-underlies-the-enhanced-antitumor-activity-of-lenvatinib-in-combination-with-everolimus
#13
Masahiro Matsuki, Yusuke Adachi, Yoichi Ozawa, Takayuki Kimura, Taisuke Hoshi, Kiyoshi Okamoto, Osamu Tohyama, Kaoru Mitsuhashi, Atsumi Yamaguchi, Junji Matsui, Yasuhiro Funahashi
The combination of lenvatinib-a multiple receptor tyrosine kinase (RTK) inhibitor-plus everolimus-a mammalian target of rapamycin (mTOR) inhibitor-significantly improved clinical outcomes versus everolimus monotherapy in a phase 2 clinical study of metastatic renal cell carcinoma (RCC). Here, we investigated potential mechanisms underlying the antitumor activity of the combination treatment in preclinical RCC models. Lenvatinib plus everolimus showed greater antitumor activity than either monotherapy in 3 human RCC xenograft mouse models (A-498, Caki-1, and Caki-2)...
January 20, 2017: Cancer Science
https://www.readbyqxmd.com/read/28107550/enhanced-trpc-channel-mediated-ca-2-influx-in-the-cells-with-phospholipase-c-%C3%AE-1-overexpression-its-possible-role-in-coronary-artery-spasm
#14
Kazuo Murakami, Tomohiro Osanai, Makoto Tanaka, Kimitaka Nishizaki, Takahiko Kinjo, Tomohiro Tanno, Yuji Ishida, Akiko Suzuki, Tomohide Endo, Hirofumi Tomita, Ken Okumura
We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca(2+) influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries-smooth-muscle cells (CASMC). Intracellular free Ca(2+) concentration ([Ca(2+) ]i ) (nM) was measured by fura-2, and Ca(2+) influx was evaluated by the increase in [Ca(2+) ]i after addition of extracellular Ca(2+) . Acetylcholine (ACh) was used to induce Ca(2+) influx...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28107544/cutaneous-hpv8-and-mmupv1-e6-proteins-target-the-notch-and-tgf-%C3%AE-tumor-suppressors-to-inhibit-differentiation-and-sustain-keratinocyte-proliferation
#15
Jordan M Meyers, Aayushi Uberoi, Miranda Grace, Paul F Lambert, Karl Munger
Cutaneous beta-papillomaviruses are associated with non-melanoma skin cancers that arise in patients who suffer from a rare genetic disorder, Epidermodysplasia verruciformis (EV) or after immunosuppression following organ transplantation. Recent studies have shown that the E6 proteins of the cancer associated beta human papillomavirus (HPV) 5 and HPV8 inhibit NOTCH and TGF-β signaling. However, it is unclear whether disruption of these pathways may contribute to cutaneous HPV pathogenesis and carcinogenesis...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107543/quantification-of-pulmonary-fibrosis-in-a-bleomycin-mouse-model-using-automated-histological-image-analysis
#16
Jean-Claude Gilhodes, Yvon Julé, Sebastian Kreuz, Birgit Stierstorfer, Detlef Stiller, Lutz Wollin
Current literature on pulmonary fibrosis induced in animal models highlights the need of an accurate, reliable and reproducible histological quantitative analysis. One of the major limits of histological scoring concerns the fact that it is observer-dependent and consequently subject to variability, which may preclude comparative studies between different laboratories. To achieve a reliable and observer-independent quantification of lung fibrosis we developed an automated software histological image analysis performed from digital image of entire lung sections...
2017: PloS One
https://www.readbyqxmd.com/read/28107533/improvement-of-therapeutic-efficacy-of-oral-immunotherapy-in-combination-with-regulatory-t-cell-inducer-kakkonto-in-a-murine-food-allergy-model
#17
Yuka Nagata, Takeshi Yamamoto, Michie Hayashi, Shusaku Hayashi, Makoto Kadowaki
Oral immunotherapy (OIT) has been considered a promising approach for food allergies (FAs). However, the current OIT strategy is limited in terms of the long-term efficacy and safety. We have previously demonstrated that kakkonto, a traditional Japanese herbal medicine, suppresses the occurrence of allergic symptoms in a murine model of ovalbumin (OVA)-induced FA, which is attributed to the induction of the Foxp3+ CD4+ regulatory T cells. In this study, we established an OIT model using the FA mice with already established allergic symptoms and determined whether kakkonto could improve the efficacy of OIT...
2017: PloS One
https://www.readbyqxmd.com/read/28107529/complement-activation-and-stat4-expression-are-associated-with-early-inflammation-in-diabetic-wounds
#18
Kenji M Cunnion, Neel K Krishna, Haree K Pallera, Angela Pineros-Fernandez, Magdielis Gregory Rivera, Pamela S Hair, Brittany P Lassiter, Ryan Huyck, Mary A Clements, Antoinette F Hood, George T Rodeheaver, Patrick S Cottler, Jerry L Nadler, Anca D Dobrian
: Diabetic non-healing wounds are a major clinical problem. The mechanisms leading to poor wound healing in diabetes are multifactorial but unresolved inflammation may be a major contributing factor. The complement system (CS) is the most potent inflammatory cascade in humans and contributes to poor wound healing in animal models. Signal transducer and activator of transcription 4 (STAT4) is a transcription factor expressed in immune and adipose cells and contributes to upregulation of some inflammatory chemokines and cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28107527/effects-of-the-administration-of-25-oh-vitamin-d3-in-an-experimental-model-of-chronic-kidney-disease-in-animals-null-for-1-alpha-hydroxylase
#19
Noelia Torremadé, Milica Bozic, David Goltzman, Elvira Fernandez, José M Valdivielso
The final step in vitamin D activation is catalyzed by 1-alpha-hydroxylase (CYP27B1). Chronic kidney disease (CKD) is characterized by low levels of both 25(OH)D3 and 1,25(OH)2D3 provoking secondary hyperparathyroidism (2HPT). Therefore, treatments with active or native vitamin D compounds are common in CKD to restore 25(OH)D3 levels and also to decrease PTH. This study evaluates the dose of 25(OH)D3 that restores parathyroid hormone (PTH) and calcium levels in a model of CKD in CYP27B1-/- mice. Furthermore, we compare the safety and efficacy of the same dose in CYP27B1+/+ animals...
2017: PloS One
https://www.readbyqxmd.com/read/28107516/liver-amp-activated-protein-kinase-is-unnecessary-for-gluconeogenesis-but-protects-energy-state-during-nutrient-deprivation
#20
Clinton M Hasenour, D Emerson Ridley, Freyja D James, Curtis C Hughey, E Patrick Donahue, Benoit Viollet, Marc Foretz, Jamey D Young, David H Wasserman
AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes...
2017: PloS One
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