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Hitesh Soni, Adebowale Adebiyi
Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs...
October 21, 2016: Renal Failure
J Zhang, P P Jin, K Fang, Q T Yi, M F Tang, C H Chen, J H Guo, M Gong
Objective: To explore the effects of varicocele on the expressions of inhibin B in rat testes and the relationship between expression of inhibin B and spermatogenesis dysfunction. Methods: Twenty specific-pathogen-free Sprague-Dawley (SD) male rats were randomly divided into two groups with random number table: 4-week control group (C4) and 4-week experimental group(V4). Experimental varicocele was created by partial ligation of left renal vein in the V4 group; vein isolation without ligation was performed in the C4 group...
September 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
C-M Chu, K-C Kao, S-H Huang, D-Y Chuang, H-P Wu
Severe sepsis is associated with significant mortality and massive immune cell lose, or apoptosis. It is unclear whether plasma apoptosis biomarkers could be used as a diagnostic test for severe sepsis. Forty patients with severe sepsis and 35 healthy controls were enrolled. The percentage and apoptosis of monocytes and lymphocytes were detected by flow cytometric analysis. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR), soluble Fas (sFas), Fas ligand (FasL), caspase-1, and procalcitonin (PCT) were measured...
September 30, 2016: Cellular and Molecular Biology
Hongliang Yu, Jian He, Qian Lu, Da Huo, Shanmei Yuan, Zhengyang Zhou, Peipei Xu, Yong Hu
Emerging evidences suggest that introduction of Fas Ligand (FasL) can enhance the Fas-dependent apoptosis and induce durable immune responses against tumor. However, selective triggering of apoptosis in tumor cells while sparing normal cells remains a great challenge for the application of FasL based therapeutic strategies. Herein, smart nanoparticles (NPs) with sandwich structure were fabricated. These NPs consist of Matrix metalloproteinase (MMP) cleavable PEG outer layer, anti-Fas antibody middle layer and camptothecin (CPT) loaded inner core...
October 18, 2016: ACS Applied Materials & Interfaces
Eun Young Park, Joo-Il Kim, Dong-Gyu Leem, Ji-Sun Shin, Kyung-Tack Kim, Sang Yoon Choi, Myung-Hee Lee, Jung-Hye Choi, Yong Sup Lee, Kyung-Tae Lee
Previously, we reported that (E)-8-acetoxy-2-[2-(3,4-diacetoxyphenyl)ethenyl]-quinazoline (8-ADEQ), a synthetic analogue of resveratrol had anti-inflammatory and G2/M cell cycle arrest activities, but the underlying molecular mechanism of cytotoxic effects of this compound was not determined. In this study, 8-ADEQ displayed potent cytotoxicity and triggered apoptosis in HL-60 cells as evidenced by DNA fragmentation, DNA ladder formation, and the externalization of Annexin V-targeted phosphatidylserine residues in HL-60 cells...
October 13, 2016: Oncology Reports
Yuh-Feng Tsai, Ching-Wen Huang, Jo-Hua Chiang, Fuu-Jen Tsai, Yuan-Man Hsu, Chi-Cheng Lu, Chen-Yu Hsiao, Jai-Sing Yang
Gadolinium (Gd) compounds are important as magnetic resonance imaging (MRI) contrast agents, and are potential anticancer agents. However, no report has shown the effect of gadolinium chloride (GdCl3) on osteosarcoma in vitro. The present study investigated the apoptotic mechanism of GdCl3 on human osteosarcoma U-2 OS cells. Our results indicated that GdCl3 significantly reduced cell viability of U-2 OS cells in a concentration-dependent manner. GdCl3 led to apoptotic cell shrinkage and DNA fragmentation in U-2 OS cells as revealed by morphologic changes and TUNEL staining...
October 14, 2016: Oncology Reports
Elisabetta Volpe, Manolo Sambucci, Luca Battistini, Giovanna Borsellino
Fas and Fas Ligand (FasL) are two molecules involved in the regulation of cell death. Their interaction leads to apoptosis of thymocytes that fail to rearrange correctly their T cell receptor (TCR) genes and of those that recognize self-antigens, a process called negative selection; moreover, Fas-FasL interaction leads to activation-induced cell death, a form of apoptosis induced by repeated TCR stimulation, responsible for the peripheral deletion of activated T cells. Both control mechanisms are particularly relevant in the context of autoimmune diseases, such as multiple sclerosis (MS), where T cells exert an immune response against self-antigens...
2016: Frontiers in Immunology
Jürgen Fritsch, Ricarda Fickers, Jan Klawitter, Vinzenz Särchen, Philipp Zingler, Dieter Adam, Ottmar Janssen, Eberhard Krause, Stefan Schütze
During apoptosis induction by TNF, the extrinsic and intrinsic apoptosis pathways converge at the lysosomal-mitochondrial interface. Earlier studies showed that the lysosomal aspartic protease Cathepsin D (CtsD) cleaves Bid to tBid, resulting in the amplification of the initial apoptotic cascade via mitochondrial outer membrane permeabilization (MOMP).The goal of this study was to identify further targets for CtsD that might be involved in activation upon death receptor ligation. Using a proteomics screen, we identified the heat shock protein 90 (HSP90) to be cleaved by CtsD after stimulation of U937 or other cell lines with TNF, FasL and TRAIL...
October 3, 2016: Oncotarget
E Budisova Svandova, B Vesela, H Lesot, A Poliard, E Matalova
Elimination of the interdigital web is considered to be the classical model for assessing apoptosis. So far, most of the molecules described in the process have been connected to the intrinsic (mitochondrial) pathway. The extrinsic (receptor mediated) apoptotic pathway has been rather neglected, although it is important in development, immunomodulation and cancer therapy. This work aimed to investigate factors of the extrinsic apoptotic machinery during interdigital regression with a focus on three crucial initiators: Fas, Fas ligand and caspase-8...
October 5, 2016: Histochemistry and Cell Biology
Hiroyuki Nakashima, Masahiro Nakashima, Manabu Kinoshita, Masami Ikarashi, Hiromi Miyazaki, Hiromi Hanaka, Junko Imaki, Shuhji Seki
We have recently reported that Kupffer cells consist of two subsets, radio-resistant resident CD68+ Kupffer cells and radio-sensitive recruited CD11b+ Kupffer cells/macrophages (Mφs). Non-alcoholic steatohepatitis (NASH) is characterized not only by hepatic steatosis but also chronic inflammation and fibrosis. In the present study, we investigated the immunological mechanism of diet-induced steatohepatitis in fibroblast growth factor 5 (FGF5) deficient mice. After consumption of a high fat diet (HFD) for 8 weeks, FGF5 null mice developed severe steatohepatitis and fibrosis resembling human NASH...
October 6, 2016: Scientific Reports
Xiangting Qiu, Xinhua Wang, Yucui Song, Lingling Chen
BACKGROUND: Hepatocellular carcinoma is a major type of liver cancer with poor prognosis. AIM: The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma. METHODS: A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry...
October 3, 2016: Digestive Diseases and Sciences
Ilana C van Rensburg, Chandre Wagman, Kim Stanley, Caroline Beltran, Katharina Ronacher, Gerhard Walzl, Andre G Loxton
Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment)...
September 22, 2016: Oncotarget
Fang Chen, Shi-Lian Zheng, Jiang-Ning Hu, Yong Sun, Yue-Ming He, Han Peng, Bing Zhang, David Julian McClements, Ze-Yuan Deng
Ginsenoside Rh2 is a potential active metabolite of ginseng that has antitumor activity against a variety of tumor cells. Previously, we reported that Rh2-O, an octyl ester derivative of ginsenoside Rh2, had a higher anticancer activity than Rh2 through activating the intrinsic apoptotic pathway. In this study, we found that the extrinsic apoptotic pathway was also involved in Rh2-O-induced HepG2 cells apoptosis as evidenced by the up-regulation of Fas, FasL, TNFR1, and TNF-α as well as the cleavage of caspase 8...
October 3, 2016: Journal of Agricultural and Food Chemistry
T T Gao, Q Long
Stevens-Johnson syndrome(SJS)and toxic epidermal necrolysis(TEN)are life-threatening cutaneous adverse drug reactions that induce widespread epidermal necrosis. Ocular and cutaneous diseases are common chronic sequelae of SJS and TEN. Several concepts have been proposed to explain the pathogenesis of severe cutaneous adverse drug reactions. Recent advances in genetic, pharmacogenomics and immunologic studies have provided evidences of genetic predispositions, drug metabolism and cytokines related to SJS and TEN...
September 11, 2016: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
José Sergio Zepeda-Nuño, Celia Guerrero-Velázquez, Susana Del Toro-Arreola, Natali Vega-Magaña, Julián Ángeles-Sánchez, Jesse Haramati, Ana L Pereira-Suárez, Miriam R Bueno-Topete
ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage...
September 14, 2016: Pathology Oncology Research: POR
Samaneh Kouzegaran, Kourosh Shahraki, Ali Makateb, Farkhondeh Shahri, Negin Hatami, Vahid Behnod, Amir Saber Tanha
In this study, expression of FasL and Ki-67 messenger RNA (FasL and Ki-67 mRNA) in human retinoblastoma (HRB) was examined by immunohistochemistry method and quantitative RealTime PCR. Positive expression of Ki-67 in tumor cells was detected in 16 of 30 patients (53.33%) and only 9 (30%) of the tissues from patients with retinoblastoma showed positive staining for FasL. Our results revealed that FasL expression was significantly higher in tumor tissue with invasion compared with the non-invasion form (p =0...
September 12, 2016: Oncology Research
Melanie Bremm, Sabine Huenecke, Olga Zimmermann, Verena Pfirrmann, Andrea Quaiser, Halvard Bonig, Jan Soerensen, Thomas Klingebiel, Eva Rettinger, Peter Bader, Claudia Cappel
BACKGROUND: Cytokine-induced-killer (CIK) cells are a promising immunotherapeutic approach for impending relapse following hematopoietic stem cell transplantation (HSCT). However, there is a high risk for treatment failure associated with severe graft versus host disease (GvHD) necessitating pharmaceutical intervention post-transplant. Whether immunosuppression with mycophenolate mofetil (MMF) or Ciclosporin A (CsA) influences the cytotoxic effect of CIK cell immunotherapy is still an open issue...
2016: Journal of Translational Medicine
Peter Kraft, Rebecca Schleicher, Marcus Olbrich, Michael K Schuhmann, Kelly Daryll Blanz, Frederic Emschermann, Sonja Ebenhoech, Christopher Starz, Ingo Hilgendorf, Sven G Meuth, Frank Edlich, Christoph Kleinschnitz, Harald F Langer
No abstract text is available yet for this article.
August 25, 2016: Thrombosis and Haemostasis
Ping He, Beiru Zhang, Dajun Liu, Xiaohui Bian, Detian Li, Yanqiu Wang, Guangping Sun, Guangyu Zhou
BACKGROUND/AIMS: The hepatitis B virus X protein (HBx) contributes to HBV-induced injury of renal tubular cells and induces apoptosis via Fas/FasL up-regulation. However, the mechanism of Fas/FasL activation is unknown. Recent studies indicated that HBx induction of apoptosis in hepatic cells depends on activating the MLK3-MKK7-JNKs signaling module, which then up-regulates FasL expression. In this study, we used NRK-52E cells transfected an HBx expression vector to examine the role of the MLK3-MKK7-JNKs signaling pathway on HBx-induced renal tubular cell injury...
2016: Cellular Physiology and Biochemistry
Jason Rosado, Sandra Morales, Giovanni Lopez, Daniel Clark, Kristien Verdonck, Eduardo Gotuzzo, Guy Van Camp, Michael Talledo
BACKGROUND: Human T-lymphotropic virus 1 (HTLV-1) is the etiologic agent of the HTLV-I-Associated Myelopathy-Tropical Spastic Paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross-linking of the FAS receptor expressed in viruses-infected cells, and the ligand FASL presented by T-cytotoxic cells. Since HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single-nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease...
September 7, 2016: Journal of Medical Virology
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