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Biliary Atresia
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Many genes have now been implicated in the pathway for specification of the left-right axis. The pathway is thought to involve at least 2 genetically distinct steps: 1) generation of an asymmetric axis; and 2) conserved positioning of structures along this axis. Several genes, including inversin, HFH-4, the Ird gene, which is mutated in the iv mouse, growth/differentiation factor-1, and the ZIC-3 gene, which is mutated in X-linked situs anomalies, appear to act early in the pathwav and are therefore likely to be involved in the generation of the asymmetric axis.98,99,101,103,108,110 Anumber of other genes appear to act later in the pathway: transforming growth factor β molecules such as nodal, lefty-1, lefty-2, activinβB; molecides involved in transforming growth factor β signaling such as activin receptor IIa and IIb, Smad 2; hepatocyte nuclear factor 3β; sonic hedgehog; FGF8; Caronte; cWNT8; patched; and ptx2.111–120
Postimplantation diabetic embryopathy
Published in Moshe Hod, Lois G. Jovanovic, Gian Carlo Di Renzo, Alberto de Leiva, Oded Langer, Textbook of Diabetes and Pregnancy, 2018
Ulf J. Eriksson, Parri Wentzel
Using an inbred Sprague Dawley strain (L) with about 20% skeletal malformations when the mother is diabetic and inbred Wistar Furth rats (no diabetes-inducible skeletal malformations), a global gene linkage analysis of the skeletal malformations was performed with microsatellites, a study that yielded strong coupling of the malformations to 7 regions on chromosomes 4, 10, 14, 18, and 19 and a weaker coupling to 14 other loci in the genome; altogether we found loci on 16 chromosomes. Searching for candidate genes within a distance of 10 cM from each microsatellite yielded 18 genes that had been implicated in previous studies of diabetic embryopathy. These genes were involved in embryonic development/morphogenesis (Map1b, Shh, Tgfb3, Vegfa, Dvl2, Nf1, Gsk3b, Gap43, Tgfbr3, Gdf1, Csf1r),308–314 regulation of DNA/RNA metabolism (En2, Brcc3, Tp53),192,308,315–317 regulation of apoptosis (Nol3, Bak1),308 and cellular metabolism (Folr1, Akr1b1).149,168,315
Current advancements in pharmacotherapy for cancer cachexia
Published in Expert Opinion on Pharmacotherapy, 2023
Guilherme Wesley Peixoto da Fonseca, Ryosuke Sato, Maria Janieire de Nazaré Nunes Alves, Stephan von Haehling
TGF-β superfamily is a large group of regulatory proteins divided into subfamilies, in which growth differentiation factors, labeled from GDF1 to GDF15, are part of one of these subfamilies. For skeletal muscle mass, GDF8, known as myostatin, inhibits muscle growth and GDF15, also named macrophage inhibitory cytokine-1 (MIC-1), prostate derived factor (PDF), and placental transforming growth factor-β (PTGF-β), plays a critical role in regulating inflammation and apoptosis in muscle tissue [56]. Initial studies have shown that GDF15 has anti-tumorigenenic effect, but now there is strong evidence associating GDF15 with tumor progression activity. Although the role of GDF15 in cancer is controversial, with various reports depending on tumor entity and stage, it appears to have two opposite effects: in early cancers, it is anti-tumorigenic by inducing apoptosis, while in advanced cancers, it is involved in tumor growth and metastasis [57].
The Function and Prognostic Significance of Cripto-1 in Colorectal Cancer
Published in Cancer Investigation, 2020
Jun Sato, Hideaki Karasawa, Takashi Suzuki, Shun Nakayama, Munetoshi Katagiri, Shimpei Maeda, Shinobu Ohnuma, Fuyuhiko Motoi, Takeshi Naitoh, Michiaki Unno
Cripto-1 is a co-receptor for the transforming growth factor-β (TGF-β) subfamily of ligands, containing Nodal, and growth differentiation factor-1 and -3 (GDF-1 and GDF-3) (25). Cripto-1 and Nodal activate serine-threonine kinase activin type I (ALK-4) and then induce phosphorylation and activation of Smad-2 and Smad-3 (26,27). Cripto-1 also activates a Nodal-independent signaling pathway via c-Src/mitogen-activated protein kinase (MAPK), and a phosphatidylinositol 3-kinase (PI3-K)/Akt signaling pathway (27–30). Although Cripto-1 regulates these pathways and contributes to tumor progression (31,32), its function in colorectal cancer has not been adequately researched.
Bacterial TLR4 and NOD2 signaling linked to reduced mitochondrial energy function in active inflammatory bowel disease
Published in Gut Microbes, 2020
Emmanuelle Ruiz, Harrison M. Penrose, Sandra Heller, Hani Nakhoul, Melody Baddoo, Erik F. Flemington, Emad Kandil, Suzana D. Savkovic
Intestinal inflammation associated with IBD is linked to low ATP levels.4 We and others have shown in animal models that reduced intestinal ATP due to deficient mitochondrial energy (ATP) production facilitates intestinal inflammation;16,17 however, how this drives disease pathobiology is unclear. We previously generated ICs with reduced mitochondrial energy function by selective targeting of mitochondrial but not nuclear DNA polymerase with low-dose ethidium bromide in parental cells.18,19 Consequently, in these cells we confirmed their viability, loss of mitochondrial DNA, and reduced ATP synthase activity.16 Following RNAseq we utilized their transcriptomes (SRP093357) to generate a specific transcriptional panel (i.e., Mito-0 transcriptional panel). Initially, DE transcripts of IC with reduced mitochondrial energy function relative to control were analyzed by DEGseq to calculate fold change between the two groups meeting stringent differential expression and statistical thresholds of log2 fold-change > |2| and an adjusted p < 0.001. This IC Mito-0 panel was comprised of 199 transcripts among which 164 were increased and 35 decreased relative to control as shown by scatter plot in which green dots represent transcripts with an adjusted p < 0.001 while red dots represent transcripts with both an adjusted p < 0.001 and an absolute value of log2 fold change > |2| (Figure 1(a,b)). Additionally, unsupervised hierarchical clustering of DE transcripts between IC with reduced mitochondrial energy function and control cells showed a distinct Mito-0 heatmap (Figure 1(c)). From this signature, we identified individual transcripts (Table 1) involved in regulation of diverse biological functions including generation of mitochondrial energy (decreased ATP production) (MT-CO, MT-ND, MT-RNR1, MT-CY, MT-ATP), extracellular matrix (VCAM, MUC13, COL13,17, FGF9), cell–cell contact (TM4SF, FLRT3, THBS, NRP), cytoskeleton (VIM, MID2, MYO15, TINAGl1), growth (IGFBP6, GDF1, GDF15, CDK1A, CDK6), metabolism (PRKAA2, CPA4, TGM2, SGK1, SLC7A11), and inflammatory response (TNFR, IL17RD, IFIT2,3, NTSE, TLR6). Also in this panel, several transcripts were encoded by unannotated genes with uncharacterized function. These data represent an IC specific transcriptional signature mediated by aberrant mitochondrial energy function and include transcripts with established and undetermined functions in IBD.