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https://www.readbyqxmd.com/read/29143599/epistasis-physical-capacity-related-genes-and-exceptional-longevity-fndc5-gene-interactions-with-candidate-genes-foxoa3-and-apoe
#1
Noriyuki Fuku, Roberto Díaz-Peña, Yasumichi Arai, Yukiko Abe, Hirofumi Zempo, Hisashi Naito, Haruka Murakami, Motohiko Miyachi, Carlos Spuch, José A Serra-Rexach, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia
BACKGROUND: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of 'modifier genes', may contribute to explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population...
November 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29142471/dachaihu-decoction-ameliorates-pancreatic-fibrosis-by-inhibiting-macrophage-infiltration-in-chronic-pancreatitis
#2
Li-Fang Duan, Xiao-Fan Xu, Lin-Jia Zhu, Fang Liu, Xiao-Qin Zhang, Nan Wu, Jian-Wei Fan, Jia-Qi Xin, Hong Zhang
AIM: To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice. METHODS: KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining...
October 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29142101/loss-of-adam9-expression-impairs-%C3%AE-1-integrin-endocytosis-focal-adhesion-formation-and-cancer-cell-migration
#3
Kasper J Mygind, Jeanette Schwarz, Pranshu Sahgal, Johanna Ivaska, Marie Kveiborg
The transmembrane protease ADAM9 is frequently upregulated in human cancers and it promotes tumour progression in mice. In vitro, ADAM9 regulates cancer cell adhesion and migration by interacting with integrins. Yet, how ADAM9 modulates integrin functions is not known. We here show that ADAM9 knockdown increases β1 integrin levels through mechanisms independent of its protease activity. In ADAM9-silenced cells, adhesion to collagen and fibronectin is reduced, suggesting an altered function of the accumulated integrins...
November 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29139224/a-polyelectrolyte-multilayer-platform-for-investigating-growth-factor-delivery-modes-in-human-liver-cultures
#4
Christine Lin, Raimundo Romero, Lioudmila V Sorokina, Kimberly R Ballinger, Laura W Place, Matt J Kipper, Salman R Khetani
Polyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) as in vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non-parenchymal cell (NPC) co-cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined...
November 15, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29137984/recombinant-human-glp-1-rhglp-1-alleviating-renal-tubulointestitial-injury-in-diabetic-stz-induced-rats
#5
Weiqin Yin, Shiqing Xu, Zai Wang, Honglin Liu, Liang Peng, Qing Fang, Tingting Deng, Wenjian Zhang, Jinning Lou
GLP-1-based treatment improves glycemia through stimulation of insulin secretion and inhibition of glucagon secretion. Recently, more and more findings showed that GLP-1 could also protect kidney from diabetic nephropathy. Most of these studies focused on glomeruli, but the effect of GLP-1 on tubulointerstitial and tubule is not clear yet. In this study, we examined the renoprotective effect of recombinant human GLP-1 (rhGLP-1), and investigated the influence of GLP-1 on inflammation and tubulointerstitial injury using diabetic nephropathy rats model of STZ-induced...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137389/targeting-src-attenuates-peritoneal-fibrosis-and-inhibits-the-epithelial-to-mesenchymal-transition
#6
Jun Wang, Li Wang, Liuqing Xu, Yingfeng Shi, Feng Liu, Hualin Qi, Na Liu, Shougang Zhuang
Src has been reported to mediate tissue fibrosis in several organs, but its role in peritoneal fibrosis remains unknown. In this study, we evaluated the therapeutic effect of KX2-391, a highly selective inhibitor of Src, on the development of peritoneal fibrosis in a rat model. Daily intraperitoneal injections of chlorhexidine gluconate induced peritoneal fibrosis, as indicated by thickening of the submesothelial area with an accumulation of collagen fibrils and activation of myofibroblasts. This was accompanied by time-dependent phosphorylation of Src at tyrosine 416...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134547/detection-of-virulence-related-genes-in-lactococcus-garvieae-and-their-expression-in-response-to-different-conditions
#7
Giovanni Eraclio, Giovanni Ricci, Mattia Quattrini, Paolo Moroni, Maria Grazia Fortina
Lactococcus garvieae has emerged as an important zoonotic pathogen. However, information regarding mechanisms and factors related to its pathogenicity is lacking. In the present study, we investigated the distribution and functionality of genes related to virulence factors in L. garvieae strains isolated from different niches (diseased fish, humans, meat and dairy products, vegetables), using both post-genomic and genotypic analysis. Putative genes encoding hemolysin, fibronectin-binding protein, and penicillin acylase were detected in all analyzed genomes/strains...
November 13, 2017: Folia Microbiologica
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#8
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29131244/a-review-on-irisin-a-new-protagonist-that-mediates-muscle-adipose-bone-neuron-connectivity
#9
B Grygiel-Górniak, M Puszczewicz
Physical activity improves the quality of life and decreases the risk of several diseases (i.e. stroke, hypertension, myocardial infarction, obesity, and malignancies). Skeletal muscles are considered as an endocrine organ that produces myokines characterized by a paracrine or endocrine activity. Irisin is a circulating hormone-like myokine and is secreted as a product of fibronectin type III domain-containing protein 5 from skeletal muscle in response to exercise. This molecule regulates the energy metabolism and acts in adipose tissue, bones, and nervous system...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29131116/detection-of-a-splice-site-variant-in-a-patient-with-glomerulopathy-and-fibronectin-deposits
#10
Yurika Tsuji, Kandai Nozu, Tadashi Sofue, Shigeo Hara, Keita Nakanishi, Tomohiko Yamamura, Shogo Minamikawa, Yoshimi Nozu, Hiroshi Kaito, Junya Fujimura, Tomoko Horinouchi, Naoya Morisada, Ichiro Morioka, Mariko Taniguchi-Ikeda, Masafumi Matsuo, Kazumoto Iijima
BACKGROUND/AIMS: Glomerulopathy with fibronectin deposits (GFND; OMIM: 601894) is a very rare inherited kidney disease caused by pathogenic variants in the FN1 gene. Only 9 exonic pathogenic variants in FN1, 9 at the heparin-binding site, and 1 at the integrin-binding site have been reported. No intronic variants in FN1 have been detected. METHODS: We found a pathogenic intronic variant in intron 36 (c.5888-2A>G) located at the heparin-binding site. To determine whether this mutation influences splicing processes, we conducted RT-PCR analysis and an in vitro splicing assay using minigene construction...
November 3, 2017: Nephron
https://www.readbyqxmd.com/read/29129979/hair-germ-model-in-vitro-via-human-postnatal-keratinocyte-dermal-papilla-interactions-impact-of-hyaluronic-acid
#11
Ekaterina Kalabusheva, Vasily Terskikh, Ekaterina Vorotelyak
Hair follicle (HF) reconstruction in vitro is a promising field in alopecia treatment and human HF development research. Here, we combined postnatal human dermal papilla (DP) cells and skin epidermal keratinocytes (KCs) in a hanging drop culture to develop an artificial HF germ. The method is based on DP cell hair-inducing properties and KC self-organization. We evaluated two protocols of aggregate assembling. Mixed HF germ-like structures demonstrated the initiation of epithelial-mesenchymal interaction, including WNT pathway activation and expression of follicular markers...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29127759/is-irisin-the-new-player-in-exercise-induced-adaptations-or-not-a-2017-update
#12
REVIEW
Ioannis G Fatouros
Irisin is produced by a proteolytic cleavage of fibronectin type III domain-containing protein 5 (FNDC5) and has emerged as a potential mediator of exercise-induced energy metabolism. The purpose of this study was to review the results of studies that investigated irisin responses to acute and chronic exercise and provide an update. A comprehensive search in the databases of MEDLINE was performed (74 exercise studies). The focus of the analysis was on data concerning FNDC5 mRNA expression in skeletal muscle and circulating irisin concentration relatively to exercise mode, intensity, frequency and duration and the characteristics of the sample used...
November 11, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29127306/upregulation-of-microrna-4417-and-its-target-genes-contribute-to-nickel-chloride-promoted-lung-epithelial-cell-fibrogenesis-and-tumorigenesis
#13
Chih-Hsien Wu, Yi-Min Hsiao, Kun-Tu Yeh, Tsui-Chun Tsou, Chih-Yi Chen, Ming-Fang Wu, Jiunn-Liang Ko
Nickel compounds have been classified as carcinogens and shown to be associated with induction of epithelial-mesenchymal transition (EMT) in fibrogenesis and tumorigenesis, as well as the crucial role of microRNAs (miRNAs) and their related genes in controlling EMT and cancer metastasis. Thus, the mechanisms involved in the regulation of EMT in nickel-treated cells are of potential interest in understanding lung fibrosis and tumor progression. We investigated the miRNA-dependent mechanisms involved in nickel-induced EMT in lung epithelial cells...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29127148/ubc9-binds-to-adap-and-is-required-for-rap1-membrane-recruitment-rac1-activation-and-integrin-mediated-t-cell-adhesion
#14
Yiwei Xiong, Chengjin Ye, Naiqi Yang, Madanqi Li, Hebin Liu
Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion...
November 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29127068/mono-vs-multilayer-fibronectin-coatings-on-polar-hydrophobic-ionic-polyurethanes-altering-surface-interactions-with-human-monocytes
#15
Audrey Gossart, Kyle G Battiston, Adeline Gand, Emmanuel Pauthe, J Paul Santerre
Monocyte interactions with materials that are biofunctionalized with fibronectin (Fn) are of interest because of the documented literature which associates this protein with white blood cell function at implant sites. A degradable-polar hydrophobic ionic polyurethane (D-PHI), has been reported to promote an anti-inflammatory response from human monocytes. The aim of the current work was to study the influence of intrinsic D-PHI material chemistry on Fn adsorption (mono and multi-layer structures), and to investigate the influence of such chemistry on the structural state of the Fn, as well as the latter's influence on the activity of human monocytes on the protein coated substrates...
November 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/29126308/nrf2-deficiency-promotes-the-progression-from-acute-tubular-damage-to-chronic-renal-fibrosis-following-unilateral-ureteral-obstruction
#16
Weiwei Kong, Jingqi Fu, Nan Liu, Congcong Jiao, Guangying Guo, Junjun Luan, Huihui Wang, Li Yao, Lining Wang, Masayuki Yamamoto, Jingbo Pi, Hua Zhou
Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central mediator of cellular responses to oxidative stress. We hypothesized that Nrf2 modulates progression from acute tubular damage to renal fibrosis. We asked whether Nrf2 deletion increases renal injury in mice following unilateral ureteral obstruction (UUO). Methods: We explored the time course of renal injury and Nrf2 expression in Nrf2+/+ mice following UUO. We compared Nrf2+/+ and Nrf2-/- mice following UUO in tubular damage, transdifferentiation [vimentin, proliferating cell nuclear antigen (PCNA)], fibrosis [fibronectin, α-smooth muscle actin (SMA)], antioxidative and inflammatory responses...
November 6, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29125428/schwann-cells-and-mesenchymal-stem-cells-in-laminin-or-fibronectin-aligned-matrices-and-regeneration-across-a-critical-size-defect-of-15-mm-in-the-rat-sciatic-nerve
#17
Francisco Gonzalez-Perez, Joaquim Hernández, Claudia Heimann, James B Phillips, Esther Udina, Xavier Navarro
OBJECTIVE Artificial nerve guides are being developed to substitute for autograft repair after peripheral nerve injuries. However, the use of conduits is limited by the length of the gap that needs to be bridged, with the success of regeneration highly compromised in long gaps. Addition of aligned proregenerative cells and extracellular matrix (ECM) components inside the conduit can be a good strategy to achieve artificial grafts that recreate the natural environment offered by a nerve graft. The purpose of this study was to functionalize chitosan devices with different cell types to support regeneration in limiting gaps in the rat peripheral nerve...
November 10, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29122983/restricted-cell-functions-on-micropillars-are-alleviated-by-surface-nanocoating-with-amino-groups
#18
Caroline Moerke, Susanne Staehlke, Henrike Rebl, Birgit Finke, J Barbara Nebe
The topographical and chemical surface features of biomaterials are sensed by the cells, affecting their physiology at the interface. On titanium we recently discovered an attempted caveolae-mediated phagocytosis of the sharp-edged microstructures by osteoblasts. This active, energy-consuming process resulted in decreased osteoblastic cell functions, e.g. extracellular matrix proteins. However, chemical modification with plasma polymerized allylamine (PPAAm) was able to amplify osteoblast adhesion and spreading, resulting in better implant osseointegration in vivo In the present in vitro study we analyzed whether this plasma polymer nanocoating is able to attenuate the microtopography-induced changes of osteoblast physiology...
November 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29122968/energy-landscape-differences-among-integrins-establish-the-framework-for-understanding-activation
#19
Jing Li, Timothy A Springer
Why do integrins differ in basal activity, and how does affinity for soluble ligand correlate with cellular adhesiveness? We show that basal conformational equilibrium set points for integrin α4β1 are cell type specific and differ from integrin α5β1 when the two integrins are coexpressed on the same cell. Although α4β1 is easier to activate, its high-affinity state binds vascular cell adhesion molecule and fibronectin 100- to 1,000-fold more weakly than α5β1 binds fibronectin. Furthermore, the difference in affinity between the high- and low-affinity states is more compressed in α4β1 (600- to 800-fold) than in α5β1 (4,000- to 6,000-fold)...
November 9, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29122645/interleukin-33-levels-are-elevated-in-chronic-allograft-dysfunction-of-kidney-transplant-recipients-and-promotes-epithelial-to-mesenchymal-transition-of-human-kidney-hk-2-cells
#20
Zhen Xu, Chunchun Zhao, Zijie Wang, Jun Tao, Zhijian Han, Wei Zhang, Ruoyun Tan, Min Gu
This study is aimed to investigate the potential role of interleukin (IL)-33 in transplanted kidney interstitial fibrosis and the associated mechanism. Serum IL-33 levels were detected using an enzyme-linked immunosorbent assay (ELISA) in healthy volunteers, stable kidney transplantation recipients (KTRs) (stable), KTRs with acute rejection (AR), and KTRs with chronic allograft dysfunction (CAD) (CAD). Immunohistochemical (IHC) staining, Western blotting, and quantitative real-time PCR (qRT-PCR) were used to detect the expression of IL-33 in human kidney tissues obtained from control and CAD patients...
November 6, 2017: Gene
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