Search results for "SIG"
showing 10 items of 19670 documents
Wnt1 Promotes Cementum and Alveolar Bone Growth in a Time-Dependent Manner
2021
The WNT/β-catenin signaling pathway plays a central role in the biology of the periodontium, yet the function of specific extracellular WNT ligands remains poorly understood. By using a Wnt1-inducible transgenic mouse model targeting Col1a1-expressing alveolar osteoblasts, odontoblasts, and cementoblasts, we demonstrate that the WNT ligand WNT1 is a strong promoter of cementum and alveolar bone formation in vivo. We induced Wnt1 expression for 1, 3, or 9 wk in Wnt1Tg mice and analyzed them at the age of 6 wk and 12 wk. Micro–computed tomography (CT) analyses of the mandibles revealed a 1.8-fold increased bone volume after 1 and 3 wk of Wnt1 expression and a 3-fold increased bone volume aft…
Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer.
2019
The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-…
Heat Shock Protein 60 in Cardiovascular Physiology and Diseases.
2020
Heat shock protein 60 (HSP60) is a highly conserved protein abundantly expressed in both prokaryotic and eukaryotic cells. In mammals, HSP60 has been primarily considered to reside in the mitochondria, where HSP60 and HSP10 form a complex and facilitate mitochondrial protein folding. However, HSP60 is also observed in the cytoplasm, the plasma membrane, and the extracellular space. HSP60 regulates a broad spectrum of cellular events including protein trafficking, peptide hormone signaling, cell survival, cell proliferation, inflammation, and immunization. In the cardiovascular system, growing evidence indicates that HSP60 could not only play an important role under physiological conditions,…
Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives
2018
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-b-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced 62% HSD1 inhibition at 5 mM and, furthermore, three of them produced 68% inhibition at 1 mM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-b-hydroxysteroid dehydrogenase 2 – a requirement for lowe…
ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta
2021
The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to verte…
Cbt modulates Foxo activation by positively regulating insulin signaling in Drosophila embryos.
2018
In late Drosophila embryos, the epidermis exhibits a dorsal hole as a consequence of germ band retraction. It is sealed during dorsal closure (DC), a morphogenetic process in which the two lateral epidermal layers converge towards the dorsal midline and fuse. We previously demonstrated the involvement of the Cbt transcription factor in Drosophila DC. However its molecular role in the process remained obscure. In this study, we used genomic approaches to identify genes regulated by Cbt as well as its direct targets during late embryogenesis. Our results reveal a complex transcriptional circuit downstream of Cbt and evidence that it is functionally related with the Insulin/insulin-like growth…
Proangiogenic TF-FVIIa-PAR2 Signaling Requires Matriptase-Independent Integrin Interaction
2016
Abstract The close link between coagulation activation and cancer progression is supported by clinical and experimental studies. A central molecular pathways by which tumor cells interact with the hemostatic system is through the expression of the cell surface receptor tissue factor (TF) that in complex with coagulation factor VIIa (FVIIa) triggers the extrinsic pathway of blood coagulation, contributes to cancer associated thrombosis, and promotes direct tumor cell signaling through protease-activated receptors (PARs). Genetic and pharmacological evidence shows that epithelial and tumor cell TF-FVIIa signaling induces a diverse set of proangiogenic and immune modulatory cytokines, chemokin…
The relationship of mandibular radiomorphometric indices to skeletal age, chronological age and skeletal malocclusion type
2017
Background The present study was performed with the following aims: (1) to assess the relationship between skeletal age, measured using the cervical vertebral maturity (CVM) method, and chronological age; (2) to determine the correlation of skeletal and chronological age to the cortical thickness of the lower border of the mandible using the linear radiomorphometric; and (3) to explore the relationship between these indices and skeletal malocclusion type. Material and methods The data were collected from the records of 180 patients, including 57 males (31.7%) and 123 females (68.3%). The data were based on the panoramic and lateral cephalograms of each patient. The CVM stages were determine…
Comparison of the root canal debridement ability of two single file systems with a conventional multiple rotary system in long oval-shaped root canal…
2016
Background This study sought to compare the root canal debridement ability of Neolix, Reciproc and ProTaper rotary systems in long oval-shaped root canals. Material and methods Eighty five extracted single-rooted human teeth with long oval-shaped single root canals were selected and divided into three experimental groups(n=25) and one control group (n= 10). Root canals were filled with Vitapex radiopaque contrast medium and prepared with Neolix, Reciproc or ProTaper systems. The control group only received irrigation. Digital radiographs were obtained at baseline and postoperatively and subjected to digital subtraction. The percentage of reduction in contrast medium was quantified at 0-5 mm…
Nobiletin and xanthohumol sensitize colorectal cancer stem cells to standard chemotherapy
2021
Simple Summary Colorectal cancer stem cells (CR-CSCs) play a pivotal role in the therapy resistance and relapse of CRC patients. Herein we demonstrate that new treatment approaches comprising polymethoxyflavones and prenylflavonoids extracted from Citrus sinensis and Humulus lupulus, respectively, hamper the viability of CR-CSCs as well as synergizing with 5-fluorouracil and oxaliplatin (FOX)-based chemotherapy. Extract fractions containing Nobiletin and Xanthohumol, in combination with chemotherapy, decreased stemness properties of CR-CSCs and restrained the outgrowth of chemoresistant metastatic CR-CSCs. These data pinpoint Nobiletin and Xanthohumol as efficacious anti-cancer compounds in…