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https://www.readbyqxmd.com/read/29790424/the-fate-of-autologous-endometrial-mesenchymal-stromal-cells-after-application-in-the-healthy-equine-uterus
#1
Elisabeth Rink, Teresa Beyer, Hilari French, Elaine Watson, Christine Aurich, Xavier Donadeu
Because of their distinct differentiation, immunomodulatory and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded and fluorescence-labeled in culture. MSCs (15 x 106) or PBS were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion...
May 23, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29785915/the-effects-of-a-synthetic-analogue-of-the-bovine-appeasing-pheromone-on-milk-yield-and-composition-in-valdostana-dairy-cows-during-the-move-from-winter-housing-to-confined-lowland-pastures
#2
Maria Cristina Osella, Alessandro Cozzi, Claudio Spegis, Germano Turille, Andrea Barmaz, Céline Lafont Lecuelle, Eva Teruel, Cécile Bienboire-Frosini, Camille Chabaud, Laurent Bougrat, Patrick Pageat
This Research Communication describes the effects of a synthetic analogue of the Bovine Appeasing Pheromone (BAP) on milk parameters in Valdostana dairy cows during the first turning out from tie-stalls to confined lowland pastures around the farms. Thirty healthy lactating Valdostana cows were enroled in the study and randomly divided into 2 groups: experimental group (EG, n = 15) and control group (CG, n = 15). The two groups were separately housed in the same farm and managed outside in two different pens...
May 2018: Journal of Dairy Research
https://www.readbyqxmd.com/read/29785042/inducible-high-efficiency-crispr-cas9-targeted-gene-editing-and-precision-base-editing-in-african-trypanosomes
#3
Eva Rico, Laura Jeacock, Julie Kovářová, David Horn
The Cas9 endonuclease can be programmed by guide RNA to introduce sequence-specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#4
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29779031/a-novel-ex-vivo-mouse-mesometrium-culture-model-for-investigating-angiogenesis-in-microvascular-networks
#5
Ariana D Suarez-Martinez, Susanne Bierschenk, Katie Huang, Dana Kaplan, Carolyn L Bayer, Stryder M Meadows, Markus Sperandio, Walter L Murfee
BACKGROUND: The development of models that incorporate intact microvascular networks enables the investigation of multicellular dynamics during angiogenesis. Our laboratory introduced the rat mesentery culture model as such a tool, which would be enhanced with mouse tissue. Since mouse mesentery is avascular, an alternative is mouse mesometrium, the connective tissue of uterine horns. The study's objective was to demonstrate that mouse mesometrium contains microvascular networks that can be cultured to investigate multicellular dynamics during angiogenesis...
May 18, 2018: Journal of Vascular Research
https://www.readbyqxmd.com/read/29775163/methylprednisolone-inhibits-the-proliferation-of-endogenous-neural-stem-cells-in-nonhuman-primates-with-spinal-cord-injury
#6
Jichao Ye, Yi Qin, Yong Tang, Mengjun Ma, Peng Wang, Lin Huang, Rui Yang, Keng Chen, Chaopeng Chai, Yanfeng Wu, Huiyong Shen
OBJECTIVE The aim of this work was to investigate the effects of methylprednisolone on the proliferation of endogenous neural stem cells (ENSCs) in nonhuman primates with spinal cord injury (SCI). METHODS A total of 14 healthy cynomolgus monkeys ( Macaca fascicularis) (4-5 years of age) were randomly divided into 3 groups: the control group (n = 6), SCI group (n = 6), and methylprednisolone therapy group (n = 2). Only laminectomy was performed in the control animals at T-10. SCI was induced in monkeys using Allen's weight-drop method (50 mm × 50 g) to injure the posterior portion of the spinal cord at T-10...
May 18, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29772390/pathobiology-of-christianson-syndrome-linking-disrupted-endosomal-lysosomal-function-with-intellectual-disability-and-sensory-impairments
#7
Mallory Kerner-Rossi, Maria Gulinello, Steven Walkley, Kostantin Dobrenis
Christianson syndrome (CS) is a recently described rare neurogenetic disorder presenting early in life with a broad range of neurological symptoms, including severe intellectual disability with nonverbal status, hyperactivity, epilepsy, and progressive ataxia due to cerebellar atrophy. CS is due to loss-of-function mutations in SLC9A6, encoding NHE6, a sodium-hydrogen exchanger involved in the regulation of early endosomal pH. Here we review what is currently known about the neuropathogenesis of CS, based on insights from experimental models, which to date have focused on mechanisms that affect the CNS, specifically the brain...
May 14, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29767677/randomized-phase-3-study-of-docetaxel-plus-bavituximab-in-previously-treated-advanced-non-squamous-non-small-cell-lung-cancer
#8
D E Gerber, L Horn, M Boyer, R Sanborn, R Natale, R Palmero, P Bidoli, I Bondarenko, P Germonpre, D Ghizdavescu, A Kotsakis, H Lena, G Losonczy, K Park, W-C Su, M Tang, J Lai, N L Kallinteris, J S Shan, M Reck, D R Spigel
Background: Bavituximab is a monoclonal antibody that targets phosphatidylserine in the presence of β2 glycoprotein 1 (β2GP1) to exert an anti-tumor immune response. This phase 3 trial determined the efficacy of bavituximab combined with docetaxel in patients with previously treated advanced non-small cell lung cancer (NSCLC). Patients and Methods: Key eligibility criteria included advanced non-squamous NSCLC with disease progression after treatment with platinum-based doublet chemotherapy, evidence of disease control after at least two cycles of first-line therapy, presence of measurable disease, ECOG performance status 0 or 1, adequate bone marrow and organ function, and no recent history of clinically significant bleeding...
May 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29763554/template-catalyzed-disulfide-conjugation-of-monoclonal-antibodies-using-a-natural-amino-acid-tag
#9
Jeremy D King, Yuelong Ma, Yi-Chui Kuo, Krzysztof P Bzymek, Leah H Goodstein, Kassondra Meyer, Roger E Moore, Desiree Crow, David Colcher, Gagandeep Singh, David A Horne, John C Williams
The high specificity and favorable pharmacological properties of monoclonal antibodies (mAbs) have prompted significant interest in re-engineering this class of molecules to add novel functionalities for enhanced therapeutic and diagnostic potential. Here, we used the high affinity, meditope-Fab interaction to template and drive the rapid, efficient, and stable site-specific formation of a disulfide bond. We demonstrate that this template-catalyzed strategy provides a consistent and reproducible means to conjugate fluorescent dyes, cytotoxins, or "click" chemistry handles to meditope-enabled mAbs (memAbs) and memFabs...
May 15, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29758384/disruption-of-shp1-nmda-receptor-signaling-in-spinal-cord-dorsal-horn-alleviated-inflammatory-pain
#10
Li Yang, Hu-Hu Bai, Zi-Yang Zhang, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Src-homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) is one of the non-receptor-like phosphatases that are highly enriched in hematopoietic cells. Although accumulating evidence has implicated the protein tyrosine phosphatases in the regulation of nociceptive transmission and plasticity, it is largely unknown whether SHP1 was expressed in pain-related spinal cord dorsal horn and engaged in the synaptic modification of nociceptive signals. Here we found that SHP1 was present in spinal neurons of rats and functionally coupled to GluN2A subunit-containing N-methyl-d-aspartate subtype of glutamate receptors, one of the key players in central sensitization of nociceptive behaviors...
April 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29758280/multi-kinase-inhibitor-with-anti-p38%C3%AE-activity-in-cutaneous-t-cell-lymphoma
#11
Xu Hannah Zhang, Sangkil Nam, Jun Wu, Chih-Hong Chen, Xuxiang Liu, Hongzhi Li, Timothy McKeithan, Qiang Gong, Wing C Chan, Hongwei Holly Yin, Yate-Ching Yuan, Raju Pillai, Christiane Querfeld, David Horne, Yuan Chen, Steven T Rosen
Current cutaneous T cell lymphoma (CTCL) therapies are marked by an abbreviated response, subsequent drug resistance, and poor prognosis for patients with advanced disease. An understanding of molecular regulators involved in CTCL is needed to develop effective targeted therapies. One candidate regulator is p38γ, a mitogen-activated protein kinase crucial for malignant T cell activity and growth. p38γ gene expression is selectively increased in CTCL patient samples as well as cell lines, but not in healthy T cells...
May 11, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29758036/benzoxaborole-treatment-perturbs-s-adenosyl-l-methionine-metabolism-in-trypanosoma-brucei
#12
Pieter C Steketee, Isabel M Vincent, Fiona Achcar, Federica Giordani, Dong-Hyun Kim, Darren J Creek, Yvonne Freund, Robert Jacobs, Kevin Rattigan, David Horn, Mark C Field, Annette MacLeod, Michael P Barrett
The parasitic protozoan Trypanosoma brucei causes Human African Trypanosomiasis and Nagana in other mammals. These diseases present a major socio-economic burden to large areas of sub-Saharan Africa. Current therapies involve complex and toxic regimens, which can lead to fatal side-effects. In addition, there is emerging evidence for drug resistance. AN5568 (SCYX-7158) is a novel benzoxaborole class compound that has been selected as a lead compound for the treatment of HAT, and has demonstrated effective clearance of both early and late stage trypanosomiasis in vivo...
May 14, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29752983/orexin-b-modulates-spontaneous-excitatory-and-inhibitory-transmission-in-lamina-ii-neurons-of-adult-rat-spinal-cord
#13
Chong Wang, Tsugumi Fujita, Eiichi Kumamoto
Cellular mechanisms underlying the antinociceptive properties of orexins, a group of neuropeptides produced by the hypothalamus, in the spinal dorsal horn have not been thoroughly investigated. We examined how orexin B affects spontaneous synaptic transmission in lamina II neurons, which play a pivotal role in regulating nociceptive transmission, by applying a whole-cell patch-clamp technique to lamina II neurons in adult rat spinal cord slices. In 66% of neurons tested, bath-applied orexin B concentration-dependently produced an inward current at -70 mV and/or increased the frequency of glutamatergic spontaneous excitatory postsynaptic current (sEPSC) without changing its amplitude, in a manner resistant to the voltage-gated Na+ -channel blocker tetrodotoxin...
May 9, 2018: Neuroscience
https://www.readbyqxmd.com/read/29746991/electrical-synapses-are-involved-in-orofacial-neuropathic-pain
#14
Omar Ouachikh, Aziz Hafidi, Yves Boucher, Wisam Dieb
Accumulated evidences suggest important roles of glial GAP-junctions in pain. However, only a few studies have explored the role of neuronal GAP-junctions or electrical synapses in neuropathic pain (NP). Therefore, the present study explores the role of connexin 36 (Cx36) in NP using the chronic constriction injury of the infraorbital nerve (CCI-IoN) model in rat. A significant increase in Cx36 labeling was observed in the medullary dorsal horn (MDH) of CCI-IoN-lesioned compared to sham rats. The expression of Cx36 in CCI-IoN-lesioned rats revealed a rostroventral gradient of punctuate labeling within lamina IIo of the MDH...
May 7, 2018: Neuroscience
https://www.readbyqxmd.com/read/29744321/morphology-of-intra-articular-structures-and-histology-of-menisci-of-knee-joint
#15
Monika Gupta, Parmod Kumar Goyal, Poonam Singh, Anu Sharma
Introduction: Menisci and cruciate ligaments are intra-articular structures of knee, and injury to these structures is common. Morphometric data gained in the study will help in analyzing the variations among humans and correlating it with the possibility, location, and type of injuries as well as better interpretation of structures during magnetic resonance imaging and arthroscopy which will further help in reconstructive surgeries of knee. Materials and Methods: Width and thickness of the medial menisci (MM), lateral menisci (LM), and maximum length and width of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) were taken on twenty knees...
April 2018: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/29743728/spatially-correlated-phenotyping-reveals-k5-positive-luminal-progenitor-cells-and-p63-k5-14-positive-stem-cell-like-cells-in-human-breast-epithelium
#16
Werner Boecker, Laura van Horn, Göran Stenman, Christine Stürken, Udo Schumacher, Thomas Loening, Lukas Liesenfeld, Eberhard Korsching, Doreen Gläser, Katharina Tiemann, Igor Buchwalow
Understanding the mechanisms regulating human mammary epithelium requires knowledge of the cellular constituents of this tissue. Different and partially contradictory definitions and concepts describing the cellular hierarchy of mammary epithelium have been proposed, including our studies of keratins K5 and/or K14 as markers of progenitor cells. Furthermore, we and others have suggested that the p53 homolog p63 is a marker of human breast epithelial stem cells. In this investigation, we expand our previous studies by testing whether immunohistochemical staining with monospecific anti-keratin antibodies in combination with an antibody against the stem cell marker p63 might help refine the different morphologic phenotypes in normal breast epithelium...
May 9, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29734842/the-beneficial-effects-of-nerolidol-and-hesperidin-on-surgically-induced-endometriosis-in-a-rat-model
#17
Rauf Melekoglu, Osman Ciftci, Sevil Eraslan, Aslı Cetin, Nese Basak
The objective of this article is to analyze the effects of nerolidol and hesperidin treatment on surgically induced endometriosis in a rat model. Endometriosis was induced in 24 healthy adult female Wistar albino rats via homologous uterine horn transplantation. Three operations were performed on each rat. After the second operation, the rats were randomized into control, nerolidol, and hesperidin treatment groups, and medications were administered for 2 weeks. The effects of the drugs on the endometriotic foci were evaluated after the third operation...
May 7, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29733975/role-of-trpv1-and-trpv4-in-surgical-incision-induced-tissue-swelling-and-fos-like-immunoreactivity-in-the-central-nervous-system-of-mice
#18
Yasuhito Motojima, Haruki Nishimura, Hiromichi Ueno, Satomi Sonoda, Kazuaki Nishimura, Kentaro Tanaka, Reiko Saito, Mitsuhiro Yoshimura, Takashi Maruyama, Takanori Matsuura, Hitoshi Suzuki, Makoto Kawasaki, Hideo Ohnishi, Akinori Sakai, Yoichi Ueta
Pain management remains a major concern regarding the treatment of postoperative patients. Transient receptor potential (TRP) channels are considered to be new therapeutic targets for pain control. We investigated whether the genes Trpv1 and Trpv4 are involved in hind paw swelling caused after surgical incision in mice or in incision-induced Fos-like immunoreactivity (Fos-LI) levels in the central nervous system. Mice were divided into four groups: wild-type (WT) control, WT incision, Trpv1 knockout (Trpv1-/- ) incision, and Trpv4 knockout (Trpv4-/- ) incision...
May 4, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29731364/covalent-inhibitors-of-nicotinamide-n-methyltransferase-nnmt-provide-evidence-for-target-engagement-challenges-in-situ
#19
Hsin-Yu Lee, Radu M Suciu, Benjamin D Horning, Ekaterina V Vinogradova, Olesya A Ulanovskaya, Benjamin F Cravatt
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide using S-adenosyl-L-methionine (SAM) as a methyl donor and, through doing so, can modulate cellular methylation potential to impact diverse epigenetic processes. NNMT has been implicated in a range of diseases, including cancer and metabolic disorders. Potent, selective, and cell-active inhibitors would constitute valuable probes to study the biological functions and therapeutic potential of NNMT. We previously reported the discovery of electrophilic small molecules that inhibit NNMT by reacting with an active-site cysteine residue in the SAM-binding pocket...
April 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29730970/spinal-glial-adaptations-occur-in-a-minimally-invasive-mouse-model-of-endometriosis-potential-implications-for-lesion-etiology-and-persistent-pelvic-pain
#20
Kelsi N Dodds, Elizabeth A H Beckett, Susan F Evans, Mark R Hutchinson
Glial adaptations within the central nervous system are well known to modulate central sensitization and pain. Recently, it has been suggested that activity of glial-related proinflammatory cytokines may potentiate peripheral inflammation, via central neurogenic processes. However, a role for altered glial function has not yet been investigated in the context of endometriosis, a chronic inflammatory condition in women associated with peripheral lesions, often manifesting with persistent pelvic pain. Using a minimally invasive mouse model of endometriosis, we investigated associations between peripheral endometriosis-like lesions and adaptations in central glial reactivity...
January 1, 2018: Reproductive Sciences
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