Read by QxMD icon Read


Fang Zhang, Catherine Sodroski, Helen Cha, Qisheng Li, T Jake Liang
BACKGROUND & AIMS: The signaling molecule and transcriptional regulator SMAD6, which inhibits the transforming growth factor beta (TGFB) signaling pathway, is required for infection of hepatocytes by hepatitis C virus (HCV). We investigated the mechanisms by which SMAD6, and another inhibitory SMAD (SMAD7), promote HCV infection in human hepatoma cells and hepatocytes. METHODS: We infected Huh7 and Huh7.5.1 cells and primary human hepatocytes with JFH1 HCVcc; we measured HCV binding, intracellular levels of HCV RNA, and expression of target genes...
September 29, 2016: Gastroenterology
Giuliana Cassinelli, Nadia Zaffaroni, Cinzia Lanzi
Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression...
September 22, 2016: Cancer Letters
K G F Gerritsen, N Bovenschen, T Q Nguyen, D Sprengers, M P Koeners, A N van Koppen, J A Joles, R Goldschmeding, R J Kok
CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min)...
September 19, 2016: Journal of Cell Communication and Signaling
Alexander Arthur, Phillip J McCall, Lisa Jolly, John Kinsella, Alan Kirk, Ben G Shelley
AIM: We investigated if the serum biomarkers of endothelial glycocalyx layer (EGL) disruption, heparan sulfate proteoglycan (HSPG) and syndecan-1 (SDC1) were elevated following lung resection surgery. METHODS: Plasma samples were collected from 16 patients undergoing lobectomy for primary lung cancer. HSPG and SDC1 were measured at five perioperative timepoints. Postoperative oxygenation was recorded. RESULTS: Post-hoc pair wise comparisons showed SDC1 concentration was significantly elevated on postoperative day 2, p < 0...
October 2016: Biomarkers in Medicine
Shin Kumagai, Kei Ishibashi, Masao Kataoka, Toshiki Oguro, Yuichirou Kiko, Tomohiko Yanagida, Ken Aikawa, Yoshiyuki Kojima
Heparan sulfate-specific endosulfatase-2, SULF-2, can modulate the signaling of HSPG-binding proteins. The involvement of SULF-2 in cancer growth varies by cancer type. The roles of SULF-2 expression in the progression and prognosis of renal cell carcinomas (RCCs) have not yet been fully clarified. In the present study, the expression levels of SULF-2 mRNA and protein in 49 clinical RCC samples were determined by RT-PCR and immunostaining. The existence of RCCs with higher SULF-2 expression and lower SULF-2 expression compared to the adjacent normal kidney tissues was suggested...
September 2, 2016: Cancer Science
Quanyin Hu, Ting Kang, Jingxian Feng, Qianqian Zhu, Tianze Jiang, Jianhui Yao, Xinguo Jiang, Jun Chen
Advances in active targeting drug delivery system (DDS) have revolutionized glioma diagnosis and therapy. However, the lack of the sufficient targets on glioma cells and limited penetration capability of DDS have significantly compromised the treatment efficacy. In this study, by taking advantages of the abundant extracellular matrix-derived heparan sulfate proteoglycan (HSPG) and enhanced tumor penetration ability mediated by neuropilin-1 (NRP-1) protein, we reported the ATWLPPR and CGKRK peptide dual-decorated nanoparticulate DDS (designated AC-NP) to achieve angiogenic blood vessels and tumor microenvironment dual-targeting effect...
September 14, 2016: ACS Applied Materials & Interfaces
Kenton T Woodard, Katharine J Liang, William C Bennett, R Jude Samulski
: Many adeno-associated virus (AAV) serotypes efficiently transduce the retina when delivered to the subretinal space but show limited success when delivered to the vitreous due to the inner limiting membrane (ILM). Subretinal delivery of AAV serotype 2 (AAV2) and its heparan sulfate (HS)-binding-deficient capsid led to similar expression, indicating transduction of the outer retina occurred by HS-independent mechanisms. However, intravitreal delivery of HS-ablated recombinant AAV2 (rAAV2) led to a 300-fold decrease in transduction compared to AAV2...
November 1, 2016: Journal of Virology
J-X Liu, Z-P Yan, Y-Y Zhang, J Wu, X-H Liu, Y Zeng
We have previously demonstrated the adaptive remodeling of endothelial glycocalyx under shear stress. However, the underlying mechanism in glycocalyx remodeling, especially the expression of the components heparan sulfate proteoglycans (HSPGs) under shear stress was not completely known. In the present study, we investigated the expression of those HSPGs (syndecan family and glypican-1) in human umbilical vein endothelial cells (HUVECs) responded to the distinct magnitude of shear stress, and performed a systematic and comprehensive analyze on the relationship between shear stress and HSPGs mRNA expression in a temporal manner...
2016: Cellular and Molecular Biology
Daniel Sepúlveda-Crespo, Rafael Ceña-Díez, José Luis Jiménez, Ma Ángeles Muñoz-Fernández
This review provides an overview of the development of different dendrimers, mainly polyanionic, against human immunodeficiency virus (HIV) and genital herpes (HSV-2) as topical microbicides targeting the viral entry process. Vaginal topical microbicides to prevent sexually transmitted infections such as HIV and HSV-2 are urgently needed. To inhibit HIV/HSV-2 entry processes, new preventive targets have been established to maximize the current therapies against wild-type and drug-resistant viruses. The entry of HIV/HSV-2 into target cells is a multistep process that triggers a cascade of molecular interactions between viral envelope proteins and cell surface receptors...
August 12, 2016: Medicinal Research Reviews
Bin Yi, Yinghe Qiu, Weidan Ji, Miaoyan Wei, Chunying Liu, Zhangxiao Peng, Yongjie Zhang, Zhiwei Quan, Zhaohui Tang, Changqing Su
Cell surface heparan sulfate proteoglycan (HSPG) is a group of critical glycoproteins that mediates signal transduction. Sulfated HSPG can mediate the activation of a variety of cell growth factor signal pathway to promote the progression of gallbladder carcinoma (GBC). This study analyzed 527 clinical GBC specimens and confirmed that the HSPG sulfation level was significantly higher in GBC tissues than in gallbladder mucosa (GBM) tissues. The high HSPG sulfation level was closely associated with poor differentiation, local metastasis, and advanced clinical stage of GBC; it was also associated with the shortening of disease-free survival (DFS) and overall survival (OS) and influenced the outcome of chemotherapy or radio-chemotherapy in patients with GBC recurrence...
October 28, 2016: Cancer Letters
Frederic Mercier
The stem cell niche refers to a specific microenvironment where stem cells proliferate and differentiate to produce new specialized cells throughout an organism's adulthood. Growth factors are crucial signaling molecules that diffuse through the extracellular space, reach the stem cell niche, and ultimately promote stem cell proliferation and differentiation. However, it is not well known how multiple growth factors, often with antagonistic activities, work together in the stem cell niche to select target stem cell populations and determine stem cell fate...
July 30, 2016: Cellular and Molecular Life Sciences: CMLS
Philip L S M Gordts, Ryan Nock, Ni-Huiping Son, Bastian Ramms, Irene Lew, Jon C Gonzales, Bryan E Thacker, Debapriya Basu, Richard G Lee, Adam E Mullick, Mark J Graham, Ira J Goldberg, Rosanne M Crooke, Joseph L Witztum, Jeffrey D Esko
Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1)...
August 1, 2016: Journal of Clinical Investigation
Stefan Seitz, Caroline Iancu, Tassilo Volz, Walter Mier, Maura Dandri, Stephan Urban, Ralf Bartenschlager
Hepatitis B virus (HBV) replication is strictly limited to the liver. Virions attach to hepatocytes through interactions of the viral PreS envelope protein domain with heparan sulfate proteoglycans (HSPGs). However, HSPG is ubiquitously present on many cell types, suggesting that HBV employs mechanisms to avoid attachment at extrahepatic sites. We demonstrate that HBV particles are released from cells in an inactive form with PreS hidden in the interior. These HSPG-non-binding (N-type) particles develop receptor binding competence by translocating PreS across the envelope onto their surface...
July 13, 2016: Cell Host & Microbe
Julien A Menard, Helena C Christianson, Paulina Kucharzewska, Erika Bourseau-Guilmain, Katrin J Svensson, Eva Lindqvist, Vineesh Indira Chandran, Lena Kjellén, Charlotte Welinder, Johan Bengzon, Maria C Johansson, Mattias Belting
Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity...
August 15, 2016: Cancer Research
Delphine Knittel, Adeline Gadzinski, Stéphane Hua, Jordan Denizeau, Alexandra Savatier, Philippe de la Rochère, Jean-Claude Boulain, Sebastian Amigorena, Eliane Piaggio, Christine Sedlik, Michel Léonetti
Heparan sulfates (HS) are carbohydrate moieties of HS proteoglycans (HSPGs). They often represent alternative attachment points for proteins or microorganisms targeting receptors. HSPGs, which are ubiquitously expressed, thereby participate in numerous biological processes. We previously showed that MHC class II-restricted antigen presentation is increased when antigens are coupled to HS ligands, suggesting that HSPGs might contribute to adaptive immune responses. Here, we examined if HSPG targeting influences other aspects of immune responses...
June 8, 2016: Vaccine
Yuan Fu, Jing Zhao, Yuka Atagi, Henrietta M Nielsen, Chia-Chen Liu, Honghua Zheng, Mitsuru Shinohara, Takahisa Kanekiyo, Guojun Bu
BACKGROUND: The accumulation, aggregation and deposition of amyloid-β (Aβ) peptides in the brain are central to the pathogenesis of Alzheimer's disease (AD). Alzheimer's disease risk increases significantly in individuals carrying one or two copies of APOE ε4 allele compared to individuals with an ε3/ε3 genotype. Growing evidence has demonstrated that apolipoprotein E (apoE) strongly influences AD pathogenesis by controlling Aβ aggregation and metabolism. Heparan sulphate proteoglycans (HSPGs) are abundant cell surface molecules that bind to both apoE and Aβ...
2016: Molecular Neurodegeneration
Ning Luo, Hongda Li, Bo Xiang, Liangjun Qiao, Jiao He, Yi Ji, Yuan Liu, Siying Li, Ran Lu, Yu Li, Wentong Meng, Yang Wu, Hong Xu, Xianming Mo
Syndecan-4 (Syn4), a single-pass transmembrane heparin sulphate proteoglycan (HSPG), plays significant role in the formation of focal adhesions and interacts with many growth factors to regulate cell migration and neural induction. Here, we show the new roles of syndecan-4(syn4) in zebrafish embryonic neurogenesis. Syn4 is broadly and dynamically expressed throughout the early stages of embryonic development. Knockdown of syn4 increases the expression of the marker genes of multiple types of neural cells. The increased expression of the marker genes is resulted from excessive proliferation of the neural cells...
2016: Scientific Reports
Hsu-Kun Wang, Qing Wei, Zina Moldoveanu, Warner K Huh, Huong Lan Vu, Thomas R Broker, Jiri Mestecky, Louise T Chow
The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia...
June 8, 2016: Vaccine
Hang Chen, Zhihui Gao, Changzheng He, Rong Xiang, Toin H van Kuppevelt, Mattias Belting, Sihe Zhang
Therapeutic macromolecules are internalized into the cell by either clathrin-mediated endocytosis (CME) or clathrin-independent endocytosis (CIE). Although some chaperone proteins play an essential role in CME (e.g. Hsc70 in clathrin uncoating), relatively few of these proteins are functionally involved in CIE. We previously revealed a role for the mitochondrial chaperone protein GRP75 in heparan sulfate proteoglycan (HSPG)-mediated, membrane raft-associated macromolecule endocytosis. However, the mechanism underlying this process remains unclear...
May 1, 2016: Experimental Cell Research
Zhou Jing, Yuan Wei-Jie, Zhu-Ge Yi-Feng, Hao Jing
Ischemic acute kidney injury (AKI) remains to have high morbidity and mortality rates. The mechanism of glomerular endothelial cells (GEnC) dysfunction in the development of ischemic AKI is still unclear. Syndecan-1, one kind of heparan sulfate proteoglycan (HSPG), is extensively studied in tumor for its effects in promoting angiogenesis. In this study, we found that, Syndecan-1 was reduced in GEnC both in vivo and in vitro after hypoxia treatment. Besides, down-regulation of Syndecan-1 could lead to dysfunction and apoptosis of GEnC, as indicated by increased cell permeability, decreased cell viability and inhibited tube formation...
August 2016: Cellular Signalling
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"