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https://www.readbyqxmd.com/read/28914813/lactoferrin-a-natural-glycoprotein-involved-in-iron-and-inflammatory-homeostasis
#1
REVIEW
Luigi Rosa, Antimo Cutone, Maria Stefania Lepanto, Rosalba Paesano, Piera Valenti
Human lactoferrin (hLf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and by neutrophils, is a key element of host defenses. HLf and bovine Lf (bLf), possessing high sequence homology and identical functions, inhibit bacterial growth and biofilm dependently from iron binding ability while, independently, bacterial adhesion to and the entry into cells. In infected/inflamed host cells, bLf exerts an anti-inflammatory activity against interleukin-6 (IL-6), thus up-regulating ferroportin (Fpn) and transferrin receptor 1 (TfR1) and down-regulating ferritin (Ftn), pivotal actors of iron and inflammatory homeostasis (IIH)...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28878310/large-scale-production-of-recombinant-human-lactoferrin-from-high-expression-marker-free-transgenic-cloned-cows
#2
Ming Wang, Zhaolin Sun, Tian Yu, Fangrong Ding, Ling Li, Xi Wang, Mingbo Fu, Haiping Wang, Jinming Huang, Ning Li, Yunping Dai
Human lactoferrin (hLF) is a valuable protein for pharmaceutical products and functional foods, and worldwide demand for this protein has steadily increased. However, large-scale recombinant human lactoferrin (rhLF) production using current animal bioreactor techniques is limited by the low expression of foreign proteins, the use of antibiotic resistance genes and the down-regulation of endogenous milk proteins. Here, we generated a herd of marker-free, hLF bacterial artificial chromosome (BAC) transgenic cloned cows, as confirmed by Polymerase chain reaction, Southern blot and Western blot analyses...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877257/rosmarinic-acid-potentiates-carnosic-acid-induced-apoptosis-in-lung-fibroblasts
#3
Sana Bahri, Frédérique Mies, Ridha Ben Ali, Mona Mlika, Saloua Jameleddine, Kathleen Mc Entee, Vadim Shlyonsky
Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA) and rosmarinic acid (RA) was reported to cure bleomycin-(BLM)-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF) viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11...
2017: PloS One
https://www.readbyqxmd.com/read/28860144/ipf-lung-fibroblasts-have-a-senescent-phenotype
#4
Diana Alvarez, Nayra Cardenes, Jacobo Sellares, Marta Bueno, Catherine Corey, Vidya Sagar Hanumanthu, Yating Peng, Hannah D'Cuhna, John Sembrat, Mehdi Nouraie, Swaroop Shanker, Chandler Caufield, Sruti Shiva, Mary Armanios, Ana L Mora, Mauricio Rojas
The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLF) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLF isolated from IPF lungs compared to age-matched controls. We investigated several hallmarks of aging in hLF from IPF patients and age-matched controls...
August 31, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28853250/-rs-1-enhanced-the-efficiency-of-crispr-cas9-mediated-knock-in-of-human-lactoferrin
#5
Wenjun Zhou, Rihong Guo, Mingtian Deng, Feng Wang, Yanli Zhang
This study aims to knock out the goat β-lactoglobulin (BLG) gene using CRISPR-Cas9 system and knock in human lactoferrin (hLF) at the BLG locus, and further study the effect of RAD51 stimulatory compound (RS-1) on homologous recombination efficiency. First, we designed an sgRNA targeting the first exon of goat BLG gene and constructed a co-expression vector pCas9-sgBLG. This sgRNA vector was then transfected into goat ear fibroblasts (GEFs), and the target region was examined by T7EN1 assay and sequencing...
August 25, 2017: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/28816009/protective-effect-of-atazanavir-sulfate-against-pulmonary-fibrosis-in-vivo-and-in-vitro
#6
Shina Song, Yunxia Ji, Guanghua Zhang, Xue Zhang, Bin Li, Defang Li, Wanglin Jiang
Atazanavir sulfate, an antiretroviral protease inhibitor, has been used to treat HIV/AIDS, but its ability to serve as an anti-pulmonary fibrosis (PF) agent remains unknown. In this study, the effects of atazanavir sulfate on various aspects of PF were examined and CoCl2 was used to induce the hypoxia-mimicking condition in vitro, including epithelial-mesenchymal transition (EMT) in A549 cells, endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells (HPMECs), proliferation in human lung fibroblasts (HLF-1) and potential protective effects in human type I alveolar epithelial cells (AT I)...
August 16, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28810065/olodaterol-shows-anti-fibrotic-efficacy-in-in-vitro-and-in-vivo-models-of-pulmonary-fibrosis
#7
Franziska Elena Herrmann, Lutz Wollin, Johannes Wirth, Florian Gantner, Bärbel Lämmle, Eva Wex
BACKGROUND AND PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a fatal respiratory disease characterized by excessive fibroblast activation ultimately leading to scarring of the lungs. Although, the activation of β2 -adrenergic receptors (β2 -AR) has been shown to inhibit pro-fibrotic events primarily in cell lines, the role of β2 -AR agonism has not yet been fully characterized. The aim of our study was to explore the anti-fibrotic activity of the long-acting β2 -AR-agonist olodaterol in primary human lung fibroblasts, and in murine models of pulmonary fibrosis...
August 15, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28763236/hinge-deficient-igg1-fc-fusion-application-to-human-lactoferrin
#8
Yuki Shiga, Daisuke Murata, Akinori Sugimoto, Yuta Oshima, Minoru Tada, Akiko Ishii-Watabe, Kenichiro Imai, Kentaro Tomii, Takashi Takeuchi, Shinji Kagaya, Atsushi Sato
Fusion of therapeutic proteins with the antibody Fc domain is a strategy widely applied to increase protein half-life in plasma. In our previous study, we generated a recombinant human lactoferrin (hLF)-immunoglobulin G1 Fc fusion protein (hLF-hinge-CH2-CH3) with improved stability, biological activity, and pharmacokinetics ( Shiga , Y. et al. Eur J Pharm Sci. , 2015 , 67 , 136 - -143 ). However, the Fc domain in fusion proteins can potentially induce antibody-dependent and complement-dependent cytotoxicity and serious side effects...
August 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28754776/the-hlf-il-6-stat3-feedforward-circuit-drives-hepatic-stellate-cell-activation-to-promote-liver-fibrosis
#9
Dai-Min Xiang, Wen Sun, Bei-Fang Ning, Teng-Fei Zhou, Xiao-Feng Li, Wei Zhong, Zhuo Cheng, Ming-Yang Xia, Xue Wang, Xing Deng, Wei Wang, Heng-Yu Li, Xiu-Liang Cui, Shi-Chao Li, Bin Wu, Wei-Fen Xie, Hong-Yang Wang, Jin Ding
BACKGROUND AND AIMS: Liver fibrosis is a wound-healing response that disrupts the liver architecture and function by replacing functional parenchyma with scar tissue. Recent progress has advanced our knowledge of this scarring process, but the detailed mechanism of liver fibrosis is far from clear. METHODS: The fibrotic specimens of patients and HLF (hepatic leukemia factor)(PB/PB) mice were used to assess the expression and role of HLF in liver fibrosis. Primary murine hepatic stellate cells (HSCs) and human HSC line Lx2 were used to investigate the impact of HLF on HSC activation and the underlying mechanism...
July 28, 2017: Gut
https://www.readbyqxmd.com/read/28728518/successful-preemptive-donor-lymphocyte-infusions-from-a-haploidentical-donor-in-a-boy-with-e2a-hlf-positive-all
#10
Maiko Hirai, Hiroshi Yagasaki, Junya Fujimura, Masami Inoue, Katsuyoshi Shimozawa, Hirotsugu Okuma, Motoaki Chin, Shori Takahashi
No abstract text is available yet for this article.
July 21, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28693249/hepatocyte-selection-medium-enriched-hepatocellular-carcinoma-cells-are-positive-for-%C3%AE-fetoprotein-and-cd44
#11
Minoru Tomizawa, Fuminobu Shinozaki, Yasufumi Motoyoshi, Takao Sugiyama, Shigenori Yamamoto, Naoki Ishige
Tissues surrounding hepatocellular carcinomas (HCCs) lack glucose. Hepatocyte selection medium (HSM) is deficient in glucose and is supplemented with galactose. HCC cells were cultured in HSM to investigate the stem cell markers α-fetoprotein (AFP) and cluster of differentiation 44 (CD44). HCC cells (HLF and PLC/PRF/5 cells) were cultured in HSM. Viable cell numbers were determined on days 0 and 7 following culture in HSM. RNA was isolated and subjected to reverse transcription-quantitative PCR (RT-qPCR) to analyze the mRNA expression levels of AFP and CD44...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28685231/hybrid-polymeric-protein-nano-carriers-hppnc-for-targeted-delivery-of-tgf%C3%AE-inhibitors-to-hepatocellular-carcinoma-cells
#12
Nemany A N Hanafy, Alessandra Quarta, Riccardo Di Corato, Luciana Dini, Concetta Nobile, Vittorianna Tasco, Sonia Carallo, Mariafrancesca Cascione, Andrea Malfettone, Jitka Soukupova, Rosaria Rinaldi, Isabel Fabregat, Stefano Leporatti
TGFβ1 pathway antagonists have been considered promising therapies to attenuate TGFβ downstream signals in cancer cells. Inhibiting peptides, as P-17 in this study, are bound to either TGFβ1 or its receptors, blocking signal transduction. However, for efficient use of these TGFβ1antagonist as target therapeutic tools, improvement in their delivery is required. Here, a plasmid carrying specific shDNA (SHT-DNA), small interfering RNA (siRNA), and the peptide (P-17) were loaded separately into folic acid (FA)-functionalized nano-carriers made of Bovine Serum Albumin (BSA)...
August 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28668848/a-novel-small-molecule-wnt-inhibitor-ic-2-has-the-potential-to-suppress-liver-cancer-stem-cells
#13
Kenzo Seto, Tomohiko Sakabe, Noriko Itaba, Junya Azumi, Hiroyuki Oka, Minoru Morimoto, Yoshihisa Umekita, Goshi Shiota
BACKGROUND/AIM: The presence of cancer stem cells (CSCs) contributes to metastasis, recurrence, and resistance to chemo/radiotherapy in hepatocellular carcinoma (HCC). The WNT signaling pathway is reportedly linked to the maintenance of stemness of CSCs. In the present study, in order to eliminate liver CSCs and improve the prognosis of patients with HCC, we explored whether small-molecule compounds targeting WNT signaling pathway suppress liver CSCs. MATERIALS AND METHODS: The screening was performed using cell proliferation assay and reporter assay...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28663751/lactoferrin-efficiently-counteracts-the-inflammation-induced-changes-of-the-iron-homeostasis-system-in-macrophages
#14
Antimo Cutone, Luigi Rosa, Maria Stefania Lepanto, Mellani Jinnett Scotti, Francesca Berlutti, Maria Carmela Bonaccorsi di Patti, Giovanni Musci, Piera Valenti
Human lactoferrin (hLf), an 80-kDa multifunctional iron-binding cationic glycoprotein, is constitutively secreted by exocrine glands and by neutrophils during inflammation. hLf is recognized as a key element in the host immune defense system. The in vitro and in vivo experiments are carried out with bovine Lf (bLf), which shares high sequence homology and identical functions with hLf, including anti-inflammatory activity. Here, in "pure" M1 human macrophages, obtained by stimulation with a mixture of 10 pg/ml LPS and 20 ng/ml IFN-γ, as well as in a more heterogeneous macrophage population, challenged with high-dose of LPS (1 µg/ml), the effect of bLf on the expression of the main proteins involved in iron and inflammatory homeostasis, namely ferroportin (Fpn), membrane-bound ceruloplasmin (Cp), cytosolic ferritin (Ftn), transferrin receptor 1, and cytokines has been investigated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28627280/the-targeting-effect-of-hm2e8b-nctd-liposomes-on-b-lineage-leukemia-stem-cells-is-associated-with-the-hlf-slug-axis
#15
Jingying Zhang, Diyin Shen, Min Jia, Haizhao Zhao, Yongmin Tang
To identify an agent with specific activity against B-lineage leukemia stem cells (B-LSCs), we generated norcantharidin (NCTD)-encapsulated liposomes modified with a novel humanized anti-human CD19 monoclonal antibody, Hm2E8b (Hm2E8b-NCTD-liposomes). These liposomes were specially designed to recognize and kill B-LSCs in vitro, and to decrease non-specific cytotoxicity to untargeted cells. Hm2E8b-NCTD-liposomes selectively ablated B-LSCs through targeting hepatic leukemia factor (HLF), which is implicated in hematopoietic stem cell regulation and is overexpressed in LSCs...
June 19, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28625151/na-k-atpase-as-a-target-for-treatment-of-tissue-fibrosis
#16
Sergei N Orlov, Jenifer La, Larisa V Smolyaninova, Nickolai O Dulin
Myofibroblast activation is a critical process in the pathogenesis of tissue fibrosis accounting for 45% of all deaths. No effective therapies are available for the treatment of fibrotic diseases. We focus our mini-review on recent data showing that cardiotonic steroids (CTS) that are known as potent inhibitors of Na+,K+-ATPase affect myofibroblast differentiation in a cell type-specific manner. In cultured human lung fibroblasts (HLF), epithelial cells, and cancer-associated fibroblasts, CTS blocked myofibroblast differentiation triggered by profibrotic cytokine TGF-β...
June 19, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28571757/hmgb1-promotes-hlf-1-proliferation-and-ecm-production-through-activating-hif1-%C3%AE-regulated-aerobic-glycolysis
#17
JianNing Xu, JingYing Li, ZhiHong Yu, HaiWei Rao, Shu Wang, HaiBing Lan
Aerobic glycolysis is a crucial event in fibroblast differentiation, and extracellular matrix (ECM) production in the progression of pulmonary fibrosis (PF). Abnormal high mobility group protein B1 (HMGB1) activation is involved in the pathogenesis of PF. However, whether aerobic glycolysis contributes to HMGB1-induced fibroblast proliferation and ECM production in PF has not yet been determined. In this study, we investigated the effects of HMGB1 on human embryonic lung fibroblast (HLF-1) proliferation, ECM production, and aerobic glycolysis...
August 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28552561/fxii-promotes-proteolytic-processing-of-the-lrp1-ectodomain
#18
Lukasz Wujak, Christina Hesse, Katherina Sewald, Danny Jonigk, Peter Braubach, Gregor Warnecke, Hans-Gerd Fieguth, Armin Braun, Günter Lochnit, Philipp Markart, Liliana Schaefer, Malgorzata Wygrecka
BACKGROUND: Factor XII (FXII) is a serine protease that is involved in activation of the intrinsic blood coagulation, the kallikrein-kinin system and the complement cascade. Although the binding of FXII to the cell surface has been demonstrated, the consequence of this event for proteolytic processing of membrane-anchored proteins has never been described. METHODS: The effect of FXII on the proteolytic processing of the low-density lipoprotein receptor-related protein 1 (LRP1) ectodomain was tested in human primary lung fibroblasts (hLF), alveolar macrophages (hAM) and in human precision cut lung slices (hPCLS)...
August 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28545024/an-unusual-intragenic-promoter-of-piwil2-contributes-to-aberrant-activation-of-oncogenic-pl2l60
#19
Shan-Shan Liu, Ning Liu, Meng-Yao Liu, Lei Sun, Wu-Yan Xia, Hong-Min Lu, Yu-Jie Fu, Guo-Liang Yang, Juan-Jie Bo, Xiao-Xing Liu, Haizhong Feng, Hailong Wu, Lin-Feng Li, Jian-Xin Gao
PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28503247/reconfigurable-microfluidic-device-with-discretized-sidewall
#20
Masahiro Oono, Keisuke Yamaguchi, Amirul Rasyid, Atsushi Takano, Masato Tanaka, Nobuyuki Futai
Various microfluidic features, such as traps, have been used to manipulate flows, cells, and other particles within microfluidic systems. However, these features often become undesirable in subsequent steps requiring different fluidic configurations. To meet the changing needs of various microfluidic configurations, we developed a reconfigurable microfluidic channel with movable sidewalls using mechanically discretized sidewalls of laterally aligned rectangular pins. The user can deform the channel sidewall at any time after fabrication by sliding the pins...
May 2017: Biomicrofluidics
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