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https://www.readbyqxmd.com/read/28715634/a-novel-strategy-utilizing-extracellular-cysteine-rich-domain-of-membrane-receptor-for-constructing-d-peptide-mediated-targeted-drug-delivery-systems-a-case-study-on-fn14
#1
Zhuoxuan Li, Jing Xie, Shan Peng, Sha Liu, Ying Wang, Weiyue Lu, Jie Shen, Chong Li
The development of proteolysis-resistant D-peptide ligands for targeted drug/gene delivery has been greatly limited, due to the challenge lies in the chemical synthesis of membrane receptors without altering their structures. In the present research, a novel strategy utilizing self-stabilized extracellular cysteine-rich domain (CRD) of membrane receptor was developed to construct D-peptide ligands and their mediated targeted drug delivery systems. Fibroblast growth factor-inducible 14 (Fn14), a cell surface receptor overexpressed in many cancers including pancreatic and triple-negative breast cancers, was selected as the model receptor...
July 17, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28639899/tweak-fn14-signaling-in-tumors
#2
REVIEW
Guanglei Hu, Weihui Zeng, Yumin Xia
TWEAK (tumor necrosis factor-related weak inducer of apoptosis), a member of the tumor necrosis factor superfamily, acts on cells by binding to its only receptor named Fn14 (fibroblast growth factor-inducible 14). Their engagement activates a number of intracellular signal transduction cascades and consequently leads to cell death, proliferation, migration, or survival depending on the cellular contexts. Studies have indicated that the expression of TWEAK and Fn14 is upregulated in many solid tumors compared with healthy tissues...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28636775/role-of-the-tumour-necrosis-factor-like-weak-inducer-of-apoptosis-tweak-fibroblast-growth-factor-inducible-14-fn14-axis-in-autoimmune-thyroid-disease
#3
Shiqiao Peng, Xiaohui Yu, Xuemin Zhao, Xinyi Wang, Xuren Sun, Cheng Han, Zhongyan Shan, Chenyan Li, Weiping Teng
BACKGROUND: TNF-like weak inducer of apoptosis (TWEAK), its receptor fibroblast growth factor-inducible 14 (Fn14) and its scavenger receptor CD163 (sCD163) have known associations with many autoimmune diseases. However, the role of the TWEAK axis in autoimmune thyroid disease (AITD) remains unclear. Therefore, the aim of this study was to investigate the role of the TWEAK-Fn14 axis in the pathogenesis of AITD. METHODS: Serum levels of soluble TWEAK (sTWEAK) and sCD163 were measured in 38 patients with Graves' disease (GD), 40 patients with Hashimoto's thyroiditis (HT), and 40 healthy controls (HCs)...
June 21, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28620393/tweak-fn14-activation-participates-in-ro52-mediated-photosensitization-in-cutaneous-lupus-erythematosus
#4
Yale Liu, Meifeng Xu, Xiaoyun Min, Kunyi Wu, Ting Zhang, Ke Li, Shengxiang Xiao, Yumin Xia
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28612578/-expression-of-tweak-fn14-in-pancreatic-cancer
#5
Ai-Lin Wei, Qiang Guo, Shu Gong
OBJECTIVES: To investigate the effect of tumor necrosis factor -related weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) on the proliferation and growth of pancreatic cancer. METHODS: Human pancreatic cancer (50 cases), chronic pancreatitis (40 cases) and normal pancreatic tissues (30 cases) were collected in West China Hospital from January 2012 to December 2013. TWEAK and Fn14 expressions in these tissues were checked with hematoxylin-eosin (HE) staining and immunohistochemistry method...
January 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28562476/fn14-blockade-on-pulmonary-microvascular-endothelial-cells-improves-the-outcome-of-sepsis-induced-acute-lung-injury
#6
Yun Zou, Suhong Bao, Fang Wang, Long Guo, Jiali Zhu, Jun Wang, Xiaoming Deng, Jinbao Li
Pulmonary microvascular leakage is one of the characteristics of blood-air barrier dysfunction in septic acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Fibroblast growth factor-inducible 14 (Fn14) exerts diverse functions under certain circumstances. However, the role of Fn14 on the integrity of pulmonary microvascular endothelial cells (PMVECs) during sepsis remains unknown. Septic ALI was induced via cecal ligation and puncture (CLP). Fn14 expression on PMVECs was measured 24 h after surgery...
May 30, 2017: Shock
https://www.readbyqxmd.com/read/28530223/tweak-mediates-inflammation-in-experimental-atopic-dermatitis-and-psoriasis
#7
Daniel Sidler, Ping Wu, Rana Herro, Meike Claus, Dennis Wolf, Yuko Kawakami, Toshiaki Kawakami, Linda Burkly, Michael Croft
Atopic dermatitis (AD) and psoriasis are driven by alternate type 2 and type 17 immune responses, but some proteins might be critical to both diseases. Here we show that a deficiency of the TNF superfamily molecule TWEAK (TNFSF12) in mice results in defective maintenance of AD-specific T helper type 2 (Th2) and psoriasis-specific Th17 cells in the skin, and impaired expression of disease-characteristic chemokines and cytokines, such as CCL17 and TSLP in AD, and CCL20 and IL-19 in psoriasis. The TWEAK receptor, Fn14, is upregulated in keratinocytes and dermal fibroblasts, and TWEAK induces these cytokines and chemokines alone and in synergy with the signature T helper cytokines of either disease, IL-13 and IL-17...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28455246/fn14%C3%A2-trail-fusion-protein-is-oligomerized-by-tweak-into-a-superefficient-trail-analog
#8
Tatyana B Prigozhina, Fanny Szafer, Alexandra Aronin, Kobi Tzdaka, Shira Amsili, Efi Makdasi, Noam Shani, Michal Dranitzki Elhalel
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) demonstrates specific anti-cancer activity, but insufficient efficacy in patients. A fusion protein Fn14·TRAIL, that combines soluble TRAIL molecule with a specific TWEAK receptor Fn14, is a better apoptosis-inducer for hepatocellular carcinomas than soluble TRAIL. However, Fn14·TRAIL does not effectively induce apoptosis in tumors of the lymphoid origin. As malignant cell apoptosis is strongly enhanced by secondary oligomerization of TRAIL, we tested the hypothesis that soluble Fn14·TRAIL can be oligomerized and become more active by adding TWEAK, a cytokine secreted in the tumor environment...
April 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28447667/tweak-blockade-decreases-atherosclerotic-lesion-size-and-progression-through-suppression-of-stat1-signaling-in-diabetic-mice
#9
Valvanera Fernández-Laso, Cristina Sastre, Nerea Méndez-Barbero, Jesús Egido, Jose L Martín-Ventura, Carmen Gómez-Guerrero, Luis M Blanco-Colio
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK/Tnfsf12) is a cytokine implicated in different steps associated with vascular remodeling. However, the role of TWEAK under hyperglycemic conditions is currently unknown. Using two different approaches, genetic deletion of Tnfsf12 and treatment with a TWEAK blocking mAb, we have analyzed the effect of TWEAK inhibition on atherosclerotic plaque progression and stability in streptozotocin-induced diabetic ApoE deficient mice. Genetic inactivation of Tnfsf12 reduced atherosclerosis extension and severity in diabetic ApoE deficient mice...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428709/disruption-of-the-tweak-fn14-pathway-prevents-5-fluorouracil-induced-diarrhea-in-mice
#10
Takuhito Sezaki, Yuki Hirata, Teruki Hagiwara, Yuki I Kawamura, Tadashi Okamura, Rieko Takanashi, Kenta Nakano, Miwa Tamura-Nakano, Linda C Burkly, Taeko Dohi
AIM: To clarify the roles of TWEAK and its receptor Fn14 in 5-fluorouracil (5-FU)-induced diarrhea. METHODS: Diarrhea was induced in wild-type (WT), Fn14 knockout (KO), and IL-13 receptor (IL-13R)α1 KO BALB/c mice using a single injection of 5-FU. Histological analysis, cytokine analysis, and flow cytometry was performed on ileal tissues and cells. Murine colon carcinoma-bearing mice were co-treated with an anti-TWEAK antibody and 5-FU. Embryonic fibroblast response to cytokines was also analyzed...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28411440/tweak-fn14-promotes-pro-inflammatory-cytokine-secretion-in-hepatic-stellate-cells-via-nf-%C3%AE%C2%BAb-stat3-pathways
#11
Aixiu Wang, Feng Zhang, Hui Xu, Mingcui Xu, Yu Cao, Chen Wang, Yuanyuan Xu, Min Su, Ming Zhang, Yuzheng Zhuge
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver disease. Hepatic stellate cells (HSCs) play a critical role in the hepatic wound-healing response after liver injury, but there is little information available on the role of the TWEAK/Fn14 pathway in human HSCs. In this study, we explored the role of TWEAK/Fn14 in activated human HSCs. The LX-2 cells were treated with TWEAK, and the expression of pro-inflammatory cytokines was assayed by enzyme-linked immunosorbent assay (ELISA) and real-time PCR (RT-PCR)...
April 12, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28358987/highly-selective-targeting-of-hepatic-stellate-cells-for-liver-fibrosis-treatment-using-a-d-enantiomeric-peptide-ligand-of-fn14-identified-by-mirror-image-mrna-display
#12
Luying Huang, Jing Xie, Qiuyan Bi, Zhuoxuan Li, Sha Liu, Qing Shen, Chong Li
Although liver fibrosis is a major public health issue, there is still no effective drug therapy in the clinic. Fibroblast growth factor-inducible 14 (Fn14), a membrane receptor highly specifically expressed in activated hepatic stellate cells (HSCs), is the key driver of liver fibrosis, and thus, it has a great potential as a novel target for the development of effective treatment. Here, we identified a d-enantiomeric peptide ligand of Fn14 through mirror-image mRNA display. This included the chemical synthesis of a d-enantiomer of the target protein (extracellular domain of Fn14), identification of an l-peptide ligand of d-Fn14 using a constructed mRNA peptide library, and identification of a d-enantiomer of the l-peptide, which is a ligand of the natural Fn14 for reasons of symmetry...
April 12, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28357912/bioinformatic-prediction-and-experimental-validation-of-a-pe38-based-recombinant-immunotoxin-targeting-the-fn14-receptor-in-cancer-cells
#13
Maryam Keshtvarz, Jafar Salimian, Mehdi Yaseri, Seyedeh Zahra Bathaie, Ehsan Rezaie, Amir Aliramezani, Zahra Norouzbabaei, Jafar Amani, Masoumeh Douraghi
AIM: AFn14R can serve as an ideal target for cancer immunotherapy. Here, a combined bioinformatic and experimental approach was applied to characterize an immunotoxin consisting of single-chain variable fragment antibody that targets Fn14 and a toxin fragment (PE38). METHODS & RESULTS: Flow cytometry results showed that the rate of PE38-P4A8 binding to Fn14 was approximately 60 and 40% in HT-29 and A549 cells, respectively. Moreover, 1 ng/µl of immunotoxin was able to lyse approximately 53 and 41% of HT-29 and A549, respectively...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28351660/tweak-fn14-activation-contributes-to-the-pathogenesis-of-bullous-pemphigoid
#14
Yale Liu, Lingling Peng, Liang Li, Chengfei Liu, Xiao Hu, Shengxiang Xiao, Yumin Xia
TWEAK participates in various cellular effects by engaging its receptor of Fn14. Increased levels of soluble TWEAK are associated with systemic autoimmunity in patients with lupus erythematosus, rheumatoid arthritis, or dermatomyositis. However, the role of TWEAK in bullous pemphigoid (BP) remains unknown. In this study, we found an elevated serum level of TWEAK and a positive correlation between serum TWEAK and anti-BP180 antibodies. Immunohistochemistry showed strong TWEAK and Fn14 expression and implied an opposite relationship between the TWEAK and BP180 expression in skin samples from BP patients...
July 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28180936/fn14-hepatic-progenitor-cells-are-associated-with-liver-fibrosis-in-biliary-atresia
#15
Lulu Zheng, Zhibao Lv, Zhenhua Gong, Qingfeng Sheng, Zhimei Gao, Yuting Zhang, Shenghua Yu, Junmei Zhou, Zhengjun Xi, Xueli Wang
PURPOSE: The liver in biliary atresia (BA) is characterized by progressing fibrosis which is promoted by unclear reasons. We aimed to understand the factors influencing liver fibrosis. This study hypothesized that HPCs (hepatic progenitor cells) are activated and associated with liver fibrosis in biliary atresia. METHODS: Liver samples from biliary atresia patients are as BA group, and the normal liver derived from hepatoblastoma infants during operation are control group...
May 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28138221/immunotherapy-for-the-treatment-of-colorectal-tumors-focus-on-approved-and-in-clinical-trial-monoclonal-antibodies
#16
REVIEW
Alex Françoso, Patricia Ucelli Simioni
Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28103571/identification-of-aurintricarboxylic-acid-as-a-selective-inhibitor-of-the-tweak-fn14-signaling-pathway-in-glioblastoma-cells
#17
Alison Roos, Harshil D Dhruv, Ian T Mathews, Landon J Inge, Serdar Tuncali, Lauren K Hartman, Donald Chow, Nghia Millard, Holly H Yin, Jean Kloss, Joseph C Loftus, Jeffrey A Winkles, Michael E Berens, Nhan L Tran
The survival of patients diagnosed with glioblastoma (GBM), the most deadly form of brain cancer, is compromised by the proclivity for local invasion into the surrounding normal brain, which prevents complete surgical resection and contributes to therapeutic resistance. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor (TNF) superfamily, can stimulate glioma cell invasion and survival via binding to fibroblast growth factor-inducible 14 (Fn14) and subsequent activation of the transcription factor NF-κB...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28095113/quantitative-analysis-of-cell-surface-antigen-antibody-interaction-using-gaussia-princeps-luciferase-antibody-fusion-proteins
#18
Juliane Kums, Johannes Nelke, Benedikt Rüth, Viktoria Schäfer, Daniela Siegmund, Harald Wajant
Cell surface antigen-specific antibodies are of substantial diagnostic and therapeutic importance. The binding properties of such antibodies are usually evaluated by cell-free assays, in particular surface plasmon resonance (SPR) analysis, or flow cytometry. SPR analyses allow the detailed quantitative and dynamic evaluation of the binding properties of antibodies, but need purified, typically recombinantly produced antigens. It can, however, be difficult to produce the required antigen. Furthermore, cellular factors influencing the antigen-antibody interaction are not considered by this method...
April 2017: MAbs
https://www.readbyqxmd.com/read/28025386/tweak-up-regulates-endothelin-1-system-in-mouse-and-human-endothelial-cells
#19
Patricia Martínez-Miguel, Diana Medrano-Andrés, Mercedes Griera-Merino, Alberto Ortiz, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Susana López-Ongil
AIM: To analyse the ability of TWEAK to modify the endothelin system, particularly endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1), studying the intracellular mechanisms implied. TNF-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily; it has different biological functions such as inflammation, angiogenesis, proliferation, and apoptosis. TWEAK and fibroblast growth-factor-inducible 14 are expressed in different cell types, including endothelial and smooth muscle cells...
February 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/27984220/molecular-mechanism-of-the-babysitter-procedure-for-nerve-regeneration-and-muscle-preservation-in-peripheral-nerve-repair-in-a-rat-model
#20
Hai-Fei Liu, Zeng-Gan Chen, William C Lineaweaver, Michael T Friel, Feng Zhang
OBJECTIVE: To investigate the molecular mechanism of nerve "babysitter" for nerve regeneration and muscle preservation in peripheral nerve repair. METHODS: Eighty rats were equalized into 4 groups: peroneal nerve transected, group A received no treatment; group B underwent end-to-end repair; group C underwent end-to-side "babysitter" with donor epineurial window; group D underwent end-to-side "babysitter" with 40% donor neurectomy. During second-stage procedure, end-to-end neurorrhaphies were executed in groups A, C, and D...
June 2017: Annals of Plastic Surgery
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