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https://www.readbyqxmd.com/read/29329585/involvement-of-hedgehog-pathway-in-early-onset-aggressive-molecular-subtypes-and-metastatic-potential-of-breast-cancer
#1
Syeda Kiran Riaz, Jahangir Sarwar Khan, Syed Tahir Abbas Shah, Fen Wang, Lin Ye, Wen G Jiang, Muhammad Faraz Arshad Malik
BACKGROUND: Dysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study. METHOD: One hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified...
January 8, 2018: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29322335/mechanobiological-modeling-of-endochondral-ossification-an-experimental-and-computational-analysis
#2
J J Vaca-González, M Moncayo-Donoso, J M Guevara, Y Hata, S J Shefelbine, D A Garzón-Alvarado
Long bone formation starts early during embryonic development through a process known as endochondral ossification. This is a highly regulated mechanism that involves several mechanical and biochemical factors. Because long bone development is an extremely complex process, it is unclear how biochemical regulation is affected when dynamic loads are applied, and also how the combination of mechanical and biochemical factors affect the shape acquired by the bone during early development. In this study, we develop a mechanobiological model combining: (1) a reaction-diffusion system to describe the biochemical process and (2) a poroelastic model to determine the stresses and fluid flow due to loading...
January 10, 2018: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/29316655/nfatc1-is-a-functional-transcriptional-factor-mediating-nell-1-induced-runx3-upregulation-in-chondrocytes
#3
Chenshuang Li, Zhong Zheng, Xinli Zhang, Greg Asatrian, Eric Chen, Richard Song, Cymbeline Culiat, Kang Ting, Chia Soo
Neural EGFL like 1 (Nell-1) is essential for chondrogenic differentiation, maturation, and regeneration. Our previous studies have demonstrated that Nell-1's pro-chondrogenic activities are predominantly reliant upon runt-related transcription factor 3 (Runx3)-mediated Indian hedgehog (Ihh) signaling. Here, we identify the nuclear factor of activated T-cells 1 (Nfatc1) as the key transcriptional factor mediating the Nell-1 → Runx3 signal transduction in chondrocytes. Using chromatin immunoprecipitation assay, we were able to determine that Nfatc1 binds to the -833--810 region of the Runx3-promoter in response to Nell-1 treatment...
January 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29299122/wnt-%C3%AE-catenin-and-hedgehog-pathways-are-involved-in-the-inflammatory-effect-of-interleukin-18-on-rat-chondrocytes
#4
Jiapeng Bao, Chiyuan Ma, Jisheng Ran, Yan Xiong, Shigui Yan, Lidong Wu
To investigate the inflammatory effect of Interleukin 18 (IL-18) on rat chondrocytes and the involvement of Wnt/β-catenin and Hedgehog pathways, the mRNA and protein level of matix-degrading enzymes (MMP-2, 3, 9,13 and aggrecanses) and chondrocyte-specific proteins (Collagen II and aggrecan) were evaluated by qRT-PCR and Western blot, and key protein level of Wnt/β-catenin and Hedgehog pathways including β-catenin, GSK-3β, DKK-1, IHH, SHH, and Gli-2 were evaluated by Western blot. Dickkopf-1 (DKK-1) and Cyclopamine were used as antagonist of Wnt/β-catenin and Hedgehog pathways to perform pathway inhibition tests...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29280744/update-on-the-genetics-of-idiopathic-hypogonadotropic-hypogonadism
#5
A Kemal Topaloğlu
Traditionally, idiopathic hypogonadotropic hypogonadism (IHH) is divided into two major categories: Kallmann syndrome (KS) and normosmic IHH (nIHH). To date, inactivating variants in more than 50 genes have been reported to cause IHH. These mutations are estimated to account for up to 50% of all apparently hereditary cases. Identification of further causative gene mutations is expected to be more feasible with the increasing use of whole exome/genome sequencing. Presence of more than one IHH-associated mutant gene in a given patient/pedigree (oligogenic inheritance) is seen in 10-20% of all IHH cases...
December 27, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29276753/indian-hedgehog-suppresses-a-stromal-cell-driven-intestinal-immune-response
#6
B Florien Westendorp, Nikè V J A Büller, Olga N Karpus, Willemijn A van Dop, Jan Koster, Rogier Versteeg, Pim J Koelink, Clinton Y Snel, Sander Meisner, Joris J T H Roelofs, Anja Uhmann, Emiel Ver Loren van Themaat, Jarom Heijmans, Heidi Hahn, Vanesa Muncan, Manon E Wildenberg, Gijs R van den Brink
Background & Aims: Upon intestinal epithelial damage a complex wound healing response is initiated to restore epithelial integrity and defend against pathogenic invasion. Epithelium-derived Indian Hedgehog (Ihh) functions as a critical sensor in this process. Signaling occurs in a paracrine manner because the receptor for Ihh is expressed only in the mesenchyme, but the exact Hedgehog target cell has remained elusive. The aim of this study was to elucidate further the nature of this target cell in the context of intestinal inflammation...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29274272/the-role-of-the-hedgehog-signaling-pathway-in-cancer-a-comprehensive-review
#7
REVIEW
Ana Marija Skoda, Dora Simovic, Valentina Karin, Vedran Kardum, Semir Vranic, Ljiljana Serman
The Hedgehog (Hh) signaling pathway was first identified in the common fruit fly. It is a highly conserved evolutionary pathway of signal transmission from the cell membrane to the nucleus. The Hh signaling pathway plays an important role in the embryonic development. It exerts its biological effects through a signaling cascade that culminates in a change of balance between activator and repressor forms of glioma-associated oncogene (Gli) transcription factors. The components of the Hh signaling pathway involved in the signaling transfer to the Gli transcription factors include Hedgehog ligands (Sonic Hh [SHh], Indian Hh [IHh], and Desert Hh [DHh]), Patched receptor (Ptch1, Ptch2), Smoothened receptor, Suppressor of fused homolog, kinesin-7, protein kinase A, and cyclic adenosine monophosphate (AMP)...
December 23, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29222391/the-g-protein-coupled-receptor-gpr161-regulates-forelimb-formation-limb-patterning-and-skeletal-morphogenesis-in-a-primary-cilium-dependent-manner
#8
Sun-Hee Hwang, Kevin A White, Bandarigoda Nipunika Somatilaka, John M Shelton, James A Richardson, Saikat Mukhopadhyay
The role of basal suppression of Sonic hedgehog (Shh) pathway and its interaction with Indian hedgehog (Ihh) signaling during limb/skeletal morphogenesis is not well understood. The orphan G-protein-coupled receptor, Gpr161 localizes to primary cilia, and functions as a negative regulator of Shh signaling by promoting Gli transcriptional repressor versus activator formation. Here, we show that forelimb buds are not formed in Gpr161 knockout mice embryos despite establishment of prospective limb fields. Limb-specific deletion of Gpr161 resulted in prematurely expanded Shh signaling and ectopic Shh-dependent patterning defects to cause polysyndactyly...
December 8, 2017: Development
https://www.readbyqxmd.com/read/29208275/synergetically-understanding-the-interaction-between-nano-microspheres-and-peptide-for-controllable-drug-loading-via-experimental-and-theoretical-approaches
#9
Chunbao Du, Xiaoling Hu, Yuan Cheng, Junfeng Gao, Yong-Wei Zhang, Kehe Su, Zhijian Li, Nan Zhang, Ninghui Chang, Kaiyang Zeng
In this paper we systematically investigate the loading capacity of raspberry-like nano/microspheres with highly cross-linked structure for the peptide, immunostimulating hexapeptide from human (IHH), by integrating both experimental and simulation efforts. The experimental results indicate that the loading capacities of raspberry-like nano/microspheres with different functionalized chains vary drastically. To provide theoretical insights into the observed phenomenon, the typical raspberry-like nano/microspheres were simplified as effective functionalized groups, thereby the interactions between them and IHH were accurately calculated by ab initio method...
February 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29204812/tumor-screening-in-beckwith-wiedemann-syndrome-parental-perspectives
#10
Kelly A Duffy, Katheryn L Grand, Kristin Zelley, Jennifer M Kalish
Children with Beckwith-Wiedemann Syndrome (BWS) and Isolated Hemihypertrophy (IHH) are at an increased risk for developing tumors. Tumor screening in this population is currently being reassessed by several groups and the effect on patients and patient-families has been argued both as a reason to screen and not to screen. Parental perspectives on this topic have never been systematically addressed for the BWS population. Here, we conducted a parent-based survey to evaluate knowledge and attitudes toward tumor screening in patients affected by BWS/IHH...
December 4, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/29201072/the-role-of-kisspeptin-in-female-reproduction
#11
REVIEW
Sareh Zeydabadi Nejad, Fahimeh Ramezani Tehrani, Azita Zadeh-Vakili
Context: Kisspeptin (KISS1), a recently discovered neuropeptide that acts upstream of gonadotropin-releasing hormone (GnRH) neurons, is critical for maturation and function of the reproductive axis. This review aimed at providing comprehensive and up-to-date information on Kisspeptin and its role in female reproduction. Evidence Acquisition: A literature review was performed using PubMed for all English language articles published between 1999 and 2016. Results: The kisspeptin system (KISS1/G protein-coupled receptor-54,GPR54) has recently been addressed as an essential gatekeeper of puberty onset and gonadotropin secretion...
July 2017: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29185949/atypical-presentation-of-infantile-hepatic-hemangioma-a-case-study
#12
Ashley Sartori, Gayle Leary Omansky, Steven Ringer
Infantile hepatic hemangioma (IHH) is the most common benign hepatic tumor of infancy. It is characterized by rapid proliferation in the first year of life, followed by slow involution during childhood. Presentation can range from asymptomatic to severe, high-output congestive heart failure (CHF). The purpose of this article is to review the case of an infant with an atypical presentation of IHH. It also addresses pathophysiology, diagnosis, management, and multidisciplinary team care.
November 1, 2017: Neonatal Network: NN
https://www.readbyqxmd.com/read/29173861/possible-alternative-treatment-for-mandibular-asymmetry-by-local-unilateral-igf-1-injection-into-the-mandibular-condylar-cavity-experimental-study-in-mice
#13
Sari Fukaya, Hiroyuki Kanzaki, Yutaka Miyamoto, Yuki Yamaguchi, Yoshiki Nakamura
INTRODUCTION: The purpose of this study was to investigate whether a local unilateral IGF-1 injection into the mandibular condylar cavity can induce unilateral endochondral mandibular growth without any systemic adverse effects. METHODS: Seventy-five 3-week-old male Jcl:ICR mice were used in this study. The mice were divided into 2 groups: control group (n = 22) and IGF-1 group (n = 53). In the IGF-1 group, human IGF-1 was injected into the right mandibular condylar cavity, and phosphate-buffered saline solution was injected into the left cavity, 3 times per week for 10 weeks...
December 2017: American Journal of Orthodontics and Dentofacial Orthopedics
https://www.readbyqxmd.com/read/29155992/ihh-gene-mutations-causing-short-stature-with-non-specific-skeletal-abnormalities-and-response-to-growth-hormone-therapy
#14
Gabriela A Vasques, Mariana F A Funari, Frederico M Ferreira, Miriam Aza-Carmona, Lucia Sentchordi-Montané, Jimena Barraza-García, Antonio M Lerario, Guilherme L Yamamoto, Michel S Naslavsky, Yeda A O Duarte, Debora R Bertola, Karen E Heath, Alexander A L Jorge
Context: Genetic evaluation has been recognized as an important tool to elucidate the causes of growth disorders. Objective: To investigate the etiology of short stature and to determine the phenotype of patients with IHH mutations, including the response to growth hormone (rhGH) therapy. Patients and Methods: We studied 17 families with autosomal dominant short stature using whole exome sequencing and screened IHH defects in 290 patients with growth disorders...
November 15, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29152903/reproductive-endocrine-phenotypes-relating-to-chd7-mutations-in-humans
#15
REVIEW
Ravikumar Balasubramanian, William F Crowley
Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in ∼60-80% of cases) and represent the letter "G" in the CHARGE syndrome acronym. The gonadal defect in CHARGE syndrome results from congenital deficiency of the hypothalamic hormone Gonadotropin-releasing hormone (GnRH), which manifests clinically as pubertal failure and infertility, and biochemically as hypogonadotropic hypogonadism (low sex steroid hormone levels with inappropriately normal or low gonadotropin levels)...
November 20, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/29137952/neural-egfl-like-1-regulates-cartilage-maturation-through-runt-related-transcription-factor-3-mediated-indian-hedgehog-signaling
#16
Chenshuang Li, Zhong Zheng, Jie Jiang, Wenlu Jiang, Kevin Lee, Emily A Berthiaume, Eric C Chen, Cymbeline T Culiat, Yan-Heng Zhou, Xinli Zhang, Kang Ting, Chia Soo
The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)-the major regulator of chondrocyte differentiation, proliferation, and maturation. Our previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, we further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: [1] Nell-1 significantly elevated Ihh signal transduction, [2] Nell-1 deficiency markedly reduced Ihh activation in chondrocytes, and [3] Nell-1-stimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor, cyclopamine...
November 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29119099/wnt-and-hedgehog-signaling-regulate-the-differentiation-of-f9-cells-into-extraembryonic-endoderm
#17
Gurjoth S J Deol, Tina N Cuthbert, Mohamed I Gatie, Danielle M Spice, Lindsay R Hilton, Gregory M Kelly
Mouse F9 cells differentiate into primitive extraembryonic endoderm (PrE) when treated with retinoic acid (RA), and this is accompanied by an up-regulation of Gata6. The role of the GATA6 network in PrE differentiation is known, and we have shown it directly activates Wnt6. Canonical Wnt/β-catenin signaling is required by F9 cells to differentiate to PrE, and this, like most developmental processes, requires input from one or more additional pathways. We found both RA and Gata6 overexpression, can induce the expression of Indian Hedgehog (Ihh) and a subset of its target genes through Gli activation during PrE induction...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29018155/clinical-characteristics-of-138-chinese-female-patients-with-idiopathic-hypogonadotropic-hypogonadism
#18
Rui-Yi Tang, Rong Chen, Miao Ma, Shou-Qing Lin, Yi-Wen Zhang, Ya-Ping Wang
OBJECTIVE: To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990-2016. RESULTS: Among the 138 patients, 82 patients (59.4%) were diagnosed with normosmic IHH and 56 patients (40...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28990069/knockdown-of-indian-hedgehog-protein-induces-an-inhibition-of-cell-growth-and-differentiation-in-osteoblast-mc3t3%C3%A2-e1-cells
#19
Ang Deng, Hongqi Zhang, Minyu Hu, Shaohua Liu, Qile Gao, Yuxiang Wang, Chaofeng Guo
Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28904260/impaired-%C3%AE-cell-function-and-decreased-insulin-sensitivity-in-subjects-with-normal-oral-glucose-tolerance-but-isolated-high-glycosylated-hemoglobin
#20
Qi Fu, Min Sun, Zhixiao Wang, Wei He, Yu Duan, Tao Yang
The pathophysiology is distinct in various state of glucose metabolism abnormalities. As the defect of individuals with normal oral glucose tolerance (NGT) but isolated high glycosylated hemoglobin (HbA1c), i.e. iHH, was ambiguous, we aimed to investigate the insulin sensitivity and β-cell function of iHH. According to the ADA criteria of HbA1c cut-off point (5.7%), 3,517 subjects with NGT screened from a total of 7,855 middle-aged and elderly Chinese without known diabetes were divided into two groups, 1,877 subjects with HbA1c < 5...
September 13, 2017: Endocrine Journal
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