keyword
https://read.qxmd.com/read/38527911/discovery-of-glpg2737-a-potent-type-2-corrector-of-cftr-for-the-treatment-of-cystic-fibrosis-in-combination-with-a-potentiator-and-a-type-1-co-corrector
#41
JOURNAL ARTICLE
Mathieu Pizzonero, Rhalid Akkari, Xavier Bock, Romain Gosmini, Elsa De Lemos, Béranger Duthion, Gregory Newsome, Thi-Thu-Trang Mai, Virginie Roques, Hélène Jary, Jean-Michel Lefrancois, Laetitia Cherel, Vanessa Quenehen, Marielle Babel, Nuria Merayo, Natacha Bienvenu, Oscar Mammoliti, Ghjuvanni Coti, Adeline Palisse, Marlon Cowart, Anurupa Shrestha, Stephen Greszler, Steven Van Der Plas, Koen Jansen, Pieter Claes, Mia Jans, Maarten Gees, Monica Borgonovi, Gert De Wilde, Katja Conrath
Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein. This epithelial anion channel regulates the active transport of chloride and bicarbonate ions across membranes. Mutations result in reduced surface expression of CFTR channels with impaired functionality. Correctors are small molecules that support the trafficking of CFTR to increase its membrane expression. Such correctors can have different mechanisms of action. Combinations may result in a further improved therapeutic benefit...
March 25, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38525830/magic-cluster-sizes-of-cationic-and-anionic-sodium-chloride-clusters-explained-by-statistical-modeling-of-the-complete-phase-space
#42
JOURNAL ARTICLE
Jessica C Hartmann, Sarah J Madlener, Christian van der Linde, Milan Ončák, Martin K Beyer
As one of the main components of sea salt aerosols, sodium chloride is involved in numerous atmospheric processes. Gas-phase clusters are ideal models to study fundamental physical and chemical properties of sodium chloride, which are significantly affected by the cluster size. Of particular interest are magic cluster sizes, which exhibit high intensities in mass spectra. In order to understand the origin of these magic cluster sizes, quantum chemical calculations at the CCSD(T)//DFT level are performed, yielding structures and binding energies of neutral (NaCl) x , anionic (NaCl) x Cl- and cationic (NaCl) x Na+ clusters up to x = 8...
March 25, 2024: Physical Chemistry Chemical Physics: PCCP
https://read.qxmd.com/read/38525817/exploring-the-therapeutic-potential-of-pomegranate-juice-for-uterine-relaxation
#43
JOURNAL ARTICLE
Omar A M Al-Habib, Lina N Adam
BACKGROUND: The effects of pomegranate juice (PJ) and its components on uterine smooth muscle are unknown. Hence, this study unequivocally demonstrates that pomegranate juice (PJ) significantly impacts myometrial function, providing crucial insights into its relaxant properties and their potential therapeutic applications for uterine-related disorders. RESEARCH DESIGN AND METHODS: Rat uterine smooth muscle horn strips were suspended in Krebs solution organ baths...
March 25, 2024: Expert Review of Endocrinology & Metabolism
https://read.qxmd.com/read/38521145/the-estrogen-receptor-alpha-regulates-the-sex-dependent-expression-and-pronociceptive-role-of-bestrophin-1-in-neuropathic-rats
#44
JOURNAL ARTICLE
Diana Laura Calvillo-Montoya, Carlos Javier Martínez-Magaña, Norma Oviedo, Janet Murbartián
Bestrophin-1, a calcium-activated chloride channel (CaCC), is involved in neuropathic pain; however, it is unclear whether it has a dimorphic role in female and male neuropathic rats. This study investigated if 17β-estradiol and estrogen receptor alpha (ERα) activation regulate bestrophin-1 activity and expression in neuropathic rats. Neuropathic pain was induced by L5-spinal nerve transection (SNT). Intrathecal administration of CaCCinh-A01 (0.1-1 µg), a CaCC blocker, reversed tactile allodynia induced by SNT in female but not male rats...
March 21, 2024: Journal of Pain
https://read.qxmd.com/read/38520402/pacemaking-in-the-lymphatic-system
#45
JOURNAL ARTICLE
Michael J Davis, Scott D Zawieja
Lymphatic collecting vessels exhibit spontaneous phasic contractions that are critical for lymph propulsion and tissue fluid homeostasis. This rhythmic activity is driven by action potentials conducted across the lymphatic muscle cell (LMC) layer to produce entrained contractions. The contraction frequency of a lymphatic collecting vessel displays exquisite mechanosensitivity, with a dynamic range from <1 to >20 contractions per minute. A myogenic pacemaker mechanism intrinsic to the LMCs was initially postulated to account for pressure-dependent chronotropy...
March 23, 2024: Journal of Physiology
https://read.qxmd.com/read/38513253/vertical-channel-cathode-host-enables-rapid-deposition-kinetics-toward-high-areal-capacity-sodium-chlorine-batteries
#46
JOURNAL ARTICLE
Chenyu Ma, Wenting Feng, Debin Kong, Xinru Wei, Xuelei Gong, Jianhang Yang, Junwei Han, Linjie Zhi
Rechargeable sodium chloride (Na-Cl2 ) batteries have emerged as promising alternatives for next-generation energy storage due to their superior energy density and sodium abundance. However, their practical applications are hindered by the sluggish chlorine cathode kinetics related to the aggregation of NaCl and its difficult transformation into Cl2 . Herein, the study, for the first time from the perspective of electrode level in Na-Cl2 batteries, proposes a free-standing carbon cathode host with customized vertical channels to facilitate the SOCl2 transport and regulate the NaCl deposition...
March 21, 2024: Small
https://read.qxmd.com/read/38511871/a-simple-cost-effective-method-to-fabricate-single-nanochannels-by-embedding-electrospun-polyethylene-oxide-nanofibers
#47
JOURNAL ARTICLE
Lei Zhou, Zhuonan Chen, Jian Ma
Solid state nanochannels provide significant practical advantages in many fields due to their interesting properties, such as controllable shape and size, robustness, ion selectivity. But their complex preparation processes severely limit their application. In this study, a simple cost-effective method to fabricate single nanochannel by embedding a single polyethylene oxide (PEO) nanofiber is presented. Firstly, PEO nanofibers are prepared by electrospinning, and then a single PEO nanofiber are precisely transferred to the target sample using a micromanipulation platform...
March 21, 2024: ChemistryOpen
https://read.qxmd.com/read/38511329/an-aquaporin-and-an-aquaglyceroporin-have-roles-in-low-temperature-adaptation-of-mosquitoes-anopheles-sinensis
#48
JOURNAL ARTICLE
Yong-Qiao Zhao, Yi-Ying Tang, Ju-Ping Hu, Yu-Zheng Huang, Kai Wan, Mei-Hua Zhang, Ju-Lin Li, Guo-Ding Zhu, Jian-Xia Tang
Mosquitoes (Anopheles sinensis), widely geographically distributed in Asia including China, are the primary vector of the malaria parasite Plasmodium vivax and other parasitic diseases such as Malayan filariasis. An. sinensis can survive through low winter temperatures. Aquaporin channels are found in all life forms, where they facilitate environmental adaptation by allowing rapid trans-cellular movement of water (classical aquaporins) or water and solutes such as glycerol (aquaglyceroporins). Here, we identified and characterized 2 aquaporin (AQP) homologs in An...
March 21, 2024: Insect Science
https://read.qxmd.com/read/38508775/adult-classic-bartter-syndrome-a-case-report-with-5-year-follow-up-and-literature-review
#49
JOURNAL ARTICLE
Le Jiang, Dongmei Li, Qiansha Guo, Yunfeng Li, Lei Zan, Rihan Ao
Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited...
March 19, 2024: Endocrine Journal
https://read.qxmd.com/read/38507469/the-clc-1-chloride-channel-inhibitor-nmd670-improves-skeletal-muscle-function-in-rat-models-and-patients-with-myasthenia-gravis
#50
RANDOMIZED CONTROLLED TRIAL
Martin Skov, Titia Q Ruijs, Thomas S Grønnebæk, Marianne Skals, Anders Riisager, Jeppe Blichfeldt Winther, Kamilla Løhde Tordrup Dybdahl, Anders Findsen, Jeanette J Morgen, Nete Huus, Martin Broch-Lips, Ole B Nielsen, Catherine M K E de Cuba, Jules A A C Heuberger, Marieke L de Kam, Martijn Tannemaat, Jan J G M Verschuuren, Lars J S Knutsen, Nicholas M Kelly, Klaus G Jensen, William D Arnold, Arthur H Burghes, Claus Olesen, Jane Bold, Thomas K Petersen, Jorge A Quiroz, John Hutchison, Eva R Chin, Geert J Groeneveld, Thomas H Pedersen
Myasthenia gravis (MG) is a neuromuscular disease that results in compromised transmission of electrical signals at the neuromuscular junction (NMJ) from motor neurons to skeletal muscle fibers. As a result, patients with MG have reduced skeletal muscle function and present with symptoms of severe muscle weakness and fatigue. ClC-1 is a skeletal muscle specific chloride (Cl- ) ion channel that plays important roles in regulating neuromuscular transmission and muscle fiber excitability during intense exercise...
March 20, 2024: Science Translational Medicine
https://read.qxmd.com/read/38505263/cell-type-specific-regulation-of-cftr-trafficking-on-the-verge-of-progress
#51
REVIEW
Carlos M Farinha, Lúcia Santos, João F Ferreira
Trafficking of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is a complex process that starts with its biosynthesis and folding in the endoplasmic reticulum. Exit from the endoplasmic reticulum (ER) is coupled with the acquisition of a compact structure that can be processed and traffic through the secretory pathway. Once reaching its final destination-the plasma membrane, CFTR stability is regulated through interaction with multiple protein partners that are involved in its post-translation modification, connecting the channel to several signaling pathways...
2024: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/38503027/synthesis-and-biological-evaluation-of-lycoctonine-derivatives-with-cardiotonic-and-calcium-channels-inhibitory-activities
#52
JOURNAL ARTICLE
Jian-Zhu Wang, Xiang-Yu Li, Min Zhang, Yan Xiao, Lin Chen, Meng-Yi Deng, Shuai Huang, Xian-Li Zhou
In our previous study, a screening of a variety of lycotonine-type diterpenoid alkaloids were screened for cardiotonic activity revealed that lycoctonine had moderate cardiac effect. In this study, a series of structurally diverse of lycoctonine were synthesized by modifying on B-ring, D-ring, E-ring, F-ring, N-atom or salt formation on lycoctonine skeleton. We evaluated the cardiotonic activity of the derivatives by isolated frog heart, aiming to identify some compounds with significantly enhanced cardiac effects, among which compound 27 with a N-isobutyl group emerged as the most promising cardiotonic candidate...
March 16, 2024: Bioorganic Chemistry
https://read.qxmd.com/read/38501963/pulmonary-vascular-dysfunctions-in-cystic-fibrosis
#53
REVIEW
Jean-Pierre Amoakon, Goutham Mylavarapu, Raouf S Amin, Anjaparavanda P Naren
Cystic Fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it has been discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells...
March 19, 2024: Physiology
https://read.qxmd.com/read/38499276/functional-and-metabolomic-analysis-of-urinary-extracellular-vesicles-from-juvenile-mice-with-renal-compensatory-hypertrophy
#54
JOURNAL ARTICLE
Rasha Aly, Sara Darwish, Niharika Bala, Areej Ebrahim, Lawrence R Shoemaker, Joel McCray, Timothy J Garrett, Abdel A Alli
Unilateral nephrectomy, a procedure reducing kidney mass, triggers a compensatory response in the remaining kidney, increasing its size and function to maintain a normal glomerular filtration rate (GFR). Recent research has highlighted the role of extracellular vesicles (EVs) in renal physiology and disease, although their involvement in unilateral nephrectomy has been underexplored. In this study, unilateral nephrectomy was performed on young mice, and urinary extracellular vesicles (uEVs) characterization and cargo were analyzed...
March 16, 2024: Biochimica et Biophysica Acta. Molecular Basis of Disease
https://read.qxmd.com/read/38498544/vasodilation-and-blood-pressure-lowering-effect-of-3-demethyl-2-geranyl-4-prenylbellidifoline-a-xanthone-obtained-from-garcinia-achachairu-in-hypertensive-rats
#55
JOURNAL ARTICLE
Luísa Nathália Bolda Mariano, Rita de Cássia Vilhena da Silva, Rivaldo Niero, Valdir Cechinel Filho, José Eduardo da Silva-Santos, Priscila de Souza
3-demethyl-2-geranyl-4-prenylbellidifoline (DGP), a natural xanthone isolated from Garcinia achachairu , has previously demonstrated remarkable diuretic and renal protective actions. The present study expands its actions on the cardiovascular system by evaluating its vasorelaxant and blood pressure-lowering effects in spontaneously hypertensive rats (SHRs). Aortic endothelium-intact (E+) preparations of SHRs pre-contracted by phenylephrine and exposed to cumulative concentrations of G. achachairu extract, fractions, and DGP exhibited a significant relaxation compared to vehicle-only exposed rings...
February 15, 2024: Plants (Basel, Switzerland)
https://read.qxmd.com/read/38495109/aav8-vector-induced-gliosis-following-neuronal-transgene-expression
#56
JOURNAL ARTICLE
Faye McLeod, Elaine McDermott, Shermin Mak, Darren Walsh, Mark Turnbull, Fiona E N LeBeau, Andrew Jackson, Andrew J Trevelyan, Gavin J Clowry
INTRODUCTION: Expression of light sensitive ion channels by selected neurons has been achieved by viral mediated transduction with gene constructs, but for this to have therapeutic uses, for instance in treating epilepsy, any adverse effects of viral infection on the cerebral cortex needs to be evaluated. Here, we assessed the impact of adeno-associated virus 8 (AAV8) carrying DNA code for a soma targeting light activated chloride channel/FusionRed (FR) construct under the CKIIa promoter...
2024: Frontiers in Neuroscience
https://read.qxmd.com/read/38494618/xdemvy-tm-lotilaner-ophthalmic-solution-0-25-topical-solution-for-the-treatment-of-demodex-blepharitis
#57
JOURNAL ARTICLE
Aditya K Gupta, Avantika Mann, Kimberly Vincent, William Abramovits
XdemvyTM (lotilaner ophthalmic solution) 0.25% topical solution was recently approved for the treatment of Demodex blepharitis in adults aged ≥18 years. As an antiparasitic agent, lotilaner selectively inhibits gamma-aminobutyric acid chloride channels specific to the parasite and induces spastic paralysis, leading to death of Demodex blepharitis mites. In two randomized, double-masked, vehicle-controlled, multi-center, phase-3 clinical trials (Saturn-1 and Satuirn-2), lotilaner 0.25% topical solution was investigated for the treatment of Demodex blepharitis...
2024: Skinmed
https://read.qxmd.com/read/38493646/microplastics-in-packaged-water-community-stored-water-groundwater-and-surface-water-in-rivers-of-tamil-nadu-after-the-covid-19-pandemic-outbreak
#58
JOURNAL ARTICLE
K Pavithra, Tharmaraj Vairaperumal, Vignesh Ks, Moitraiyee Mukhopadhyay, P Malar, Paromita Chakraborty
The increased load of plastic in waste streams after the COVID-19 pandemic outbreak has increased the possibility of microplastics (MPs) contamination channelling through the rivers and infiltrating the aquatic ecosystems. MPs in packaged water, community-stored water, groundwater, and surface water of Kaveri River (KR), Thamirabarani River (TR), Adyar River (AR), and Cooum River (CR) in Tamil Nadu were therefore investigated about 2 years after the COVID-19 pandemic outbreak. Using μFTIR and μRaman spectroscopy, polyamide, polypropylene, polyethylene, ethylene vinyl alcohol copolymer resin, and polyvinyl chloride were identified as the primary polymer types...
March 16, 2024: Journal of Environmental Management
https://read.qxmd.com/read/38493004/cftr-function-is-impaired-in-a-subset-of-patients-with-pancreatitis-carrying-rare-cftr-variants
#59
JOURNAL ARTICLE
Dora Angyal, Karina Kleinfelder, Fabiana Ciciriello, Tessa A Groeneweg, Giulia De Marchi, Nicolò de Pretis, Laura Bernardoni, Luca Rodella, Francesco Tomba, Paola De Angelis, Cecilia Surace, Emily Pintani, Federico Alghisi, Hugo R de Jonge, Paola Melotti, Claudio Sorio, Vincenzina Lucidi, Marcel J C Bijvelds, Luca Frulloni
BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies...
March 10, 2024: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://read.qxmd.com/read/38484520/polyelectrolyte-modified-black-phosphorus-titania-nanosheet-heterojunction-enhanced-photocatalysis-synergistic-enhancement-effect-of-interface-affinity-and-electron-transport-channel
#60
JOURNAL ARTICLE
Hui Zhao, Derui Liang, Qian Zhang, Zihan Zhang, Xu Ma, Ning Zhang, Menglan Zhao, Yu Wang, Zilin Meng, Hailin Cong
The instability and high electron-hole recombination have limited the application of black phosphorus (BP) as an excellent photocatalyst. To address these challenges, poly dimethyl diallyl ammonium chloride (PDDA), poly (allylamine hydrochloride) (PAH), and polyethyleneimine (PEI) are introduced to the functionalization of BP (F-BP), which can not only enhance its stability, but also boost the carrier transfer. Furthermore, a high-performance heterojunction photocatalyst is fabricated using F-BP and titania nanosheets (TNs) via a layer-by-layer self-assembly approach...
March 11, 2024: Journal of Colloid and Interface Science
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