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https://www.readbyqxmd.com/read/28537883/preclinical-characterization-of-abemaciclib-in-hormone-receptor-positive-breast-cancer
#1
Raquel Torres-Guzmán, Bruna Calsina, Ana Hermoso, Carmen Baquero, Beatriz Alvarez, Joaquín Amat, Ann M McNulty, Xueqian Gong, Karsten Boehnke, Jian Du, Alfonso de Dios, Richard P Beckmann, Sean Buchanan, María José Lallena
Abemaciclib is an ATP-competitive, reversible kinase inhibitor selective for CDK4 and CDK6 that has shown antitumor activity as a single agent in hormone receptor positive (HR+) metastatic breast cancer in clinical trials. Here, we examined the mechanistic effects of abemaciclib treatment using in vitro and in vivo breast cancer models. Treatment of estrogen receptor positive (ER+) breast cancer cells with abemaciclib alone led to a decrease in phosphorylation of Rb, arrest at G1, and a decrease in cell proliferation...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535611/sea-buckthorn-hippophae-rhamnoides-l-leaf-extracts-protect-neuronal-pc-12-cells-from-oxidative-stress
#2
Chi Heung Cho, Ho Lim Jang, Migi Lee, Hee Kang, Ho Jjn Heo, Dae-Ok Kim
The present study was carried out to investigate the antioxidative and neuroprotective effects of sea buckthorn (Hippophae rhamnoides L.) leaves (SBL) harvested at different times. Reversed-phase high-performance liquid chromatography analysis revealed five major phenolic compounds: ellagic acid, gallic acid, isorhamnetin, kaempferol, and quercetin. SBL harvested in August had the highest total phenolic and flavonoid contents and antioxidant capacity. Treatment of neuronal PC-12 cells with the ethyl acetate fraction of SBL harvested in August in increased their viability and membrane integrity and reduced intracellular oxidative stress in a dose-dependent manner...
May 24, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28534973/role-of-x%C3%A2-linked-inhibitor-of-apoptosis%C3%A2-associated-factor%C3%A2-1-in-vasculogenic-mimicry-in-ovarian-cancer
#3
Yunxia Wang, Peishu Liu, Xietong Wang, Hongluan Mao
X-linked inhibitor of apoptosis‑associated factor 1 (XAF1) was identified as a novel X-linked inhibitor of apoptosis (XIAP) binding partner that may reverse the anti‑apoptotic effect of XIAP. Previous studies have revealed that XAF1 serves an important role in cancer angiogenesis. Vasculogenic mimicry (VM) describes the formation of fluid‑conducting channels by highly invasive and genetically dysregulated tumor cells. VM is critical for tumor blood supply and is associated with aggressive actions and metastasis...
May 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534954/uncaria-alkaloids-reverse-abcb1-mediated-cancer-multidrug-resistance
#4
Bao-Yuan Huang, Yu Zeng, Ying-Jie Li, Xiao-Jun Huang, Nan Hu, Nan Yao, Min-Feng Chen, Zai-Gang Yang, Zhe-Sheng Chen, Dong-Mei Zhang, Chang-Qing Zeng
The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-reversal activities of uncaria alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine (Icory), hirsutine and hirsuteine, were screened; they all exhibited potent reversal efficacy when combined with doxorubicin...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534914/covalent-inhibition-of-protein-tyrosine-phosphatases
#5
REVIEW
Kasi Viswanatharaju Ruddraraju, Zhong-Yin Zhang
Protein tyrosine phosphatases (PTPs) are a large family of 107 signaling enzymes that catalyze the hydrolytic removal of phosphate groups from tyrosine residues in a target protein. The phosphorylation status of tyrosine residues on proteins serve as a ubiquitous mechanism for cellular signal transduction. Aberrant function of PTPs can lead to many human diseases, such as diabetes, obesity, cancer, and autoimmune diseases. As the number of disease relevant PTPs increases, there is urgency in developing highly potent inhibitors that are selective towards specific PTPs...
May 23, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28534887/when-is-early-antiretroviral-therapy-early-enough-for-hiv-remission
#6
Eva Poveda, Manuelo Cresp
Several strategies to reduce and control the HIV reservoir are being evaluating to achieve the great challenge of HIV remission or functional cure. Some of these are based on immune and gene therapy, or in the use of agents with latency reversing properties. Moreover, acute HIV infection and the impact of early antiretroviral treatment (ART) initiation is another key issue of current research. It has been demonstrated that ART initiation during acute HIV infection minimizes the establishment of the latent HIV reservoir...
May 23, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28534853/the-1-tosylpentan-3-one-protects-against-6-hydroxydopamine-induced-neurotoxicity
#7
Chien-Jen Kao, Wu-Fu Chen, Bo-Lin Guo, Chien-Wei Feng, Han-Chun Hung, Wen-Ya Yang, Chun-Sung Sung, Kuan-Hao Tsui, Hsin Chu, Nan-Fu Chen, Zhi-Hong Wen
Previous studies have demonstrated that the marine compound austrasulfone, isolated from the soft coral Cladiella australis, exerts a neuroprotective effect. The intermediate product in the synthesis of austrasulfone, dihydroaustrasulfone alcohol, attenuates several inflammatory responses. The present study uses in vitro and in vivo methods to investigate the neuroprotective effect of dihydroaustrasulfone alcohol-modified 1-tosylpentan-3-one (1T3O). Results from in vitro experiments show that 1T3O effectively inhibits 6-hydroxydopamine-induced (6-OHDA-induced) activation of both p38 mitogen-activated protein kinase (MAPK) and caspase-3 in SH-SY5Y cells; and enhances nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression via phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling...
May 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28533887/lidocaine-suppresses-glioma-cell-proliferation-by-inhibiting-trpm7-channels
#8
Tiandong Leng, Suizhen Lin, Zhigang Xiong, Jun Lin
BACKGROUND: Malignant glioma is the most common brain cancer with devastating prognosis. Recurrence of malignant glioma following surgery is very common with few preventive and therapeutic options. Novel targets and therapeutic agents are constantly sought for better outcome. Our previous study established that inhibition of transient receptor potential melastatin 7 (TRPM7) channels resulted in significant decrease of human glioma cell growth and proliferation. As local anesthetic lidocaine has been shown to inhibit TRPM7 currents, we hypothesize that lidocaine may suppress glioma cell proliferation through TRPM7 channel inhibition...
2017: International Journal of Physiology, Pathophysiology and Pharmacology
https://www.readbyqxmd.com/read/28533752/protocatechuic-acid-a-phenolic-from-sansevieria-roxburghiana-leaves-suppresses-diabetic-cardiomyopathy-via-stimulating-glucose-metabolism-ameliorating-oxidative-stress-and-inhibiting-inflammation
#9
Niloy Bhattacharjee, Tarun K Dua, Ritu Khanra, Swarnalata Joardar, Ashis Nandy, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Persistent hyperglycemia, impairment of redox status and establishment of inflammatory pathophysiology integrally play important role in the pathogenesis of diabetic cardiomyopathy (DC). Present study examined the therapeutic potential of protocatechuic acid isolated from the Sansevieria roxburghiana rhizomes against DC employing rodent model of type 2 diabetes (T2D). T2D was induced by high fat diet + a low-single dose of streptozotocin (35 mg/kg, i.p.). T2D rats exhibited significantly (p < 0.01) high fasting blood glucose level...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28533430/heme-thiolate-sulfenylation-of-human-cytochrome-p450-4a11-functions-as-a-redox-switch-for-catalytic-inhibition
#10
Matthew E Albertolle, Donghak Kim, Leslie D Nagy, Chul-Ho Yun, Ambra Pozzi, Uzen Savas, Eric F Johnson, F Peter Guengerich
Cytochrome P450 (P450, CYP) 4A11 is a human fatty acid ω-hydroxylase that catalyzes the oxidation of arachidonic acid to the eicosanoid 20- hydroxyeicosatetraenoic acid (20-HETE), which plays important roles in regulating blood pressure regulation. Variants of P450 4A11 have been associated with high blood pressure and resistance to anti-hypertensive drugs, and 20-HETE has both pro- and antihypertensive properties relating to increased vasoconstriction and natriuresis, respectively. These physiological activities are likely influenced by the redox environment, but the mechanisms are unclear...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533239/plasmodium-falciparum-and-p-vivax-demonstrate-contrasting-chloroquine-resistance-reversal-phenotypes
#11
Grennady Wirjanata, Irene Handayuni, Pak Prayoga, Leo Leonardo, Dwi Apriyanti, Leily Trianty, Ruland Wandosa, Basbak Gobay, Enny Kenangalem, Jeanne Rini Poespoprodjo, Rintis Noviyanti, Dennis E Kyle, Qin Cheng, Ric N Price, Jutta Marfurt
High-grade chloroquine (CQ) resistance has emerged in both P. falciparum and P. vivax The aim of the present study was to investigate phenotypic differences of CQ resistance in both of these species and the ability of known CQ resistance reversal agents (CQRRAs) to alter CQ susceptibility.Between April 2015 and April 2016, the potential of verapamil (VP), mibefradil (MF), L703,606 (L7), and primaquine (PQ) to reverse CQ resistance was assessed in 46 P. falciparum and 34 P. vivax clinical isolates in Papua, Indonesia, where CQ resistance is present in both species, using a modified schizont maturation assay...
May 22, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28532824/puppy-survival-and-vigor-associated-with-the-use-of-low-dose-medetomidine-premedication-propofol-induction-and-maintenance-of-anesthesia-using-sevoflurane-gas-inhalation-for-cesarean-section-in-the-bitch
#12
K G M De Cramer, K E Joubert, J O Nöthling
The safety of an anesthetic protocol consisting of medetomidine hydrochloride (7 μg/kg iv) as premedicant, propofol, (1-2 mg/kg iv) as induction agent and sevoflurane, at 2% in oxygen for maintenance of anesthesia was studied in 292 cesarean sections (CSs) and 2232 puppies delivered. Medetomidine effects were reversed using atipamezole hydrochloride at 50 μg/puppy sc immediately following delivery and in the bitch iv immediately following surgery. The protocol's safety for puppies was expressed using survival immediately, 2 h and 7 d after delivery, and Apgar scores (measurement starting 15 min after delivery of the last puppy)...
July 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28532644/increasing-gaba-reverses-age-related-alterations-in-excitatory-receptive-fields-and-intensity-coding-of-auditory-midbrain-neurons%C3%A2-in%C3%A2-aged-mice
#13
Elliott J Brecht, Kathy Barsz, Benjamin Gross, Joseph P Walton
A key feature of age-related hearing loss is a reduction in the expression of inhibitory neurotransmitters in the central auditory system. This loss is partially responsible for changes in central auditory processing, as inhibitory receptive fields play a critical role in shaping neural responses to sound stimuli. Vigabatrin (VGB), an antiepileptic agent that irreversibly inhibits γ-amino butyric acid (GABA) transaminase, leads to increased availability of GABA throughout the brain. This study used multi-channel electrophysiology measurements to assess the excitatory frequency response areas in old CBA mice to which VGB had been administered...
April 12, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28531942/target-signalling-pathways-of-natural-plant-derived-radioprotective-agents-from-treatment-to-potential-candidates-a-reverse-thought-on-anti-tumour-drugs
#14
REVIEW
Ke-Li Yun, Zhen Yu Wang
Radiation damage can occur in nuclear power plant workers when physical protections fail, which results in nuclear leakage through the protective layers. Alternatively, workers may be unable to use physical protection in time (in the case of a sudden nuclear weapons attack). In addition, patients who receive local radiotherapy and are not allowed to adopt local physical protection may experience radiation damage. Thus, protection against chemical radiation has become indispensable. In view of the side effects caused by synthetic radioprotective agents (such as amisfostine), searching for radioprotective agents from plant sources is an alternative strategy...
May 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28531193/raman-microscopy-investigation-of-vitrification-induced-structural-damages-in-mature-bovine-oocytes
#15
Giulia Rusciano, Carolina De Canditiis, Gianluigi Zito, Marcello Rubessa, Maria Serena Roca, Rosa Carotenuto, Antonio Sasso, Bianca Gasparrini
Although oocyte cryopreservation has great potentials in the field of reproductive technologies, it still is an open challenge in the majority of domestic animals and little is known on the biochemical transformation induced by this process in the different cellular compartments. Raman micro-spectroscopy allows the non-invasive evaluation of the molecular composition of cells, based on the inelastic scattering of laser photons by vibrating molecules. The aim of this work was to assess the biochemical modifications of both the zona pellucida and cytoplasm of vitrified/warmed in vitro matured bovine oocytes at different post-warming times...
2017: PloS One
https://www.readbyqxmd.com/read/28531117/immunobiology-of-newcastle-disease-virus-and-its-use-for-prophylactic-vaccination-in-poultry-and-as-adjuvant-for-therapeutic-vaccination-in-cancer-patients
#16
REVIEW
Volker Schirrmacher
Newcastle disease (ND) is one of the most important diseases of poultry worldwide. In the last decades, molecular research has gained a lot of new information about its causative agent, newcastledisease virus (NDV). In poultry industry, certain strains of NDV have been used for preventive vaccination for more than 60 years. NDV has also been applied to cancer patients with beneficial effects for about 50 years, but this is less well known. The molecular basis for these differential effects of NDV in birds and man have been elucidated in the last decades and are explained in this review...
May 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28529584/anti-microrna-21-221-and-microrna-199a-transfected-by-ultrasound-microbubbles-induces-the-apoptosis-of-human-hepatoma-hepg2-cells
#17
Xinmin Guo, Shunhua Guo, Liwen Pan, Li Ruan, Yingshi Gu, Jichuang Lai
Gene therapy, particularly microRNA (miRNA), is a promising candidate in the treatment of cancer; however, it is challenging to develop gene delivery systems. Ultrasound microbubbles have been used for gene delivery with excellent results. The present study aimed to investigate the transfection efficiency of HepG2 cells using ultrasound microbubbles. The effects of three miRNAs (miR-21, miR-221 and miR-199a) on HepG2 cells were also determined by performing ultrasound microbubble-mediated gene transfection...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529249/improved-hydrops-imaging-of-endolymphatic-hydrops-after-intravenous-administration-of-gadolinium
#18
Shinji Naganawa, Hisashi Kawai, Toshiaki Taoka, Michihiko Sone
To improve the imaging protocol for the evaluation of endolymphatic hydrops after intravenous administration of a gadolinium-based contrast agent, we modified our previously reported hybrid of reversed image of positive endolymph signal and native image of positive perilymph signal (HYDROPS) method. Although the scan time of the new protocol was half that of the previous one, there were no significant differences between two protocols in the mean contrast noise ratio between the endolymph and perilymph and the area ratio of the endolymph size values in nine patients...
May 22, 2017: Magnetic Resonance in Medical Sciences: MRMS
https://www.readbyqxmd.com/read/28529036/qx-oh-a-qx-314-derivative-agent-produces-long-acting-local-anesthesia-in-rats
#19
YuJun Zhang, Jun Yang, QinQin Yin, LingHui Yang, Jin Liu, WenSheng Zhang
QX-314 has been shown to produce long-acting local anesthesia in vivo in animals; however, translation to humans has been impeded by concerns about toxicity. We investigated whether the newly emerged QX-OH molecule could confer long-lasting anesthesia with a low local toxicity in rats. In rat sciatic nerve block model, QX-OH 25mM produced a longer sensory block than QX-314 25mM (median [25th, 75th percentiles], 5.5 [4.25, 6] h vs. 3 [3, 4] h; P=0.03). QX-OH 35mM produced a longer sensory block than QX-314 35mM (8 [6, 12] h vs...
May 18, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28529033/high-throughput-characterization-of-hiv-1-reservoir-reactivation-using-a-single-cell-in-droplet-pcr-assay
#20
Robert W Yucha, Kristen S Hobbs, Emily Hanhauser, Louise E Hogan, Wildaliz Nieves, Mehmet O Ozen, Fatih Inci, Vanessa York, Erica A Gibson, Cassandra Thanh, Hadi Shafiee, Rami El Assal, Maja Kiselinova, Yvonne P Robles, Helen Bae, Kaitlyn S Leadabrand, ShuQi Wang, Steven G Deeks, Daniel R Kuritzkes, Utkan Demirci, Timothy J Henrich
Reactivation of latent viral reservoirs is on the forefront of HIV-1 eradication research. However, it is unknown if latency reversing agents (LRAs) increase the level of viral transcription from cells producing HIV RNA or harboring transcriptionally-inactive (latent) infection. We therefore developed a microfluidic single-cell-in-droplet (scd)PCR assay to directly measure the number of CD4(+) T cells that produce unspliced (us)RNA and multiply spliced (ms)RNA following ex vivo latency reversal with either an histone deacetylase inhibitor (romidepsin) or T cell receptor (TCR) stimulation...
May 4, 2017: EBioMedicine
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