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Mariana Verdelho Machado, Anna Mae Diehl
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high prevalence of obesity-related fatty liver (hepatic steatosis) and the lack of specific treatments to prevent hepatic steatosis from progressing to more serious forms of liver damage, including nonalcoholic steatohepatitis (NASH), cirrhosis, and primary liver cancer...
March 20, 2018: Critical Reviews in Biochemistry and Molecular Biology
Gurpreet Kaur, Praveen Sharma, Nilambra Dogra, Sandeep Singh
The cells of malignant cancers result in the evolution of cells with stem-like characteristics, commonly known as cancer stem cells (CSCs). Progress of anticancer therapies is severely hampered because of disease relapse mostly in a more aggressive form due to CSCs. These CSCs are more or less like embryonic or tissue stem cells, known for their capacity of self-renewal, exactly recapitulate of the original tumor. Deregulation of key stem cell pathways like Wnt, Hedgehog (Hh), and Notch is attributed towards the rise of CSCs...
March 20, 2018: Current Treatment Options in Oncology
Fang Wang, Jingyi Wu, Zhichao Qiu, Xiaosong Ge, Xingxiang Liu, Chun Zhang, Wenhuan Xu, Fengming Wang, Dong Hua, Xiaowei Qi, Yong Mao
Acyl-CoA thioesterase 1 (ACOT1) is an important isoform of the ACOT family that catalyzes the reaction of fatty acyl-CoAs to CoA-SH and free fatty acids. Recent studies of gastrointestinal tumor metabolism suggest that there is abnormal metabolism of lipids and fatty acids during tumor progression. However, the function and contribution of ACOT1 in gastric cancer development are still poorly understood. Additionally, GLI3 is a major transcription factor in the regulation of hedgehog (Hh) signaling. GLI3 mutations induce glandular expansion and intestinal metaplasia in gastric cancer, which indicates a role for GLI3 in the preneoplastic process...
March 16, 2018: Human Pathology
Xueling Song, Liying Yan, Cuiling Lu, Chunyu Zhang, Fuli Zhu, Jingjing Yang, Hongyan Jing, Yang Zhang, Jie Qiao, Hongyan Guo
Few studies have evaluated Hedgehog (Hh) signaling pathway activation in different types of ovarian tumors including benign, borderline and malignant ovarian tumors. The present study investigated the expression of Hh signaling pathway components (SHH, SMO, PTCH, and GLI1) in 193 ovarian epithelial tumor specimens (including 147 malignant epithelial ovarian cancers, 30 borderline ovarian tumors, 16 benign ovarian epithelial tumors) and 11 normal ovarian epithelial tissues by immunohistochemistry. The results demonstrated widespread expression of Hh pathway molecules in ovarian tumors...
April 2018: Oncology Letters
Natsuki Hemmi, Yasuko Akiyama-Oda, Koichi Fujimoto, Hiroki Oda
One of the conserved traits of arthropod embryonic development is striped expression of homologs of Drosophila segment polarity genes, including hedgehog (hh). Although a diversity of stripe-forming processes is recognized among arthropod embryos, such varied stripe-forming processes have not been well characterized from cellular and quantitative perspectives. The spider Parasteatoda tepidariorum embryo, which has a hh-dependent mechanism of axis formation, offers a cell-based field where the stripes of Pt-hh (a hh homolog) expression dynamically develop in accordance with axis formation and growth, with the patterning processes varying among the regions of the field...
March 15, 2018: Developmental Biology
Arianna L Kim, Jung Ho Back, Sandeep C Chaudhary, Yucui Zhu, Mohammad Athar, David R Bickers
Currently available SMO targeted therapies in patients with basal cell nevus syndrome (BCNS) are associated with substantial tumor recurrence and clinical resistance. Strategies bypassing SMO and/or identifying additional downstream components of the Hedgehog (Hh) pathway could provide novel anti-tumor targets with a better therapeutic index. SOX9 is a Hh/GLI-regulated transcription factor known to be overexpressed in BCCs. A sequence motif search for SOX9-responsive elements identified three motifs in the promoter region of mTOR...
March 14, 2018: Journal of Investigative Dermatology
Jing Zhang, Yinghong Cui, Shuwen Sun, Jianguo Cao, Xiaoling Fang
Casticin inhibits migration, invasion and induced apoptosis in numerous cancer cells; however, the Hedgehog (Hh) signaling pathway is a key factor in the epithelial-mesenchymal transition (EMT). The present study aimed to assess whether casticin affects the expression of members of the Hh signaling pathway and EMT effectors in ovarian carcinoma. The ovarian cancer SKOV3 cell line was incubated in the presence of various concentrations of casticin or cyclopamine. Next, the expression levels of the main Hh signaling effector glioma-associated oncogene-1 (Gli-1) and EMT-associated factors [Twist-related protein 1 (Twist1), E-cadherin and N-cadherin] were determined by western blotting and reverse transcription-quantitative polymerase chain reaction...
April 2018: Oncology Letters
Ryan L Sheppard, Joshua M Swift, Aaron Hall, Richard T Mahon
Introduction: Individuals with a known susceptibility to high altitude pulmonary edema (HAPE) demonstrate a reduced ventilation response and increased pulmonary vasoconstriction when exposed to hypoxia. It is unknown whether reduced sensitivity to hypercapnia is correlated with increased incidence and/or severity of HAPE, and while acute exercise at altitude is known to exacerbate symptoms the effect of exercise training on HAPE susceptibility is unclear. Purpose: To determine if chronic intermittent hypercapnia and exercise increases the incidence of HAPE in rats...
2018: Frontiers in Physiology
Yun Zuo, Yan Lv, Xiaolan Qian, Shaokai Wang, Zhipen Chen, Qin Jiang, Cong Cao, Yu Song
BACKGROUND/AIMS: Human hedgehog-interacting protein (HHIP) is a negative regulator of the hedgehog (HH) signaling pathway. It is deregulated in gastric cancer. The underlying molecular mechanism of HHIP-induced inhibition of HH signaling remains to be determined. METHODS: A lentiviral HHIP expression vector ("LV-HHIP") was established to exogenously over-express HHIP in gastric cancer cells. HHIP protein and mRNA were tested by Western blotting assay and quantitative real-time PCR assay, respectively...
February 28, 2018: Cellular Physiology and Biochemistry
J W Kim, B Koo, I H Kim, C M Nyachoti
An experiment was carried out to determine the apparent total tract digestibility (ATTD) and the standardized total tract digestibility (STTD) of P and the effects of extrusion and microbial phytase on ATTD and STTD of P in hemp hulls (HH). Thirty-six pigs (30.3 ± 2.7 kg) were randomly allotted to 1 of 6 experimental diets in a complete randomized design with 6 replicates per diet. A corn-soybean meal (SBM)-based basal diet was formulated. Two additional diets were formulated by replacing 40% of corn and SBM (on a 100% of total diet basis) with HH or extruded HH (EHH)...
March 10, 2018: Journal of Animal Science
Kirti K Chahal, Milind Parle, Ruben Abagyan
The hedgehog (Hh) pathway plays an important role in cancer development and maintenance, as ~25% of all cancers have aberrant Hh pathway activation. Targeted therapy for inhibition of the Hh pathway was thought to be promising for achieving clinical response in the Hh-dependent cancers. However, the results of new clinical trials with smoothened (SMO) antagonists do not show much success in cancers other than basal cell carcinoma. The studies suggest that the Hh pathway involves multiple mechanisms of activation or inhibition in primary cilia and interactions between several related pathways in different types of cells, which makes this pathway extremely complex...
March 13, 2018: Anti-cancer Drugs
Md Asaduzzaman Shishir, Md Al Mamun, Md Mahmuduzzaman Mian, Umme Tamanna Ferdous, Noor Jahan Akter, Rajia Sultana Suravi, Suvamoy Datta, Md Ehsanul Kabir
The scarcity of hygienic drinking water is a normal phenomenon in the coastal areas of Bangladesh due to the high salinity of ground water. The inhabitants of this locality, therefore, live on alternative supplies of water including rain-fed pond water, and rainwater with persistent complex microbial interactions therein, often contaminated with life-threatening pathogens. Hence, this study was aimed at analyzing the prevalence of Vibrio cholerae ( Vc ) in the alternative drinking waters of Mathbaria, a coastal subdistrict neighboring the Bay of Bengal, the efficacy of pond sand filter (PSF) and the co-association among Bacillus -like spore formers (Sf) and Vc ...
2018: Frontiers in Public Health
Xin Shi, Shengcai Wei, Kevin J Simms, Devan N Cumpston, Thomas J Ewing, Ping Zhang
Activation and reprogramming of hematopoietic stem/progenitor cells play a critical role in the granulopoietic response to bacterial infection. Our current study determined the significance of Sonic hedgehog (SHH) signaling in the regulation of hematopoietic precursor cell activity during the host defense response to systemic bacterial infection. Bacteremia was induced in male Balb/c mice via intravenous injection (i.v.) of Escherichia coli (5 × 107 CFUs/mouse). Control mice received i.v. saline. SHH protein level in bone marrow cell (BMC) lysates was markedly increased at both 24 and 48 h of bacteremia...
2018: Frontiers in Immunology
Yuji Hayashino, Masatake Sugita, Hidetoshi Arima, Tetsumi Irie, Takeshi Kikuchi, Fumio Hirata
It has been found that a cyclodextrin derivative, 2-hydroxypropyl-β-cyclodextrin (HPβCD), has reasonable therapeutic effect on Niemann-Pick disease type C which is caused by abnormal accumulation of unesterified cholesterol and glycolipids in the lysosomes and shortage of esterified cholesterol in other cellular compartments. We study the binding affinity and mode of HPβCD with cholesterol in order to elucidate the possible mechanism of HPβCD for removing cholesterol from the lysosomes. The dominant binding mode of HPβCD with cholesterol is found based on the Molecular Dynamics (MD) simulation and a statistical mechanics theory of liquids, or the 3D reference interaction site model theory with Kovalenko-Hirata closure relation (3D-RISM-KH)...
March 13, 2018: Journal of Physical Chemistry. B
Miki Iwasaki, Junpei Kuroda, Koichi Kawakami, Hironori Wada
Bone is a connective tissue composed of many cell types, including osteoblasts. How bones acquire their unique size and shape during development remains poorly understood. Herein we investigated the molecular and cellular mechanisms of bone morphogenesis in the zebrafish scale by using transgenic lines to enable visualization of specific types of osteoblasts. We demonstrate that the zebrafish scale contains three distinct types of osteoblasts: (i) a monolayer of central osteoblasts along the inner surface of scales; (ii) marginal osteoblasts elongated along the scale edge; and (iii) submarginal osteoblasts located between the central and marginal osteoblast populations...
March 7, 2018: Developmental Biology
Sabine Schürmann, Georg Steffes, Dominique Manikowski, Philipp Kastl, Ursula Malkus, Shyam Bandari, Stefanie Ohlig, Corinna Ortmann, Rocio Rebollido-Rios, Mandy Otto, Harald Nüsse, Daniel Hoffmann, Christian Klämbt, Milos Galic, Jürgen Klingauf, Kay Grobe
Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3-4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors...
March 9, 2018: ELife
Jichun Gu, Hexige Saiyin, Deliang Fu, Ji Li
Pancreatic cancer is a uniformly lethal malignancy with an abundant dense desmoplastic stroma. Because of its dense stroma, conventional drugs were considered to not penetrate this physical barrier, and this caused a systemic drug resistance. Thus, abolishing this barrier with targeted agents is considered to improve the efficiency of chemotherapeutic treatment. The Hedgehog (Hh) signaling pathway is a critical regulator of pancreas development and plays diversified roles in pancreatic cancer stroma and neoplastic cells...
April 2018: Pancreas
A M Castilhos, C L Francisco, R H Branco, S F M Bonilha, M E Z Mercadante, P R L Meirelles, C M Pariz, A M Jorge
Evaluation of the body chemical composition of beef cattle can only be measured postmortem and those data cannot be used in real production scenarios to adjust nutritional plans. The objective of this study was to develop multiple linear regression equations from in vivo measurements, such as ultrasound parameters [backfat thickness (uBFT, mm), rump fat thickness (uRF, mm), and ribeye area (uLMA, cm2)], shrunk body weight (SBW, kg), age (AG, d), hip height (HH, m), as well as from postmortem measurements (composition of the 9th to 11th rib section) to predict the empty body and carcass chemical composition for Nellore cattle...
March 6, 2018: Journal of Animal Science
Paola Infante, Roberta Faedda, Flavia Bernardi, Francesca Bufalieri, Ludovica Lospinoso Severini, Romina Alfonsi, Daniela Mazzà, Mariangela Siler, Sonia Coni, Agnese Po, Marialaura Petroni, Elisabetta Ferretti, Mattia Mori, Enrico De Smaele, Gianluca Canettieri, Carlo Capalbo, Marella Maroder, Isabella Screpanti, Marcel Kool, Stefan M Pfister, Daniele Guardavaccaro, Alberto Gulino, Lucia Di Marcotullio
Suppressor of Fused (SuFu), a tumour suppressor mutated in medulloblastoma, is a central player of Hh signalling, a pathway crucial for development and deregulated in cancer. Although the control of Gli transcription factors by SuFu is critical in Hh signalling, our understanding of the mechanism regulating this key event remains limited. Here, we show that the Itch/β-arrestin2 complex binds SuFu and induces its Lys63-linked polyubiquitylation without affecting its stability. This process increases the association of SuFu with Gli3, promoting the conversion of Gli3 into a repressor, which keeps Hh signalling off...
March 7, 2018: Nature Communications
Changjun Jia, Chaoliu Dai, Hailiang Wang, Yi Wan, Yunyu Qiao, Feng Xu, Songlin Peng, Yang Zhao, Chuang Zhao, Liang Zhao
Background/Aims: Hepatic ischemia-reperfusion (I/R) injury is a serious concern during hepatic vascular occlusion. The objectives of this study were to assess effects of three techniques for hepatic vascular occlusion on I/R injury and to explore the underlying mechanisms. Methods: Liver cirrhotic rats had undertaken Pringle maneuver (PR), hemihepatic vascular occlusion (HH), or hepatic blood inflow occlusion without hemihepatic artery control (WH). Levels of tumor necrosis factor alpha (TNF- α ), nuclear factor kappa B (NF- κ B), toll-like receptor 4 (TLR4), TIR-domain-containing adapter-inducing interferon- β (TRIF), and hemeoxygenase 1 (HMOX1) were assayed...
2018: Gastroenterology Research and Practice
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