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https://www.readbyqxmd.com/read/28447667/tweak-blockade-decreases-atherosclerotic-lesion-size-and-progression-through-suppression-of-stat1-signaling-in-diabetic-mice
#1
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
#2
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
#3
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
#4
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
#5
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
#6
Yale Liu, Lingling Peng, Liang Li, Chengfei Liu, Xiao Hu, Shengxiang Xiao, Yumin Xia
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in various cellular effects by engaging its receptor of fibroblast growth factor inducible 14 (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...
March 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28180936/fn14-hepatic-progenitor-cells-are-associated-with-liver-fibrosis-in-biliary-atresia
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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...
December 14, 2016: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/27888541/tweak-increases-sirt1-expression-and-promotes-p53-deacetylation-affecting-human-hepatic-stellate-cell-senescence
#13
Feng Zhang, Ming Zhang, Aixiu Wang, Mingcui Xu, Chen Wang, Guifang Xu, Bin Zhang, Xiaoping Zou, Yuzheng Zhuge
To detect the effects of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) on SIRT1 expression and p53 deacetylation, involving cell senescence, in activated human hepatic stellate cell (HSC) in vitro, human HSC LX-2 was cultured with TWEAK for 24 h. The result showed that the expression of membrane receptor Fn14 was remarkably increased by TWEAK, which upregulated SIRT1 in LX-2 cells, detected by Western blotting and real-time PCR. The expression of p53 was not significantly altered; however, the ac-p53 was decreased...
February 2017: Cell Biology International
https://www.readbyqxmd.com/read/27822714/tweak-fn14-influences-neurogenesis-status-via-modulating-nf-%C3%AE%C2%BAb-in-mice-with-spinal-cord-injury
#14
Jing Xu, Jian He, Huang He, Renjun Peng, Jian Xi
The aim of our research is to investigate the regulatory role of TNF-like weak inducer of apoptosis- fibroblast growth factor-inducible 14 (TWEAK-Fn14) pathway in nuclear factor-kappa B (NF-κB) expression and neurogenesis status after spinal cord injury (SCI). We constructed a mice model of spinal cord injury and injected different lentiviral vectors which were transfected with TWEAK, TWEAK small interfering RNA (siRNA) and Fn14 siRNA into different groups of mice. Locomotor functional recovery status of the hind limb in mice was assessed using the Basso, Beattie and Bresnahan (BBB) test...
November 7, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27821799/tweak-activation-of-the-non-canonical-nf-%C3%AE%C2%BAb-signaling-pathway-differentially-regulates-melanoma-and-prostate-cancer-cell-invasion
#15
Cheryl L Armstrong, Rebeca Galisteo, Sharron A N Brown, Jeffrey A Winkles
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a multifunctional cytokine that binds with high affinity to a plasma membrane-anchored receptor named Fn14. Both TWEAK and Fn14 expression has been detected in human cancer tissue, and studies have shown that TWEAK/Fn14 signaling can promote either "pro-cancer" or "anti-cancer" cellular effects in vitro, depending on the cancer cell line under investigation. In this study, we engineered murine B16 melanoma cells to secrete high levels of soluble TWEAK and examined their properties...
December 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27786399/roles-of-tumour-necrosis-factor-related-weak-inducer-of-apoptosis-fibroblast-growth-factor-inducible-14-pathway-in-lupus-nephritis
#16
REVIEW
Jingyun Chen, Linlin Wei, Yumin Xia
As one of the manifestations of patients with systemic lupus erythematosus, lupus nephritis (LN) has high morbidity and mortality. Although the explicit mechanism of LN remains to be fully elucidated, there is increasing evidence to support the notion that tumour necrosis factor-related weak inducer of apoptosis (TWEAK), acting via its sole receptor, fibroblast growth factor-inducible 14 (Fn14), plays a pivotal role in such pathologic process. TWEAK/Fn14 interactions occur prominently in kidneys of LN, inducing inflammatory responses, angiogenesis, mesangial proliferation, filtration barrier injuries, renal fibrosis, etc...
February 2017: Nephrology
https://www.readbyqxmd.com/read/27725864/tweak-protects-cardiomyocyte-against-apoptosis-in-a-pi3k-akt-pathway-dependent-manner
#17
Bin Yang, Ping Yan, Hui Gong, Lin Zuo, Ying Shi, Jian Guo, Rui Guo, Jun Xie, Bao Li
Myocyte apoptosis is a key determinant of cardiac recovery and prognosis of patients with acute myocardial infarction (AMI). Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK), a member of TNF superfamily, is a pro-inflammatory and pro-angiogenic cytokine implicated in physiological tissue regeneration and wound repair and is closely related to cardiac remodeling, dysfunction and fibrosis. However, the role of TWEAK and its receptor Fn14 in the cardiomyocyte apoptosis is still poorly understood...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27634763/protective-role-for-tweak-fn14-in-regulating-acute-intestinal-inflammation-and-colitis-associated-tumorigenesis
#18
Luca Di Martino, Maneesh Dave, Paola Menghini, Wei Xin, Kristen O Arseneau, Theresa T Pizarro, Fabio Cominelli
Inflammatory bowel disease causes chronic, relapsing intestinal inflammation that can lead to the development of colorectal cancer. Members of the TNF superfamily are key regulators of intestinal inflammation. In particular, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, Fn14, are involved in normal and pathologic intestinal tissue remodeling. In this study, we show that the TWEAK/Fn14 signaling complex plays a protective role during the acute stage of intestinal inflammation and contributes to the prevention of colitis-associated cancer during chronic inflammation through its proapoptotic effects...
November 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27631226/serum-soluble-tweak-levels-are-decreased-in-treatment-naive-noncirrhotic-chronic-hepatitis-b-patients
#19
Mehmet Asil, Ramazan Dertli
The mechanisms underlying hepatic inflammation and fibrogenesis in chronic hepatitis B (CHB) are complex and several cytokines are involved. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily which also acts as a cytokine. This study was conducted to evaluate serum soluble TWEAK (sTWEAK) levels in noncirrhotic CHB patients.Fifty-two treatment naive CHB patients and 30 healthy controls were included in the study and serum sTWEAK concentrations were measured using commercially available ELISA kits...
September 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27631110/molecular-survey-of-cell-source-usage-during-subtotal-hepatectomy-induced-liver-regeneration-in-rats
#20
Andrey Elchaninov, Timur Fatkhudinov, Natalia Usman, Evgeniya Kananykhina, Irina Arutyunyan, Andrey Makarov, Galina Bolshakova, Dmitry Goldshtein, Gennady Sukhikh
Proliferation of hepatocytes is known to be the main process in the hepatectomy-induced liver regrowth; however, in cases of extensive loss it may be insufficient for complete recovery unless supported by some additional sources e.g. mobilization of undifferentiated progenitors. The study was conducted on rat model of 80% subtotal hepatectomy; the objective was to evaluate contributions of hepatocytes and resident progenitor cells to the hepatic tissue recovery via monitoring specific mRNA and/or protein expression levels for a panel of genes implicated in growth, cell differentiation, angiogenesis, and inflammation...
2016: PloS One
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