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https://www.readbyqxmd.com/read/29025594/gene-expression-profiling-pathway-analysis-and-subtype-classification-reveal-molecular-heterogeneity-in-hepatocellular-carcinoma-and-suggest-subtype-specific-therapeutic-targets
#1
Rahul Agarwal, Jitendra Narayan, Amitava Bhattacharyya, Mayank Saraswat, Anil Kumar Tomar
A very low 5-year survival rate among hepatocellular carcinoma (HCC) patients is mainly due to lack of early stage diagnosis, distant metastasis and high risk of postoperative recurrence. Hence ascertaining novel biomarkers for early diagnosis and patient specific therapeutics is crucial and urgent. Here, we have performed a comprehensive analysis of the expression data of 423 HCC patients (373 tumors and 50 controls) downloaded from The Cancer Genome Atlas (TCGA) followed by pathway enrichment by gene ontology annotations, subtype classification and overall survival analysis...
October 2017: Cancer Genetics
https://www.readbyqxmd.com/read/28992339/stat3-inhibition-attenuates-the-progressive-phenotypes-of-alport-syndrome-mouse-model
#2
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Misato Kamura, Haruka Kojima, Ryosuke Fukuda, Keishi Motomura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Toru Takeo, Naomi Nakagata, Tsuyoshi Shuto, Hirofumi Kai
Background: Alport syndrome (AS) is a hereditary, progressive nephritis caused by mutation of type IV collagen. Previous studies have shown that activation of signal transducer and activator of transcription 3 (STAT3) exacerbates other renal diseases, but whether STAT3 activation exacerbates AS pathology is still unknown. Here we aim to investigate the involvement of STAT3 in the progression of AS. Method: Phosphorylated STAT3 expression was assessed by immunoblotting analysis of kidneys and glomeruli of an AS mouse model ( Col4a5 G5X mutant)...
August 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28973641/l-carnitine-via-ppar%C3%AE-and-sirt1-dependent-mechanisms-attenuates-epithelial-mesenchymal-transition-and-renal-fibrosis-caused-by-perfluorooctanesulfonate
#3
Hsiu-Chu Chou, Li-Li Wen, Chih-Cheng Chang, Chien-Yu Lin, Lu Jin, Shu-Hui Juan
We have previously reported that perfluorooctanesulfonate (PFOS) causes cell apoptosis in renal tubular epithelial cells (RTCs). Here, we extend our findings and provide evidence of epithelial-mesenchymal transition (EMT)-associated renal fibrosis caused by PFOS and the protection by L-carnitine. Our results demonstrate that PFOS increased the expression of EMT and renal injury biomarkers (e.g., N-cadherin, vimentin, Snail, Kim1, and Lcn2). Additionally, PFOS caused EMT induction through Sirt1-mediated PPARγ deacetylation and inactivation...
August 30, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28938414/sex-and-tissue-specific-role-of-estrogen-sulfotransferase-in-energy-homeostasis-and-insulin-sensitivity
#4
Wojciech G Garbacz, Mengxi Jiang, Meishu Xu, Jun Yamauchi, H Henry Dong, Wen Xie
Estrogen Sulfotransferase (EST) catalyzes the sulfoconjugation and deactivation of estrogens. Previously we showed that loss of Est in male ob/ob mice, but not in female ob/ob mice, exacerbated the diabetic phenotype, but the underlying mechanism was unclear. Here we show that transgenic reconstitution of Est in the adipose tissue, but not in the liver, attenuated diabetic phenotype in Est deficient ob/ob mice (obe). Mechanistically, adipose reconstitution of Est in obe mice (oae) resulted in reduced local and systemic inflammation, improved insulin sensitivity, and increased energy expenditure...
September 5, 2017: Endocrinology
https://www.readbyqxmd.com/read/28914974/mucocutaneous-inflammation-in-the-ikaros-family-zinc-finger-1-ikzf1-keratin-5-specifc-transgenic-mice
#5
Mayumi Ueta, Junji Hamuro, Hiromi Nishigaki, Naomi Nakamura, Katsuhiko Shinomiya, Katsura Mizushima, Yuki Hitomi, Risa Tamagawa-Mineoka, Norihiko Yokoi, Yuji Naito, Katsushi Tokunaga, Norito Katoh, Chie Sotozono, Shigeru Kinoshita
BACKGROUND: Our genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). Few studies examined biological and pathological functions of IKZF1 in mucosal immunity. We hypothesized that IKZF1 contributes to the mucocutaneous inflammation. METHODS: Human skin and conjunctival tissues were obtained for immunohistological studies. Primary human conjunctival epithelial cells (PHCjECs) and adult human epidermal keratinocytes (HEKa) also used for gene expression analysis...
September 15, 2017: Allergy
https://www.readbyqxmd.com/read/28877044/novel-insights-into-microbiome-in-colitis-and-colorectal-cancer
#6
Ye Yang, Christian Jobin
PURPOSE OF REVIEW: Microbiota is a major player in the pathogenesis of inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Here, we summarize the key advances achieved in the past 18 months (ending June 2017) toward a better understanding of the role of microbiota in colitis and CRC development. RECENT FINDINGS: Accumulating evidence shows the essential role of intestinal barrier function (e.g. mucus, IgA, LCN2, LYPD8) in protecting against bacteria-induced inflammation and tumor development...
November 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28873450/bromide-supplementation-exacerbated-the-renal-dysfunction-injury-and-fibrosis-in-a-mouse-model-of-alport-syndrome
#7
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Haruka Kojima, Misato Kamura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Tsuyoshi Shuto, Hirofumi Kai
A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28859238/lipocalin-2-negatively-regulates-cell-proliferation-and-emt-through-changing-metabolic-gene-expression-in-colorectal-cancer
#8
Se-Lim Kim, Soo Teik Lee, In Suk Min, Young Ran Park, Ju Hyung Lee, Dae-Ghon Kim, Sang-Wook Kim
Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of this study was to investigate whether LCN2 is associated with proliferation and the epithelial-mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. LCN2 was preferentially expressed in CRC cells compared to normal tissues...
August 31, 2017: Cancer Science
https://www.readbyqxmd.com/read/28828208/protein-microarray-analysis-identifies-key-cytokines-associated-with-malignant-middle-cerebral-artery-infarction
#9
Zhonghe Zhou, Jinghua Zhang, Xiaoqiu Li, Cheng Xia, Yaling Han, Huisheng Chen
INTRODUCTION: We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction (MMI) and elucidate their underlying regulatory mechanisms. METHODS: We first developed a cytokine profile by Quantibody(®) Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non-acute cerebral infarction (NACI). The differentially expressed cytokines were then identified in patients with MMI using two-tailed Student's t-test and Fisher's Exact Test compared with patients with NACI...
August 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28804221/s1p-provokes-tumor-lymphangiogenesis-via-macrophage-derived-mediators-such-as-il-1%C3%AE-or-lipocalin-2
#10
REVIEW
Shahzad N Syed, Michaela Jung, Andreas Weigert, Bernhard Brüne
A pleiotropic signaling lipid, sphingosine-1-phosphate (S1P), has been implicated in various pathophysiological processes supporting tumor growth and metastasis. However, there are only a few descriptive studies suggesting a role of S1P in tumor lymphangiogenesis, which is critical for tumor growth and dissemination. Corroborating own data, the literature suggests that apoptotic tumor cell-derived S1P alters the phenotype of tumor-associated macrophages (TAMs) to gain protumor functions. However, mechanistically, the role of TAM-induced lymphangiogenesis has only been poorly described, mostly linked to the production of lymphangiogenic factors such as vascular endothelial growth factor C (VEGF-C) and VEGF-D, or transdifferentiation into lymphatic endothelial cells...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28791009/preconditioning-with-lipopolysaccharide-or-lipoteichoic-acid-protects-against-staphylococcus-aureus-mammary-infection-in-mice
#11
Koen Breyne, Jonas Steenbrugge, Kristel Demeyere, Tom Vanden Berghe, Evelyne Meyer
Staphylococcus aureus is one of the most causative agents of mastitis and is associated with chronic udder infections. The persistency of the pathogen is believed to be the result of an insufficient triggering of local inflammatory signaling. In this study, the preclinical mastitis model was used, aiming to evaluate if lipopolysaccharide (LPS) or lipoteichoic acid (LTA) preconditioning could aid the host in more effectively clearing or at least limiting a subsequent S. aureus infection. A prototypic Gram-negative virulence factor, i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28771045/expression-patterns-and-changes-of-the-lcn2-gene-in-the-testes-of-induced-cryptorchidism-and-busulfan-treated-mice
#12
Zhenlong Kang, Na Qiao, Zhigang Tan, Zhaoxin Tang, Ying Li
Lipocalin-2 (LCN2) was known to play various roles in different type cells; however, little was known about the effect of LCN2 in male fertility. In this study, we aimed to explore the expression pattern of LCN2 with increasing age in mice, and to obtain insight into the role of LCN2 in mice testes by induced cryptorchidism and busulfan-treated infertility. In situ hybridization showed that LCN2 was localized primarily in Leydig cells, but was absent in Sertoli and germ cells. Its expression in testes exhibited an age-related increase from day 1 to 8 months, then reduced by the twelth month...
August 3, 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28736440/repin1-deficiency-in-adipose-tissue-improves-whole-body-insulin-sensitivity-and-lipid-metabolism
#13
N Hesselbarth, A Kunath, M Kern, M Gericke, N Mejhert, M Rydén, M Stumvoll, M Blüher, N Klöting
BACKGROUND/OBJECTIVES: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo. SUBJECTS/METHODS: We have inactivated the Repin1 gene in adipose tissue (iARep(-/-)) at an age of four weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice...
July 24, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28725667/data-on-lipocalin-2-and-phosphatidylinositol-3-kinase-signaling-in-a-methionine-and-choline-deficient-model-of-non-alcoholic-steatohepatitis
#14
Anastasia Asimakopoulou, Erawan Borkham-Kamphorst, Eddy Van de Leur, Ralf Weiskirchen
The data presented in this brief report support the research article "Altered mitochondrial and peroxisomal integrity in lipocalin-2-deficient mice with hepatic steatosis" [1, doi: 10.1016/j.bbadis.2017.04.006]. We tested whether the absence of Lipocalin-2 (LCN2) could dysregulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K-PKB) pathway and hepatic homeostasis in Non-Alcoholic-Steatohepatitis (NASH). The article highlights the role of LCN2 in hepatic homeostasis.
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#15
Kefeng Yang, Christopher Adin, Qiwen Shen, Ly James Lee, Lianbo Yu, Paolo Fadda, Arpad Samogyi, Kathleen Ham, Lu Xu, Chen Gilor, Ouliana Ziouzenkova
BACKGROUND: Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes...
September 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28692472/quantification-of-immune-dysregulation-by-next-generation-polymerase-chain-reaction-to-improve-sepsis-diagnosis-in-surgical-patients
#16
Raquel Almansa, Alicia Ortega, Ana Ávila-Alonso, Maria Heredia-Rodríguez, Silvia Martín, Diana Benavides, Marta Martín-Fernandez, Lucia Rico, César Aldecoa, Jesús Rico, Iñigo López de Cenarruzabeitia, Juan Beltrán de Heredia, Esther Gomez-Sanchez, Marta Aragón, Cristina Andrés, Dolores Calvo, David Andaluz-Ojeda, Pilar Liu, Francisco Blanco-Antona, Lydia Blanco, Jose Ignacio Gómez-Herreras, Eduardo Tamayo, Jesus F Bermejo-Martin
OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis...
July 7, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28662101/specific-gene-expression-signatures-induced-by-the-multiple-oncogenic-alterations-that-occur-within-the-pten-pi3k-akt-pathway-in-lung-cancer
#17
Carmela De Marco, Carmelo Laudanna, Nicola Rinaldo, Duarte Mendes Oliveira, Maria Ravo, Alessandro Weisz, Michele Ceccarelli, Elvira Caira, Antonia Rizzuto, Pietro Zoppoli, Donatella Malanga, Giuseppe Viglietto
Hyperactivation of the phosphatydil-inositol-3' phosphate kinase (PI3K)/AKT pathway is observed in most NSCLCs, promoting proliferation, migration, invasion and resistance to therapy. AKT can be activated through several mechanisms that include loss of the negative regulator PTEN, activating mutations of the catalytic subunit of PI3K (PIK3CA) and/or mutations of AKT1 itself. However, number and identity of downstream targets of activated PI3K/AKT pathway are poorly defined. To identify the genes that are targets of constitutive PI3K/AKT signalling in lung cancer cells, we performed a comparative transcriptomic analysis of human lung epithelial cells (BEAS-2B) expressing active mutant AKT1 (AKT1-E17K), active mutant PIK3CA (PIK3CA-E545K) or that are silenced for PTEN...
2017: PloS One
https://www.readbyqxmd.com/read/28636560/lipocalin-2-regulates-intestine-bacterial-survival-by-interplaying-with-siderophore-in-a-weaned-piglet-model-of-escherichia-coli-infection
#18
Bing-Xiu Guo, Qian-Qian Wang, Jia-Hui Li, Zhen-Shun Gan, Xiao-Feng Zhang, Yi-Zhen Wang, Hua-Hua Du
Iron is an essential nutrient that facilitates cell proliferation and growth, which plays a pivotal role in modulating the battle for survival between mammalian hosts and their pathogens. Pathogenic bacteria secrete siderophores to acquire iron from the host. However, lipocalin 2 (Lcn2), a siderophore-binding antimicrobial protein, binds to siderophores to prevent bacterial uptake of iron, which is critical for the control of systemic infection with Escherichia coli (E. coli). But few studies focus on the anti-infective response of Lcn2 in the intestines by inhibiting bacterial proliferation based on microbial iron metabolism...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28628361/lipocalin-2-an-emerging-player-in-iron-homeostasis-and-inflammation
#19
REVIEW
Xia Xiao, Beng San Yeoh, Matam Vijay-Kumar
Lipocalin 2 (Lcn2), an innate immune protein, has emerged as a critical iron regulatory protein during physiological and inflammatory conditions. As a bacteriostatic factor, Lcn2 obstructs the siderophore iron-acquiring strategy of bacteria and thus inhibits bacterial growth. As part of host nutritional immunity, Lcn2 facilitates systemic, cellular, and mucosal hypoferremia during inflammation, in addition to stabilizing the siderophore-bound labile iron pool. In this review, we summarize recent advances in understanding the interaction between Lcn2 and iron, and its effects in various inflammatory diseases...
August 21, 2017: Annual Review of Nutrition
https://www.readbyqxmd.com/read/28615213/experimental-and-human-evidence-for-lipocalin-2-neutrophil-gelatinase-associated-lipocalin-ngal-in-the-development-of-cardiac-hypertrophy-and-heart-failure
#20
Francine Z Marques, Priscilla R Prestes, Sean G Byars, Scott C Ritchie, Peter Würtz, Sheila K Patel, Scott A Booth, Indrajeetsinh Rana, Yosuke Minoda, Stuart P Berzins, Claire L Curl, James R Bell, Bryan Wai, Piyush M Srivastava, Antti J Kangas, Pasi Soininen, Saku Ruohonen, Mika Kähönen, Terho Lehtimäki, Emma Raitoharju, Aki Havulinna, Markus Perola, Olli Raitakari, Veikko Salomaa, Mika Ala-Korpela, Johannes Kettunen, Maree McGlynn, Jason Kelly, Mary E Wlodek, Paul A Lewandowski, Lea M Delbridge, Louise M Burrell, Michael Inouye, Stephen B Harrap, Fadi J Charchar
BACKGROUND: Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants...
June 14, 2017: Journal of the American Heart Association
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