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https://www.readbyqxmd.com/read/29147465/myricetin-possesses-potential-protective-effects-on-diabetic-cardiomyopathy-through-inhibiting-i%C3%AE%C2%BAb%C3%AE-nf%C3%AE%C2%BAb-and-enhancing-nrf2-ho-1
#1
Hai-Han Liao, Jin-Xiu Zhu, Hong Feng, Jian Ni, Nan Zhang, Si Chen, Huang-Jun Liu, Zheng Yang, Wei Deng, Qi-Zhu Tang
Diabetic cardiomyopathy (DCM) is associated with a greater risk of mortality in patients with diabetes mellitus. Currently, no specific treatment has been suggested for DCM treatment. This study demonstrated that myricetin (M) attenuated DCM-associated cardiac injury in mice subjected to streptozotocin (SZT) and in neonatal rat cardiomyocytes (NRCM) challenged with high glucose. In vivo investigation demonstrated 6 months of M treatment (200 mg/kg/d) significantly alleviated cardiac hypertrophy, apoptosis, and interstitial fibrosis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29146913/autophagy-acts-through-traf3-and-relb-to-regulate-gene-expression-via-antagonism-of-smad-proteins
#2
Alice C Newman, Alain J Kemp, Yvette Drabsch, Christian Behrends, Simon Wilkinson
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29144234/lrp1-integrates-murine-macrophage-cholesterol-homeostasis-and-inflammatory-responses-in-atherosclerosis
#3
Xunde Xian, Yinyuan Ding, Marco Dieckmann, Li Zhou, Florian Plattner, Mingxia Liu, John S Parks, Robert E Hammer, Philippe Boucher, Shirling Tsai, Joachim Herz
Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional cell surface receptor with diverse physiological roles, ranging from cellular uptake of lipoproteins and other cargo by endocytosis to sensor of the extracellular environment and integrator of a wide range of signaling mechanisms. As a chylomicron remnant receptor, LRP1 controls systemic lipid metabolism in concert with the LDL receptor in the liver, whereas in smooth muscle cells (SMC) LRP1 functions as a co-receptor for TGFβ and PDGFRβ in reverse cholesterol transport and the maintenance of vascular wall integrity...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29142074/stat3-controls-col1a2-enhancer-activation-cooperatively-with-junb-regulates-type-i-collagen-synthesis-post-transcriptionally-and-is-essential-for-lung-myofibroblast-differentiation
#4
Ioannis Papaioannou, Shiwen Xu, Christopher P Denton, David J Abraham, Markella Ponticos
Fibroblast differentiation is key cellular process that underlies the process of fibrosis, a deadly complication of fibrotic diseases like Scleroderma (SSc). This transition coincides with the overproduction of Collagen type I (COL1) and other extracellular matrix proteins. High level expression of the collagen type 1α2 subunit (COL1A2), requires the engagement of a far upstream enhancer, whose activation is strongly dependent on the AP1 factor JunB. We now report that STAT3 also binds the COL1A2 enhancer and is essential for RNA polymerase recruitment, without affecting JunB binding...
November 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29140250/gdf3-is-required-for-robust-nodal-signaling-during-germ-layer-formation-and-left-right-patterning
#5
Jose L Pelliccia, Granton A Jindal, Rebecca D Burdine
Vertebrate embryonic patterning depends on signaling from Nodal, a TGFβ superfamily member. There are three Nodal orthologs in zebrafish; southpaw directs left-right asymmetries, while squint and cyclops function earlier to pattern mesendoderm. TGFβ member Vg1 is implicated in mesoderm formation but the role of the zebrafish ortholog, Growth differentiation factor 3 (Gdf3), has not been fully explored. We show that zygotic expression of gdf3 is dispensable for embryonic development, while maternally deposited gdf3 is required for mesendoderm formation and dorsal-ventral patterning...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29139224/a-polyelectrolyte-multilayer-platform-for-investigating-growth-factor-delivery-modes-in-human-liver-cultures
#6
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/29137393/synergistic-effect-of-eribulin-and-cdk-inhibition-for-the-treatment-of-triple-negative-breast-cancer
#7
Shreyas S Rao, Jenna Stoehr, Danijela Dokic, Lei Wan, Joseph T Decker, Kristine Konopka, Alexandra L Thomas, Jia Wu, Virginia G Kaklamani, Lonnie D Shea, Jacqueline S Jeruss
Activation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGFβ signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137154/two-sulfur-glycoside-compounds-isolated-from-lepidium-apetalum-willd-protect-nrk52e-cells-against-hypertonic-induced-adhesion-and-inflammation-by-suppressing-the-mapk-signaling-pathway-and-raas
#8
Peipei Yuan, Xiaoke Zheng, Meng Li, Yingying Ke, Yang Fu, Qi Zhang, Xiaolan Wang, Weisheng Feng
Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla...
November 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29135311/atm-bcl2-and-tgf%C3%AE-gene-polymorphisms-as-radiotherapy-outcome-biomarkers-in-head-and-neck-squamous-cell-carcinoma-patients
#9
Lidiane P Agostini, Elaine Stur, Fernanda M Garcia, Diego P Ventorim, Raquel S Dos Reis, Raquel S Dettogni, Eldamária V W Dos Santos, Gabriela T Peterle, Lucas L Maia, Suzanny O Mendes, Marcos B de Carvalho, Eloiza H Tajara, Flavia de Paula, Marcelo Dos Santos, Adriana M A da Silva, Iúri Drumond Louro
AIMS: Polymorphisms in cell cycle genes are considered prognostic and radiosensitivity markers in patients with head and neck squamous cell carcinoma. Therefore, we have aimed to investigate the relationship of ATM 5557G>A, ATM IVS62 + 60G>A, TP53 215G>C, BCL2-938C>A, TGFβ-509C>T, and TGFβ 29C>T with radiotherapy response. MATERIALS AND METHODS: Genotyping was performed by polymerase chain reaction followed by restriction fragment length polymorphism in 210 patients with oral cavity/oropharynx carcinoma and 101 patients with larynx tumors...
November 14, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/29132871/the-role-of-tgf%C3%AE-in-wound-healing-pathologies
#10
REVIEW
Dimitra Kiritsi, Alexander Nyström
Wound healing is one of the most complex processes in multicellular organisms, involving numerous intra- and intercellular signalling pathways in various cell types. It involves extensive communication between the cellular constituents of diverse skin compartments and its extracellular matrix. Miscommunication during healing may have two distinct damaging consequences: the development of a chronic wound or the formation of a hypertrophic scar/keloid. Chronic wounds are defined as barrier defects that have not proceeded through orderly and timely reparation to regain structural and functional integrity...
November 10, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29129643/tgf%C3%AE-pathway-inhibition-in-the-treatment-of-non-small-cell-lung-cancer
#11
REVIEW
Pınar Ö Eser, Pasi A Jänne
Advanced non-small cell lung cancer (NSCLC) continues to be an incurable family of thoracic malignancies that is chronically managed with chemotherapy, targeted therapy, and immunotherapy. While the discovery of driver oncogenes and the advent of targeted and immunotherapies in the last decade have vastly improved clinical disease management for patients harboring druggable mutations, the mainstay treatment for the majority of NSCLC patients remains cytotoxic chemotherapy. The clinical efficacy of targeted, immune, and cytotoxic therapies is limited by the development of drug resistance...
November 9, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29129515/amygdalin-improves-microcirculatory-disturbance-and-attenuates-pancreatic-fibrosis-by-regulating-the-expression-of-endothelin-1-and-calcitonin-gene-related-peptide-in-rats
#12
Xiangqun Zhang, Jiangong Hu, Yuzhen Zhuo, Lihua Cui, Caixia Li, Naiqiang Cui, Shukun Zhang
BACKGROUND: The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. METHODS: The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein...
November 9, 2017: Journal of the Chinese Medical Association: JCMA
https://www.readbyqxmd.com/read/29129392/targeting-obesity-and-cachexia-identification-of-the-gfral-receptor-mic-1-gdf15-pathway
#13
Samuel N Breit, Vicky Wang-Wei Tsai, David A Brown
Macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15) is a divergent transforming growth factor (TGFβ) superfamily cytokine implicated in biological and disease processes including metabolism, cancer, and chronic inflammation, but whose receptor has remained elusive. Four laboratories have recently identified GFRAL, an orphan receptor of the glial-derived neurotrophic factor (GDNF) receptor α family, as the receptor for MIC-1/GDF15, signaling though the coreceptor Ret. These data identify a new systemic to central nervous system (CNS) circuit that regulates metabolism in response to stress and which could be targeted to treat both severe obesity and anorexia/cachexia syndrome...
November 9, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29128493/molecular-characterization-of-a-cc-motif-chemokine-19-like-gene-in-ayu-plecoglossus-altivelis-and-its-role-in-leukocyte-trafficking
#14
Feng Chen, Xin-Jiang Lu, Li Nie, Ying-Jun Ning, Jiong Chen
The CC motif chemokine 19 (CCL19) functions in acute inflammation by recruiting lymphocytes and other cells. However, CCL19 has only been investigated in few fish species. In this study, we characterized a CCL19-like molecule (PaCCL19l) in ayu (Plecoglossus altivelis), a teleost fish. Sequence analysis revealed that PaCCL19l was most closely related to Atlantic salmon (Salmon salar) CCL19l1, which belonged to the fish CCL19a.1 subcluster. PaCCL19l was constitutively expressed in the tested ayu tissues and peripheral blood mononuclear cells (PBMCs), with the highest transcript level in PBMCs...
November 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29127033/the-role-of-tgf%C3%AE-receptor-1-smad3-signaling-in-regulating-the-osteoclastic-mode-caused-by-fluoride
#15
Haolan Yu, Ningning Jiang, XiuHua Yu, Zhitao Zhao, Xiuyun Zhang, Hui Xu
Studies that have focused on the role TGFβ signaling plays in osteoclast activity are gradually increasing; however, literature is rare in terms of fluorosis. The aim of this study is to observe the role the TβR1/Smad3 pathway plays in fluoride regulating cellsosteoclast-like cells that are under the treatment of TGFβ receptor 1 kinase. The RANKL-mediated osteoclast-like cells from RAW264.7 cells were used as osteoclast precursor model. The profile of miRNA expression in fluoride-treated osteoclast-like cells exhibited 303 upregulated miRNAs, 61 downregulated miRNAs, and further drew 37 signaling pathway maps by KEGG and Biocarta pathway enrichment analysis...
November 7, 2017: Toxicology
https://www.readbyqxmd.com/read/29126441/tgf%C3%AE-3-recruits-endogenous-mesenchymal-stem-cells-to-initiate-bone-regeneration
#16
Moyuan Deng, Tieniu Mei, Tianyong Hou, Keyu Luo, Fei Luo, Aijun Yang, Bo Yu, Hao Pang, Shiwu Dong, Jianzhong Xu
BACKGROUND: The recruitment of a sufficient number of endogenous mesenchymal stem cells (MSCs) is the first stage of in-situ tissue regeneration. Transforming growth factor beta-3 (TGFβ3) could recruit stem or progenitor cells and endothelial cells to participate in tissue regeneration. However, the mechanism of TGFβ3 recruiting MSCs toward bone regeneration has remained obscure. METHODS: We estimated the promigratory property of TGFβ3 on human bone marrow MSCs (hBMSCs) cocultured with the vascular cells (human umbilical artery smooth muscle cells or human umbilical vein endothelial cells) or not by Transwell assay...
November 10, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29126308/nrf2-deficiency-promotes-the-progression-from-acute-tubular-damage-to-chronic-renal-fibrosis-following-unilateral-ureteral-obstruction
#17
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/29121102/histopathologic-and-immunohistochemical-features-of-capsular-tissue-around-failed-ahmed-glaucoma-valves
#18
Alka Mahale, Fatma Fikri, Khitam Al Hati, Sami Al Shahwan, Ibrahim Al Jadaan, Hind Al Katan, Rajiv Khandekar, Azza Maktabi, Deepak P Edward
Impervious encapsulation around Ahmed glaucoma valve (AGV) results in surgical failure raising intraocular pressure (IOP). Dysregulation of extracellular matrix (ECM) molecules and cellular factors might contribute to increased hydraulic resistance to aqueous drainage. Therefore, we examined these molecules in failed AGV capsular tissue. Immunostaining for ECM molecules (collagen I, collagen III, decorin, lumican, chondroitin sulfate, aggrecan and keratan sulfate) and cellular factors (αSMA and TGFβ) was performed on excised capsules from failed AGVs and control tenon's tissue...
2017: PloS One
https://www.readbyqxmd.com/read/29118904/inhibiting-post-translational-core-fucosylation-protects-against-albumin-induced-proximal-tubular-epithelial-cell-injury
#19
Dapeng Wang, Ming Fang, Nan Shen, Longkai Li, Weidong Wang, Lingyu Wang, Hongli Lin
Albuminuria is an independent risk factor for renal interstitial fibrosis (RIF). Glomerular-filtered albumin in endocytic and non-endocytic pathways may injure proximal tubular epithelial cells (PTECs) via megalin and TGFβRII, respectively. Since megalin and TGFβRII are both modified by post-translational core fucosylation, which plays a critical role in RIF. Thus, we sought to identify whether core fucosylation is a potential target for reducing albumin-induced injury to PTECs. We constructed a human PTEC-derived cell line (HK-2 cells) and established an in vitro model of bovine serum albumin (BSA) injury...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29118761/immunological-and-clinical-effect-of-diet-modulation-of-the-gut-microbiome-in-multiple-sclerosis-patients-a-pilot-study
#20
Marina Saresella, Laura Mendozzi, Valentina Rossi, Franca Mazzali, Federica Piancone, Francesca LaRosa, Ivana Marventano, Domenico Caputo, Giovanna E Felis, Mario Clerici
Pathogenesis of autoimmune disorders, including multiple sclerosis (MS), has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR) MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10) or a "Western Diet" (WD group; N = 10) for at least 12 months...
2017: Frontiers in Immunology
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