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Luigi Rosa, Antimo Cutone, Maria Stefania Lepanto, Mellani Jinnett Scotti, Maria Pia Conte, Rosalba Paesano, Piera Valenti
Human and bovine lactoferrin (hLf and bLf) are multifunctional iron-binding glycoprotein constitutively synthesized and secreted by glandular epithelial cells and by neutrophils following induction. HLf and bLf possess very high similarity of sequence. Therefore, most of the in vitro and in vivo studies are carried out with commercial bLf (cbLf), available in large quantities and recognized by Food and Drug Administration (FDA, USA) as a safe substance. Physico-chemical heterogeneity of different cbLf preparations influences their effectiveness...
March 7, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Bhavna Rani, Andrea Malfettone, Francesco Dituri, Jitka Soukupova, Luigi Lupo, Serena Mancarella, Isabel Fabregat, Gianluigi Giannelli
Cancer stem cells (CSCs) niche in the tumor microenvironment is responsible for cancer recurrence and therapy failure. To better understand its molecular and biological involvement in hepatocellular carcinoma (HCC) progression, one can design more effective therapies and tailored then to individual patients. While sorafenib is currently the only approved drug for first-line treatment of advanced stage HCC, its role in modulating the CSC niche is estimated to be small. By contrast, transforming growth factor (TGF)-β pathway seems to influence the CSC and thus may impact hallmarks of HCC, such as liver fibrosis, cirrhosis, and tumor progression...
March 7, 2018: Cell Death & Disease
Nemany Abdelhamid Nemany Hanafy, Alessandra Quarta, Marzia Maria Ferraro, Luciana Dini, Concetta Nobile, Maria Luisa De Giorgi, Sonia Carallo, Cinzia Citti, Antonio Gaballo, Giuseppe Cannazza, Rosaria Rinaldi, Gianluigi Giannelli, Stefano Leporatti
LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a "nano-elastic" carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH...
March 6, 2018: International Journal of Molecular Sciences
Rosalba D'Alessandro, Maria Grazia Refolo, Catia Lippolis, Nicola Carella, Caterina Messa, Aldo Cavallini, Brian Irving Carr
PURPOSE: Emerging evidence indicates that combining Sorafenib with vitamin K1 (VK1) may result in a synergistic inhibition of hepatocellular carcinoma (HCC) cell migration and proliferation. Despite this synergy, its benefits may be limited due to drug resistance resulting from cross-talk with the tumor microenvironment. Insulin-like growth factor-1 (IGF1) signaling acts as an important modulator of HCC cell growth, motility and drug resistance. Therefore, we aimed to explore the effects of Sorafenib in combination with VK1 and/or IGF1-R antagonists on HCC cells...
February 22, 2018: Cellular Oncology (Dordrecht)
Christopher D Gardner, John F Trepanowski, Liana C Del Gobbo, Michelle E Hauser, Joseph Rigdon, John P A Ioannidis, Manisha Desai, Abby C King
Importance: Dietary modification remains key to successful weight loss. Yet, no one dietary strategy is consistently superior to others for the general population. Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets. Objective: To determine the effect of a healthy low-fat (HLF) diet vs a healthy low-carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss...
February 20, 2018: JAMA: the Journal of the American Medical Association
Irene Scharf, Lisa Bierbaumer, Heidemarie Huber, Philipp Wittmann, Christine Haider, Christine Pirker, Walter Berger, Wolfgang Mikulits
Genomic editing using the CRISPR/Cas9 technology allows selective interference with gene expression. With this method, a multitude of haploid and diploid cells from different organisms have been employed to successfully generate knockouts of genes coding for proteins or small RNAs. Yet, cancer cells exhibiting an aberrant ploidy are considered to be less accessible to CRISPR/Cas9-mediated genomic editing, as amplifications of the targeted gene locus could hamper its effectiveness. Here we examined the suitability of CRISPR/Cas9 to knockout the receptor tyrosine kinase Axl in the human hepatoma cell lines HLF and SNU449...
February 2018: Oncology Letters
Minhui Dai, Pinhua Pan, Haitao Li, Shuai Liu, Lemeng Zhang, Chao Song, Yi Li, Qian Li, Zhi Mao, Yuan Long, Xiaoli Su, Chengping Hu
Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections, including bacterial pneumonia. The hLF(1-11) peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo and was highly effective against multidrug-resistant A. baumannii strains in vitro and in vivo. Pyroptosis is a caspase-1-dependent inflammatory cell death process and is induced by various microbial infections...
February 1, 2018: Experimental Cell Research
Richard G James, Stephen R Reeves, Kaitlyn A Barrow, Maria P White, Veronika A Glukhova, Candace Haghighi, Dana Seyoum, Jason S Debley
RATIONALE: Bronchial epithelial cells (BECs) from healthy children inhibit human lung fibroblast (HLF) expression of collagen and fibroblast-myofibroblast transition (FMT) while asthmatic BECs do so less effectively, suggesting diminished epithelial-derived regulatory factors contribute to airway remodeling. Preliminary data demonstrated secretion of the activin A-inhibitor FSTL3 by healthy BECs was greater than that by asthmatic BECs. OBJECTIVES: Determine the relative secretion of FSTL3 and activin A by asthmatic and healthy BECs and if FSTL3 inhibits FMT...
February 2, 2018: American Journal of Respiratory Cell and Molecular Biology
Lukas Wisgrill, Isabelle Wessely, Andreas Spittler, Elisabeth Förster-Waldl, Angelika Berger, Kambis Sadeghi
Bioactive components of human milk such as human lactoferrin (hLF) play an essential role in gut microbiome homeostasis and protection against neonatal inflammatory diseases. Neonatal intestinal macrophages display a pro-inflammatory profile that might contribute to inflammatory mucosal injury. Therefore, the aim of the study was to investigate the immunomodulatory effects of hLF on differentiation and activation of monocyte-derived macrophages (moMϕ). Monocytes isolated from umbilical cord blood of term neonates and peripheral blood of healthy adults were differentiated in the absence or presence of hLF and differentiation, apoptosis and phagocytosis were evaluated...
February 2, 2018: Clinical and Experimental Immunology
Yan Li, Pengcheng Wang, Chuanlin Hu, Kun Wang, Qing Chang, Lieju Liu, Zhenggang Han, Yang Shao, Ying Zhai, Zhengyu Zuo, Zhiyong Gong, Yang Wu
Exposure to PM2.5 has become one of the most important factors affecting public health in the world. Both clinical and research studies have suggested that PM2.5 inhalation is associated with impaired lung function. In this study, material characterization identified the existence of nanoscale particulate matter (NPM) in airborne PM2.5 samples. When coming into contact with protein-rich fluids, the NPM becomes covered by a protein layer that forms a "protein corona". Based on a 3D organotypic cell culture, the protein corona was shown to mitigate NPM cytotoxicity and further stimulate the proliferation of human lung fibroblasts (HLFs)...
January 31, 2018: Scientific Reports
Priyadarshini Kachroo, Silke Szymczak, Femke-Anouska Heinsen, Michael Forster, Jörn Bethune, Georg Hemmrich-Stanisak, Lewis Baker, Martin Schrappe, Martin Stanulla, Andre Franke
AIM: To determine whether methylation differences between mostly fatal TCF3-HLF and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be associated with differential gene expression and remission. MATERIALS & METHODS: Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were sampled before and after remission and analyzed using reduced representation bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000 differentially methylated CpG sites between subtypes, of which 78% had lower methylation levels in TCF3-HLF...
January 15, 2018: Epigenomics
Karolina Komorowska, Alexander Doyle, Martin Wahlestedt, Agatheeswaran Subramaniam, Shubhranshu Debnath, Jun Chen, Shamit Soneji, Ben Van Handel, Hanna K A Mikkola, Kenichi Miharada, David Bryder, Jonas Larsson, Mattias Magnusson
The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable with essentially normal hematopoietic parameters, including an intact HSC pool during steady-state hematopoiesis. In contrast, when challenged through transplantation, Hlf-deficient HSCs showed an impaired ability to reconstitute hematopoiesis and became gradually exhausted upon serial transplantation...
December 19, 2017: Cell Reports
Kenta Yokoi, Akira Kobayashi, Hiroaki Motoyama, Masato Kitazawa, Akira Shimizu, Tsuyoshi Notake, Takahide Yokoyama, Tomio Matsumura, Michiko Takeoka, Shin-Ichi Miyagawa
Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses...
February 2018: Oncology Reports
Chen Hou, Danyi Peng, Li Gao, Daiyin Tian, Jihong Dai, Zhengxiu Luo, Enmei Liu, Hong Chen, Lin Zou, Zhou Fu
The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts...
January 8, 2018: Biochemical and Biophysical Research Communications
Qing Min, Yuting Bai, Yuchen Zhang, Wei Yu, Minli Zhang, Dongyang Liu, Tingting Diao, Wei Lv
Objectives: DCM has become one of the main reasons of death in diabetic patients. In this study, we aimed to explore the hawthorn leaf flavonoids (HLF) protective effect against diabetes-induced cardiac injury and the underlying mechanisms in experimental rats. Methods: Experimental diabetic model was induced by intraperitoneal injection of streptozotocin (STZ, 40 mg/kg) in rats after feeding with high-fat diet for 8 weeks. The diabetic rats received a 16-week treatment of different doses of HLF (50, 100, and 200)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Roberta Fais, Mariagrazia Di Luca, Cosmeri Rizzato, Paola Morici, Daria Bottai, Arianna Tavanti, Antonella Lupetti
Candida parapsilosis is a major cause of hospital-acquired infection, often related to parenteral nutrition administered via catheters and hand colonization of health care workers, and its peculiar biofilm formation ability on plastic surfaces. The mortality rate of 30% points to the pressing need for new antifungal drugs. The present study aimed at analyzing the inhibitory activity of the N-terminal lactoferrin-derived peptide, further referred to as hLF 1-11, against biofilms produced by clinical isolates of C...
2017: Frontiers in Microbiology
Martin Wahlestedt, Vasileios Ladopoulos, Isabel Hidalgo, Manuel Sanchez Castillo, Rebecca Hannah, Petter Säwén, Haixia Wan, Monika Dudenhöffer-Pfeifer, Mattias Magnusson, Gudmundur L Norddahl, Berthold Göttgens, David Bryder
A gradual restriction in lineage potential of multipotent stem/progenitor cells is a hallmark of adult hematopoiesis, but the underlying molecular events governing these processes remain incompletely understood. Here, we identified robust expression of the leukemia-associated transcription factor hepatic leukemia factor (Hlf) in normal multipotent hematopoietic progenitors, which was rapidly downregulated upon differentiation. Interference with its normal downregulation revealed Hlf as a strong negative regulator of lymphoid development, while remaining compatible with myeloid fates...
November 21, 2017: Cell Reports
Stephane Esnault, Ksenija Bernau, Elizabeth E Torr, Yury A Bochkov, Nizar N Jarjour, Nathan Sandbo
BACKGROUND: The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release of toxic granule proteins and other mediators, including cytokines. Tissue remodeling and consequent functional defects are affected by activity of connective tissue fibroblasts. Exaggerated fibroblast activation, accumulation and change of phenotype may lead to fibrosis and loss of tissue function. So far, little information has been reported on how eosinophils affect inflammation and tissue remodeling via the activation of fibroblasts...
November 10, 2017: Respiratory Research
C Criscitiello, M A Bayar, G Curigliano, F W Symmans, C Desmedt, H Bonnefoi, B Sinn, G Pruneri, C Vicier, J Y Pierga, C Denkert, S Loibl, C Sotiriou, S Michiels, F André
INTRODUCTION: In patients with triple-negative breast cancer (TNBC), the extent of tumor-infiltrating lymphocytes (TILs) in the residual disease (RD) after neoadjuvant chemotherapy (NACT) is associated with better prognosis. Our objective was to develop a gene signature from pre-treatment samples to predict the extent of TILs after NACT, and then to test its prognostic value on survival. PATIENTS AND METHODS: Using 99 pre-treatment samples, we generated a four-gene signature associated with high post-NACT TILs...
October 25, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Takehiro Hayashi, Taro Yamashita, Hikari Okada, Kouki Nio, Yasumasa Hara, Yoshimoto Nomura, Tomoyuki Hayashi, Yoshiro Asahina, Mariko Yoshida, Naoki Oishi, Hajime Sunagozaka, Hajime Takatori, Masao Honda, Shuichi Kaneko
BACKGROUND: The relationship between specific genome alterations and hepatocellular carcinoma (HCC) cancer stem cells (CSCs) remains unclear. In this study, we evaluated the relationship between somatic mutations and epithelial cell adhesion molecule positive (EpCAM(+)) CSCs. METHODS: Two patient-derived HCC samples (HCC1 and HCC2) were sorted by EpCAM expression and analyzed by whole exome sequence. We measured PCDH18 expression level in eight HCC cell lines as well as HCC1 and HCC2 by real-time quantitative RT-PCR...
2017: Cancer Cell International
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