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https://www.readbyqxmd.com/read/28073291/future-of-raav-gene-therapy-platform-for-rnai-gene-editing-and-beyond
#1
Paul Valdmanis, Mark A Kay
The use of recombinant adeno-associated viruses (rAAVs) ushered in a new millennium of gene transfer for therapeutic treatment of a number of conditions including congenital blindness, hemophilia, and spinal muscular atrophy (SMA). rAAV vectors have remarkable staying power from a therapeutic standpoint withstanding several ebbs and flows. As new technologies such as clustered regularly interspaced short palindromic repeat (CRISPR) genome editing emerge, it is now the delivery tool - the AAV vector - that is the stalwart...
January 10, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28040992/tweak-is-not-elevated-in-patients-with-newly-diagnosed-inflammatory-bowel-disease
#2
Tore Grimstad, Inger Marie Skoie, Jessica Doerner, Kjetil Isaksen, Lars Karlsen, Lars Aabakken, Roald Omdal, Chaim Putterman
OBJECTIVE: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) may be involved in the pathogenesis of inflammatory bowel disease. The aim was to investigate if TWEAK may reflect disease activity in inflammatory bowel disease. MATERIALS AND METHODS: In this cohort study, 139 consecutive patients with newly diagnosed and previously untreated inflammatory bowel disease - 95 with ulcerative colitis (UC) and 44 with Crohn's disease (CD) - underwent colonoscopy...
December 31, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28025386/tweak-up-regulates-endothelin-1-system-in-mouse-and-human-endothelial-cells
#3
Patricia Martínez-Miguel, Diana Medrano-Andrés, Mercedes Griera-Merino, Alberto Ortiz, Manuel Rodríguez-Puyol, Diego Rodríguez-Puyol, Susana López-Ongil
: 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 Fn14 are expressed in different cell types, including endothelial and smooth muscle cells. Despite their presence in endothelial cells, the effect of TWEAK on endothelial function is incompletely defined. AIM: To analyze the ability of TWEAK to modify the endothelin system, particularly ET-1 and ECE-1, studying the intracellular mechanisms implied...
December 25, 2016: 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
#4
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/27983476/tnf-superfamily-members-promote-hepatitis-c-virus-entry-via-an-nf-%C3%AE%C2%BAb-and-myosin-light-chain-kinase-dependent-pathway
#5
Nicola Fletcher, Andrew R Clark, Peter Balfe, Jane McKeating
Preventing viral induced liver disease begins with an understanding of the host factors that define susceptibility to infection. Hepatitis C Virus (HCV) is a global health issue with an estimated 170 million infected individuals at risk of developing liver disease including fibrosis and hepatocellular carcinoma. The liver is the major reservoir supporting HCV replication and this hepatocellular tropism is defined by HCV engagement of cellular entry receptors. Hepatocytes are polarised in vivo and this barrier function limits HCV entry...
December 15, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27966453/oncolytic-virus-synergizes-with-smac-mimetic-compounds-to-induce-rhabdomyosarcoma-cell-death-in-a-syngeneic-murine-model
#6
Christine C Dobson, Thet Naing, Shawn T Beug, Mame D Faye, Janelle Chabot, Martin St-Jean, Danielle E Walker, Eric C LaCasse, David F Stojdl, Robert G Korneluk, Martin Holcik
Rhabdomyosarcoma (RMS), a neoplasm characterized by undifferentiated myoblasts, is the most common soft tissue tumour in children. Therapeutic resistance is common in RMS and is often caused by acquired defects in the cellular apoptotic program. Smac mimetic compounds (SMCs) are a novel class of inhibitor of apoptosis (IAP) antagonists that are currently under clinical development as cancer therapeutics. We previously reported that cIAP1 is overexpressed in human primary RMS tumours and in patient-derived RMS cell lines where it drives resistance to apoptosis...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27907201/tumor-necrosis-factor-like-weak-inducer-of-apoptosis-promotes-hepatic-stellate-cells-migration-via-canonical-nf-%C3%AE%C2%BAb-mmp9-pathway
#7
Mingcui Xu, Feng Zhang, Aixiu Wang, Chen Wang, Yu Cao, Ming Zhang, Mingming Zhang, Min Su, Xiaoping Zou, Guifang Xu, Yuzheng Zhuge
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65...
2016: PloS One
https://www.readbyqxmd.com/read/27903221/in-vitro-generated-mesenchymal-stem-cells-suitable-tools-to-target-insulin-dependent-diabetes-mellitus
#8
Shruti D Dave, Patel C N, Patel J V, Thakkar U G
A synergy of a pre-accumulated genes with an autoimmunity advancing to slow abolition of pancreatic beta-cells causes insulin deficiency and results enrooting insulin dependent diabetes mellitus (IDDM). As per WHO data worldwide about 150 million people are diabetic and the number may rise to more than double by the year 2025. Any absolute cure for IDDM is not available yet, and one of the credible advent in the field include cell-based therapy. At this conjecture, mesenchymal stem cells (MSC) seems to have a specific and beneficial characteristics due to their in vivo as well as in vitro potential to mimic a pancreatic endocrine phenotype and immune-regulatory actions...
November 21, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27900956/evaluation-of-interleukin-2-interleukin-8-and-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-in-hemodialysis-and-renal-transplant-patients-and-healthy-controls
#9
Nasar Alwahaibi, Halima Alissaei, Amal Al-Kalbani, Nadia Alabri, Zainab Allawati, Mohammed Albalooshi
There is an increasing evidence which suggests that cytokines have an important role in hemodialysis (HD) and renal transplant patients. The aim of this study was to evaluate the levels of interleukin (IL)-2, IL-8 and tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in HD and renal transplant patients and healthy controls. A total of 152 individuals participated in this study over two years including 53 HD patients, 45 renal transplant patients, and 54 healthy controls. Serum levels of IL-2, IL-8 and TWEAK were measured by enzyme-linked immunosorbent assay...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27889570/inhibitor-of-apoptosis-protein-1-regulates-tumor-necrosis-factor-mediated-destruction-of-intestinal-epithelial-cells
#10
Thomas Grabinger, Konstantin J Bode, Janine Demgenski, Carina Seitz, M Eugenia Delgado, Feodora Kostadinova, Cindy Reinhold, Nima Etemadi, Sabine Wilhelm, Matthias Schweinlin, Kay Hänggi, Janin Knop, Christof Hauck, Heike Walles, John Silke, Harald Wajant, Ueli Nachbur, W Wei-Lynn Wong, Thomas Brunner
BACKGROUND AND AIMS: Tumor necrosis factor (TNF) is a cytokine that promotes inflammation and contributes to pathogenesis of inflammatory bowel diseases. Unlike other cells and tissues, intestinal epithelial cells undergo rapid cell death upon exposure to TNF, by unclear mechanisms. We investigated the roles of inhibitor of apoptosis proteins (IAPs) in the regulation of TNF-induced cell death in the intestinal epithelium of mice and intestinal organoids. METHODS: RNA from cell lines and tissues and analyzed by quantitative PCR, protein levels were analyzed by immunoblot assays...
November 23, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27888541/tweak-increases-sirt1-expression-and-promotes-p53-deacetylation-affecting-human-hepatic-stellate-cell-senescence
#11
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...
November 26, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27847340/relevance-of-pre-analytical-blood-management-on-the-emerging-cardiovascular-protein-biomarkers-tweak-and-hmgb1-and-on-mirna-serum-and-plasma-profiling
#12
Daniela Basso, Andrea Padoan, Thomas Laufer, Vittorio Aneloni, Stefania Moz, Hannah Schroers, Michela Pelloso, Anna Saiz, Medea Krapp, Paola Fogar, Paola Cornoldi, Carlo-Federico Zambon, Elisa Rossi, Marco La Malfa, Alberto Marotti, Thomas Brefort, Tanja M Weis, Hugo A Katus, Mario Plebani
BACKGROUND: Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers. METHODS: An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0...
November 12, 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27822714/tweak-fn14-influences-neurogenesis-status-via-modulating-nf-%C3%AE%C2%BAb-in-mice-with-spinal-cord-injury
#13
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
#14
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...
November 3, 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
#15
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/27781256/-expression-of-tumor-necrosis-factor-like-weak-inducer-of-apoptosis-in-patients-with-gastric-cancer-and-its-relationship-with-nutritional-status
#16
Hang Lu, Yuanshui Sun
OBJECTIVE: To investigate the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the serum and the rectus abdominis muscle in patients with gastric cancer and its relationship with the nutritional status. Method Clinical data of 102 patients with gastric cancer (gastric cancer group) and 53 patients with benign abdominal disease (control group) who were admitted to Zhejiang Province People's Hospital from January 2008 to October 2013 were analyzed retrospectively...
October 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/27760772/downregulation-of-kidney-protective-factors-by-inflammation-role-of-transcription-factors-and-epigenetic-mechanisms
#17
REVIEW
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belen Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression, and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD, and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27753135/anti-tweak-monoclonal-antibodies-reduce-vascular-damage-and-leucocyte-infiltration-in-a-mouse-model-of-cutaneous-reverse-passive-arthus-reaction
#18
T Chen, Z-P Guo, L-X Fu, N Cao, S Qin
BACKGROUND: Tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a pro-inflammatory cytokine, which is closely associated with the pathogenesis of various types of cutaneous vasculitis (CV). AIM: To investigate the therapeutic effects of an anti-TWEAK monoclonal antibody (mAb) in a mouse model of cutaneous reverse passive Arthus (RPA) reaction. METHODS: Cutaneous RPA reaction was induced in BALB/c mice by intradermal injection of anti-ovalbumin IgG into the left ear followed immediately by intravenous injection of chicken ovalbumin...
December 2016: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27727910/urinary-tweak-and-ngal-as-a-biomarker-of-lupus-nephritis-activity
#19
R S Ahlawat, V Batra, S Pendharkar
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27725864/tweak-protects-cardiomyocyte-against-apoptosis-in-a-pi3k-akt-pathway-dependent-manner
#20
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
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