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Avishai Shemesh, Aleksandra Kugel, Naama Steiner, Michal Yezersky, Dan Tirosh, Avishay Edri, Omri Teltsh, Benyamin Rosental, Eyal Sheiner, Eitan Rubin, Kerry S Campbell, Angel Porgador
NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue...
September 27, 2016: Oncotarget
J Y Dong, F Song, Y K Liu, X Q Wang
Objective: To simulate the environmental factors during the process of formation and evolution of hypertrophic scar, so as to explore the effects of moderate and severe hypoxia and low concentration of serum protein on the function of human hypertrophic scar fibroblasts (HSFs). Methods: Human HSFs were routinely cultured. Cells of the 3rd to the 6th passage were divided into 10.0% oxygen+ 10.0% fetal calf serum (FCS), 5.0% oxygen+ 5.0% FCS, and 0.5% oxygen+ 0.5% FCS groups according to the random number table...
October 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
L Chen, D L Wang, Z R Wei, B Wang, J P Qi, G F Sun
Objective: To investigate the effects of local transplantation of autologous adipose-derived mesenchymal stem cells (ADSCs) on the formation of hyperplastic scar on rabbit ears. Methods: ADSCs were isolated from inguinal fat of six New Zealand rabbits and then sub-cultured. ADSCs of the third passage of each rabbit were used in the following experiments. Six full-thickness skin defect wounds with diameter of 6 mm on the ventral surface of every rabbit ear were made. Wound healing and local-tissue proliferation were observed, and complete epithelization time of wounds and formation time of hyperplastic scar were recorded...
October 20, 2016: Zhonghua Shao Shang za Zhi, Zhonghua Shaoshang Zazhi, Chinese Journal of Burns
Yan Wang, Jung-Mao Hsu, Ya'an Kang, Yongkun Wei, Pei-Chih Lee, Shing-Jyh Chang, Yi-Hsin Hsu, Jennifer L Hsu, Hung-Ling Wang, Wei-Chao Chang, Chia-Wei Li, Hsin-Wei Liao, Shih-Shin Chang, Weiya Xia, How-Wen Ko, Chao-Kai Chou, Jason B Fleming, Huamin Wang, Rosa F Hwang, Yue Chen, Jun Qin, Mien-Chie Hung
The oncogenic transcription factor Gli1 is a critical effector in the Hedgehog (Hh) pathway which is necessary for the development and progression of pancreatic ductal adenocarcinoma (PDAC). While TGF-β and K-Ras are known regulators of Gli1 gene transcription in this setting, it is not understood how Gli1 functional activity is regulated. Here we report the identification of Gli1 as a substrate for the protein arginine N-methyltransferase PRMT1 in PDAC. We found that PRMT1 methylates Gli1 at R597, promoting its transcriptional activity by enhancing the binding of Gli1 to its target gene promoters...
October 6, 2016: Cancer Research
Mohammad Massumi, Farzaneh Pourasgari, Amarnadh Nalla, Battsetseg Batchuluun, Kristina Nagy, Eric Neely, Rida Gull, Andras Nagy, Michael B Wheeler
The ability to yield glucose-responsive pancreatic beta-cells from human pluripotent stem cells in vitro will facilitate the development of the cell replacement therapies for the treatment of Type 1 Diabetes. Here, through the sequential in vitro targeting of selected signaling pathways, we have developed an abbreviated five-stage protocol (25-30 days) to generate human Embryonic Stem Cell-Derived Beta-like Cells (ES-DBCs). We showed that Geltrex, as an extracellular matrix, could support the generation of ES-DBCs more efficiently than that of the previously described culture systems...
2016: PloS One
Qiongying Wang, Peng Chang, Han Xu, Feng Bai, Jing Yu
OBJECTIVE: Hypertension induced hypertrophy and diastolic dysfunction and is associated with cardiac oxidation and reduced NO production. We hypothesized that tetrahydrobiopterin (BH4) can regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and reverse cardiac hypertrophy and diastolic dysfunction in spontaneously hypertensive rats. DESIGN AND METHOD: Ten-week-old male spontaneously hypertensive rats (SHR) and age-matched normotensive control Wistar-Kyoto (WKY) rats were divided into five groups, WKY,WKY + BH4, SHR, SHR + BH4 and SHR + VAL...
September 2016: Journal of Hypertension
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Sadhvi Nithiananthan, Aileen Crawford, Johnathan Cooper Knock, Daniel W Lambert, Simon A Whawell
Fibroblasts are the major cellular component of connective tissue and experience mechanical perturbations due to matrix remodelling and interstitial fluid movement. Transforming growth factor β1 (TGF-β1) can promote differentiation of fibroblasts in vitro to a contractile myofibroblastic phenotype characterised by the presence of α-smooth muscle actin (α-SMA) rich stress fibres. To study the role of mechanical stimulation in this process, we examined the response of primary human fibroblasts to physiological levels of fluid movement and its influence on fibroblast differentiation and responses to TGF-β1...
October 17, 2016: Journal of Cellular Biochemistry
Piero Pingitore, Paola Dongiovanni, Benedetta Maria Motta, Marica Meroni, Saverio Massimo Lepore, Rosellina Margherita Mancina, Serena Pelusi, Cristina Russo, Andrea Caddeo, Giorgio Rossi, Tiziana Montalcini, Arturo Pujia, Olov Wiklund, Luca Valenti, Stefano Romeo
Liver fibrosis is a pathological scarring response to chronic hepatocellular injury and hepatic stellate cells (HSCs) are key players in this process. PNPLA3 I148M is a common variant robustly associated with liver fibrosis but the mechanisms underlying this association are unknown.We aimed to examine a) the effect of fibrogenic and proliferative stimuli on PNPLA3 levels in HSCs and b) the role of wild type and mutant PNPLA3 overexpression on markers of HSC activation and fibrosis.Here we show that PNPLA3 is upregulated by the fibrogenic cytokine transforming growth factor-beta (TGF-β), but not by platelet-derived growth factor (PDGF), and is involved in the TGF-β-induced reduction in lipid droplets in primary human HSCs...
October 13, 2016: Human Molecular Genetics
L F S Batista, Y T Utsunomiya, T B F da Silva, R A Dias, T Y Tomokane, A D Pacheco, V L R da Matta, F T Silveira, M Marcondes, C M Nunes, M D Laurenti
A genome-wide association study (GWAS) could unravel the complexity of the cell-mediated immunity (CMI) to canine leishmaniasis (CanL). Thereby we committed to scan 110,165 single-nucleotide polymorphisms (SNPs) aiming to identify chromosomal regions associated to leishmanin skin test (LST), lymphocyte proliferation assay (LPA) and cytokines responses to further understanding the role played by the CMI in the outcome of the natural Leishmania infantum infection in 189 dogs. Based on LST and LPA, four CMI profiles were identified (LST-/LPA-, LST+/LPA-, LST-/LPA+ and LST+/LPA+), which were not associated to subclinical infected or diseased dogs...
October 10, 2016: Infection and Immunity
J Wang, Y Qiu, N-W Shi, J-N Zhao, Y-C Wang, H Jiang, H-B Qian
OBJECTIVE: The aim of this study was to investigate the molecular mechanism into the keratinocyte migration, which is promoted by Transforming growth factor-β1 (TGF-β1) during wound healing. MATERIALS AND METHODS: In the present study, we investigated the regulation by TGF-β1 on phosphatase and tensin homolog (PTEN) expression, and microRNA-21 (miR-21) level with real-time quantitative PCR or/and Western blotting, and then examined the regulatory role of miR-21 on the PTEN expression and the mesenchymal transition, with real-time quantitative PCR, western blotting and luciferase reporter assay, and the migration of keratinocytic HaCaT cells with scratch assay...
September 2016: European Review for Medical and Pharmacological Sciences
H-L Fu, H-X Pan, B Zhao, B-C Dong, L Shao, G-S Fu, Q Wang, M Li
OBJECTIVE: MicroRNAs (miRNAs) act as key regulators of diverse cellular activities by regulating the expression of protein-coding genes. Osteoblast differentiation, a fundamental step in skeletal development, involves the activation of several signaling pathways, including transforming growth factor β (TGF-β), bone morphogenetic protein (BMP), and Wnt signaling pathways. MATERIALS AND METHODS: miRNA expression was measured using TaqManRT-PCR. Western blot was used to detect the protein expression of Smad1...
September 2016: European Review for Medical and Pharmacological Sciences
Lisa S Thomas, Stephan R Targan, Masato Tsuda, Qi T Yu, Brenda C Salumbides, Talin Haritunians, Emebet Mengesha, Dermot P B McGovern, Kathrin S Michelsen
TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong costimulation of these TH subsets, particularly of mucosal CCR9(+) T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. We investigated the function of TL1A on human TH17 cells. TL1A, together with TGF-β, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN-γ from human CD4(+) memory T cells...
October 12, 2016: Journal of Leukocyte Biology
Niina K Palin, Johanna Savikko, Arja Pasternack, Jukka M Rintala, Bhanu Kalra, Shivani Mistry, Ajay Kumar, Marie-Paule Roth, Heikki Helin, Olli Ritvos
BACKGROUND: Activins are members of the TGF-beta superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. METHODS: The study was done in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling...
October 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Hideyuki Maruki, Masato Sato, Toshiaki Takezawa, Yoshiki Tani, Munetaka Yokoyama, Takumi Takahashi, Eriko Toyoda, Eri Okada, Shigehisa Aoki, Joji Mochida, Yoshiharu Kato
We studied the ability of collagen vitrigel material to repair cartilage in vivo when used alone or with transforming growth factor-β (TGF-β). We measured the time course and quantity of TGF-β1 released from the collagen vitrigel in vitro to quantify the controlled release of TGF-β1. Over 14 days, 0.91 ng of TGF-β was released from the collagen vitrigel. Osteochondral defects were made in the femoral trochlear groove in 36 Japanese white rabbits, which were divided into three groups: untreated group (group A), collagen vitrigel-implanted group (group B), and TGF-β1-incorporated collagen vitrigel-implanted group (group C)...
October 12, 2016: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Daniel M Vasconcelos, Raquel M Gonçalves, Catarina R Almeida, Inês O Pereira, Marta I Oliveira, Nuno Neves, Andreia M Silva, António C Ribeiro, Carla Cunha, Ana R Almeida, Cristina C Ribeiro, Ana M Gil, Elisabeth Seebach, Katharina L Kynast, Wiltrud Richter, Meriem Lamghari, Susana G Santos, Mário A Barbosa
The hypothesis behind this work is that fibrinogen (Fg), classically considered a pro-inflammatory protein, can promote bone repair/regeneration. Injury and biomaterial implantation naturally lead to an inflammatory response, which should be under control, but not necessarily minimized. Herein, porous scaffolds entirely constituted of Fg (Fg-3D) were implanted in a femoral rat bone defect and investigated at two important time points, addressing the bone regenerative process and the local and systemic immune responses, both crucial to elucidate the mechanisms of tissue remodelling...
December 2016: Biomaterials
Ravendra Garg, Michael Theaker, Elisa C Martinez, Sylvia van Drunen Littel-van den Hurk
Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice...
October 6, 2016: Virology
Sanjay B Rathod, Anuradha S Tripathy
BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute viral infections is limited. Having established that the Tregs in self-limiting hepatitis E infection are elevated and functional, this study has focused on characterizing the specificity, phenotypes and identifying the molecules or factors responsible for enhancement of Treg cells and abrogation of Treg-mediated suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency, subset analysis and expression of surface and intracellular markers on Tregs and CFSE based functional analysis by flow cytometry (b) key cytokines quantification by multiplex (c) suppressive functional assay in the presence of anti-TGF-β1 or anti-IL-10 or both antibodies or Transwell insert or in combination were performed on samples from 58 acute patients (AVH-E), 45 recovered individuals from hepatitis E and 55 controls...
October 6, 2016: Human Immunology
Xudong Sun, Jianyu Liu, Cuicui Zhuang, Xu Yang, Yanfei Han, Bing Shao, Miao Song, Yanfei Li, Yanzhu Zhu
Aluminum (Al) is recognized worldwide as serious inorganic contaminants. Exposure to Al is associated with low BMD and an increased risk of osteoporosis. However, the precise molecular mechanisms remains unclear. Thus, in this study, rats were orally exposed to 0 (control group, CG) and 0.4g/L AlCl3 (AlCl3 treated group, AG) in drinking water for 120 days; osteoblasts were treated with AlCl3 (0.12mg/mL) and/or TGF-β1 (4.5ng/mL) for 24h. We found that AlCl3 decreased the BMD, damaged femoral ultrastructure, decreased the activities of GSH-Px and SOD, and increased the levels of ROS and MDA in bone, decreased the activity of B-ALP and content of PINP, and increased the activity of TRACP-5b and content of NTX-I in serum, decreased mRNA expressions of TGF-β1, TβRI, TβRII and Smad4, protein expressions of TGF-β1, p-Smad2/3 and Smad2/3/4 complex, and increased Smad7 mRNA expression in bone and in osteoblasts...
October 5, 2016: Toxicology
Şükrü Kartalcı, Lale Gönenir Erbay, Esra Porgalı Zayman, Önder Otlu, Aysun Bay Karabulut, Gülşen Kartalcı
OBJECTIVE: Schizophrenia is a chronic psychotic disorder in which genetics and environmental factors such as infection and the corresponding immune response play a role in the etiopathogenesis. The aim of this study was to compare some immune factors such as nuclear factor-B (NF-B) activation, myeloperoxidase (MPO), the anti-inflammatory cytokine interleukin-4 (IL-4), and regulatory cytokine transforming growth factor- (TGF-) in schizophrenia patients and an age- and gender-matched control group...
2016: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
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