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Current Opinion in Chemical Biology Oct 2023The long luminescence lifetimes and sharp emission bands of luminescent lanthanide complexes have long been recognized as invaluable strengths for sensing and imaging in... (Review)
Review
The long luminescence lifetimes and sharp emission bands of luminescent lanthanide complexes have long been recognized as invaluable strengths for sensing and imaging in complex aqueous biological or environmental media. Herein we discuss the recent developments of these probes for sensing metal ions and, increasingly, anions. Underappreciated in the field, buffers and metal hydrolysis influence the response of many responsive lanthanide probes. The inherent complexities arising from these interactions are further discussed.
Topics: Lanthanoid Series Elements; Luminescence; Cations; Anions; Luminescent Measurements
PubMed: 37517109
DOI: 10.1016/j.cbpa.2023.102374 -
Pflugers Archiv : European Journal of... Dec 2023Optogenetic actuators are rapidly advancing tools used to control physiology in excitable cells, such as neurons and cardiomyocytes. In neuroscience, these tools have...
Optogenetic actuators are rapidly advancing tools used to control physiology in excitable cells, such as neurons and cardiomyocytes. In neuroscience, these tools have been used to either excite or inhibit neuronal activity. Cell type-targeted actuators have allowed to study the function of distinct cell populations. Whereas the first described cation channelrhodopsins allowed to excite specific neuronal cell populations, anion channelrhodopsins were used to inhibit neuronal activity. To allow for simultaneous excitation and inhibition, opsin combinations with low spectral overlap were introduced. BiPOLES (Bidirectional Pair of Opsins for Light-induced Excitation and Silencing) is a bidirectional optogenetic tool consisting of the anion channel Guillardia theta anion-conducting channelrhodopsin 2 (GtACR2 with a blue excitation spectrum and the red-shifted cation channel Chrimson. Here, we studied the effects of BiPOLES activation in cardiomyocytes. For this, we knocked in BiPOLES into the adeno-associated virus integration site 1 (AAVS1) locus of human-induced pluripotent stem cells (hiPSC), subjected these to cardiac differentiation, and generated BiPOLES expressing engineered heart tissue (EHT) for physiological characterization. Continuous light application activating either GtACR2 or Chrimson resulted in cardiomyocyte depolarization and thus stopped EHT contractility. In contrast, short light pulses, with red as well as with blue light, triggered action potentials (AP) up to a rate of 240 bpm. In summary, we demonstrate that cation, as well as anion channelrhodopsins, can be used to activate stem cell-derived cardiomyocytes with pulsed photostimulation but also to silence cardiac contractility with prolonged photostimulation.
Topics: Humans; Optogenetics; Channelrhodopsins; Myocytes, Cardiac; Anions; Cations
PubMed: 37863976
DOI: 10.1007/s00424-023-02869-x -
The Science of the Total Environment Aug 2023Cellulose can be modified for the loading of functional groups such as amino groups, sulfydryl groups, and carboxyl groups. Cellulose-modified adsorbents generally have...
Cellulose can be modified for the loading of functional groups such as amino groups, sulfydryl groups, and carboxyl groups. Cellulose-modified adsorbents generally have specific adsorption capacities for either heavy metal anions or cations, and possess the advantages of wide raw material source, high modification efficiency, high adsorbent recyclability, and great convenience in recovery of the adsorbed heavy metals. At present, preparation of amphoteric heavy metal adsorbents from lignocellulose has attracted great attention. However, the difference in efficiency of preparing heavy metal adsorbents by modification of various plant straw materials and mechanism for the difference remain to be further explored. In this study, three plant straws, including Eichhornia crassipes (EC), sugarcane bagasse (SB) and metasequoia sawdust (MS), were sequentially modified by tetraethylene-pentamine (TEPA) and biscarboxymethyl trithiocarbonate (BCTTC) to obtain amphoteric cellulosic adsorbents (EC-TB, SB-TB and MS-TB, respectively), which can simultaneously adsorb heavy metal cations or anions. The heavy metal adsorption properties and mechanism before and after modification were compared. Pb(II) and Cr(VI) removal rates by the three adsorbents were 2.2-4.3 folds and 3.0-13.0 folds of those before modification, respectively, following the order of MS-TB > EC-TB > SB-TB. In the five-cycle adsorption-regeneration test, the Pb(II) and Cr(VI) removal rate by MS-TB decreased by 58.1 % and 21.5 %, respectively. Among the three plant straws, MS possessed the most abundant hydroxyl groups and the largest specific surface area (SSA), and accordingly MS-TB had the highest load of adsorption functional groups [(C)NH, (S)CS and (HO)CO] and also the largest SSA among the three adsorbents, which contribute to its highest modification and adsorption efficiency. This study is of great significance for screening suitable raw plant materials to prepare amphoteric heavy metal adsorbents with superior adsorption performance.
Topics: Cellulose; Adsorption; Lead; Saccharum; Metals, Heavy; Plants; Anions; Cations; Eichhornia; Water Pollutants, Chemical; Kinetics
PubMed: 37142006
DOI: 10.1016/j.scitotenv.2023.163887 -
European Journal of Medicinal Chemistry Dec 2023Neutrophils are the most abundant immune cells. However, neutrophil dysregulation leads to acute and chronic inflammation and is involved in various diseases. The aim of...
Neutrophils are the most abundant immune cells. However, neutrophil dysregulation leads to acute and chronic inflammation and is involved in various diseases. The aim of this study was to develop anti-inflammatory agents in human neutrophils. A drug screening was conducted on in-house compounds with the potential to inhibit the respiratory burst, which involves the generation of superoxide anions in human neutrophils. Bioisosteric replacement was then applied to design more active derivatives. The most potent inhibitors of superoxide anion generation activity were compounds 58 and 59, which had IC values of 13.30 and 9.06 nM, respectively. The inhibitory effects of 58 and 59 were reversed by H89, a PKA inhibitor. PDE selective screening indicated that the best inhibitory effects were PDE4B1 and PDE4D2, and the inhibitory activities were 83% and 85%, respectively, at a 10 μM concentration of 59. The final molecular simulation experiment highlighted the slightly different binding poses of 58 and 59 in the PDE4 active site. An in vivo pharmacokinetic study revealed that the half-life of 59 was approximately 79 min when using intravenous bolus administration. This work introduced a new class structure of PDE4 inhibitors resulting in potent neutrophil inactivation activity, with the aim of contributing to new anti-inflammatory drug discovery.
Topics: Humans; Superoxides; Anti-Inflammatory Agents; Phosphodiesterase 4 Inhibitors; Inflammation; Pyrazoles; Neutrophils
PubMed: 37918036
DOI: 10.1016/j.ejmech.2023.115874 -
Scientific Reports Nov 2023Acetylation could improve the bioavailability of (-)-Epigallocatechin-3-Gallate (EGCG), but the relationship of substitution degree and antioxidant capacity of...
Acetylation could improve the bioavailability of (-)-Epigallocatechin-3-Gallate (EGCG), but the relationship of substitution degree and antioxidant capacity of acetylated EGCG was unclear. The acetylated EGCG products were separated by preparation high performance liquid chromatography (HPLC). Two mono substituted acetylated EGCG, three substituted acetylated EGCG (T-AcE), eight substituted acetylated EGCG (E-AcE) and (-)-Epigallocatechin gallate (EGCG) were isolated. The 7-acetyl-EGCG (S7-ACEGCG) and 7-acetyl-EGCG (T-AcE) were identified for the first time. The antioxidant capacity, superoxide anion radical scavenging capacities, and hydroxyl radical scavenging capacities of EGCG decreased significantly after acetylation modification. The more EGCG acetylation modification sites, the lower the total antioxidant capacity, superoxide anion radical scavenging capacities, and hydroxyl radical scavenging capacities. The antioxidant capacity, superoxide anion radical scavenging capacities, and hydroxyl radical scavenging capacities of 5-acetyl-EGCG (S5-ACE) were higher than 7-acetyl-EGCG (S7-AcE). Combining all the results in this and previous studies, acetylation modification is not conducive to the performance of EGCG antioxidant capacity.
Topics: Antioxidants; Superoxides; Hydroxyl Radical; Catechin
PubMed: 38017306
DOI: 10.1038/s41598-023-48387-9 -
Molecules (Basel, Switzerland) Oct 2023The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts,...
The formulation of magnetic ionic liquids (MILs) or organic salts based on lanthanides as anions has been explored. In this work, a set of choline-family-based salts, and two other, different cation families, were combined with Gadolinium(III) and Terbium(III) anions. Synthetic methodologies were previously optimized, and all organic salts were obtained as solids with melting temperatures higher than 100 °C. The magnetic moments obtained for the Gd(III) salts were, as expected, smaller than those obtained for the Tb(III)-based compounds. The values for Gd(III) and Tb(III) magnetic salts are in the range of 6.55-7.30 MB and 8.22-9.34 MB, respectively. It is important to note a correlation between the magnetic moments obtained for lanthanides, and the structural features of the cation. The cytotoxicity of lanthanide-based salts was also evaluated using 3T3, 293T, Caco2, and HepG2 cells, and it was revealed that most of the prepared compounds are not toxic.
Topics: Humans; Lanthanoid Series Elements; Salts; Caco-2 Cells; Anions; Cations
PubMed: 37894633
DOI: 10.3390/molecules28207152 -
ACS Sensors Aug 2023We report here a small library of a new type of acyclic squaramide receptors (-) as selective ionophores for the detection of ketoprofen and naproxen anions (KF and NS,...
We report here a small library of a new type of acyclic squaramide receptors (-) as selective ionophores for the detection of ketoprofen and naproxen anions (KF and NS, respectively) in aqueous media. H NMR binding studies show a high affinity of these squaramide receptors toward KF and NS, suggesting the formation of H-bonds between the two guests and the receptors through indole and -NH groups. Compounds - have been tested as ionophores for the detection of KF and NS inside solvent PVC-based polymeric membranes. The optimal membrane compositions were established through the careful variation of the ligand/tridodecylmethylammonium chloride (TDMACl) anion-exchanger ratio. All of the tested acyclic squaramide receptors - have high affinity toward KF and NS and anti-Hofmeister selectivity, with and showing the highest sensitivity and selectivity to NS. The utility of the developed sensors for a high precision detection of KF in pharmaceutical compositions with low relative errors of analysis (RSD, 0.99-1.4%) and recoveries, %, in the range 95.1-111.8% has been demonstrated. Additionally, the chemometric approach has been involved to effectively discriminate between the structurally very similar KF and NS, and the possibility of detecting these analytes at concentrations as low as 0.07 μM with of 0.947 and at 0.15 μM with of 0.919 for NS and KF, respectively, was shown.
Topics: Ionophores; Anions; Quinine
PubMed: 37530141
DOI: 10.1021/acssensors.3c00981 -
ACS Applied Bio Materials Nov 2023Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule...
Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule nanocomplexes are promising drug carriers due to their simple and all-aqueous manufacturing process. However, these systems can present issues of colloidal instability over time and cellular toxicity due to the cationic polymer. In this study, we finely modulate the formation parameters of poly(allylamine-tripolyphosphate) complexes to jointly optimize the robustness and safety. Polyallylamine was ionically assembled with tripolyphosphate anions to form liquid-like nanocomplexes with a size of around 200 nm and a zeta potential of -30 mV. We found that nanocomplexes exhibit tremendous long-term stability (9 months of storage) in colloidal dispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced by tripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. In addition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, these nanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immune system activation.
Topics: Allylamine; Polyphosphates; Drug Carriers; Polymers
PubMed: 37863908
DOI: 10.1021/acsabm.3c00489 -
American Journal of Physiology. Renal... Sep 2023The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized....
The urinary potassium (K) excretion machinery is upregulated with increasing dietary K, but the role of accompanying dietary anions remains inadequately characterized. Poorly absorbable anions, including [Formula: see text], are thought to increase K secretion through a transepithelial voltage effect. Here, we tested if they also influence the K secretion machinery. Wild-type mice, aldosterone synthase (AS) knockout (KO) mice, or pendrin KO mice were randomized to control, high-KCl, or high-KHCO diets. The K secretory capacity was assessed in balance experiments. Protein abundance, modification, and localization of K-secretory transporters were evaluated by Western blot analysis and confocal microscopy. Feeding the high-KHCO diet increased urinary K excretion and the transtubular K gradient significantly more than the high-KCl diet, coincident with more pronounced upregulation of epithelial Na+ channels (ENaC) and renal outer medullary K (ROMK) channels and apical localization in the distal nephron. Experiments in AS KO mice revealed that the enhanced effects of [Formula: see text] were aldosterone independent. The high-KHCO diet also uniquely increased the large-conductance Ca-activated K (BK) channel β-subunit, stabilizing BKα on the apical membrane, the Cl/[Formula: see text] exchanger, pendrin, and the apical KCl cotransporter (KCC3a), all of which are expressed specifically in pendrin-positive intercalated cells. Experiments in pendrin KO mice revealed that pendrin was required to increase K excretion with the high-KHCO diet. In summary, [Formula: see text] stimulates K excretion beyond a poorly absorbable anion effect, upregulating ENaC and ROMK in principal cells and BK, pendrin, and KCC3a in pendrin-positive intercalated cells. The adaptive mechanism prevents hyperkalemia and alkalosis with the consumption of alkaline ash-rich diets but may drive K wasting and hypokalemia in alkalosis. Dietary anions profoundly impact K homeostasis. Here, we found that a K-rich diet, containing [Formula: see text] as the counteranion, enhances the electrogenic K excretory machinery, epithelial Na channels, and renal outer medullary K channels, much more than a high-KCl diet. It also uniquely induces KCC3a and pendrin, in B-intercalated cells, providing an electroneutral KHCO secretion pathway. These findings reveal new K balance mechanisms that drive adaption to alkaline and K-rich foods, which should guide new treatment strategies for K disorders.
Topics: Animals; Mice; Alkalosis; Anion Transport Proteins; Anions; Diet; Mice, Knockout; Potassium; Potassium, Dietary; Sodium; Sulfate Transporters
PubMed: 37498547
DOI: 10.1152/ajprenal.00193.2023 -
The Journal of Physical Chemistry. B Apr 2024Since Hofmeister's seminal studies in the late 19th century, it has been known that salts and buffers can drastically affect the properties of peptides and proteins....
Since Hofmeister's seminal studies in the late 19th century, it has been known that salts and buffers can drastically affect the properties of peptides and proteins. These Hofmeister effects can be conceived of in terms of three distinct phenomena/mechanisms: water-salt interactions that indirectly induce the salting-out of a protein by water sequestration by the salt, and direct salt-protein interactions that can either salt-in or salt-out the protein. Unfortunately, direct salt-protein interactions responsible for Hofmeister effects are weak and difficult to quantify. As such, they are frequently construed of as being nonspecific. Nevertheless, there has been considerable effort to better specify these interactions. Here, we use pentapeptides to demonstrate the utility of the H-dimension of nuclear magnetic resonance (NMR) spectroscopy to assess anion binding using N-H signal shifts. We qualify binding using these, demonstrating the upfield shifts induced by anion association and revealing how they are much larger than the corresponding downfield shifts induced by magnetic susceptibility and other ionic strength change effects. We also qualify binding in terms of how the pattern of signal shifts changes with point mutations. In general, we find that the observed upfield shifts are small compared with those induced by anion binding to amide-based hosts, and MD simulations suggest that this is so. Thus, charge-diffuse anions associate mostly with the nonpolar regions of the peptide rather than directly interacting with the amide N-H groups. These findings reveal the utility of H NMR spectroscopy for qualifying affinity to peptides─even when affinity constants are very low─and serve as a benchmark for using NMR spectroscopy to study anion binding to more complex systems.
Topics: Peptides; Anions; Proteins; Amides; Sodium Chloride; Water
PubMed: 38592238
DOI: 10.1021/acs.jpcb.4c00657