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Chuang Guo, Zhao-Hui Yang, Shuai Zhang, Rui Chai, Han Xue, Yan-Hui Zhang, Jia-Yi Li, Zhan-You Wang
Growing evidence suggests that lactoferrin (Lf), an iron-binding glycoprotein, is a pleiotropic functional nutrient. Additionally, Lf was recently implicated as a neuroprotective agent. These properties make Lf a valuable therapeutic candidate for the treatment of Alzheimer's disease (AD). However, the mechanisms regulating the physiological roles of Lf in the pathologic condition of AD remain unknown. In the present study, an APPswe/PS1DE9 transgenic mouse model of AD was used. We explored whether intranasal human Lf (hLf) administration could reduce β-amyloid (Aβ) deposition and ameliorate cognitive decline in this AD model...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Siri H Strand, Michal Switnicki, Mia Moller, Christa Haldrup, Tine M Storebjerg, Jakob Hedegaard, Iver Nordentoft, Soren Hoyer, Michael Borre, Jakob S Pedersen, Peter J Wild, Jong Y Park, Torben F Orntoft, Karina D Sorensen
PURPOSE: The lack of biomarkers that can distinguish aggressive from indolent prostate cancer has caused substantial overtreatment of clinically insignificant disease. Here, by genome-wide DNA methylome profiling, we sought to identify new biomarkers to improve the accuracy of prostate cancer diagnosis and prognosis. EXPERIMENTAL DESIGN: Eight novel candidate markers, COL4A6, CYBA, TCAF1 (FAM115A), HLF, LINC01341 (LOC149134), LRRC4, PROM1, and RHCG, were selected from Illumina Infinium HumanMethylation450 BeadChip analysis of 21 tumor (T) and 21 non-malignant (NM) prostate specimens...
December 30, 2016: Oncotarget
Jun-Yi Hou, Yu-Gang Wang, Shi-Jie Ma, Bing-Yin Yang, Qian-Ping Li
PURPOSE: Gastric cancer (GC) is a major tumor throughout the world with remaining high morbidity and mortality. The aim is to generate a gene model to assess the prognoses risk of patients with GC. METHODS: Gene expression profiling of gastric cancer patients, GSE62254 (300 samples) and GSE26253 (432 samples), was downloaded from Gene Expression Omnibus (GEO) database. Univariate survival analysis and LASSO (Least Absolute Shrinkage and Selectionator operator) (1000 iterations) of differentially expressed genes in GSE62254 was assessed using survival and glmnet in R package, respectively...
December 29, 2016: Journal of Cancer Research and Clinical Oncology
Baijiao An, Shun Zhang, Jun Yan, Ling Huang, Xingshu Li
In this paper, a series of millepachine derivatives were synthesized and evaluated as tubulin polymerization inhibitors. The optimal compound 5i, (3-hydroxy-4-methoxyphenyl)(5-methoxy-2,2-dimethyl-2H-chromen-8-yl)methanone, displayed the highest cytotoxicity toward a series of cancer cells (ranging from 18 to 45 nM of IC50). Further investigation revealed that 5i significantly repressed the multidrug resistant cells (A549/CDDP, A2780/TAX) and had little cytotoxicity towards human normal cells (HLF, BJ). Cellular mechanism studies demonstrated that 5i induced G2/M phase arrest and apoptosis, which was associated with the collapse of the mitochondrial membrane potential (MMP)...
December 23, 2016: Organic & Biomolecular Chemistry
Ruizhuo Ouyang, Yang Yang, Xiao Tong, Kai Feng, Yaoqin Yang, Huihong Tao, Xiaoshen Zhang, Tianyu Zong, Penghui Cao, Fei Xiong, Ning Guo, Yuhao Li, Yuqing Miao, Shuang Zhou
The aim of this work is experimental study of an interesting bismuth(III) complex derived from pentadentate 2,6-pyridinedicarboxaldehyde bis((4)N-methylthiosemicarbazone), [BiL(NO3)2]NO3 {L=2,6-pyridinedicarboxaldehyde bis((4)N-methylthiosemicarbazone)}. A series of in vitro biological studies indicate that the newly prepared [BiL(NO3)2]NO3 greatly suppressed colony formation, migration and significantly induced apoptosis of human lung cancer cells A549 and H460, but did not obviously decrease the cell viability of non-cancerous human lung fibroblast (HLF) cell line, showing much higher anticancer activities than its parent ligands, especially with half maximum inhibitory concentration (IC50) <3...
December 11, 2016: Journal of Inorganic Biochemistry
Jennifer La, Eleanor Reed, Lan Chan, Larisa V Smolyaninova, Olga A Akomova, Gökhan M Mutlu, Sergei N Orlov, Nickolai O Dulin
Transforming growth factor-beta (TGF-β) is a multi-functional cytokine implicated in the control of cell growth and differentiation. TGF-β signals through a complex of TGF-β receptors 1 and 2 (TGFβR1 and TGFβR2) that phosphorylate and activate Smad2/3 transcription factors driving transcription of the Smad-target genes. The Na+/K+-ATPase is an integral plasma membrane protein critical for maintaining the electro-chemical gradient of Na+ and K+ in the cell. We found that inhibition of the Na+/K+ ATPase by ouabain results in a dramatic decrease in the expression of TGFβR2 in human lung fibrobalsts (HLF) at the mRNA and protein levels...
2016: PloS One
Shuya Kasai, Shinji Kajimoto, Yuma Ito, Tomo Saito, Ken-Ichi Yasumoto, Makio Tokunaga, Kumiko Sakata-Sogawa, Hiroshi Fukumura, Kazuhiro Sogawa
Inhibitory PAS domain protein (IPAS) is a dual function protein acting as a transcriptional repressor and as a pro-apoptotic protein. Simultaneous dual-color single-molecule imaging of EGFP-IPAS coexpressed with Mit-TagRFP-T in living HeLa cells revealed that fraction of EGFP-IPAS was arrested in the nucleus and on mitochondria. Transiently expressed Cerulean-IPAS in HEK293T cells was present in nuclear speckles when coexpressed with Citrine-HIF-1α or Citrine-HLF. Fluorescence lifetime imaging microscopy (FLIM) analysis of Citrine-IPAS-Cerulean in living CHO-K1 cells clarified the presence of intramolecular FRET...
December 21, 2016: Journal of Biochemistry
Yu-Guo Yuan, Shao-Zheng Song, Meng-Ming Zhu, Zheng-Yi He, Rui Lu, Ting Zhang, Fei Mi, Jin-Yu Wang, Yong Cheng
Objective: To create genetically modified goat as a biopharming source of recombinant human lacotoferrin (hLF) with TALEN. Methods: TALENs and targeting vector were transferred into cultured fibroblasts to insert hLF cDNA in the goat beta-lactoglobulin (BLG) locus with homology-directed repair (HDR). The gene targeted efficiency was checked using sequencing and TE7I assay. The bi-allelic gene targeted colonies were isolated and conformed with PCR, and used as donor cells for somatic cell nuclear transfer (SCNT)...
December 17, 2016: Asian-Australasian Journal of Animal Sciences
Sang Lee, Jae Chong, Seon Min, Seon Bak, Kyung Kim
<p>Falciform ligaments in the liver are surrounded by adipose tissue. We investigated the capability of adipose derived stem cells from human liver falciform ligaments (hLF-ADSCs) to differentiate into hepatic type cells and confirm the functional capacity.</p><p>Mesenchymal stem cells (MSCs) were isolated from the liver falciform ligament and abdominal subcutaneous adipose tissue in patients undergoing partial hepatectomy for liver disease. Cells were cultivated in MSCs culture medium. Properties of MSCs were confirmed by flow cytometry, RT-PCR analysis, immunocytochemistry assays, and multi-lineage differentiation...
24, 2016: Cell Transplantation
Jinhua Piao, Shiori Takai, Takahiro Kamiya, Takeshi Inukai, Kanji Sugita, Kazuma Ohyashiki, Domenico Delia, Mitsuko Masutani, Shuki Mizutani, Masatoshi Takagi
Poly (ADP-ribose) polymerase (PARP) is an indispensable component of the DNA repair machinery. PARP inhibitors are used as cutting-edge treatments for patients with homologous recombination repair (HRR)-defective breast cancers harboring mutations in BRCA1 or BRCA2. Other tumors defective in HRR, including some hematological malignancies, are predicted to be good candidates for treatment with PARP inhibitors. Screening of leukemia-derived cell lines revealed that lymphoid lineage-derived leukemia cell lines, except for those derived from mature B cells and KMT2A (MLL)-rearranged B-cell precursors, were relatively sensitive to PARP inhibitors...
February 1, 2017: Cancer Letters
Afrah Sattikar, Mark R Dowling, Elizabeth M Rosethorne
BACKGROUND AND PURPOSE: Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expressed of the LPA receptor family is the LPA1 receptor, which predominantly couples to Gq/11 , Gi/o and G12/13 proteins. This promiscuity of coupling raises the possibility that some of the LPA analogues may bias the LPA1 receptor towards one signalling pathway over another...
November 16, 2016: British Journal of Pharmacology
Jun Xie, Jia-Hui Liu, Heng Liu, Xiao-Zhong Liao, Yuling Chen, Mei-Gui Lin, Yue-Yu Gu, Tao-Li Liu, Dong-Mei Wang, Hui Ge, Sui-Lin Mo
BACKGROUND: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle...
November 18, 2016: BMC Cancer
Irene Vacca, Elena Del Tordello, Gianmarco Gasperini, Alfredo Pezzicoli, Martina Di Fede, Silvia Rossi Paccani, Sara Marchi, Tsisti D Mubaiwa, Lauren E Hartley-Tassell, Michael P Jennings, Kate L Seib, Vega Masignani, Mariagrazia Pizza, Davide Serruto, Beatrice Aricò, Isabel Delany
Neisserial Heparin Binding Antigen (NHBA) is a surface-exposed lipoprotein ubiquitously expressed by Neisseria meningitidis strains and an antigen of the Bexsero® vaccine. NHBA binds heparin through a conserved Arg-rich region that is the target of two proteases, the meningococcal NalP and human lactoferrin (hLf). In this work, in vitro studies showed that recombinant NHBA protein was able to bind epithelial cells and mutations of the Arg-rich tract abrogated this binding. All N-terminal and C-terminal fragments generated by NalP or hLf cleavage, regardless of the presence or absence of the Arg-rich region, did not bind to cells, indicating that a correct positioning of the Arg-rich region within the full length protein is crucial...
2016: PloS One
Takaaki Higashi, Hiromitsu Hayashi, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Shigeki Nakagawa, Hirohisa Okabe, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery...
November 2016: Medical Oncology
Doan Duy Hai Tran, Alexandra Koch, Aldrige Allister, Shashank Saran, Florian Ewald, Martina Koch, Björn Nashan, Teruko Tamura
Over 100 putative driver genes that are associated with multiple recurrently altered pathways were detected in hepatocellular carcinoma (HCC), suggesting that multiple pathways will need to be inhibited for any therapeutic method to be effective. In this context, functional modification of the RNA regulating protein, tristetraprolin (TTP) that regulates approximately 2500 genes represents a promising strategy in HCC therapy. Since overexpression of TTP induces cell death in all cell types, it would be useful to target the regulator of TTP...
December 2016: Cellular Signalling
Shannon H Lacy, Collynn F Woeller, Thomas H Thatcher, Krishna Rao Maddipati, Kenneth V Honn, Patricia J Sime, Richard P Phipps
Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify the inflammatory response to injurious stimuli. Here, we use targeted lipidomics to explore the hypothesis that HLFs also play an active role in the resolution of inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both proinflammatory and proresolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a proinflammatory stimulus, IL-1β. Among the proresolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor whose activation in the lung yields potent anti-inflammatory, antifibrotic, and proresolving effects...
November 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Hui Zhang, Alvin T Kho, Qing Wu, Andrew J Halayko, Karen Limbert Rempel, Robert P Chase, Neil B Sweezey, Scott T Weiss, Feige Kaplan
Chronic lung disease of prematurity/bronchopulmonary dysplasia (BPD) is the leading cause of perinatal morbidity in developed countries. Inflammation is a prominent finding. Currently available interventions have associated toxicities and limited efficacy. While BPD often resolves in childhood, survivors of preterm birth are at risk for acquired respiratory disease in early life and are more likely to develop chronic obstructive pulmonary disease (COPD) in adulthood. We previously cloned Crispld2 (Lgl1), a glucocorticoid-regulated mesenchymal secretory protein that modulates lung branching and alveogenesis through mesenchymal-epithelial interactions...
September 2016: Physiological Reports
Asahiro Morishita, Hisakazu Iwama, Shintaro Fujihara, Teppei Sakamoto, Koji Fujita, Joji Tani, Hisaaki Miyoshi, Hirohito Yoneyama, Takashi Himoto, Tsutomu Masaki
Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide. Although surgery is considered the most effective treatment for patients with HCC, its indication is restricted by limited criteria and a high relapse rate following surgery; therefore, systemic chemotherapy is required for patients with advanced-stage HCC to prolong their survival. MicroRNAs (miRNAs) are endogenous non-coding RNAs of 18-22 nucleotides in length. It has been reported that aberrant expression of miRNAs is a feature shared by various types of human cancer...
September 2016: Oncology Letters
Shaper Mirza, William H Benjamin, Patricia A Coan, Shen-An Hwang, Anne-Kathryn Winslett, Janet Yother, Susan K Hollingshead, Kohtaro Fujihashi, David E Briles
Pneumococcal surface protein A (PspA) is the only pneumococcal surface protein known to strongly bind lactoferrin on the bacterial surface. In the absence of PspA Streptococcus pneumoniae becomes more susceptible to killing by human apolactoferrin (apo-hLf), the iron-free form of lactoferrin. In the present study we examined diverse strains of S. pneumoniae that differed by 2 logs in their susceptibility to apo-hLf. Among these strains, the amount of apo-hLf that bound to cell surface PspA correlated directly with the resistance of the strain to killing by apo-hLf...
October 2016: Microbial Pathogenesis
Jian Ping Zhou, Wei Tang, Yun Feng, Ning Li, Chen Juan Gu, Qing Yun Li, Huan Ying Wan
Previous studies have shown that the RAS (renin-angiotensin system) might participate in airway remodelling in asthma. As a main component of the RAS, Ang-(1-7) [angiotensin-(1-7)] has been reported in few studies regarding its protective effect on asthma. However, the functional roles and relevant signalling pathways of Ang-(1-7) have not been well illustrated. In the present study, we analysed the effect of Ang-(1-7) on AngII (angiotensin II)-induced HLF (human lung fibroblast)-MF (myofibroblast) transition by detecting Col-I (collagen type I), TGF-β1 (transforming growth factor-β1) and α-SMA (α-smooth muscle actin) expression...
November 1, 2016: Clinical Science (1979-)
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