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https://www.readbyqxmd.com/read/29137952/neural-egfl-like-1-regulates-cartilage-maturation-through-runt-related-transcription-factor-3-mediated-indian-hedgehog-signaling
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28901584/the-primary-cilium-as-a-signaling-nexus-for-growth-plate-function-and-subsequent-skeletal-development
#6
REVIEW
Emily R Moore, Christopher R Jacobs
The primary cilium is a solitary, antenna-like sensory organelle with many important roles in cartilage and bone development, maintenance, and function. The primary cilium's potential role as a signaling nexus in the growth plate makes it an attractive therapeutic target for diseases and disorders associated with bone development and maintenance. Many signaling pathways that are mediated by the cilium - such as Hh, Wnt, Ihh/PTHrP, TGFβ, BMP, FGF, and Notch - are also known to influence endochondral ossification, primarily by directing growth plate formation and chondrocyte behavior...
September 13, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28882981/characteristics-of-a-nationwide-cohort-of-patients-presenting-with-isolated-hypogonadotropic-hypogonadism-ihh
#7
Marco Bonomi, Valeria Vezzoli, Csilla Gabriella Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzoccaro, Gianni Russo, Mirella Moro, Letizia Maria Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvatore Cannavò, Andrea M Isidori, Angela I Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Francesca Pregnolato, Mohammad Maghnie, Mario Maggi, Luca Persani
OBJECTIVE: IHH is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present altough information on their frequency are scanty, particularly according to the age of presentation. DESIGN: Observational cohort study carried out between January 2008-June 2016 within a national network of academic or general hospitals Methods: We performed a detailed phenotyping of 503 IHH patients with: 1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; 2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects...
September 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28874841/epiphyseal-bone-formation-occurs-via-thyroid-hormone-regulation-of-chondrocyte-to-osteoblast-transdifferentiation
#8
Patrick Aghajanian, Weirong Xing, Shaohong Cheng, Subburaman Mohan
Endochondral ossification in the diaphysis of long bones has been studied in-depth during fetal development but not postnatally in the epiphysis. Immunohistochemical studies revealed that Sox9 and Col2 expressing immature chondrocytes in the epiphysis transition into prehypertrophic and hypetrophic chondrocytes and finally into osteoblasts expressing Col1 and BSP during postnatal day 7-10, when serum levels of thyroid hormone (TH) rise. Lineage tracing using Rosa-td tomato (Col2-Cre-ERT2) mice treated with tamoxifen indicated that the same Col2 expressing chondrocytes expressed prehypertrophic, hypertrophic, and subsequently bone formation markers in a sequential manner in euthyroid but not hypothyroid mice, thus providing evidence that chondrocyte to osteoblast transdifferentiation is TH-dependent...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874334/girl-with-idiopathic-childhood-hypercalcemia-reveals-new-disease-causing-cyp24a1-mutation
#9
Jens Otto Broby Madsen, Sabrina Sauer, Bodo Beck, Jesper Johannesen
CONTEXT: Idiopathic Infantile Hypercalcemia (IHH) was associated with vitamin-D supplementation in the 1950's. 50 years later mutations in the CYP241A gene, involved in the degradation of vitamin-D, have been identified as being a part of the etiology. CASE DESCRIPTION: We hereby report a case of a 21 months old girl initially hospitalized due to excessive consumption of water and behavioral difficulties. Blood tests showed hypercalcemia, borderline high vitamin-D levels, and renal ultrasound revealed medullary nephrocalcinosis...
September 6, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28870599/hepatocyte-nuclear-factor-4a-improves-hepatic-differentiation-of-immortalized-adult-human-hepatocytes-and-improves-liver-function-and-survival
#10
Hua-Lian Hang, Xin-Yu Liu, Hai-Tian Wang, Ning Xu, Jian-Min Bian, Jian-Jun Zhang, Lei Xia, Qiang Xia
Immortalized human hepatocytes (IHH) could provide an unlimited supply of hepatocytes, but insufficient differentiation and phenotypic instability restrict their clinical application. This study aimed to determine the role of hepatocyte nuclear factor 4A (HNF4A) in hepatic differentiation of IHH, and whether encapsulation of IHH overexpressing HNF4A could improve liver function and survival in rats with acute liver failure (ALF). Primary human hepatocytes were transduced with lentivirus-mediated catalytic subunit of human telomerase reverse transcriptase (hTERT) to establish IHH...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28870428/retro-and-orthonasal-olfactory-function-in-relation-to-olfactory-bulb-volume-in-patients-with-hypogonadotrophic-hypogonadism
#11
Murat Salihoglu, Onuralp Kurt, Seyid Ahmet Ay, Kamil Baskoy, Aytug Altundag, Muzaffer Saglam, Ferhat Deniz, Hakan Tekeli, Arif Yonem, Thomas Hummel
INTRODUCTION: Idiopathic hypogonadotrophic hypogonadism (IHH) with an olfactory deficit is defined as Kallmann syndrome (KS) and is distinct from normosmic IHH. OBJECTIVE: Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with IHH. METHODS: This case-control study included 31 controls and 45 IHH patients...
August 24, 2017: Brazilian Journal of Otorhinolaryngology
https://www.readbyqxmd.com/read/28863112/disruption-of-hedgehog-signaling-by-vismodegib-leads-to-cleft-palate-and-delayed-osteogenesis-in-experimental-design
#12
Shixian Zhang, Chengyong Wang, Changfu Xie, Yongzhen Lai, Di Wu, Guowu Gan, Weihui Chen
The function of hedgehog signaling has previously been shown to be crucial for craniofacial development. In this study, we treated C57/BL6J mice with the hedgehog pathway inhibitor vismodegib by oral gavage to establish a stable vismodegib-induced cleft palate model. At E10.5 and E12.5, mice in the experimental group were treated with 100 mg/kg of vismodegib, whereas mice in the control group were treated with solvent. The treated pregnant mice were sacrificed on E13.5, E14.5, E15.5, and E16.5. Palatal shelf growth was evaluated via histological and immunohistochemical analyses as well as palatal organ culture...
September 2017: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28846100/composition-and-dosage-of-a-multipartite-enhancer-cluster-control-developmental-expression-of-ihh-indian-hedgehog
#13
Anja J Will, Giulia Cova, Marco Osterwalder, Wing-Lee Chan, Lars Wittler, Norbert Brieske, Verena Heinrich, Jean-Pierre de Villartay, Martin Vingron, Eva Klopocki, Axel Visel, Darío G Lupiáñez, Stefan Mundlos
Copy number variations (CNVs) often include noncoding sequences and putative enhancers, but how these rearrangements induce disease is poorly understood. Here we investigate CNVs involving the regulatory landscape of IHH (encoding Indian hedgehog), which cause multiple, highly localized phenotypes including craniosynostosis and synpolydactyly. We show through transgenic reporter and genome-editing studies in mice that Ihh is regulated by a constellation of at least nine enhancers with individual tissue specificities in the digit anlagen, growth plates, skull sutures and fingertips...
October 2017: Nature Genetics
https://www.readbyqxmd.com/read/28811125/pharmacokinetics-and-pharmacodynamics-of-thiopurines-in-an-in%C3%A2-vitro-model-of-human-hepatocytes-insights-from-an-innovative-mass-spectrometry-assay
#14
Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti
AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival...
September 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28794911/severe-form-of-brachydactyly-type-a1-in-a-child-with-a-c-298g%C3%A2-%C3%A2-a-mutation-in-ihh-gene
#15
Smrithi Salian, Anju Shukla, Gen Nishimura, Katta M Girisha
Brachydactyly type A1 (BDA1) is characterized by short middle phalanges. We report the case of a child with a severe form of BDA1 with complete absence of the middle phalanges of all extremities. He had c.298G > A (p.D100N) mutation in IHH gene.
September 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#16
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In a previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition (EMT) state and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV-associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of an HCV core-expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28780519/analysis-of-genetic-and-clinical-characteristics-of-a-chinese-kallmann-syndrome-cohort-with-anos1-mutations
#17
Min Nie, Hongli Xu, Rongrong Chen, Jiangfeng Mao, Xi Wang, Shuyu Xiong, Junjie Zheng, Bingqing Yu, Mingxuan Cui, Wanlu Ma, Qibin Huang, Hongbing Zhang, Xueyan Wu
OBJECTIVE: To analyze ANOS1 gene mutations in a large Chinese Kallmann syndrome (KS) cohort and to characterize the clinical presentation of the disease in patients with ANOS1 mutations. PATIENTS AND METHODS: Chinese patients with KS, including 187 sporadic and 23 pedigree cases were recruited. Patients' ANOS1 gene sequences were analyzed by direct sequencing of PCR-amplified products. In silico analysis was used to assess functional relevance of newly identified missense mutations...
October 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28768930/curcumin-inhibits-chondrocyte-hypertrophy-of-mesenchymal-stem-cells-through-ihh-and-notch-signaling-pathways
#18
Zhen Cao, Ce Dou, Shiwu Dong
Using tissue engineering technique to repair cartilage damage caused by osteoarthritis is a promising strategy. However, the regenerated tissue usually is fibrous cartilage, which has poor mechanical characteristics compared to hyaline cartilage. Chondrocyte hypertrophy plays an important role in this process. Thus, it is very important to find out a suitable way to maintain the phenotype of chondrocytes and inhibit chondrocyte hypertrophy. Curcumin deriving from turmeric was reported with anti-inflammatory and anti-tumor pharmacological effects...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28767690/a-simplified-prevention-bundle-with-dual-hand-hygiene-audit-reduces-early-onset-ventilator-associated-pneumonia-in-cardiovascular-surgery-units-an-interrupted-time-series-analysis
#19
Kang-Cheng Su, Yu Ru Kou, Fang-Chi Lin, Chieh-Hung Wu, Jia-Yih Feng, Shiang-Fen Huang, Tao-Fen Shiung, Kwei-Chun Chung, Yu-Hsiu Tung, Kuang-Yao Yang, Shi-Chuan Chang
BACKGROUND: To investigate the effect of a simplified prevention bundle with alcohol-based, dual hand hygiene (HH) audit on the incidence of early-onset ventilation-associated pneumonia (VAP). METHODS: This 3-year, quasi-experimental study with interrupted time-series analysis was conducted in two cardiovascular surgery intensive care units in a medical center. Unaware external HH audit (eHH) performed by non-unit-based observers was a routine task before and after bundle implementation...
2017: PloS One
https://www.readbyqxmd.com/read/28749439/effects-of-melatonin-on-early-pregnancy-in-mouse-involving-the-regulation-of-star-cyp11a1-and-ihh-expression
#20
Shengyu Guan, Lu Xie, Teng Ma, Dongying Lv, Wang Jing, Xiuzhi Tian, Yukun Song, Zhiping Liu, Xianghong Xiao, Guoshi Liu
To test whether melatonin plays an important role in the process of early pregnancy, melatonin was given in drinking water to pregnant mice at different gestation stages. These included mice who were given melatonin 14 days prior to their successful mating (confirmed by vaginal plug) (Group A), after successful mating (Group B), and 14 days prior to and until after successful mating (Group C). Melatonin administration significantly enhanced serum as well as ovarian melatonin levels in the mice. It was observed that melatonin did not affect the natural estrous of mice...
July 27, 2017: International Journal of Molecular Sciences
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