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H R Shin, H S Bae, B S Kim, H I Yoon, Y D Cho, W J Kim, K Y Choi, Y S Lee, K M Woo, J H Baek, H M Ryoo
Gain-of-function mutations in fibroblast growth factor receptors (FGFRs) cause congenital skeletal anomalies including craniosynostosis (CS), which is characterized by the premature closure of craniofacial sutures. Apert syndrome (AS) is one of the severest forms of CS, and the only treatment is surgical expansion of prematurely fused sutures in infants. Previously, we demonstrated that the prolyl isomerase PIN1 plays a critical role in mediating FGFR signaling, and that Pin1+/- mice exhibit delayed closure of cranial sutures...
July 11, 2018: Human Molecular Genetics
Jinshan Jin, Ying-Hsin Hsieh, Arpana S Chaudhary, Jianmei Cui, John E Houghton, Sen-Fang Sui, Binghe Wang, Phang C Tai
Sec-dependent protein translocation is an essential process in bacteria. SecA is a key component of the translocation machinery and has multiple domains that interact with various ligands. SecA acts as an ATPase motor to drive the precursor protein/peptide through the SecYEG protein translocation channels. As SecA is unique to bacteria and there is no mammalian counterpart, it is an ideal target for the development of new antimicrobials. Several reviews detail the assays for ATPase and protein translocation, as well as the search for SecA inhibitors...
August 1, 2018: FEMS Microbiology Letters
Jinjin Cui, Fengyun Zhang, Wei Cao, Yongshun Wang, Jingjin Liu, Xinxin Liu, Tao Chen, Ling Li, Jinwei Tian, Bo Yu
BACKGROUND: Erythropoietin (EPO), which is clinically used for renal anaemia, reportedly exerts beneficial pleiotropic effects in atherosclerosis. This aim of this study was to investigate the effects of EPO on macrophage inflammation and polarization under hyperglycaemic conditions and to identify the effects of EPO-treated macrophage supernatants (SNs) on endothelial cell (EC) function. METHODS: Peritoneal macrophages (pMΦs) were isolated from normal, diabetic or EPO-injected mice...
July 11, 2018: Molecular Immunology
Qinyang Xu, Fei Du, Ye Zhang, Yincheng Teng, Minfang Tao, Alex F Chen, Rongzhen Jiang
To explore new ideas about the pathogeny of preeclampsia (PE) proteinuria, this study focused on whether severe PE serum (PES) could induce high-molecular-weight protein (HMWP) hyperpermeability in glomerular endothelial cells (GEC) via the HMGB1-Caveolin-1 (CAV-1) pathway. Normal pregnancy serum (NPS) and severe PES were used to treat primary human GEC monolayer for 24 h. The CAV-1 inhibitor methyl-beta-cyclodextrin (MBCD), the HMGB1 inhibitor glycyrrhizicacid (GA), recombinant HMGB1 (rHMGB1) were also used to treat GEC monolayer that were stimulated by NPS or severe PES...
July 6, 2018: Journal of Reproductive Immunology
Grazia Rutigliano, Martina Stazi, Ottavio Arancio, D Martin Watterson, Nicola Origlia
Neuroinflammation is a fundamental mechanism in Alzheimer's disease (AD) progression. The stress-induced activation of the p38α mitogen-activated protein kinase (MAPK) leads to increased production of proinflammatory cytokines and neurodegeneration. We investigated the effects of an isoform selective p38α MAPK inhibitor, MW01-18-150SRM (MW150), administered at 2.5 mg/kg/d (i.p.; 14 days) on early entorhinal cortex (EC) alterations in an AD mouse model carrying human mutations of the amyloid precursor protein (mhAPP)...
June 12, 2018: Neurobiology of Aging
H Akbar, X Duan, R Piatt, S Saleem, A K Davis, N N Tandon, W Bergmeier, Y Zheng
BACKGROUND: Platelets from patients with X-linked chronic granulomatous disease or mice deficient in NADPH oxidase isoform NOX2 exhibit diminished reactive oxygen species (ROS) generation and platelet activation. Binding of Rac1 GTPase to p67phox plays a critical role in NOX2 activation by facilitating the assembly of the NOX2 enzyme complex. OBJECTIVE: We tested the hypothesis that Phox-I, a rationally designed small molecule inhibitor of Rac-p67phox interaction, may serve as an anti-thrombosis agent by suppressing ROS production and platelet activation...
July 14, 2018: Journal of Thrombosis and Haemostasis: JTH
Lili Wei, Haofei Xiong, Wei Li, Bo Li, Yong Cheng
BACKGROUND: The human salivary gland cell line (HSG) has so far been used as in vitro models for study of the influence of cytokines and pharmacologic agents on salivary glands, as well as a model system for inflammation in Sjögren's syndrome (SS). This study aimed to determine the effect of IL-17 on IL-6 production and the underlying molecular mechanism regulated by the HSG cell line. METHODS: Immunofluorescence analyses, RT-PCR, and Western blot were conducted to evaluate the IL-17 receptor (IL-17R) expression in cultured HSG cells...
July 14, 2018: Journal of Oral Pathology & Medicine
Youichirou Higashi, Takahiro Shimizu, Masaki Yamamoto, Kenjiro Tanaka, Toshio Yawata, Shogo Shimizu, Suo Zou, Tetsuya Ueba, Kazunari Yuri, Motoaki Saito
BACKGROUND AND PURPOSE: We have demonstrated that icv administered (±)-epibatidine, a nicotinic acetylcholine receptor (nAChR) agonist, induced secretion of noradrenaline and adrenaline (catecholamines) from the rat adrenal medulla with dihydro-β-erythroidin (an α4β2 nAChR antagonist)-sensitive brain mechanisms. Here, we examined central mechanisms for the (±)-epibatidine-induced responses, focusing on brain nitric oxide (NO) synthases (NOSs) and NO-mediated mechanisms, soluble guanylate cyclase and protein S-nitrosylation (a posttranslational modification of protein cysteine thiol groups), in urethane-anaesthetized (1...
July 14, 2018: British Journal of Pharmacology
Lucas Barretto-de-Souza, Mariane B Adami, Ricardo Benini, Carlos C Crestani
BACKGROUND AND PURPOSE: The aim of the present study was to assess the interaction of nitrergic neurotransmission within the bed nucleus of the stria terminalis (BNST) with local glutamatergic and noradrenergic neurotransmission in the control of cardiovascular responses to acute restraint stress in rats. EXPERIMENTAL APPROACH: Interaction with local noradrenergic neurotransmission was evaluated by investigating the effect of local pretreatment with the selective α1 -adrenoceptor antagonist WB4101 before microinjection of the nitric oxide donor NOC-9 into the BNST...
July 14, 2018: British Journal of Pharmacology
Tetsuo Kiso, Toshihiro Sekizawa, Hiroshi Uchino, Mina Tsukamoto, Shuichiro Kakimoto
BACKGROUND AND PURPOSE: Glucocorticoids are a major class of stress hormones that have been reported to participate in stress-induced hyperalgesia. Although 11β-hydroxysteroid dehydrogenase1 (11β-HSD1) is known to be a key enzyme in the intracellular regeneration of glucocorticoids in the central nervous system (CNS), its role in pain perception has not been elucidated. Here, we examined the effects of ASP3662, a novel 11β-HSD1 inhibitor, on neuropathic and dysfunctional pain. EXPERIMENTAL APPROACH: The enzyme inhibitory activities and pharmacokinetics of ASP3662 were examined, and its antinociceptive effects were evaluated in neuropathic pain, fibromyalgia, and inflammatory pain rat models...
July 14, 2018: British Journal of Pharmacology
Gabriel Hancu, Monica Budău, Daniela Lucia Muntean, Laszlo Gagyi, Aura Rusu
Chirality is a primordial subject in modern drug research as well as in pharmaceutical industry and development. Almost all second-generation modern antidepressants are chiral substances; however in therapy some are used as racemic mixtures while others as pure enantiomers. The development of enantioseparation methods of chiral antidepressants and their metabolites is one of the keys towards understanding their enantioselective drug action. For this purpose, efficient and reliable analytical methods are needed, and capillary electrophoresis proved to be an interesting and advantageous alternative to the more frequently used chromatographic techniques...
July 13, 2018: Biomedical Chromatography: BMC
Hyeongjoo Choi, Yongwon Jung
Multivalent interactions between more than one interconnected biomolecule are easily found in diverse natural systems. With cooperation of many interacting pairs, this clustered binding can achieve highly enhanced affinities. While the binding of an individual pair remains reversible, the binding between multivalent biomolecules can become nearly irreversible. Although the underlying principles of the multivalent effect have yet to be revealed, this intriguing concept of multivalent interaction has been widely applied to diverse fields...
July 14, 2018: Chemistry: a European Journal
Hsiang-Ju Chen, Rui-Lan Huang, Phui-Ly Liew, Po-Hsuan Su, Lin-Yu Chen, Yu-Chun Weng, Cheng-Chang Chang, Yu-Chi Wang, Michael Wing-Yan Chan, Hung-Cheng Lai
Ovarian high-grade serous carcinoma (HGSC) is the most lethal gynecological malignancy. Prevailing evidences suggest that drug resistance and recurrence of ovarian HGSC are caused by the presence of cancer stem cells. Therefore, targeting cancer stems is appealing, however, all attempts to date, have failed. To circumvent this limit, we analyzed differential transcriptomes at early differentiation of ovarian HGSC stem cells and identified the developmental transcription factor GATA3 as highly expressed in stem, compared to progenitor cells...
July 14, 2018: International Journal of Cancer. Journal International du Cancer
Sumit Kunwar, Christopher E Collins, Florina Constantinescu
Janus kinases (JAKs) play an important role in intracellular signaling for multiple cytokines in the pathogenesis of RA. Baricitinib is an oral, selective JAK 1 and 2 inhibitor which has been shown to be effective in the treatment of RA in several clinical trials. This meta-analysis aims to aggregate currently available data to assess the overall efficacy and safety of baricitinib in RA. We searched PubMed, EMBASE, and Cochrane CENTRAL from inception through 09/24/17 with restriction to English language. We excluded meeting abstracts without full text publication...
July 13, 2018: Clinical Rheumatology
M Fatih Aşula, I Umut Onur, F Ulviye Yigit
PURPOSE: Fumagillin has been previously used to treat corneal microsporidial keratitis and also identified as an angiogenesis inhibitor. This study aimed to evaluate efficacy of fumagillin bicyclohexylamine on the rat model of corneal neovascularization induced by silver nitrate cauterization. METHODS: Twenty-four Albino Wistar rats (n = 24) were divided into three groups. Following silver nitrate-induced corneal injury, eyes in Group 1 received one drop of 5 mg/mL topical fumagillin bicyclohexylamine four times daily for 10 days...
July 13, 2018: International Ophthalmology
V F Caparbo, C G S Saad, J C Moraes, A J de Brum-Fernandes, R M R Pereira
The present study investigates the osteoclastogenic capacity of peripheral blood mononuclear cells (PBMCs) in male patients with ankylosing spondylitis (AS). We demonstrated that monocytes from these patients display a lower capacity to generate osteoclasts compared to cells from healthy controls, and osteoclastogenesis was negatively correlated with disease duration. INTRODUCTION: Ankylosing spondylitis (AS) is a disease characterized by new bone growth that leads to syndesmophyte formation but AS patients frequently present with low bone mineral density/fractures...
July 13, 2018: Osteoporosis International
Michele Ghidini, Jens C Hahne, Melissa Frizziero, Gianluca Tomasello, Francesco Trevisani, Andrea Lampis, Rodolfo Passalacqua, Nicola Valeri
Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer...
July 13, 2018: Targeted Oncology
Li Hou, Ling Liu, Hongfei Zhang, Lin Zhang, Lan Zhang, Jian Zhang, Qiang Gao, Depei Wang
In this work, we constructed the aox1 disruption strains 3-4 and 4-10, as well as the aox1 overexpression strains 72 and 102 in Aspergillus niger. The energy metabolism, EMP, TCA pathways, and flux were investigated for the citric acid (CA) overproduction via the aox1 overexpression among them. As expected, the overexpression of the aox1 gene enabled a higher growth rate than that of the rate of its parent strain in medium with respiratory chain inhibitors. In liquefied corn starch medium supplemented with 0...
July 13, 2018: Applied Microbiology and Biotechnology
Hui-Fang Chiu, Michael W Y Chan, Chiung-Yin Cheng, Jian-Liang Chou, Jora Meng-Ju Lin, Yi-Ling Yang, Kwok-Tung Lu
Previous studies showed that neonatal dexamethasone treatment (NDT) transiently impaired hippocampal function in male rats. Hippocampal estrogen receptors (ERs) participate in avoidance learning. As previous studies focused on males only, this study was aimed to investigate the NDT effects on the hippocampal function of female rats. Newborn Wistar female rats were subjected to a tapering dose of dexamethasone (0.5 mg, 0.3 mg, and 0.1 mg/kg, subcutaneously) from postnatal days 1 to 3 and were subjected to experiments at the age of 6 weeks (adolescence)...
July 13, 2018: Molecular Neurobiology
Olfa Rebai, Mohamed Amri
In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities...
July 13, 2018: Neurotoxicity Research
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