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George Inana, Christopher Murat, Weijun An, Xiang Yao, Ian R Harris, Jing Cao
BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly characterized by retinal pigment epithelium (RPE) degeneration with accumulation of abnormal intracellular deposits (lipofuscin) and photoreceptor death. RPE is vital for the retina and integrity of photoreceptors through its phagocytic function which is closely linked to formation of lipofuscin through daily phagocytosis of discarded photoreceptor outer segments (POS). Although phagocytosis has been implicated in AMD, it has not been directly shown to be altered in AMD...
March 13, 2018: Journal of Translational Medicine
Chien-Liang Liu, Po-Sheng Yang, Ming-Nan Chien, Yuan-Ching Chang, Chi-Hsin Lin, Shih-Ping Cheng
SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer...
March 12, 2018: Histochemistry and Cell Biology
Karen L Price, Maria Kolatsi-Joannou, Chiara Mari, David A Long, Paul J D Winyard
Kidney function is directly linked to the number of nephrons which are generated until 32-36 weeks gestation in humans. Failure to make nephrons during development leads to congenital renal malformations, whilst nephron loss in adulthood occurs in progressive renal disease. Therefore, an understanding of the molecular processes which underlie human nephron development may help design new treatments for renal disease. Mesenchyme to epithelial transition (MET) is critical for forming nephrons, and molecular pathways which control rodent MET have been identified...
December 2018: Cell Death Discovery
Chakradhari Inampudi, Emmanuel Akintoye, Tomo Ando, Alexandros Briasoulis
Peripheral arterial disease (PAD) refers to narrowing of the peripheral arteries and atherosclerosis is the most important cause. In patients with PAD, revascularization is the preferred therapeutic strategy; nonetheless several patients are not deemed candidates for it due to advanced disease or several comorbidities. The main target of therapeutic angiogenesis is to promote development of new arterial vessels and improve perfusion of ischemic tissue. Angiogenic growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), administered intramuscularly or intra-arterially, have been shown to promote angiogenesis and development of collateral vasculature in preclinical studies...
March 9, 2018: Current Opinion in Pharmacology
Chenyue Ding, Qinyan Zou, Fuxin Wang, Huihua Wu, Rulei Chen, Jinghuan Lv, Mingfa Ling, Jian Sun, Wei Wang, Hong Li, Boxian Huang
BACKGROUND: Although many reports show that various kinds of stem cells have the ability to recover function in premature ovarian aging, few studies have looked at stem cell treatment of natural ovarian aging (NOA). We designed this experimental study to investigate whether human amniotic mesenchymal stem cells (hAMSCs) retain the ability to restore ovarian function, and how hAMSCs work in this process. METHODS: To build the NOA mouse model, the mice were fed for 12-14 months normally with young fertile female mice as the normal control group (3-5 months old)...
March 9, 2018: Stem Cell Research & Therapy
Jason C Marvin, Silvia I Gallegos, Shaida Parsaei, Danieli C Rodrigues
PURPOSE: To evaluate the biocompatibility of five dental cement compositions after directly exposing human gingival fibroblast (HGF) and MC3T3-E1 preosteoblast cells to cement alone and cement applied on commercially pure titanium (cpTi) specimens. MATERIALS AND METHODS: Nanostructurally integrated bioceramic (NIB), resin (R), resin-modified glass ionomer (RMGIC), zinc oxide eugenol (ZOE), and zinc phosphate (ZP) compositions were prepared according to the respective manufacturer's instructions...
March 9, 2018: Journal of Prosthodontics: Official Journal of the American College of Prosthodontists
Artur Jurczyszyn, Anna Zebzda, Joanna Gdula-Argasińska, Jacek Czepiel, David H Vesole, William Perucki, Marcin Majka
BACKGROUND: Numerous studies have shown a role of the hepatocyte growth factor (HGF) as a ligand for the MET receptor in promoting aggressiveness in myeloma cells. OBJECTIVES: The aim of this study was to confirm the presence of the MET receptor in myeloma cell lines, to establish a stable lentiviral construct directed against MET receptor mRNA and then to evaluate the effect of blocking MET receptor expression both in vitro and in vivo. MATERIAL AND METHODS: The U266 and INA6 cells were transduced using a lentiviral vector carrying siRNA to achieve the reduction of MET receptor expression...
February 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
M Graupp, B Rinner, M T Frisch, G Weiss, J Fuchs, M Sundl, A El-Heliebi, G Moser, L P Kamolz, M Karbiener, M Gugatschka
BACKGROUND: Vocal fold (VF) scarring remains a therapeutic dilemma and challenge in modern laryngology. To facilitate corresponding research, we aimed to establish an in vitro fibrogenesis model employing human VF fibroblasts (hVFF) and the principles of macromolecular crowding (MMC). METHODS: Fibrogenesis was promoted by addition of transforming growth factor-β1 to standard medium and medium containing inert macromolecules (MMC). Hepatocyte growth factor (HGF) and Botox type A were tested for their antifibrotic properties in various doses...
March 8, 2018: European Archives of Oto-rhino-laryngology
Firas Awaja, Giorgio Speranza, Heike Kaltenegger, Débora Coraça-Huber, Birgit Lohberger
Osteo-integration and tissue regeneration are vital for the longevity, durability, and unremitting functionality of medical implants/scaffolds implanted in vivo. It's essential for biomaterials used for in vivo implantation to induce the cellular secretion of growth factors, necessary for the desired tissue generation, since the administration of artificial growth factors, in vivo, is largely prohibited. Plasma functionalized (N2 and O2 ) and stabilized Graphene Oxide (GO) thin layers in a hybrid with amorphous carbon (aC) induced the expression of vascular endothelial growth factor (VEGF) and osteoprotegerin (OPG) growth factors in fibroblasts (hGF) and, more remarkably, in osteoblasts (hFOB) cells confirming the suitability for tissue regeneration and osteo-integration applications...
March 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
M А Boldyreva, I V Bondar, I S Stafeev, P I Makarevich, I B Beloglazova, E S Zubkova, E K Shevchenko, Y D Molokotina, M N Karagyaur, Е I Rаtner, Ye V Parfyonova
Peripheral nerve injury remains a common clinical problem with no satisfactory treatment options. Numerous studies have shown that hepatocyte growth factor (HGF) exerts neurotrophic effect in motor, sensory, and parasympathetic neurons in addition to mitogenic, morphogenic, angiogenic, antiapoptotic, antifibrotic, and anti-inflammatory effect on various tissues and cells. In our study we examined efficacy of gene therapy with HGF-bearing plasmid (pC4W-hHGF) to improve consequences of traumatic nerve injury in mice...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Christian Patry, Christian Betzen, Farnoosh Fathalizadeh, Alexander Fichtner, Jens H Westhoff, Thomas Fleming, Volker Eckstein, Tom Bruckner, Martina Bielaszewska, Helge Karch, Georg F Hoffmann, Burkhard Tönshoff, Neysan Rafat
Endothelial injury with consecutive microangiopathy and endothelial dysfunction plays a central role in the pathogenesis of the post-enteropathic hemolytic uremic syndrome (D+HUS). To identify new treatment strategies, we examined the regenerative potential of endothelial progenitor cells (EPC) in an in vitro model of Shiga toxin (Stx) 2a-induced glomerular endothelial injury present in D+HUS and the mechanisms of EPC-triggered endothelial regeneration. We simulated the pro-inflammatory milieu present in D+HUS by priming human renal glomerular endothelial cells (HRGEC) with Tumor Necrosis Factor (TNF)-α prior to stimulation with Stx2a...
March 7, 2018: American Journal of Physiology. Renal Physiology
Qian Wen, Shimeng Zhang, Xialin Du, Ruining Wang, Yanfen Li, Honglin Liu, Shengfeng Hu, Chaoying Zhou, Xinying Zhou, Li Ma
Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world's medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined...
March 5, 2018: International Journal of Molecular Sciences
Jacey J Liu, Yanjie Li, Wendy S Chen, Yan Liang, Gaowei Wang, Min Zong, Kota Kaneko, Ruiyun Xu, Michael Karin, Gen-Sheng Feng
BACKGROUND AND AIMS: Shp2 is an SH2-tyrosine phosphatase acting downstream of receptor tyrosine kinases (RTKs). Most recent data demonstrated a liver tumor-suppressing role for Shp2, as ablating Shp2 in hepatocytes aggravated hepatocellular carcinoma (HCC) induced by chemical carcinogen or Pten loss. We further investigated the effect of Shp2 deficiency on liver tumorigenesis driven by classical oncoproteins c-Met (receptor for HGF), β-catenin and PIK3CA. METHODS: We performed hydrodynamic tail vein injection of two pairs of plasmids expressing c-Met and ΔN90-β-catenin (MET/CAT), or c-Met and PIK3CAH1047R (MET/PIK), into WT and Shp2hep-/- mice...
March 2, 2018: Journal of Hepatology
Wen-Jiao Xian, Xue-Er Wang, Lin Zhang
OBJECTIVE: To explore the optimum conditions for preparing poly(lactic-co-glycolic) acid (PLGA) nanoparticles and evaluate the bioactivity of hepatocyte growth factor (HGF)-loaded PLGA nanoparticles. METHODS: Bovine serum albumin (BSA)-loaded PLGA nanoparticles were prepared using a double emulsion-solvent evaporation method. The preparation process of nanoparticles was optimized by orthogonal test with the particle size, encapsulation efficiency (EE), drug loading (DD), and recovery as the indexes...
February 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Fan Li, Yang Liu, Yingyu Cai, Xin Li, Min Bai, Ting Sun, Lianfang Du
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment...
February 28, 2018: Ultrasound in Medicine & Biology
Fernanda Marconi Roversi, Sara Teresinha Olalla Saad, João Agostinho Machado-Neto
Understanding the molecular basis and mechanisms involved in neoplastic transformation and progression is important for the development of novel selective target therapeutic strategies. Hepatocyte growth factor (HGF)/c-MET signaling plays an important role in cell proliferation, survival, migration and motility of cancer cells. Serine peptidase inhibitor Kunitz type 2 (SPINT2) binds to and inactivates the HGF activator (HGFA), behaving as an HGFA inhibitor (HAI) and impairing the conversion of pro-HGF into bioactive HGF...
February 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ruizeng Dong, Jianmin Guo, Zewei Zhang, Yimin Zhou, Yonghong Hua
The aim of this study was to identify the anti-cancer mechanism of Polyphyllin I (PPI) on gastric cancer cells via its activity on cancer-associated fibroblasts (CAFs). We cultured purified gastric CAFs obtained from fresh human gastric cancer tissue and examined the effect of Polyphyllin I on CAF proliferation using a colorimetric viability assay. In addition, we established a nude mouse xenograft model to examine the effect of Polyphyllin I administration on tumorigenesis. Using Western analysis, we quantified protein expression of the CAF-derived cytokines fibroblast activation protein alpha (FAP), secreted protein acidic and cysteine rich (SPARC), stromal cell-derived factor 1 (SDF-1), hepatocyte growth factor tenascin-C (TNC), and hepatocyte growth factor (HGF) in both in vitro and in vivo models...
February 27, 2018: Biochemical and Biophysical Research Communications
Grace Limandjaja, Lenie J van den Broek, Melanie Breetveld, Taco Waaijman, Stan Monstrey, Edith de Boer, Rik Scheper, Frank Niessen, Susan Gibbs
To understand scar pathology, develop new drugs, and provide a platform for personalized medicine, physiologically relevant human scar models are required which are characteristic of different scar pathologies. Hypertrophic scars and keloids are two types of abnormal scar resulting from unknown abnormalities in the wound healing process. While they display different clinical behavior, differentiation between the two can be difficult - which in turn means that it is difficult to develop optimal therapeutic strategies...
February 28, 2018: Tissue Engineering. Part C, Methods
Suneel Gupta, Michael K Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R Sinha, Ajay Sharma, Nathan P Hesemann, Shyam S Chaurasia, Elizabeth A Giuliano, Rajiv R Mohan
Purpose: We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models. Methods: Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n = 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n = 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n = 6)...
February 1, 2018: Investigative Ophthalmology & Visual Science
Zhong-Guo Fan, Xin-Liang Qu, Peng Chu, Ya-Li Gao, Xiao-Fei Gao, Shao-Liang Chen, Nai-Liang Tian
MicroRNA-210 (miRNA-210) has been reported to be associated with angiogenesis and may serve important roles in acute myocardial infarction (AMI), which remain unclear. The present study sought to evaluate the efficacy of miRNA‑210 in AMI and to examine the potential associated mechanisms. AMI models were established in Sprague‑Dawley rats. The expression of miRNA‑210 was upregulated via transfection with lentivirus‑mediated agonists and quantitative analysis was performed using the reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
February 20, 2018: Molecular Medicine Reports
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