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https://www.readbyqxmd.com/read/28813646/antihelminthic-drug-niclosamide-inhibits-cip2a-and-reactivates-tumor-suppressor-protein-phosphatase-2a-in-non-small-cell-lung-cancer-cells
#1
Myeong-Ok Kim, Min Ho Choe, Yi Na Yoon, Jiyeon Ahn, Minjin Yoo, Kwan-Young Jung, Sungkwan An, Sang-Gu Hwang, Jeong Su Oh, Jae-Sung Kim
Protein phosphatase 2A (PP2A) is a critical tumor suppressor complex responsible for the inactivation of various oncogenes. Recently, PP2A reactivation has emerged as an anticancer strategy. Cancerous inhibitor of protein phosphatase 2A (CIP2A), an endogenous inhibitor of PP2A, is upregulated in many cancer cells, including non-small cell lung cancer (NSCLC) cells. We demonstrated that the antihelminthic drug niclosamide inhibited the expression of CIP2A and reactivated the tumor suppressor PP2A in NSCLC cells...
August 13, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28808448/relevance-of-the-nr4a-sub-family-of-nuclear-orphan-receptors-in-trophoblastic-bewo-cell-differentiation
#2
Sudha Saryu Malhotra, Satish Kumar Gupta
Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28800037/primary-cilia-deficiency-induces-intracranial-aneurysm
#3
Min Liu, Jizong Zhao, Qian Zhou, Yong Peng, Yu Zhou, Yugang Jiang
BACKGROUND: Intracranial aneurysm (IA) rupture is life-threatening. However, the mechanisms underlying IA initiation, progression, and rupture remain poorly understood. In the present study, we examined the role of primary cilia in IA development. RESULTS: IA was experimentally induced in mice with elastase and angiotensin II treatment. The number of cells with primary cilia was determined in both IA and peri-IA regions. The role of primary cilia in IA development was assessed through knocking out or manipulating the expression of important components of primary cilia...
August 9, 2017: Shock
https://www.readbyqxmd.com/read/28798775/maintenance-of-a-schwann-like-phenotype-in-differentiated-adipose-derived-stem-cells-requires-the-synergistic-action-of-multiple-growth-factors
#4
Alice E Mortimer, Alessandro Faroni, Mahmut A Kilic, Adam J Reid
Differentiating human adipose-derived stem cells (ASCs) towards Schwann cells produces an unstable phenotype when stimulating factors are withdrawn. Here, we set out to examine the role of glial growth factor 2 (GGF-2) in the maintenance of Schwann-like cells. Following ASC differentiation to Schwann-like cells, stimulating factors were withdrawn such that cells either remained in media supplemented with all stimulating factors, GGF-2 alone, or underwent complete withdrawal of all factors. Furthermore, each stimulating factor was also removed from the growth medium individually...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28782270/a-concise-synthesis-of-forskolin
#5
Ondřej Hylse, Lukáš Maier, Roman Kučera, Tomáš Perečko, Aneta Svobodová, Lukáš Kubala, Kamil Paruch, Jakub Svenda
We report a 24-step synthesis of ()-forskolin, which delivered hundred-milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: (a) a strategic allylic transposition, (b) stepwise assembly of a sterically encumbered isoxazole ring, and (c) citric acid-modified Upjohn dihydroxylation of a resilient tetrasubstituted olefin. We demonstrate that the developed route has an exciting potential for the preparation of new forskolin analogs inaccessible by semisynthesis...
August 6, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28771736/characterization-of-primary-rat-nasal-epithelial-cultures-in-cftr-knockout-rats-as-a-model-for-cf-sinus-disease
#6
Kiranya E Tipirneni, Do-Yeon Cho, Daniel F Skinner, Shaoyan Zhang, Calvin Mackey, Dong-Jin Lim, Bradford A Woodworth
OBJECTIVE: The objectives of the current experiments were to develop and characterize primary rat nasal epithelial cultures and evaluate their usefulness as a model of cystic fibrosis (CF) sinonasal transepithelial transport and CF transmembrane conductance regulator (CFTR) function. STUDY DESIGN: Laboratory in vitro and animal studies. METHODS: CFTR(+/+) and CFTR(-/-) rat nasal septal epithelia (RNSE) were cultured on semipermeable supports at an air-liquid interface to confluence and full differentiation...
August 3, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28771527/claudin5a-is-required-for-proper-inflation-of-kupffer-s-vesicle-lumen-and-organ-laterality
#7
Jeong-Gyun Kim, Sung-Jin Bae, Hye Shin Lee, Ji-Hyeon Park, Kyu-Won Kim
Left-right asymmetric organ development is critical to establish a proper body plan of vertebrates. In zebrafish, the Kupffer's vesicle (KV) is a fluid-filled sac which controls asymmetric organ development, and a properly inflated KV lumen by means of fluid influx is a prerequisite for the asymmetric signal transmission. However, little is known about the components that support the paracellular tightness between the KV luminal epithelial cells to sustain hydrostatic pressure during KV lumen expansion. Here, we identified that the claudin5a (cldn5a) is highly expressed at the apical surface of KV epithelial cells and tightly seals the KV lumen...
2017: PloS One
https://www.readbyqxmd.com/read/28759570/camp-dependent-activation-of-protein-kinase-a-attenuates-respiratory-syncytial-virus-induced-human-airway-epithelial-barrier-disruption
#8
Fariba Rezaee, Terri J Harford, Debra T Linfield, Ghaith Altawallbeh, Ronald J Midura, Andrei I Ivanov, Giovanni Piedimonte
Airway epithelium forms a barrier to the outside world and has a crucial role in susceptibility to viral infections. Cyclic adenosine monophosphate (cAMP) is an important second messenger acting via two intracellular signaling molecules: protein kinase A (PKA) and the guanidine nucleotide exchange factor, Epac. We sought to investigate effects of increased cAMP level on the disruption of model airway epithelial barrier caused by RSV infection and the molecular mechanisms underlying cAMP actions. Human bronchial epithelial cells were infected with RSV-A2 and treated with either cAMP releasing agent, forskolin, or cAMP analogs...
2017: PloS One
https://www.readbyqxmd.com/read/28745837/prosecretory-effect-of-loperamide-in-ileal-and-colonic-mucosae-of-mice-displaying-high-or-low-swim-stress-induced-analgesia-associated-with-high-and-low-endogenous-opioid-system-activity
#9
A Wasilewski, A Misicka, M Sacharczuk, J Fichna
BACKGROUND: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and changes in bowel habit. The aim of this study was to characterize the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal and colonic mucosae and to estimate the possible influence of divergent activity of the endogenous opioid system (EOS) on IBS therapy. METHODS: Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low EOS activity were used in this study...
July 26, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28736082/differential-proteome-expression-analysis-of-androgen-dependent-and-independent-pathways-in-lncap-prostate-cancer-cells
#10
Seho Cha, Dong Hoon Shin, Jun Ryeong Seok, Jae Kyung Myung
Prostate cancer (PC) is one of the leading causes of cancer death in men. It commonly develops in older males, but the number of younger men diagnosed with the disease has increased in recent years. Hormone therapies, such as chemical and surgical methods that inhibit androgen synthesis or androgen receptor (AR) activation, have been used for advanced disease. However, castration-resistant PC (CRPC), which exhibits androgen-independent mechanisms for activating AR, develops after a few years of such treatment and no therapy is available...
July 20, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28733452/chronic-hypertension-increases-aortic-endothelial-hydraulic-conductivity-by-upregulating-endothelial-aquaporin-1-expres-sion
#11
Jimmy Deon Toussaint, Chirag Bharavi Raval, Tieuvi Nguyen, Hadi Fadaifard, Shripad Joshi, George Wolberg, Steven Quarfordt, Kung-Ming Jan, David S Rumschitzki
Numerous studies examine aquaporins' role in osmotic water transport in various systems but virtually none focus on aquaporins' role in hydrostatically-driven water transport involving mammalian cells save for our laboratory's recent study of aortic endothelial cells. Here we inves-tigate aquaporin-1 expression and function in the aortic endothelium in two high-renin rat mod-els of hypertension, the spontaneously hypertensive genetically altered Wystar-Kyoto rat variant and Sprague-Dawley rats made hypertensive by two kidney, one clip Goldblatt surgery...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28728156/predicting-the-risk-to-develop-preeclampsia-in-the-first-trimester-combining-promoter-variant-98a-c-of-lgals13-placental-protein-13-black-ethnicity-previous-preeclampsia-obesity-and-maternal-age
#12
Liora Madar-Shapiro, Ido Karady, Alla Trahtenherts, Argryo Syngelaki, Ranjit Akolekar, Liona Poon, Ruth Cohen, Adi Sharabi-Nov, Berthold Huppertz, Marei Sammar, Kata Juhasz, Nandor Gabor Than, Zoltan Papp, Roberto Romero, Kypros H Nicolaides, Hamutal Meiri
BACKGROUND: LGALS13 (placental protein 13 [PP13]) promoter DNA polymorphisms was evaluated in predicting preeclampsia (PE), given PP13's effects on hypotension, angiogenesis, and immune tolerance. METHODS: First-trimester plasma samples (49 term and 18 intermediate) of PE cases matched with 196 controls were collected from King's College Hospital, London, repository. Cell-free DNA was extracted and the LGALS13 exons were sequenced after PCR amplification. Expression of LGALS13 promoter reporter constructs was determined in BeWo trophoblast-like cells with luciferase assays...
July 21, 2017: Fetal Diagnosis and Therapy
https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#13
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28718638/semisynthesis-and-kappa-opioid-receptor-activity-of-derivatives-of-columbin-a-furanolactone-diterpene
#14
Anil Yilmaz, Rachel Saylor Crowley, Alexander M Sherwood, Thomas E Prisinzano
Columbin (1) is a furanolactone diterpene isolated from the roots of Jateorhiza and Tinospora species. These species generally grow in Asia and Africa and have been used in folk medicine for their apparent analgesic and antipyretic activities. Columbin (1) is of particular interest due to its structural similarity to the known kappa-opioid receptor (KOR) agonist salvinorin A. Given that the KOR is of interest in the study of many serious diseases, such as anxiety, depression, and drug addiction, obtaining natural or semisynthetic molecules with KOR activity recently has gained much interest...
July 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28717253/prostacyclin-reverses-platelet-stress-fibre-formation-causing-platelet-aggregate-instability
#15
M Z Yusuf, Z Raslan, L Atkinson, A Aburima, S G Thomas, K M Naseem, S D J Calaminus
Prostacyclin (PGI2) modulates platelet activation to regulate haemostasis. Evidence has emerged to suggest that thrombi are dynamic structures with distinct areas of differing platelet activation. It was hypothesised that PGI2 could reverse platelet spreading by actin cytoskeletal modulation, leading to reduced capability of platelet aggregates to withstand a high shear environment. Our data demonstrates that post-flow of PGI2 over activated and spread platelets on fibrinogen, identified a significant reduction in platelet surface area under high shear...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715817/amp010014a09-in-sus-scrofa-encodes-an-analog-of-g-protein-coupled-receptor-109a-which-mediates-the-anti-inflammatory-effects-of-beta-hydroxybutyric-acid
#16
Guangxin Chen, Shoupeng Fu, Wenqian Feng, Bingxu Huang, Shiyao Xu, Wei Wang, Juxiong Liu
BACKGROUND: Hydroxy-carboxylic acid receptor 2 (HCA2, also called GPR109A) belongs to the G protein-coupled receptor (GPCR) family and is found in humans, rats, mice, hamsters and guinea pigs, but there are almost no reports of this protein in other species. In this investigation, we speculated that AMP010014A09 (AMP+) is a homologue of GPR109A in swine. METHODS: To test this hypothesis, the following experiments were designed: monocytes isolated from the peripheral blood of swine were treated with LPS after pretreating with or without β-hydroxybutyric acid (BHBA), and the levels of pro-inflammatory cytokines and inflammatory proteins were assessed...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28715496/transition-of-phase-response-properties-and-singularity-in-the-circadian-limit-cycle-of-cultured-cells
#17
Satoshi Koinuma, Hiroshi Kori, Isao T Tokuda, Kazuhiro Yagita, Yasufumi Shigeyoshi
The circadian system has been regarded as a limit cycle oscillator constructed by the integrated interaction of clock genes and proteins. Here, we investigated a mammalian circadian oscillation geometrically before and after a perturbation. We detected the singular point and transition from a type 1 to type 0 phase response curve (PRC) and determined the embedding dimension to show how many variables are needed to describe the limit cycle oscillation and relaxation process after a perturbation. As a perturbation, forskolin (FK) was administered to Rat-1 cells expressing the Per2::luc gene...
2017: PloS One
https://www.readbyqxmd.com/read/28713902/establishment-and-characterization-of-cell-lines-derived-from-complete-hydatidiform-mole
#18
Eiko Yamamoto, Kaoru Niimi, Tohru Kiyono, Toshimichi Yamamoto, Kimihiro Nishino, Kenichi Nakamura, Tomomi Kotani, Hiroaki Kajiyama, Kiyosumi Shibata, Fumitaka Kikkawa
Gestational trophoblastic diseases (GTDs) are a group of diseases characterized by abnormal cellular proliferation of atypical trophoblasts. A hydatidiform mole is an abnormal pregnancy caused by genetic fertilization disorders, and it can be classified as a complete hydatidiform mole (CHM) or a partial hydatidiform mole. The aim of this study was to establish cell lines from CHMs and to characterize the cells for future studies concerning GTD. HMol1-2C, HMol1-3B, HMol1-8 and HMol3-1B were established from primary cultures of CHM explants following the introduction of different combinations of genes including human telomerase reverse transcriptase (hTERT), a mutant form of CDK (CDK4R24C), cyclin D1, p53C234, MYC and HRAS...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28712885/detection-of-cftr-function-and-modulation-in-primary-human-nasal-cell-spheroids
#19
John J Brewington, Erin T Filbrandt, F J LaRosa, Alicia J Ostmann, Lauren M Strecker, Rhonda D Szczesniak, John P Clancy
BACKGROUND: Expansion of CFTR modulators to patients with rare/undescribed mutations will be facilitated by patient-derived models quantifying CFTR function and restoration. We aimed to generate a personalized model system of CFTR function and modulation using non-surgically obtained nasal epithelial cells (NECs). METHODS: NECs obtained by curettage from healthy volunteers and CF patients were expanded and grown in 3-dimensional culture as spheroids, characterized, and stimulated with cAMP-inducing agents to activate CFTR...
July 13, 2017: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
https://www.readbyqxmd.com/read/28709639/ganoderma-triterpenes-retard-renal-cyst-development-by-downregulating-ras-mapk-signaling-and-promoting-cell-differentiation
#20
Limin Su, Liying Liu, Yingli Jia, Lei Lei, Jiangfeng Liu, Shuai Zhu, Hong Zhou, Ruoyun Chen, Hua Ann Jenny Lu, Baoxue Yang
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disease characterized by the progressive development of renal cysts with further need for effective therapy. Here our aim was to investigate the effect of Ganoderma triterpenes (GT) on the development of kidney cysts. Importantly, GT attenuated cyst development in two mouse models of ADPKD with phenotypes of severe cystic kidney disease. Assays for tubulogenesis showed that GT promoted epithelial tubule formation in MDCK cells, suggesting a possible effect on epithelial cell differentiation...
July 11, 2017: Kidney International
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