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Kappa Receptor

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https://www.readbyqxmd.com/read/29330050/production-and-characterization-of-a-novel-site-specific-modifiable-anti-ox40-receptor-single-chain-variable-fragment-for-targeted-drug-delivery
#1
Aki Tanabe, Kazumi Nakano, Makoto Nakakido, Satoru Nagatoishi, Yuetsu Tanaka, Kouhei Tsumoto, Kaoru Uchimaru, Toshiki Watanabe
OX40 receptor (tumor necrosis factor receptor superfamily, member 4; CD134) is a T-cell co-stimulatory molecule that plays an important role in T-cell activation and survival. OX40 receptor is activated by its ligand, OX40L; and modulation of the OX40-OX40L interaction is a promising target for the treatment of autoimmune diseases and cancers. Here, we generated a high-affinity anti-OX40 single-chain variable fragment carrying a C-terminal cysteine residue (scFvC). Physicochemical and functional analyses revealed that the scFvC bound to OX40-expressing cells and was internalized via OX40-mediated endocytosis without inducing phosphorylation of IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha), an important complex in the classical NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway...
January 9, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29329944/use-of-superarms-egfr-mutation-detection-kit-to-detect-egfr-in-plasma-cell-free-dna-of-patients-with-lung-adenocarcinoma
#2
Shaohua Cui, Lin Ye, Huimin Wang, Tianqing Chu, Yizhuo Zhao, Aiqin Gu, Liwen Xiong, Chunlei Shi, Liyan Jiang
BACKGROUND: The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly selective and sensitive and able to detect 41 of the most common somatic mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR). It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8% to 99.2% normal DNA. The present study assessed the performance of SuperARMS in detecting EGFR mutations in cell-free DNA (cfDNA) samples derived from plasma in patients with advanced lung adenocarcinoma...
December 21, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/29329668/helicobacter-pylori-induces-direct-activation-of-the-lymphotoxin-beta-receptor-and-non-canonical-nuclear-factor-kappa-b-signaling
#3
Michael Hartmut Feige, Michael Vieth, Olga Sokolova, Christian Täger, Michael Naumann
The pathogen Helicobacter pylori, which infects half of the world's population, is a major risk factor for the development of gastric diseases including chronic gastritis and gastric cancer. Among H. pylori's virulence factors is the cytotoxin-associated gene pathogenicity island (cagPAI), which encodes for a type IV secretion system (T4SS). The T4SS induces fast canonical nuclear factor-kappa B (NF-κB) signaling, a major factor increasing inflammation, supressing apoptotic cell death and thereby promoting the development of neoplasia...
January 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29323736/mapk-and-nf-%C3%AE%C2%BAb-signalling-pathways-regulate-the-expression-of-mirna-let-7f-in-human-endocervical-epithelial-cells
#4
Kanchana K Ayyar, Kvr Reddy
MicroRNAs (miRNAs) mediate post-transcriptional gene suppression and are a critical component of the complex regulatory networks in epithelial immune responses. Transcription of miRNA genes in epithelial cells can be elaborately controlled through Toll-like receptors (TLRs), and associated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, leading to nuclear transcription factor associated-transactivation and transrepression of miRNAs. MiRNA, let-7f is involved in the regulation of innate immune responses post TLR3 stimulation in human endocervical cells (End1/E6E7) and decreased let-7f is associated with poor immune activation...
January 11, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29322004/thoughts-modulate-the-expression-of-inflammatory-genes-and-may-improve-the-coronary-blood-flow-in-patients-after-a-myocardial-infarction
#5
Carlo Dal Lin, Mariela Marinova, Giorgio Rubino, Elisabetta Gola, Alessandra Brocca, Giorgia Pantano, Laura Brugnolo, Cristiano Sarais, Umberto Cucchini, Biancarosa Volpe, Chiara Cavalli, Maura Bellio, Emilia Fiorello, Sofia Scali, Mario Plebani, Sabino Iliceto, Francesco Tona
Background: Mental stress is one of the main risk factors for cardiovascular disease. Meditation and music listening are two techniques that are able to counteract it through the activation of specific brain areas, eliciting the so-called Relaxing Response (RR). Epidemiological evidence reveals that the RR practice has a beneficial prognostic impact on patients after myocardial infarction. We aimed to study the possible molecular mechanisms of RR underlying these findings. Methods: We enrolled 30 consecutive patients after myocardial infarction and 10 healthy controls...
January 2018: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29316404/the-cxcl12-cxcr4-axis-promotes-migration-invasion-and-emt-in-human-papillary-thyroid-carcinoma-b-cpap-cells-via-nf-%C3%AE%C2%BAb-signaling
#6
Yuanqiang Lin, Qingjie Ma, Lin Li, Hui Wang
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy involving local and distant metastasis. It is known that CXC chemokine ligand 12 (CXCL12) interacts specifically with CXC chemokine receptor 4 (CXCR4) to guide the migration of PTC cells. However, the signaling pathway downstream of the CXCL12/CXCR4 axis in PTC is not fully understood. In the present study, high expression of CXCR4 was detected in 38 out of 82 PTC specimens, and the expression level of CXCR4 was significantly correlated with the stage of PTC...
January 9, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/29315012/development-of-an-anti-her2-monoclonal-antibody-h2mab-139-against-colon-cancer
#7
Mika K Kaneko, Shinji Yamada, Shunsuke Itai, Yukinari Kato
Human epidermal growth factor receptor 2 (HER2) expression has been reported in several cancers, such as breast, gastric, lung, pancreatic, and colorectal cancers. HER2 is overexpressed in those cancers and is associated with poor clinical outcomes. Trastuzumab, a humanized anti-HER2 antibody, provides significant survival benefits for patients with HER2-overexpressing breast cancers and gastric cancers. In this study, we developed a novel anti-HER2 monoclonal antibody (mAb), H2Mab-139 (IgG1, kappa) and investigated it against colon cancers using flow cytometry, western blot, and immunohistochemical analyses...
January 9, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29314619/naringin-protects-pancreatic-%C3%AE-cells-against-oxidative-stress-induced-apoptosis-by-inhibiting-both-intrinsic-and-extrinsic-pathways-in-insulin-deficient-diabetic-mice
#8
Ye Jin Lim, Jung Ho Kim, Jeong Hoon Pan, Jae Kyeom Kim, Tae-Sik Park, Young Jun Kim, Jin Hyup Lee, Jun Ho Kim
SCOPE: Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear. METHODS AND RESULTS: To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ)...
January 4, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29314204/telmisartan-ameliorates-vascular-endothelial-dysfunction-in-coronary-slow-flow-phenomenon-csfp
#9
Zhe Jin, Qindong Tan, Bei Sun
Coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder with an increasing morbidity, and currently, available therapies are of limited clinical value for its cure. Hence, it is urgent to find a novel approach to CSFP treatment. Several studies show that endothelial dysfunction plays a critical role in the aetiology of CSFP. Telmisartan (TMST) is a clinically available anti-hypertensive medicine and has shown its potential properties for improving vascular endothelial function. Thus, we aimed to investigate the effect of TMST on endothelial dysfunction in CSFP, Endothelial-dependent flow-mediated vasodilation, serum levels of nitric oxide, adiponectin, and endothelin-1 were surveyed before and after 3 months of TMST treatment...
January 2018: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29305989/the-immune-response-of-mytilus-edulis-hemocytes-exposed-to-vibrio-splendidus-lgp32-strain-a-transcriptomic-attempt-at-identifying-molecular-actors
#10
Marion Tanguy, Sophie Gauthier-Clerc, Jocelyne Pellerin, Jean-Michel Danger, Ahmed Siah
The marine mussel Mytilus edulis, tolerant to a wide range of environmental changes, combines a key role as a sentinel species for environmental monitoring programs and a significant economic importance. Mortality events caused by infective agents and parasites have not been described in mussels, which suggests an efficient immune system. This study aims at identifying the molecular mechanisms involved in the early immune responses M. edulis' hemocytes challenged with Vibrio splendidus LGP32 strain during 2, 4 and 6 h...
January 3, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29301147/amentoflavone-inhibits-osteoclastogenesis-and-wear-debris-induced-osteolysis-via-suppressing-nf-%C3%AE%C2%BAb-and-mapks-signaling-pathways
#11
Zhen Zhang, Shuai Zhao, Xiaolei Li, Xiaoqi Zhuo, Wu Zhang, Qian Nie, Shuguang Wang, Lianqi Yan, Yu Sun
Wear debris-induced osteolysis is one of the major reasons for subsequent aseptic loosening after cementless hip arthroplasty. Increasing evidence suggests that receptor activator of nuclear factor kappa-B (NF-κB) ligand-mediated osteoclastogenesis and osteolysis are responsible for wear debris-induced aseptic loosening. In the present study, we explored the effect of amentoflavone (AMF) on inhibiting osteoclast generation and wear debris-induced osteolysis in vitro and in vivo. Twenty-four male C57BL/J6 mice were randomly divided into four groups: a sham group and groups with titanium wear debris treatment followed by intraperitoneal injection of various concentrations of AMF (0, 20, and 40 mg/kg/day)...
January 4, 2018: Planta Medica
https://www.readbyqxmd.com/read/29296674/dynamic-strategic-bond-analysis-yields-a-ten-step-synthesis-of-20-nor-salvinorin-a-a-potent-%C3%AE%C2%BA-or-agonist
#12
Jeremy J Roach, Yusuke Sasano, Cullen L Schmid, Saheem Zaidi, Vsevolod Katritch, Raymond C Stevens, Laura M Bohn, Ryan A Shenvi
Salvinorin A (SalA) is a plant metabolite that agonizes the human kappa-opioid receptor (κ-OR) with high affinity and high selectivity over mu- and delta-opioid receptors. Its therapeutic potential has stimulated extensive semisynthetic studies and total synthesis campaigns. However, structural modification of SalA has been complicated by its instability, and efficient total synthesis has been frustrated by its dense, complex architecture. Treatment of strategic bonds in SalA as dynamic and dependent on structural perturbation enabled the identification of an efficient retrosynthetic pathway...
December 27, 2017: ACS Central Science
https://www.readbyqxmd.com/read/29288400/anti-inflammatory-and-antiresorptive-effects-of-calendula-officinalis-on-inflammatory-bone-loss-in-rats
#13
Joanna Trycia M Alexandre, Luzia Hermínia Teixeira Sousa, Mario Roberto Pontes Lisboa, Flávia A C Furlaneto, Danielle Rocha do Val, Mirna Marques, Hellíada C Vasconcelos, Iracema Matos de Melo, Renata Leitão, Gerly Anne Castro Brito, Paula Goes
OBJECTIVE: The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. MATERIAL AND METHODS: Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG)...
December 29, 2017: Clinical Oral Investigations
https://www.readbyqxmd.com/read/29287198/upregulation-of-peroxisome-proliferator-activated-receptor-alpha-by-fenofibrate-in-induced-testicular-ischemia-reperfusion
#14
Marwa M M Refaie
Torsion of the spermatic cord is a common urological emergency among infants and adolescents that can lead to testicular necrosis and infertility. We investigated the effect of fenofibrate (FEN) on induced testicular ischemia reperfusion (testicular (I-R). FEN (100, 300 mg/kg/day) was administered orally in presence or absence of testicular (I-R). We measured testicular weight changes and serum testosterone level. In addition; Testicular tissue reduced glutathione (GSH), malondialdehyde (MDA), total nitrites (NOx) and superoxide dismutase (SOD) activity were measured...
December 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29286200/relevance-of-megalin-receptor-injury-with-nuclear-factor-kappa-b-upregulation-in-acute-kidney-injury-induced-in-rats
#15
Shereen Saeid Elshaer, Hend Mohamed Anwar
Proximal tubule protein take-up is interceded by 2 receptors, megalin and cubilin. These receptors rescue an assortment of filtered ligands including fundamental vitamins and hormones. The objective of this study was to investigate the potential relation of megalin receptor injury with nuclear factor-kappa B (NF-κB) upregulation in acute kidney injury rat model. Twenty four rats were allocated into two groups: control group received saline, while the second group was intoxicated with cadmium chloride (2.4 mg Cd/kg/day i...
December 29, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29285221/a-c-jun-n-terminal-kinase-inhibitor-jnk-in-8-sensitizes-triple-negative-breast-cancer-cells-to-lapatinib
#16
Nancy D Ebelt, Tamer S Kaoud, Ramakrishna Edupuganti, Sabrina Van Ravenstein, Kevin N Dalby, Carla L Van Den Berg
Triple negative breast cancers (TNBC) have poor prognosis compared to other breast cancer subtypes and represent 15-20% of breast cancers diagnosed. Unique targets and new molecularly-targeted therapies are urgently needed for this subtype. Despite high expression of Epidermal Growth Factor Receptor, inhibitors such as lapatinib have not shown therapeutic efficacy in TNBC patients. Herein, we report that treatment with the covalent JNK inhibitor, JNK-IN-8, synergizes with lapatinib to cause cell death, while these compounds as single agents have little effect...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284595/molecular-genetic-investigation-clinical-features-and-response-to-treatment-in-21-patients-with-schnitzler-s-syndrome
#17
Dorota M Rowczenio, Shelly Pathak, Juan I Arostegui, Anna Mensa-Vilaro, Ebun Omoyinmi, Paul Brogan, Dan Lipsker, Thomas Scambler, Roger Owen, Hadija Trojer, Anna Baginska, Julian D Gillmore, Ashutosh D Wechalekar, Thirusha Lane, Rene Williams, Taryn Youngstein, Philip N Hawkins, Sinisa Savic, Helen J Lachmann
To date, the pathogenic mechanisms underlying Schnitzler's syndrome remain obscure, in particular the interplay between the monoclonal protein and increased IL-1beta production, although interest in the contribution of genetic factors has been fuelled by detection of somatic NLRP3 mosaicism in two patients with the variant-type Schnitzler's syndrome. At two specialist UK centres we have identified 21 patients, who fulfilled diagnostic criteria for Schnitzler's syndrome with urticarial rash, fever, arthralgia and bone pain; 47% reported weight loss, 40% fatigue and 21% lymphadenopathy...
December 28, 2017: Blood
https://www.readbyqxmd.com/read/29283384/high-mobility-group-box-1-mediates-fibroblast-activity-via-rage-mapk-and-nf-%C3%AE%C2%BAb-signaling-in-keloid-scar-formation
#18
Jihee Kim, Jong-Chul Park, Mi Hee Lee, Chae Eun Yang, Ju Hee Lee, Won Jai Lee
Emerging studies have revealed the involvement of high-mobility group box 1 (HMGB1) in systemic fibrotic diseases, yet its role in the cutaneous scarring process has not yet been investigated. We hypothesized that HMGB1 may promote fibroblast activity to cause abnormal cutaneous scarring. In vitro wound healing assay with normal and keloid fibroblasts demonstrated that HMGB1 administration promoted the migration of both fibroblasts with increased speed and a greater traveling distance. Treatment of the HMGB1 inhibitor glycyrrhizic acid (GA) showed an opposing effect on both activities...
December 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29282319/expression-of-an-active-g%C3%AE-s-mutant-in-skeletal-stem-cells-is-sufficient-and-necessary-for-fibrous-dysplasia-initiation-and-maintenance
#19
Xuefeng Zhao, Peng Deng, Ramiro Iglesias-Bartolome, Panomwat Amornphimoltham, Dana J Steffen, Yunyun Jin, Alfredo A Molinolo, Luis Fernandez de Castro, Diana Ovejero, Quan Yuan, Qianming Chen, Xianglong Han, Ding Bai, Susan S Taylor, Yingzi Yang, Michael T Collins, J Silvio Gutkind
Fibrous dysplasia (FD) is a disease caused by postzygotic activating mutations of GNAS (R201C and R201H) that encode the α-subunit of the Gs stimulatory protein. FD is characterized by the development of areas of abnormal fibroosseous tissue in the bones, resulting in skeletal deformities, fractures, and pain. Despite the well-defined genetic alterations underlying FD, whether GNAS activation is sufficient for FD initiation and the molecular and cellular consequences of GNAS mutations remains largely unresolved, and there are no currently available targeted therapeutic options for FD...
December 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29280352/mg-al-and-zn-al-layered-double-hydroxides-promote-dynamic-expression-of-marker-genes-in-osteogenic-differentiation-by-modulating-mitogen-activated-protein-kinases
#20
Ha Ram Kang, Célio Junior da Costa Fernandes, Rodrigo Augusto da Silva, Vera Regina Leopoldo Constantino, Ivan Hong Jun Koh, Willian F Zambuzzi
The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes...
December 27, 2017: Advanced Healthcare Materials
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