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Sajjad Karim, Jaudah A Al-Maghrabi, Hasan M A Farsi, Ahmad J Al-Sayyad, Hans-Juergen Schulten, Abdelbaset Buhmeida, Zeenat Mirza, Alaa A Al-Boogmi, Fai T Ashgan, Manal M Shabaad, Hend F NourEldin, Khalid B M Al-Ghamdi, Adel Abuzenadah, Adeel G A Chaudhary, Mohammed H Al-Qahtani
BACKGROUND: Renal cell carcinoma (RCC) is a seventh ranked malignancy with poor prognosis. RCC is lethal at metastatic stage as it does not respond to conventional systemic treatments, and there is an urgent need to find out promising novel biomarkers for effective treatment. The goal of this study was to evaluate the biomarkers that can be potential therapeutic target and predict effective inhibitors to treat the metastatic stage of RCC. METHODS: We conducted transcriptomic profiling to identify differentially expressed genes associated with RCC...
September 30, 2016: BMC Cancer
Joern Pezoldt, Jochen Huehn
Upon differentiation, T cells acquire tissue-specific homing properties allowing efficient targeting of effector T cells into distinct inflamed organs. Priming of T cells within skin-draining, peripheral lymph nodes (pLNs) leads to the expression of E- and P-selectin ligands, which facilitate migration into inflamed skin, whereas activation within gut-draining, mesenteric LNs (mLNs) results in induction of chemokine receptor CCR9 and integrin α4β7, both required for migration of effector T cells into mucosal tissues...
September 29, 2016: European Journal of Microbiology & Immunology
Patrick Mucka, Nicholas Levonyak, Elena Geretti, Bernadette M M Zwaans, Xiaoran Li, Irit Adini, Michael Klagsbrun, Rosalyn M Adam, Diane R Bielenberg
The vasculature influences the progression and resolution of tissue inflammation. Capillaries express vascular endothelial growth factor (VEGF) receptors, including neuropilins (NRPs), which regulate interstitial fluid flow. NRP2, a receptor of VEGFA and semaphorin (SEMA) 3F ligands, is expressed in the vascular and lymphatic endothelia. Previous studies have demonstrated that blocking VEGF receptor 2 attenuates VEGFA-induced vascular permeability. The inhibition of NRP2 was hypothesized to decrease vascular permeability as well...
October 12, 2016: American Journal of Pathology
G Wang, P-P Wang, P-P Meng, C Han, S-W Yue
OBJECTIVE: Cerebral ischemia-reperfusion is the major pathophysiological process in stroke and can cause severe and lasting sequel. However, an intensive exercise training can potentially effect a quick and efficient recovery. We used swimming training on rats with cerebral ischemia-reperfusion (CIR) and explore the underlying neuroprotective mechanism(s), including the effects of intensive training on the expression of semaphorin 3A (Sema3A) and its receptor Neuropilin-1 (NRP-1). MATERIALS AND METHODS: The middle cerebral artery occlusion/reperfusion (MCAO/R) model was established by inserting a thread into the middle cerebral artery of Sprague-Dawley (SD) rats, and randomly dividing into the control group and training groups for different training intensities...
September 2016: European Review for Medical and Pharmacological Sciences
Tamas Yelland, Snezana Djordjevic
Neuropilins (NRPs) are single-pass transmembrane receptors involved in several signaling pathways that regulate key physiological processes such as vascular morphogenesis and axon guidance. The MAM domain of NRP, which has previously been implicated in receptor multimerization, was the only portion of the ectopic domain of the NRPs for which the structure, until now, has been elusive. Using site-directed mutagenesis in the linker region preceding the MAM domain we generated a protein construct amenable to crystallization...
October 3, 2016: Structure
Man Ying, Qing Shen, Changyou Zhan, Xiaoli Wei, Jie Gao, Cao Xie, Bingxin Yao, Weiyue Lu
Peptide ligands consisting of l-amino acids are subject to proteolysis in vivo. When modified on the surface of nanocarriers, those peptide ligands would readily degrade and the targeting efficacy is significantly attenuated. It has received increasing scrutiny to design stable peptide ligands for targeted drug delivery. Here, we present the design of a stable peptide ligand by the formation of a head-to-tail amide bond as an example. Even though the linear l-peptide A7R (termed (L)A7R) can bind specifically to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) that are overexpressed on glioma cells, neovasculature and glioma vasculogenic mimicry (VM), the tumor-homing capacity of (L)A7R is greatly impaired in vivo due to proteolysis (e...
September 29, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
Teclise Ng, Catherine H H Hor, Benjamin Chew, Jing Zhao, Zhong Zhong, Jae Ryun Ryu, Eyleen L K Goh
Proper positioning of neurons is fundamental for brain functions. However, little is known on how adult-born neurons generated in the hilar side of hippocampal dentate gyrus (DG) migrate into the granular cell layer (GCL). Since class 3 Semaphorins (Sema3) are involved in dendritic growth of these newborn neurons, we examined if they are essential for cell positioning. We disrupted Sema3 signaling by silencing neuropilin 1 (NRP1) or 2 (NRP2), the main receptors for Sema3A and 3F, in neural progenitors of adult mouse DG...
September 29, 2016: Journal of Biological Chemistry
Shelley Gorman, Sian Geldenhuys, Melinda Judge, Clare E Weeden, Jason Waithman, Prue H Hart
Skin inflammatory responses in individuals with allergic dermatitis may be suppressed by dietary vitamin D through induction and upregulation of the suppressive activity of regulatory T (TReg) cells. Vitamin D may also promote TReg cell tropism to dermal sites. In the current study, we examined the capacity of dietary vitamin D3 to modulate skin inflammation and the numbers and activity of TReg cells in skin and other sites including lungs, spleen, and blood. In female BALB/c mice, dietary vitamin D3 suppressed the effector phase of a biphasic ear swelling response induced by dinitrofluorobenzene in comparison vitamin D3-deficient female BALB/c mice...
2016: Journal of Immunology Research
Hani Al-Shareef, Shin-Ichiro Hiraoka, Noriaki Tanaka, Yosuke Shogen, Atsushi-Doksa Lee, Sanam Bakhshishayan, Mikihiko Kogo
Lymph node (LN) metastasis has been suggested as a major prognostic factor for oral cancer. Knockdown of the growth factors and receptors involved in these metastatic mechanisms could significantly reduce LN metastasis and improve the survival of oral cancer patients after treatment. The present study, therefore, aimed to evaluate the expression levels of the following growth factors and receptors in squamous cell carcinoma (SCC) of the tongue: the vascular endothelial growth factor (VEGF)‑C and VEGF‑D, which bind to the cell surface tyrosine kinase receptor VEGF receptor‑3 (VEGFR‑3); C‑C motif chemokine receptor 7 (CCR7); neuropilin (NRP)1 and NRP2; and semaphorin 3E (SEMA3E)...
September 21, 2016: Oncology Reports
Armania Nurdin, Yutaro Hoshi, Toshihiro Yoneyama, Eisuke Miyauchi, Masanori Tachikawa, Michitoshi Watanabe, Tetsuya Terasaki
Prostate-specific antigen is currently the only protein biomarker routinely used as a diagnostic tool for early detection and treatment monitoring of prostate cancer. However, it remains questionable whether prostate-specific antigen-based screening can sensitively and selectively identify the presence and progression status of primary and metastatic prostate cancers. Hence, the purpose of this study was to identify potential biomarker candidates in the secretome of primary and metastatic prostate cancer cells by using a combination of global and targeted proteomics...
November 2016: Journal of Pharmaceutical Sciences
Hong Xin, Cuiling Zhong, Eric Nudleman, Napoleone Ferrara
The VEGF-A isoforms play a crucial role in vascular development, and the VEGF signaling pathway is a clinically validated therapeutic target for several pathological conditions. Alternative mRNA splicing leads to the generation of multiple VEGF-A isoforms, including VEGF165. A recent study reported the presence of another isoform, VEGF-Ax, arising from programmed readthrough translation. Compared to VEGF165, VEGF-Ax has a 22-amino-acid extension in the COOH terminus and has been reported to function as a negative regulator of VEGF signaling in endothelial cells, with potent anti-angiogenic effects...
September 22, 2016: Cell
Chang Liu, Sen Yao, Xuqian Li, Feng Wang, Yanyan Jiang
iRGD (internalizing RGD) with high affinity to αν integrins was reported to enhance tumor penetrability by binding to neuropilin-1 (NRP-1). Based on our previous study, chitosan surface-modified poly (lactide-co-glycolides) nanoparticles (PLGA/CS NPs), loaded with carmustine (BCNU) and its sensitizer (O(6)-benzylguanine, BG) showed stronger anti-tumor effect than free drugs. In present study, PLGA/CS NPs (NPs) with core-shell structure were prepared and modified with iRGD or mPEG. F98, C6 or U87 cell lines with different receptors levels were selected for in vitro and in vivo studies...
October 6, 2016: Journal of Drug Targeting
Mylène Richard, Alicia Chateau, Christian Jelsch, Claude Didierjean, Xavier Manival, Christophe Charron, Bernard Maigret, Muriel Barberi-Heyob, Yves Chapleur, Cédric Boura, Nadia Pellegrini-Moïse
Neuropilin-1 (NRP-1), a transmembrane glycoprotein acting as a co-receptor of VEGF-A, is expressed by cancer and angiogenic endothelial cells and is involved in the angiogenesis process. Taking advantage of functionalities and stereodiversities of sugar derivatives, the design and the synthesis of carbohydrate based peptidomimetics are here described. One of these compounds (56) demonstrated inhibition of VEGF-A165 binding to NRP-1 (IC50=39μM) and specificity for NRP-1 over VEGF-R2. Biological evaluations were performed on human umbilical vein endothelial cells (HUVECs) through activation of downstream proteins (AKT and ERK phosphorylation), viability/proliferation assays and in vitro measurements of anti-angiogenic abilities...
November 1, 2016: Bioorganic & Medicinal Chemistry
Ludovic Telley, Christelle Cadilhac, Jean-Michel Cioni, Veronique Saywell, Céline Jahannault-Talignani, Rosa E Huettl, Catherine Sarrailh-Faivre, Alexandre Dayer, Andrea B Huber, Fabrice Ango
Subcellular target recognition in the CNS is the culmination of a multiple-step program including axon guidance, target recognition, and synaptogenesis. In cerebellum, basket cells (BCs) innervate the soma and axon initial segment (AIS) of Purkinje cells (PCs) to form the pinceau synapse, but the underlying mechanisms remain incompletely understood. Here, we demonstrate that neuropilin-1 (NRP1), a Semaphorin receptor expressed in BCs, controls both axonal guidance and subcellular target recognition. We show that loss of Semaphorin 3A function or specific deletion of NRP1 in BCs alters the stereotyped organization of BC axon and impairs pinceau synapse formation...
September 21, 2016: Neuron
Berna Senturk, M Ozgur Cubuk, M Cuneyt Ozmen, Bahri Aydin, Mustafa O Guler, Ayse B Tekinay
Atypical angiogenesis is one of the major symptoms of severe eye diseases, including corneal neovascularization, and the complex nature of abnormal vascularization requires targeted methods with high biocompatibility. The targeting of VEGF is the most common approach for preventing angiogenesis, and the LPPR peptide sequence is known to strongly inhibit VEGF activity by binding to the VEGF receptor neuropilin-1. Here, the LPPR epitope is presented on a peptide amphiphile nanofiber system to benefit from multivalency and increase the anti-angiogenic function of the epitope...
November 2016: Biomaterials
Nathalie Van Acker, Michael Ragé, Hilde Vermeirsch, Dorien Schrijvers, Rony Nuydens, Geert Byttebier, Maarten Timmers, Stefanie De Schepper, Johannes Streffer, Luc Andries, Léon Plaghki, Patrick Cras, Theo Meert
The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). Since mismatches between functional and morphological nerve fiber recovery are described for this model, we aimed at determining the capability of the capsaicin model to truly mimic the morphological manifestations of SFN in diabetes. As nerve and blood vessel growth and regenerative capacities are defective in diabetes, we focused on studying the key regulator of these processes, the neuropilin-1 (NRP-1)/semaphorin pathway...
2016: PloS One
Ying Wang, Ying Cao, Ashutosh K Mangalam, Yong Guo, Reghann G LaFrance-Corey, Jeffrey D Gamez, Pascal Aliihnui Atanga, Benjamin D Clarkson, Yuebo Zhang, Enfeng Wang, Ramcharan Singh Angom, Kirthica Dutta, Baoan Ji, Istvan Pirko, Claudia F Lucchinetti, Charles L Howe, Debabrata Mukhopadhyay
Inflammatory response of blood-brain barrier (BBB) endothelial cells plays an important role in pathogenesis of many central nervous system inflammatory diseases, including multiple sclerosis; however, the molecular mechanism mediating BBB endothelial cell inflammatory response remains unclear. In this study, we first observed that knockdown of neuropilin-1 (NRP1), a co-receptor of several structurally diverse ligands, suppressed interferon-γ (IFNγ)-induced C-X-C motif chemokine 10 expression and activation of STAT1 in brain microvascular endothelial cells in a Rac1-dependent manner...
October 15, 2016: Journal of Cell Science
Tomokazu Fujimoto, Toshihiro Inoue, Kei Maki, Miyuki Inoue-Mochita, Hidenobu Tanihara
PURPOSE: Anti-vascular endothelial growth factor (VEGF) antibody therapy is an effective treatment for ocular angiogenesis. Although the intraocular pressure of some patients increases after anti-VEGF therapy, the effects of VEGF-A on the aqueous humor outflow pathway remain unknown. This study investigated the effects of VEGF-A on the aqueous humor outflow pathway. METHODS: We used human recombinant VEGF121 and VEGF165. Trabecular meshwork (TM) and Schlemm's canal endothelial (SCE) cells were isolated from the eyes of cynomolgus monkeys...
2016: PloS One
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
Alexis Assens, Julien Dal Col, Anthony Njoku, Quentin Dietschi, Chenda Kan, Paul Feinstein, Alan Carleton, Ivan Rodriguez
The building of the topographic map in the mammalian olfactory bulb is explained by a model based on two axes along which sensory neurons are guided: one dorso-ventral and the other antero-posterior. This latter axis relies on specific expression levels of Neuropilin 1 (Nrp1). To evaluate the role played by this receptor in this process, we used an in vivo genetic approach to decrease or suppress it in specific neuronal populations and at different time points during axonal targeting. We observed, in neurons that express either the M71 or the M72 odorant receptors, that the inactivation of Nrp1 leads to two distinct wiring alterations, whose incidence depends on the time at which Nrp1 expression is altered: first, a surprising dorsal shift of the M71 and M72 glomeruli that often fuse with their contralateral counterparts, and second, the formation of anteriorized glomeruli...
August 30, 2016: Development
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