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https://www.readbyqxmd.com/read/29330881/cocaine-and-hiv-1-tat-disrupt-cholesterol-homeostasis-in-astrocytes-implications-for-hiv-associated-neurocognitive-disorders-in-cocaine-user-patients
#1
Bianca Cotto, Kalimuthusamy Natarajaseenivasan, Kimberly Ferrero, Leroy Wesley, Matthew Sayre, Dianne Langford
Cholesterol synthesis and clearance by astrocytes are tightly regulated to maintain constant levels within the brain. In this context, liver X receptors (LXRs) are the master regulators of cholesterol homeostasis in the central nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR activation leading to the transcription of target genes involved in cholesterol trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, and several ATP-binding cassette transporter proteins...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29324503/%C3%AE-asarone-alleviated-chronic-constriction-injury-induced-neuropathic-pain-through-inhibition-of-spinal-endoplasmic-reticulum-stress-in-an-liver-x-receptor-dependent-manner
#2
Yulong Gui, Aiyuan Li, Jie Zhang, Guan Li, Xia Ruan, Qulian Guo, Wangyuan Zou
BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent studies have shown a close relationship between endoplasmic reticulum (ER) stress and neuropathic pain. Here, we investigated the effect of α-asarone, an ER stress inhibitor, on chronic constriction injury (CCI)-induced neuropathic pain. METHODS: Two parts were included in this study. In part 1, rats were assigned to 7 groups: the sham group, the sham + α-asarone 20 mg/kg group, the CCI group, the CCI + vehicle group, the CCI + α-asarone 5 mg/kg group, the CCI + α-asarone 10 mg/kg group, and the CCI + α-asarone 20 mg/kg group...
January 9, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29323721/brain-derived-neurotrophic-factor-modulates-cholesterol-homeostasis-and-apolipoprotein-e-synthesis-in-human-cell-models-of-astrocytes-and-neurons
#3
Maria Stefania Spagnuolo, Aldo Donizetti, Lucia Iannotta, Vincenza Aliperti, Chiara Cupidi, Amalia Cecilia Bruni, Luisa Cigliano
In the central nervous system, cholesterol is critical to maintain membrane plasticity, cellular function, and synaptic integrity. In recent years, much attention was focused on the role of cholesterol in brain since a breakdown of cholesterol metabolism has been associated with different diseases. Brain-derived neurotrophic factor (BDNF) was previously reported to elicit cholesterol biosynthesis and promote the accumulation of presynaptic proteins in cholesterol-rich lipid rafts, but no data are available on its ability to modulate physiological mechanisms involved in cholesterol homeostasis...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29321595/microrna-7-mediates-cross-talk-between-metabolic-signaling-pathways-in-the-liver
#4
Ragunath Singaravelu, Curtis Quan, Megan H Powdrill, Tyler A Shaw, Prashanth Srinivasan, Rodney K Lyn, Rhea C Alonzi, Daniel M Jones, Roxana Filip, Rodney S Russell, John P Pezacki
MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29298812/25-hydroxycholesterol-activates-the-expression-of-cholesterol-25-hydroxylase-in-an-lxr-dependent-mechanism
#5
Ying Liu, Zhuo Wei, Xingzhe Ma, Xiaoxiao Yang, Yuanli Chen, Lei Sun, Chuanrui Ma, Qing R Miao, David P Hajjar, Jihong Han, Yajun Duan
Cholesterol 25-hydroxylase (CH25H) catalyzes the production of 25-hydroxycholesterol (25-HC), an oxysterol which can play an important role in different biological processes. However, the mechanisms regulating CH25H expression have not been fully elucidated. In this study, we determined that CH25H is highly expressed in mouse liver and peritoneal macrophages. We identified several liver X receptor (LXR) response elements (LXREs) in the human CH25H promoter. In HepG2 cells, activation of LXR by 25-HC or other oxysterols and synthetic ligands [T0901317 (T317) and GW3965] induced CH25H protein expression which was associated with increased CH25H mRNA expression...
January 3, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29298513/andrographolide-inhibits-oxidized-ldl-induced-cholesterol-accumulation-and-foam-cell-formation-in-macrophages
#6
Hung-Chih Lin, Chong-Kuei Lii, Hui-Chun Chen, Ai-Hsuan Lin, Ya-Chen Yang, Haw-Wen Chen
oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells...
January 3, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29297151/liver-x-receptor-agonist-gw3965-regulates-synaptic-function-upon-amyloid-beta-exposure-in-hippocampal-neurons
#7
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29286311/comparative-proteomics-analysis-of-urine-reveals-down-regulation-of-acute-phase-response-signaling-and-lxr-rxr-activation-pathways-in-prostate-cancer
#8
Katarina Davalieva, Sanja Kiprijanovska, Ivana Maleva Kostovska, Sotir Stavridis, Oliver Stankov, Selim Komina, Gordana Petrusevska, Momir Polenakovic
Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively...
December 29, 2017: Proteomes
https://www.readbyqxmd.com/read/29273438/curcuma-comosa-reduces-visceral-adipose-tissue-and-improves-dyslipidemia-in-ovariectomized-rats
#9
Nareerat Sutjarit, Jetjamnong Sueajai, Nittaya Boonmuen, Nilubon Sornkaew, Apichart Suksamrarn, Patoomratana Tuchinda, Weiming Zhu, Jittima Weerachayaphorn, Pawinee Piyachaturawat
ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma comosa Roxb. (C. comosa) or Wan chak motluk Zingiberaceae family, is widely used in Thai traditional medicine for treatment of gynecological problems as well as relief of postmenopausal symptoms. Since C. comosa contains phytoestrogen and causes lipid lowering effect by an unknown mechanism, we investigated its effect on adiposity and lipid metabolism in estrogen-deprived rats. MATERIALS AND METHODS: Adult female rats were ovariectomized (OVX) and received daily doses of either a phytoestrogen from C...
December 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29250170/liver-x-receptors-as-potential-targets-for-cancer-therapeutics
#10
Xiaoli Ju, Pan Huang, Miao Chen, Qiang Wang
Liver X receptors (LXRs) are important members of the nuclear receptor family that were originally determined to function in cholesterol transport and the regulation of immune responses. Synthetic LXR ligands have been developed to treat various diseases including diabetes, Alzheimer's disease and atherosclerosis. Previous studies have suggested that LXRs are also involved in numerous types of cancer and are therefore potential targets for cancer therapeutics. The present review summarizes LXR ligands and their mechanisms of action, the effects of LXRs in different types of cancer and their potential applications in clinical treatment...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29231996/molecular-mechanisms-of-tributyltin-induced-alterations-in-cholesterol-homeostasis-and-steroidogenesis-in-hamster-testis-in-vivo-and-in-vitro-studies
#11
V Kanimozhi, K Palanivel, M A Akbarsha, B Kadalmani
Tributyltins (TBT) are ubiquitous and persistent environmental contaminants that disturb normal endocrine function including gonadal function in humans and marine organisms. TBT was administered through oral route to male Syrian hamsters at daily doses of 50, 100 and 150 ppm/kg for 65 days. Changes in testis morphology, immunohistochemistry of iNOS, 3β-HSD and 17β-HSD, cholesterol transport receptor, nuclear receptors, and transcription factors were analyzed. TBT treatment affected each of these parameters to significant levels in a dose-dependent manner compared to vehicle treated control...
December 12, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29230000/snail-mediates-crosstalk-between-tgf%C3%AE-and-lxr%C3%AE-in-hepatocellular-carcinoma
#12
Claudia Bellomo, Laia Caja, Isabel Fabregat, Wolfgang Mikulits, Dimitris Kardassis, Carl-Henrik Heldin, Aristidis Moustakas
Understanding the complexity of changes in differentiation and cell survival in hepatocellular carcinoma (HCC) is essential for the design of new diagnostic tools and therapeutic modalities. In this context, we have analyzed the crosstalk between transforming growth factor β (TGFβ) and liver X receptor α (LXRα) pathways. TGFβ is known to promote cytostatic and pro-apoptotic responses in HCC, and to facilitate mesenchymal differentiation. We here demonstrate that stimulation of the nuclear LXRα receptor system by physiological and clinically useful agonists controls the HCC response to TGFβ...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29220720/induction-of-thymic-stromal-lymphopoietin-by-a-steroid-alkaloid-derivative-in-mouse-keratinocytes
#13
Yan Weng, Natsumi Mizuno, Jiangxu Dong, Ryosuke Segawa, Takayuki Yonezawa, Byung Yoon Cha, Je-Tae Woo, Takahiro Moriya, Masahiro Hiratsuka, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) plays critical roles in inducing and exacerbating allergic diseases. Chemical compounds that induce TSLP production can enhance sensitization to antigens and exacerbate allergic inflammation. Hence, identifying such chemicals will be important to prevent an increase in allergic diseases. In the present study, we found, for the first time, that a steroid alkaloid derivative, code no. 02F04, concentration and time dependently induced mRNA expression and production of TSLP in a mouse keratinocyte cell line, PAM212...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29212953/the-e3-ubiquitin-ligase-siah1-regulates-adrenal-gland-organization-and-aldosterone-secretion
#14
Marzia Scortegagna, Annabel Berthon, Nikolaos Settas, Andreas Giannakou, Guillermina Garcia, Jian-Liang Li, Brian James, Robert C Liddington, José G Vilches-Moure, Constantine A Stratakis, Ze'ev A Ronai
Primary and secondary hypertension are major risk factors for cardiovascular disease, the leading cause of death worldwide. Elevated secretion of aldosterone resulting from primary aldosteronism (PA) is a key driver of secondary hypertension. Here, we report an unexpected role for the ubiquitin ligase Siah1 in adrenal gland development and PA. Siah1a-/- mice exhibit altered adrenal gland morphology, as reflected by a diminished X-zone, enlarged medulla, and dysregulated zonation of the glomerulosa as well as increased aldosterone levels and aldosterone target gene expression and reduced plasma potassium levels...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29208033/evaluating-the-oxysterol-combination-of-22-s-hydroxycholesterol-and-20-s-hydroxycholesterol-in-periodontal-regeneration-using-periodontal-ligament-stem-cells-and-alveolar-bone-healing-models
#15
Jin-Sun Lee, EunJi Kim, Seonggu Han, Kyung Lhi Kang, Jung Sun Heo
BACKGROUND: Oxysterols, oxygenated by-products of cholesterol biosynthesis, play roles in various physiological and pathological systems. However, the effects of oxysterols on periodontal regeneration are unknown. This study investigated the effects of the specific oxysterol combination of 22(S)-hydroxycholesterol and 20(S)-hydroxycholesterol (SS) on the regeneration of periodontal tissues using in-vitro periodontal ligament stem cells (PDLSCs) and in-vivo models of alveolar bone defect...
December 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29207817/immunohistochemical-expression-of-cyclo-oxygenase-2-and-liver-x-receptor-%C3%AE-in-acne-vulgaris
#16
Ola Ahmed Bakry, Shawky Mahmoud El Farargy, Noha Nour El Din El Kady, Hend Farag Abu Dawy
Introduction: Acne Vulgaris (AV) is a common inflammatory disease of pilosebaceous units. Liver X Receptor-α (LXR-α) is a ligand activated transcription factor. It controls transcription of genes involved in lipid and fatty acid synthesis. Cyclo-oxygenase 2 (COX2) is a rate limiting enzyme in prostaglandin synthesis. It plays important role in inflammation. Aim: To evaluate the immunohistochemical expression of LXR-α and COX2 in acne vulgaris skin biopsies to explore their possible pathogenic role in this disease...
September 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/29207101/diosgenin-prevents-high-fat-diet-induced-rat-non-alcoholic-fatty-liver-disease-through-the-ampk-and-lxr-signaling-pathways
#17
Silu Cheng, Shufang Liang, Qun Liu, Zhengting Deng, Yuanhui Zhang, Juan Du, Ya'ni Zhang, Shu Li, Binbin Cheng, Changquan Ling
Non-alcoholic fatty liver disease (NAFLD) is a major public health concern worldwide. The aim of the present study was to observe the effect of diosgenin on NAFLD and investigate the underlying mechanisms. Diosgenin treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells. Diosgenin significantly inhibited high glucose (HG)-induced triglyceride (TG) accumulation and sterol regulatory element‑binding protein-1c (SREBP-1c) mRNA increase in HepG2 cells, which were partially abolished by the AMPK inhibitor compound C...
November 28, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29199269/dendrogenin-a-drives-lxr-to-trigger-lethal-autophagy-in-cancers
#18
Gregory Segala, Marion David, Philippe de Medina, Mathias C Poirot, Nizar Serhan, François Vergez, Aurelie Mougel, Estelle Saland, Kevin Carayon, Julie Leignadier, Nicolas Caron, Maud Voisin, Julia Cherier, Laetitia Ligat, Frederic Lopez, Emmanuel Noguer, Arnaud Rives, Bruno Payré, Talal Al Saati, Antonin Lamaziere, Gaëtan Despres, Jean-Marc Lobaccaro, Silvere Baron, Cecile Demur, Fabienne de Toni, Clément Larrue, Helena Boutzen, Fabienne Thomas, Jean-Emmanuel Sarry, Marie Tosolini, Didier Picard, Michel Record, Christian Récher, Marc Poirot, Sandrine Silvente-Poirot
Dendrogenin A (DDA) is a newly discovered cholesterol metabolite with tumor suppressor properties. Here, we explored its efficacy and mechanism of cell death in melanoma and acute myeloid leukemia (AML). We found that DDA induced lethal autophagy in vitro and in vivo, including primary AML patient samples, independently of melanoma Braf status or AML molecular and cytogenetic classifications. DDA is a partial agonist on liver-X-receptor (LXR) increasing Nur77, Nor1, and LC3 expression leading to autolysosome formation...
December 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/29196136/discovery-of-molecular-mechanism-of-a-clinical-herbal-formula-upregulating-serum-hdl-c-levels-in-treatment-of-metabolic-syndrome-by-in-vivo-and-computational-studies
#19
Meimei Chen, Fafu Yang, Jie Kang, Huijuan Gan, Xinmei Lai, Yuxing Gao
Decreased HDL cholesterol (HDL-c) is considered as an independent risk factor of cardiovascular disease in metabolic syndrome (Mets). Wendan decoction (WDD), a famous clinical traditional Chinese medicine formula in Mets in China, which can obviously up-regulate serum HDL-c levels in Mets. However, till now, the molecular mechanism of up-regulation still remained unclear. In this study, an integrated approach that combined serum ABCA1 in vivo assay, QSAR modeling and molecular docking was developed to explore the molecular mechanism and chemical substance basis of WDD upregulating HDL-c levels...
November 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29181837/expression-of-liver-x-receptors-in-normal-and-refractory-carcinoma-tissues-of-the-human-lung-and-pancreas
#20
Korehito Kashiwagi, Mai Yanagida, Daiki Matsui, Mizuko Tanaka, Kotaro Sugimoto, Honglei Chen, Naoki Ichikawa-Tomikawa, Shigeru Marubashi, Hiroyuki Suzuki, Hideki Chiba
Liver X receptors (LXRs) participate not only in maintaining cholesterol homeostasis but also in controlling cellular growth in many types of normal and tumor cells. We previously reported that LXRα was aberrantly expressed in human oral squamous cell carcinoma (HOSCC) tissues and cell lines, and that LXR stimulation led to significant reduction of proliferation of HOSCC cells via accelerating cholesterol efflux. Since LXRs and downstream proteins involved in cholesterol metabolism could be also applied as therapeutic targets in small cell lung carcinoma (SCLC) and pancreatic ductal adenocarcinoma (PDAC), we herein analyzed the distribution of LXR proteins in these refractory cancers as well as in normal human lung and pancreatic tissues...
November 28, 2017: Histology and Histopathology
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