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https://www.readbyqxmd.com/read/29160747/lipopolysaccharide-mediates-hepatic-stellate-cell-activation-by-regulating-autophagy-and-retinoic-acid-signaling
#1
Ming Chen, Jiaxing Liu, Wenqi Yang, Wenhua Ling
Bacterial translocation and lipopolysaccharide (LPS) leakage occur at a very early stage of liver fibrosis in animal models. We studied the role of LPS in hepatic stellate cell (HSC) activation and the underlying mechanisms in vitro and in vivo. Herein, we demonstrated that LPS treatment led to a dramatic increase in autophagosome formation and autophagic flux in LX-2 cells and HSCs, which was mediated through the AKT-MTOR and AMPK-ULK1 pathway. LPS significantly decreased the lipid content, including the lipid droplet (LD) number and lipid staining area in HSCs; pretreatment with macroautophagy/autophagy inhibitors or silencing ATG5 attenuated this decrease...
November 21, 2017: Autophagy
https://www.readbyqxmd.com/read/29140249/maternal-gdf3-is-an-obligatory-cofactor-in-nodal-signaling-for-embryonic-axis-formation-in-zebrafish
#2
Brent W Bisgrove, Yi-Chu Su, H Joseph Yost
Zebrafish Gdf3 (Dvr1) is a member of the TGFb superfamily of cell signaling ligands that includes Xenopus Vg1 and mammalian Gdf1/3. Surprisingly, engineered homozygous mutants in zebrafish have no apparent phenotype. Elimination of Gdf3 in oocytes of maternal-zygotic mutants results in embryonic lethality that can be fully rescued with gdf3 RNA, demonstrating that Gdf3 is required only early in development, beyond which mutants are viable and fertile. Gdf3 mutants are refractory to Nodal ligands and Nodal repressor Lefty1...
November 15, 2017: ELife
https://www.readbyqxmd.com/read/29089047/whole-exome-sequencing-in-342-congenital-cardiac-left-sided-lesion-cases-reveals-extensive-genetic-heterogeneity-and-complex-inheritance-patterns
#3
Alexander H Li, Neil A Hanchard, Dieter Furthner, Susan Fernbach, Mahshid Azamian, Annarita Nicosia, Jill Rosenfeld, Donna Muzny, Lisa C A D'Alessandro, Shaine Morris, Shalini Jhangiani, Dhaval R Parekh, Wayne J Franklin, Mark Lewin, Jeffrey A Towbin, Daniel J Penny, Charles D Fraser, James F Martin, Christine Eng, James R Lupski, Richard A Gibbs, Eric Boerwinkle, John W Belmont
BACKGROUND: Left-sided lesions (LSLs) account for an important fraction of severe congenital cardiovascular malformations (CVMs). The genetic contributions to LSLs are complex, and the mutations that cause these malformations span several diverse biological signaling pathways: TGFB, NOTCH, SHH, and more. Here, we use whole exome sequence data generated in 342 LSL cases to identify likely damaging variants in putative candidate CVM genes. METHODS: Using a series of bioinformatics filters, we focused on genes harboring population-rare, putative loss-of-function (LOF), and predicted damaging variants in 1760 CVM candidate genes constructed a priori from the literature and model organism databases...
October 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29050273/tgf%C3%AE-induced-factor-homeobox-1-promotes-colorectal-cancer-development-through-activating-wnt-%C3%AE-catenin-signaling
#4
Ji-Lian Wang, Zhen Qi, Ye-Hua Li, Hong-Mei Zhao, Ye-Guang Chen, Wei Fu
Colorectal cancer (CRC) is one of the most common cancers, but the mechanisms underlying its initiation and progression are largely unknown. TGIF1 (TGFB induced factor homeobox 1) is a transcriptional corepressor that belongs to the three-amino acid loop extension (TALE) superclass of atypical homeodomains. It has been reported that TGIF1 is highly expressed in mammary cancer and non-small cell lung cancer and can enhance tumor progression. However, the role of TGIF1 in colorectal cancer remains unknown. Here, we report that TGIF1 is significantly upregulated in colorectal cancers, and its high expression predicts poor prognosis...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29031499/micrornas-15a-and-16-1-activate-signaling-pathways-that-mediate-chemotaxis-of-immune-regulatory-b-cells-to-colorectal-tumors
#5
Ronghua Liu, Zhou Lu, Jie Gu, Jiajing Liu, Enyu Huang, Xiaoming Liu, Luman Wang, Jiao Yang, Yuting Deng, Jiawen Qian, Feifei Luo, Zhiming Wang, Hushan Zhang, Xuechao Jiang, Dan Zhang, Jing Qian, Guangwei Liu, Hongguang Zhu, Youcun Qian, Zhanju Liu, Yiwei Chu
BACKGROUND & AIMS: B cells infiltrate tumors but little is known about how they affect tumor growth and progression. microRNA15A (MIR15A or miRNA15A) and microRNA16-1 (MIR16-1 or miRNA16-1) regulate cell proliferation, apoptosis and drug resistance. We investigated their involvement in B cell-mediated immune suppression by colorectal tumors. METHODS: Mice with disruptions of the gene cluster that encodes MIR15A and MIR16-1 (KO mice), and control (C57BL/B6) mice were given azoxymethane with dextran sodium sulfate (AD) to induce formation of colorectal tumors...
October 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/29029802/early-life-environmental-exposures-interact-with-genetic-susceptibility-variants-in-pediatric-patients-with-eosinophilic-esophagitis
#6
Elizabeth T Jensen, Jonathan T Kuhl, Lisa J Martin, Carl D Langefeld, Evan S Dellon, Marc E Rothenberg
BACKGROUND: Although eosinophilic esophagitis (EoE) is associated with certain gene variants, the rapidly increasing incidence of EoE suggests that environmental factors contribute to disease development. OBJECTIVE: We tested for gene-environment interaction between EoE-predisposing polymorphisms (within TSLP, LOC283710/KLF13, CAPN14, CCL26, and TGFB) and implicated early-life factors (antibiotic use in infancy, cesarean delivery, breast-feeding, neonatal intensive care unit [NICU] admission, and absence of pets in the home)...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29017945/healing-and-mucosal-immunity-in-the-skin-of-experimentally-wounded-gilthead-seabream-sparus-aurata-l
#7
Diana Ceballos-Francisco, Héctor Cordero, Francisco A Guardiola, Alberto Cuesta, María Ángeles Esteban
Skin lesions are very common in fisheries, increasing the risk of pathogens entering through the wounded skin of the fish. In the present assay, the progression of wound healing was studied over a 7 day period in gilthead seabream (Sparus aurata L.) after making experimental wounds in two different locations: above (group A) or below (group B) the lateral line. Macroscopic observation confirmed faster wound healing of the wounds of fish from group B. Furthermore, several immune-related components were studied in the skin mucus of wounded fish to ascertain whether wounding altered the mucus composition compared with the values obtained from non-wounded fish (group C, control)...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28981455/a-unique-tgfb1-driven-genomic-program-links-astrocytosis-low-grade-inflammation-and-partial-demyelination-in-spinal-cord-periplaques-from-progressive-multiple-sclerosis-patients
#8
Serge Nataf, Marc Barritault, Laurent Pays
We previously reported that, in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses did not allow providing a comprehensive view of molecular events in astrocytes vs. oligodendrocytes. Here, we re-assessed our transcriptomic data and performed co-expression analyses to characterize astrocyte vs...
October 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28966149/zearalenone-zen-disrupts-the-anti-inflammatory-response-of-bovine-oviductal-epithelial-cells-to-sperm-in-vitro
#9
Mohamed S Yousef, Mitsuhiro Takagi, Anup K Talukder, Mohamed A Marey, Rasoul Kowsar, Abdel-Razek Kh Abdel-Razek, Takashi Shimizu, Johanna Fink-Gremmels, Akio Miyamoto
Dietary contamination by Zearalenone (ZEN) has a detrimental effect on bovine fertility. Recently, we showed a novel anti-inflammatory response of bovine oviductal epithelial cells (BOEC) to active sperm cells in vitro. The aim of the present study was to investigate the effect of ZEN exposure of BOEC on the immune-related cytokine expression in response to bovine sperm. At concentrations of 100 and 1000ng/mL, ZEN induced the expression of TNF and IL1B (pro-inflammatory cytokines) as well as IL8 (chemokine) in BOEC in a dose-dependent manner...
September 28, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28939895/a-single-sphingomyelin-species-promotes-exosomal-release-of-endoglin-into-the-maternal-circulation-in-preeclampsia
#10
Leonardo Ermini, Jonathan Ausman, Megan Melland-Smith, Behzad Yeganeh, Alessandro Rolfo, Michael L Litvack, Tullia Todros, Michelle Letarte, Martin Post, Isabella Caniggia
Preeclampsia (PE), an hypertensive disorder of pregnancy, exhibits increased circulating levels of a short form of the auxillary TGF-beta (TGFB) receptor endoglin (sENG). Until now, its release and functionality in PE remains poorly understood. Here we show that ENG selectively interacts with sphingomyelin(SM)-18:0 which promotes its clustering with metalloproteinase 14 (MMP14) in SM-18:0 enriched lipid rafts of the apical syncytial membranes from PE placenta where ENG is cleaved by MMP14 into sENG. The SM-18:0 enriched lipid rafts also contain type 1 and 2 TGFB receptors (TGFBR1 and TGFBR2), but not soluble fms-like tyrosine kinase 1 (sFLT1), another protein secreted in excess in the circulation of women with PE...
September 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28937434/th17-response-of-borderline-lepromatous-leprosy-inhibits-rash-manifestation-of-dapsone-hypersensitivity-syndrome-case-report
#11
Tamara de Nardo Vanzela, Fred Bernardes Filho, Carlos Gustavo Wambier, Francesca Maia Faria, Norma Tiraboschi Foss, Marco Andrey Cipriani Frade
BACKGROUND: Dapsone hypersensitivity syndrome (DHS) is a rare, but potentially life-threatening reaction to dapsone. OBJECTIVE: Evaluation of immunological factors involved in the sparing of borderline-lepromatous (BL) leprosy patches by the severe exanthema related to DHS. METHODS: The authors describe a 19-year-old man with borderline-lepromatous leprosy with a recent diffuse rash, sparing only the hypochromic patches of leprosy, generalized lymphadenopathy, hepatomegaly, and jaundice 25 days after the start of multibacillary multidrug therapy...
September 11, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28856758/gonadal-soma-controls-ovarian-follicle-proliferation-through-gsdf-in-zebrafish
#12
Yi-Lin Yan, Thomas Desvignes, Ruth Bremiller, Catherine Wilson, Danielle Dillon, Samantha High, Bruce Draper, Charles Loren Buck, John Postlethwait
BACKGROUND: Aberrant signaling between germ cells and somatic cells can lead to reproductive disease and depends on diffusible signals, including transforming growth factor-beta (TGFB) -family proteins. The TGFB-family protein Gsdf (gonadal soma derived factor) controls sex determination in some fish and is a candidate for mediating germ cell/soma signaling. RESULTS: Zebrafish expressed gsdf in somatic cells of bipotential gonads and expression continued in ovarian granulosa cells and testicular Sertoli cells...
August 30, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28817834/mdm2-promotes-epithelial-mesenchymal-transition-and-metastasis-of-ovarian-cancer-skov3-cells
#13
Ying Chen, Dan-Dan Wang, Ye-Ping Wu, Dan Su, Tian-Yi Zhou, Ren-Hua Gai, Ying-Ying Fu, Lin Zheng, Qiao-Jun He, Hong Zhu, Bo Yang
BACKGROUND: Metastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-%C3%AE-promotes-liver-tumorigenesis-in%C3%A2-mice-via-up-regulation-of-snail
#14
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGF-β) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGF-β signaling pathway prevents tumor growth. We investigated the effects of TGF-β inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail-vein injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to down-regulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89A), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
November 2017: Gastroenterology
https://www.readbyqxmd.com/read/28733348/molecular-forms-of-ruminant-bmp15-and-gdf9-and-putative-interactions-with-receptors
#15
Derek A Heath, Janet Pitman, Kenneth P McNatty
Bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) are oocyte-secreted factors with demonstrable effects on ovarian follicular development and ovulation-rate. However, the molecular forms of BMP15 and GDF9 produced by oocytes remains unclear. The aims herein, using Western blotting (WB) procedures with specific monoclonal antibodies (mabs), were to identify the molecular forms of BMP15 and GDF9 synthesised and secreted by isolated ovine (o) and bovine (b) oocytes in vitro. The mabs were known to recognise the biological forms of BMP15 or GDF9 since they had previously been shown to inhibit their bioactivities in vitro and in vivo...
July 21, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28679671/breast-regression-protein-39-chitinase-3-like-1-promotes-renal-fibrosis-after-kidney-injury-via-activation-of-myofibroblasts
#16
Tinika A Montgomery, Leyuan Xu, Sherene Mason, Amirtha Chinnadurai, Chun Geun Lee, Jack A Elias, Lloyd G Cantley
The normal response to kidney injury includes a robust inflammatory infiltrate of PMNs and macrophages. We previously showed that the small secreted protein breast regression protein-39 (BRP-39), also known as chitinase 3-like 1 (CHI3L1) and encoded by the Chi3l1 gene, is expressed at high levels by macrophages during the early stages of kidney repair and promotes tubular cell survival via IL-13 receptor α2 (IL13Rα2)-mediated signaling. Here, we investigated the role of BRP-39 in profibrotic responses after AKI...
November 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28665611/comprehensive-myocardial-proteogenomics-profiling-reveals-c-ebp%C3%AE-as-the-key-factor-in-the-lipid-storage-of-arvc
#17
Liang Chen, Fan Yang, Xiao Chen, Man Rao, Ning-Ning Zhang, Kai Chen, HaiTeng Deng, Jiang-Ping Song, Sheng-Shou Hu
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is hereditary cardiomyopathy characterized by the fibro-fatty replacement of the myocardium. A small number of noncomprehensive profiling studies based on human cardiac tissues have been conducted and reported; consequently, ARVC's gene expression pattern characteristics remain largely undocumented. Our study applies large-scaled, quantitative proteomics based on TMT-labeled LC-MS/MS to analyze the left and right ventricular myocardium of four ARVC and four DCM explanted hearts to compare them with normal hearts...
July 13, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28662367/inhibition-of-the-mir-17-92-cluster-separates-stages-of-palatogenesis
#18
R J Ries, W Yu, N Holton, H Cao, B A Amendt
The role that noncoding regions of the genome play in the etiology of cleft palate is not well studied. A novel method of microRNA (miR) inhibition that allows for specific miR knockdown in vivo has been developed by our laboratory. To further understand the role of miRs in palatogenesis, we used a new mouse model to inhibit specific miRs within the miR-17-92 cluster. Transgenic mice expressing inhibitory complexes for miR-17 and miR-18 manifested a clefting phenotype that was distinct from that observed in mice carrying inhibitory complexes for miR-17, miR-18, miR-19, and miR-92...
October 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28659758/chronic-oxidative-stress-mitochondrial-dysfunction-nrf2-activation-and-inflammation-in-the-hippocampus-accompany-heightened-systemic-inflammation-and-oxidative-stress-in-an-animal-model-of-gulf-war-illness
#19
Geetha A Shetty, Bharathi Hattiangady, Dinesh Upadhya, Adrian Bates, Sahithi Attaluri, Bing Shuai, Maheedhar Kodali, Ashok K Shetty
Memory and mood dysfunction are the key symptoms of Gulf war illness (GWI), a lingering multi-symptom ailment afflicting >200,000 veterans who served in the Persian Gulf War-1. Research probing the source of the disease has demonstrated that concomitant exposures to anti-nerve gas agent pyridostigmine bromide (PB), pesticides, and war-related stress are among the chief causes of GWI. Indeed, exposures to GWI-related chemicals (GWIR-Cs) and mild stress in animal models cause memory and mood impairments alongside reduced neurogenesis and chronic low-level inflammation in the hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28657664/conditional-abrogation-of-transforming-growth-factor-%C3%AE-receptor-1-in-pten-inactivated-endometrium-promotes-endometrial-cancer-progression-in-mice
#20
Yang Gao, Pengfei Lin, John P Lydon, Qinglei Li
Although a putative role for transforming growth factor-β (TGFB) signalling in the pathogenesis of human endometrial cancer has long been proposed, the precise function of TGFB signalling in the development and progression of endometrial cancer remains elusive. Depletion of phosphatase and tensin homologue (PTEN) in the mouse uterus causes endometrial cancer. To identify the potential role of TGFB signalling in endometrial cancer, we simultaneously deleted TGFB receptor 1 (Tgfbr1) and Pten in the mouse uterus by using Cre-recombinase driven by the progesterone receptor (termed Pten(d/d) ;Tgfbr1(d/d) )...
September 2017: Journal of Pathology
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