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https://www.readbyqxmd.com/read/29341457/different-effects-of-dexmedetomidine-and-midazolam-on-the-expression-of-nr2b-and-gabaa-%C3%AE-1-following-peripheral-nerve-injury-in-rats
#1
Jiayu Chen, Hanjun Li, Grewo Lim, Michael F McCabe, Wei Zhao, Yunli Yang, Weiqing Ma, Na Li
Neuropathic pain is a complex, chronic pain condition and the treatment is a major clinical challenge. Recent studies have shown that two FDA approved drugs dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic pain, but the mechanism is not fully dementated. Here, we investigated the effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury model. Intramuscular injection with DEX and MZL attenuated the development of mechanical allodynia and thermal hyperalgesia in rats with chronic constriction injury (CCI)...
January 17, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29331808/simultaneous-inhibition-of-hedgehog-signaling-and-tumor-proliferation-remodels-stroma-and-enhances-pancreatic-cancer-therapy
#2
Jun Zhao, Huamin Wang, Cheng-Hui Hsiao, Diana S-L Chow, Eugene J Koay, Yaan Kang, Xiaoxia Wen, Qian Huang, Ying Ma, James A Bankson, Stephen E Ullrich, Willem Overwijk, Anirban Maitra, David Piwnica-Worms, Jason B Fleming, Chun Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has an excessive desmoplastic stroma that can limit the intratumoral delivery of chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both stromal and tumor compartments need to be addressed in order to effectively treat PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts (CAFs), while PTX can inhibit tumor proliferation...
January 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29329377/endometrial-stem-cell-derived-g-csf-attenuates-endometrial-fibrosis-via-sonic-hedgehog-transcriptional-activator-gli2
#3
Xiaona Lin, Yanling Zhang, Yibin Pan, Shilin He, Yongdong Dai, Bingqing Zhu, Cheng Wei, Liaobing Xin, Wenzhi Xu, Chunsheng Xiang, Songying Zhang
Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which ultimately leads to menstrual abnormalities, infertility and recurrent miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis and regeneration; Gli2 activation induces profibrogenic effects in various tissues, such as the liver and kidney. However, the role of Gli2 in endometrial fibrosis remains unknown. The purpose of this study was to test the hypothesis that activated Gli2 promotes endometrial fibrosis. Endometrial samples from moderate and severe IUA patients exhibited significantly enhanced expression of Gli2 compared with normal endometrial samples and mild IUA samples...
January 10, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29321670/clinical-and-experimental-evidence-suggest-a-link-between-kif7-and-c5orf42-related-ciliopathies-through-sonic-hedgehog-signaling
#4
Reza Asadollahi, Justin E Strauss, Martin Zenker, Oliver Beuing, Simon Edvardson, Orly Elpeleg, Tim M Strom, Pascal Joset, Dunja Niedrist, Christine Otte, Beatrice Oneda, Paranchai Boonsawat, Silvia Azzarello-Burri, Deborah Bartholdi, Michael Papik, Markus Zweier, Cordula Haas, Arif B Ekici, Alessandra Baumer, Eugen Boltshauser, Katharina Steindl, Michael Nothnagel, Albert Schinzel, Esther T Stoeckli, Anita Rauch
Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental disorder caused by KIF7 defects and belongs to the heterogeneous group of ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism, facial dysmorphism has not been emphasized in JBTS cohorts with molecular diagnosis. To evaluate the specificity and etiology of ACLS craniofacial features, we performed whole exome or targeted Sanger sequencing in patients with the aforementioned overlapping craniofacial appearance but variable additional ciliopathy features followed by functional studies...
January 10, 2018: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#5
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29318530/a-novel-heterozygous-gli2-mutation-in-a-patient-with-congenital-urethral-stricture-and-renal-hypoplasia-dysplasia-leading-to-end-stage-renal-failure
#6
Toshihiko Shirakawa, Yumiko Nakashima, Satoshi Watanabe, Sadatomo Harada, Mariko Kinoshita, Toshiharu Kihara, Yuko Hamasaki, Seiichiro Shishido, Koh-Ichiro Yoshiura, Hiroyuki Moriuchi, Sumito Dateki
Glioblastoma 2 (GLI2) is a mediator of Sonic hedgehog signaling pathway that plays an important role in development of the central nervous system and limbs. Heterozygous GLI2 mutations have been associated with postaxial polydactyly, various pituitary dysfunction, and holoprosencephaly-like phenotype. Herein, we report a Japanese boy who presented with isolated growth hormone deficiency with ectopic posterior pituitary, postaxial polydactyly, atrioventricular septal defect, intellectual disability and dysmorphic facial features including mid-facial hypoplasia...
January 9, 2018: CEN Case Reports
https://www.readbyqxmd.com/read/29314724/genipin-cross-linked-type-ii-collagen-scaffold-promotes-the-differentiation-of-adipose-derived-stem-cells-into-nucleus-pulposus-like-cells
#7
Xiaopeng Zhou, Yiqing Tao, Erman Chen, Jingkai Wang, Weijing Fang, Tengfei Zhao, Chengzhen Liang, Fangcai Li, Qixin Chen
Adipose-derived stem cells (ADSCs)-based tissue engineering was a promising method to treat intervertebral disc degeneration. Type II collagen is a native component in the nucleus pulposus (NP), and has the ability to promote ADSCs to differentiate into NP-like cells. In this article, we aimed to establish a genipin-cross-linked three-dimensional (3D) type II collagen scaffold, and determine the biological effects of the scaffold on ADSCs differentiating into a NP-like phenotype. Different concentrations of genipin were used to cross-link the 3D type II collagen scaffold...
January 3, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29311593/neogenin-a-regulator-of-adult-hippocampal-neurogenesis-prevents-depressive-like-behavior
#8
Dong Sun, Xiang-Dong Sun, Lu Zhao, Dae-Hoon Lee, Jin-Xia Hu, Fu-Lei Tang, Jin-Xiu Pan, Lin Mei, Xiao-Juan Zhu, Wen-Cheng Xiong
Adult neurogenesis in hippocampal dentate gyrus (DG) is a complex, but precisely controlled process. Dysregulation of this event contributes to multiple neurological disorders, including major depression. Thus, it is of considerable interest to investigate how adult hippocampal neurogenesis is regulated. Here, we present evidence for neogenin, a multifunctional transmembrane receptor, to regulate adult mouse hippocampal neurogenesis. Loss of neogenin in adult neural stem cells (NSCs) or neural progenitor cells (NPCs) impaired NSCs/NPCs proliferation and neurogenesis, whereas increased their astrocytic differentiation...
January 8, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29309307/a-distinct-malignant-epithelioid-neoplasm-with-gli1-gene-rearrangements-frequent-s100-protein-expression-and-metastatic-potential-expanding-the-spectrum-of-pathologic-entities-with-actb-malat1-ptch1-gli1-fusions
#9
Cristina R Antonescu, Narasimhan P Agaram, Yun-Shao Sung, Lei Zhang, David Swanson, Brendan C Dickson
ACTB-GLI1 fusions have been reported as the pathognomonic genetic abnormality defining an unusual subset of actin-positive, perivascular myoid tumors, known as "pericytoma with the t(7;12) translocation." In addition, GLI1 oncogenic activation through a related MALAT1-GLI1 gene fusion has been recently reported in 2 unrelated gastric tumors, namely plexiform fibromyxoma and gastroblastoma. Triggered by unexpected targeted RNA-sequencing results detecting GLI1-related fusions in a group of malignant neoplasms with round to epithelioid morphology, and frequently strong S100 protein immunoreactivity, we investigated their clinicopathologic features in relation to other known pathologic entities sharing similar genetics...
January 5, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29307715/bisphenol-a-stimulates-adrenal-cortical-cell-proliferation-via-er%C3%AE-mediated-activation-of-the-sonic-hedgehog-signalling-pathway
#10
Samantha Medwid, Haiyan Guan, Kaiping Yang
We previously demonstrated that prenatal exposure to bisphenol A (BPA) resulted in increased adrenal gland weight independent of changes in plasma ACTH levels in adult mouse offspring. This finding suggested that BPA exposure likely had a direct effect on adrenal development. Given that (1) sonic hedgehog (Shh) signaling is essential for adrenal development; (2) deletion of the Shh gene in mice results in adrenal hypoplasia; (3) BPA is known to signal through estrogen receptor β (ERβ); and (4) ERβ is highly expressed in adrenal glands; we hypothesized that BPA stimulates adrenal cell proliferation via ERβ-mediated activation of the Shh pathway...
January 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29298444/human-malformation-syndromes-of-defective-gli-opposite-phenotypes-of-2q14-2-gli2-and-7p14-2-gli3-microdeletions-and-a-glia-r-balance-model
#11
Yo Niida, Mika Inoue, Mamoru Ozaki, Etsuko Takase
GLI family zinc finger proteins are transcriptional effectors of the sonic hedgehog signaling pathway. GLI regulates gene expression and repression at various phases of embryonic morphogenesis. In humans, 4 GLI genes are known, and GLI2 (2q14.2) and GLI3 (7p14.1) mutations cause different syndromes. Here, we present 2 distinctive cases with a chromosomal microdeletion in one of these genes. Patient 1 is a 14-year-old girl with Culler-Jones syndrome. She manifested short stature, cleft palate, and mild intellectual/social disability caused by a 6...
January 4, 2018: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29295693/novel-homeodomain-transcription-factor-nkx2-2-in-the-brain-tumor-development
#12
Mubeena Pm Mariyath, Mehdi Hayat Shahi, Shirin Farheen, Mohd Tayyab, Nabeela Khanam, Asif Ali
BACKGROUND: Complex central nervous system (CNS) is made of neuronal cells and glial cells. Cells of central nervous system are able to regenerate after injury and during repairing. Sonic hedgehog pathway initiated by Shh-N a glycoprotein plays vital role in CNS patterning growth, development and now tumorigenesis. Nkx2.2 homeodomain transcription factor is an effecter molecule, which is positively regulated by Shh during normal growth. Nkx2.2 is essential for V3 domain specification during neural tube patterning at embryonic stage...
January 1, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29290584/crispr-screens-uncover-genes-that-regulate-target-cell-sensitivity-to-the-morphogen-sonic-hedgehog
#13
Ganesh V Pusapati, Jennifer H Kong, Bhaven B Patel, Arunkumar Krishnan, Andreas Sagner, Maia Kinnebrew, James Briscoe, L Aravind, Rajat Rohatgi
To uncover regulatory mechanisms in Hedgehog (Hh) signaling, we conducted genome-wide screens to identify positive and negative pathway components and validated top hits using multiple signaling and differentiation assays in two different cell types. Most positive regulators identified in our screens, including Rab34, Pdcl, and Tubd1, were involved in ciliary functions, confirming the central role for primary cilia in Hh signaling. Negative regulators identified included Megf8, Mgrn1, and an unannotated gene encoding a tetraspanin protein we named Atthog...
December 26, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29285739/sonic-hedgehog-regulation-of-the-neural-precursor-cell-fate-during-chicken-optic-tectum-development
#14
Ciqing Yang, Xiaoying Li, Qiuling Li, Han Li, Liang Qiao, Zhikun Guo, Juntang Lin
During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29285189/sulforaphane-reverses-gefitinib-tolerance-in-human-lung-cancer-cells-via-modulation-of-sonic-hedgehog-signaling
#15
Fanping Wang, Wenjun Wang, Junpeng Li, Jingjing Zhang, Xia Wang, Mingyong Wang
Gefitinib is a targeted anticancer drug that was developed as an effective clinical therapy for lung cancer. Numerous patients develop gefitinib resistance in response to treatment. Sulforaphane (SFN) is present in cruciferous vegetables, and has been demonstrated to inhibit the malignant growth of various types of cancer cells. To investigate the role of SFN in gefitinib resistance, a gefitinib-tolerant PC9 (PC9GT) cell model was established by continually exposing PC9 cells to gefitinib. Cell viability was measured using a cell proliferation assay...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29284139/coordinated-d-cyclin-foxd1-activation-drives-mitogenic-activity-of-sonic-hedgehog-signaling-pathway
#16
Dustin M Fink, Miranda R Sun, Galen W Heyne, Joshua L Everson, Hannah M Chung, Sookhee Park, Michael D Sheets, Robert J Lipinski
Sonic Hedgehog (Shh) signaling plays key regulatory roles in embryonic development and postnatal homeostasis and repair. Modulation of the Shh pathway is known to cause malformations and malignancies associated with dysregulated tissue growth. However, our understanding of the molecular mechanisms by which Shh regulates cellular proliferation is incomplete. Here, using mouse embryonic fibroblasts, we demonstrate that the Forkhead box gene Foxd1 is transcriptionally regulated by canonical Shh signaling and required for downstream proliferative activity...
December 25, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/29280566/%C3%AE-secretase-inhibition-induces-muscle-hypertrophy-in-a-notch-independent-mechanism
#17
Ivone Rosa de Andrade, Stephany Corrêa, Marcio Fontenele, John Douglas de Oliveira Teixeira, Eliana Abdelhay, Manoel Luis Costa, Claudia Mermelstein
A wide variety of cellular processes and signaling events are regulated by the proteolytic enzyme γ-secretase. Notch-1 is one of the substrates of γ-secretase and its role in the regulation of muscle differentiation has been well described. Importantly, besides Notch-1 a number of proteins have been identified to undergo proteolysis by γ-secretase. To date, the specific role of γ-secretase during embryonic skeletal muscle differentiation has not been studied. Therefore, we address this question through the analysis of in vitro grown chick myogenic cells during the formation of multinucleated myotubes...
December 27, 2017: Proteomics
https://www.readbyqxmd.com/read/29279401/neuronal-delivery-of-hedgehog-directs-spatial-patterning-of-taste-organ-regeneration
#18
Wan-Jin Lu, Randall K Mann, Allison Nguyen, Tingting Bi, Max Silverstein, Jean Y Tang, Xiaoke Chen, Philip A Beachy
How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory organs in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but the underlying mechanism has remained unknown. Here, we show that Sonic hedgehog (Shh), which encodes a secreted protein signal, is expressed in these sensory neurons, and that experimental ablation of neuronal Shh expression causes loss of taste receptor cells (TRCs)...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29278511/the-adrenal-gland-microenvironment-in-health-disease-and-during-regeneration
#19
REVIEW
Waldemar Kanczkowski, Mariko Sue, Stefan R Bornstein
The adrenal gland is a key component of the stress system in the human body. Multiple direct and paracrine interactions between different cell types and their progenitors take place within the adrenal gland microenvironment. These unique interactions are supported by high vascularization and the adrenal cortex extracellular matrix. Alterations in the adrenal gland microenvironment are known to influence the progression of several pathological conditions, such as obesity and sepsis, and to be influenced by these disorders...
July 2017: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29274272/the-role-of-the-hedgehog-signaling-pathway-in-cancer-a-comprehensive-review
#20
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
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