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Giuseppina De Simone
Based on the initial studies of J. Folkman in 1970s, which led to the proposal of the antiangiogenic therapy, many drugs targeting VEGF or its receptors have been developed with some of them approved for cancer treatment. However, these molecules so far have shown only a limited effect on survival benefits in patients. Thus, new approaches are needed to treat this disease. Considering that cancer utilizes both aerobic and anaerobic glycolytic pathway, authors of patents US2016279084 and US2017056350 propose a method to eradicate the disease, able to affect both metabolic pathways...
December 17, 2018: Expert Opinion on Therapeutic Patents
Soumi Dutta, Saumya Kanti Ray, G H Pailan, V R Suresh, Subrata Dasgupta
Hilsa (Tenualosa ilisha) is a clupeid that migrates from the off-shore area through the freshwater river for spawning. The purpose of this study was to investigate the involvement of branchial Na+ /K+ -ATPase (NKA) and Na+ /K+ /2Cl- cotransporter (NKCC) in maintaining ionic homeostasis in hilsa while moving across the salt barriers. Hilsa, migrating through marine and brackish waters, did not show any significant decline in NKA activity, plasma osmolality, and plasma ionic concentration. In contrast, all the parameters declined significantly, after the fish reached in freshwater zone of the river...
November 27, 2018: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
Jūratė Stanevičiūtė, Milda Juknevičienė, Jolita Palubinskienė, Ingrida Balnytė, Angelija Valančiūtė, Rūta Vosyliūtė, Kęstutis Sužiedėlis, Vaiva Lesauskaitė, Donatas Stakišaitis
The study objective was to investigate a possible sodium dichloroacetate (DCA) pharmacological mechanism causing an increase in diuresis in rats. The aim was to define characteristics of 24-hour urinary Na+ , K+ , Cl- , Ca2+ , and Mg2+ excretion in Wistar male rats and to evaluate effect of a single-dose DCA and repeated DCA dosage on diuresis. Six control and 6 DCA-treated male rats aged 5 to weeks after a single DCA dose and repeated dosage were tested. The single DCA dose treatment caused a significantly higher 24-hour diuresis when compared to control ( P < ...
October 2018: Dose-response: a Publication of International Hormesis Society
K Keano Pavlosky, Yoko Yamaguchi, Darren T Lerner, Andre P Seale
The Mozambique tilapia, Oreochromis mossambicus, is a teleost fish native to estuarine waters that vary in salinity between fresh water (FW) and seawater (SW). The neuroendocrine system plays a key role in salinity acclimation by directing ion uptake and extrusion in osmoregulatory tissues such as gill. While most studies with O. mossambicus have focused on acclimation to steady-state salinities, less is known about the ability of adult fish to acclimate to dynamically-changing salinities. Plasma osmolality, prolactin (PRL) levels, and branchial gene expression of PRL receptors (PRLR1 and PRLR2), Na+ /Cl- and Na+ /K+ /2Cl- co-transporters (NCC and NKCC), Na+ /K+ -ATPase (NKAα1a and NKAα1b), cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporin 3 (AQP3) were measured in fish reared in FW and SW steady-state salinities, in a tidal regimen (TR) where salinities changed between FW and SW every six hours, and in fish transferred from FW or SW to TR...
January 2019: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Xinxin You, Jieming Chen, Chao Bian, Yunhai Yi, Zhiqiang Ruan, Jia Li, Xinhui Zhang, Hui Yu, Junmin Xu, Qiong Shi
Mudskippers are typical amphibious fishes and possess various strategies to ameliorate ammonia toxicity during exposure to environmental ammonia. The present study aimed to provide transcriptomic evidence through profiling the gill and liver transcriptomes of Boleophthalmus pectinirostris (BP) and Periophthalmus magnuspinnatus (PM), which were subjected to treatment with high environmental ammonia for up to 72 h. The results of gene function annotation showed that most of the differentially expressed genes were involved in metabolic pathways...
September 24, 2018: Genomics
Dennis Kolosov, Michael J O'Donnell
Excretion in insects is accomplished by the combined actions of the Malpighian tubules (MTs) and hindgut, which together form the functional kidney. MTs of many insect groups consist of principal cells (PC) and secondary cells (SC). In most insect groups SCs are reported to secrete ions from haemolymph into the tubule lumen. Paradoxically, SCs in the MTs of the lepidopteran cabbage looper T. ni are used to reabsorb Na+ and K+ back into haemolymph. The current study was designed to investigate the effects and mode of action of the lepidopteran kinin, Helicokinin (HK), on ion transport in the SC-containing region of MT of T...
July 19, 2018: General and Comparative Endocrinology
Aylin R Rodan
WNK [with no lysine (K)] kinases regulate renal epithelial ion transport to maintain homeostasis of electrolyte concentrations, extracellular volume, and blood pressure. The SLC12 cation-chloride cotransporters, including the sodium-potassium-2-chloride (NKCC) and sodium chloride cotransporters (NCC), are targets of WNK regulation via the intermediary kinases SPAK (Ste20-related proline/alanine-rich kinase) and OSR1 (oxidative stress response). The pathway is activated by low dietary potassium intake, resulting in increased phosphorylation and activity of NCC...
October 1, 2018: American Journal of Physiology. Renal Physiology
Dennis Kolosov, Maria Tauqir, Sabitha Rajaruban, Peter M Piermarini, Andrew Donini, Michael J O'Donnell
Classical studies have described in detail the complex and regionalized morphology of the Malpighian tubule (MT) in larval Lepidoptera. Recent studies revealed unusual aspects of ion transport in the Malpighian tubules of the larva of the cabbage looper, Trichoplusia ni. These included: cation reabsorption via secondary cells (SC); coupling of SCs to neighbouring PCs via gap junctions to enable reabsorption; and a reversal from cation secretion to reabsorption by the principal cells in the distal ileac plexus region of the in situ tubule in response to dietary ion loading...
August 2018: Journal of Insect Physiology
Sebastian N Politis, David Mazurais, Arianna Servili, Jose-Luis Zambonino-Infante, Joanna J Miest, Jonna Tomkiewicz, Ian A E Butts
European eel (Anguilla anguilla) is a euryhaline species, that has adapted to cope with both, hyper- and hypo-osmotic environments. This study investigates the effect of salinity, from a morphological and molecular point of view on European eel larvae reared from 0 to 12 days post hatch (dph). Offspring reared in 36 practical salinity units (psu; control), were compared with larvae reared in six scenarios, where salinity was decreased on 0 or 3 dph and in rates of 1, 2 or 4 psu/day, towards iso-osmotic conditions...
2018: PloS One
Huilong Luo, Matthieu Gauthier, Xi Tan, Christophe Landry, Joël Poupon, Marie-Pierre Dehouck, Fabien Gosselet, Nicolas Perrière, Frank Bellivier, Salvatore Cisternino, Xavier Declèves
Variability in drug response to lithium (Li+ ) is poorly understood and significant, as only 40% of patients with bipolar disorder highly respond to Li+ . Li+ can be transported by sodium (Na+ ) transporters in kidney tubules or red blood cells, but its transport has not been investigated at the blood-brain barrier (BBB). Inhibition and/or transcriptomic strategies for Na+ transporters such as NHE (SLC9), NBC (SLC4), and NKCC (SLC12) were used to assess their role on Li+ transport in human brain endothelial cells...
July 2, 2018: Molecular Pharmaceutics
Simona Latronico, Maria Elena Giordano, Emanuela Urso, Maria Giulia Lionetto, Trifone Schettino
Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is one of the most diffused phosphorus flame retardants in the environment and is highly persistent and abundant in residential dust samples. To date the cellular targets and mechanisms underlying its toxic effects are not completely understood. The aim of this work was to study the effects of TDCPP on ion transport mechanisms fundamental for the cellular ionic homeostasis, such as Na+ -K+ -ATPase and Cl- transport. HeLa cells were used as experimental model. TDCPP showed a dose-dependent effect on cell viability in cells exposed for 24 h as assessed by MTT test (IC50  = 52...
October 2018: Toxicology Mechanisms and Methods
Natalie Y Yuen, Olga V Chechneva, Yi-Je Chen, Yi-Chen Tsai, Logan K Little, James Dang, Daniel J Tancredi, Jacob Conston, Steven E Anderson, Martha E O'Donnell
Cerebral edema is exacerbated in diabetic ischemic stroke through poorly understood mechanisms. We showed previously that blood-brain barrier (BBB) Na-K-Cl cotransport (NKCC) and Na/H exchange (NHE) are major contributors to edema formation in normoglycemic ischemic stroke. Here, we investigated whether hyperglycemia-exacerbated edema involves changes in BBB NKCC and NHE expression and/or activity and whether inhibition of NKCC or NHE effectively reduces edema and injury in a type I diabetic model of hyperglycemic stroke...
May 9, 2018: Journal of Cerebral Blood Flow and Metabolism
Mary Ann Fletcher, Zachary Barnes, Gordon Broderick, Nancy G Klimas
Natural killer (NK) cells are an essential component of innate immunity. These lymphocytes are also sensitive barometers of the effects of endogenous and exogenous stressors on the immune system. This chapter describes a chromium (51 Cr)-release bioassay designed to measure to the target cell killing capacity of NK cells (NKCC). Key features of the cytotoxicity assay are that it is done with whole blood and that numbers of effector cells are determined for each sample by flow cytometry and lymphocyte count...
2018: Methods in Molecular Biology
Eric Delpire, Kenneth B Gagnon
Two genes encode the Na+ -K+ -2Cl- cotransporters, NKCC1 and NKCC2, that mediate the tightly coupled movement of 1Na+ , 1K+ , and 2Cl- across the plasma membrane of cells. Na+ -K+ -2Cl- cotransport is driven by the chemical gradient of the three ionic species across the membrane, two of them maintained by the action of the Na+ /K+ pump. In many cells, NKCC1 accumulates Cl- above its electrochemical potential equilibrium, thereby facilitating Cl- channel-mediated membrane depolarization. In smooth muscle cells, this depolarization facilitates the opening of voltage-sensitive Ca2+ channels, leading to Ca2+ influx, and cell contraction...
March 25, 2018: Comprehensive Physiology
Xiao-Fang Lu, Meng-Di Jia, Sheng-Sheng Zhang, Lu-Qing Zhao
AIM: To investigate the effect of Hemp seed soft capsule (HSCC) on colonic ion transport and its related mechanisms in constipation rats. METHODS: Sprague-Dawley male rats were randomly divided into three groups: normal group, constipation group and HSSC group. Rats in the constipation and HSSC groups were administrated loperamide 3 mg/kg per day orally for 12 d to induce the constipation model. Then, the HSSC group was given HSSC 0.126 g/kg per day by gavage for 7 d...
November 14, 2017: World Journal of Gastroenterology: WJG
A R Jayakumar, M Taherian, K S Panickar, N Shamaladevi, M E Rodriguez, B G Price, M D Norenberg
Brain edema and the associated increase in intracranial pressure are major consequences of traumatic brain injury (TBI) that accounts for most early deaths after TBI. We recently showed that acute severe trauma to cultured astrocytes results in cell swelling. We further examined whether trauma induces cell swelling in neurons and microglia. We found that severe trauma also caused cell swelling in cultured neurons, whereas no swelling was observed in microglia. While severe trauma caused cell swelling in both astrocytes and neurons, mild trauma to astrocytes, neurons, and microglia failed to cell swelling...
February 2018: Neurochemical Research
Jin Sun Cho, Mi-Hyang Lee, Seung Il Kim, Seho Park, Hyung Seok Park, Ein Oh, Jong Ho Lee, Bon-Nyeo Koo
Introduction: Perioperative anesthesia and analgesia exacerbate immunosuppression in immunocompromised cancer patients. The natural killer (NK) cell is a critical part of anti-tumor immunity. We compared the effects of two different anesthesia and analgesia methods on the NK cell cytotoxicity (NKCC) in patients undergoing breast cancer surgery. Methods: Fifty patients undergoing breast cancer resection were randomly assigned to receive propofol-remifentanil anesthesia with postoperative ketorolac analgesia (Propofol-ketorolac groups) or sevoflurane-remifentanil anesthesia with postoperative fentanyl analgesia (Sevoflurane-fentanyl group)...
2017: International Journal of Medical Sciences
Peter M Piermarini, Daniel C Akuma, John C Crow, Taylor L Jamil, Willa G Kerkhoff, Kenyatta C M F Viel, Christopher M Gillen
The yellow fever mosquito, Aedes aegypti, has three genes that code for proteins with sequence similarity to vertebrate Na+ -K+ -Cl- cotransporters (NKCCs) of the solute-linked carrier 12 superfamily of cation-chloride cotransporters (CCCs). We hypothesized that these mosquito NKCC orthologues have diverged to perform distinct roles in salt secretion and absorption. In phylogenetic analyses, one protein (aeNKCC1) groups with a Drosophila melanogaster NKCC that mediates salt secretion whereas two others (aeCCC2 and aeCCC3) group with a Drosophila transporter that is not functionally characterized...
December 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Muhammad Y Ali, Ana Pavasovic, Lalith K Dammannagoda, Peter B Mather, Peter J Prentis
Systemic acid-base balance and osmotic/ionic regulation in decapod crustaceans are in part maintained by a set of transport-related enzymes such as carbonic anhydrase (CA), Na(+)/K(+)-ATPase (NKA), H(+)-ATPase (HAT), Na(+)/K(+)/2Cl(-) cotransporter (NKCC), Na(+)/Cl(-)/HCO[Formula: see text] cotransporter (NBC), Na(+)/H(+) exchanger (NHE), Arginine kinase (AK), Sarcoplasmic Ca(+2)-ATPase (SERCA) and Calreticulin (CRT). We carried out a comparative molecular analysis of these genes in three commercially important yet eco-physiologically distinct freshwater crayfish, Cherax quadricarinatus, C...
2017: PeerJ
Fadi Kandarian, Gemalene M Sunga, Diana Arango-Saenz, Maura Rossetti
Within the innate immune system, effector lymphocytes known as natural killer (NK) cells play an essential role in host defense against aberrant cells, specifically eliminating tumoral and virally infected cells. Approximately 30 known monogenic defects, together with a host of other pathological conditions, cause either functional or classic NK cell deficiency, manifesting in reduced or absent cytotoxic activity. Historically, cytotoxicity has been investigated with radioactive methods, which are cumbersome, expensive and potentially hazardous...
August 9, 2017: Journal of Visualized Experiments: JoVE
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