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1.
Environ Sci Pollut Res Int ; 31(49): 59592-59609, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39361204

RESUMEN

Fungal biomass is as a cost-effective and sustainable biosorbent utilized in both active and inactive forms. This study investigated the efficacy of inactivated and dried biomass of Fusarium sp. in adsorbing Ni2+ and Pb2+ from aqueous solutions. The strain underwent sequential cultivation and was recovered by filtration. Then, the biomass was dried in an oven at 80 ± 2 °C and sieved using a 0.1-cm mesh. The biosorbent was thoroughly characterized, including BET surface area analysis, morphology examination (SEM), chemical composition (XRF and FT-IR), thermal behavior (TGA), and surface charge determination (pH-PZC and zeta potential). The biosorption mechanism was elucidated by fitting equilibrium models of kinetics, isotherm, and thermodynamic to the data. The biosorbent exhibited a neutral charge, a rough surface, a relatively modest surface area, appropriate functional groups for adsorption, and thermal stability above 200 °C. Optimal biosorption was achieved at 25 ± 2 °C, using 0.05 g of adsorbent per 50 mL of metallic ion solution at initial concentrations ranging from 0.5 to 2.0 mg L-1 and at pH 4.5 for Pb2+ and Ni2+. Biosorption equilibrium was achieved after 240 min for Ni2+ and 1440 min for Pb2+. The process was spontaneous, mainly through chemisorption, in monolayer for Ni2+ and multilayer for Pb2+, with efficiencies of over 85% for both metallic ion removal. These findings underscore the potential of inactive and dry Fusarium sp. biomass (IDFB) as a promising material for the biosorption of Ni2+ and Pb2+.


Asunto(s)
Biomasa , Fusarium , Plomo , Níquel , Termodinámica , Fusarium/metabolismo , Níquel/química , Cinética , Adsorción , Contaminantes Químicos del Agua/química
2.
Artículo en Inglés | MEDLINE | ID: mdl-39280840

RESUMEN

Background: Acid-sensing ion channel 1a (ASIC1a) plays a critical role in physiological and pathological processes. To further elucidate the biological functions of ASICs and their relationships with disease occurrence and development, it is advantageous to investigate and develop additional regulatory factors for ASICs. Methods: In this study, cation exchange chromatography was used to separate seven chromatographic components from Naja naja atra venom. Capillary electrophoresis was employed to detect that Ⅶ peak component containing a main protein Ⅶ-2, which could bind to ASIC1a. The analgesic effects of Ⅶ-2 protein were determined using hot plate methods, and ASIC1a expression in spinal cord tissue from rats with inflammatory pain was detected using western blot. Results: The purified Ⅶ-2 protein named Naja naja atra venom-Ⅶ-2 (NNAV-Ⅶ-2) was obtained by Sephadex G-50 gel filtration, which exhibited a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with a molecular weight of 6.7 kD. Remarkably, the NNAV-Ⅶ-2 protein demonstrated a significant analgesic effect and downregulated ASIC1a expression in the spinal cord tissue of rats with inflammatory pain. Conclusions: The analgesic mechanism of the NNAV-Ⅶ-2 protein may be associated with its binding to ASIC1a, consequently downregulating ASIC1a expression in neural tissues.

3.
Molecules ; 29(16)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39203022

RESUMEN

Currently, antimicrobial resistance (AMR) is a serious health problem in the world, mainly because of the rapid spread of multidrug-resistant (MDR) bacteria. These include bacteria that produce ß-lactamases, which confer resistance to ß-lactams, the antibiotics with the most prescriptions in the world. Carbapenems are particularly noteworthy because they are considered the ultimate therapeutic option for MDR bacteria. However, this group of antibiotics can also be hydrolyzed by ß-lactamases, including metallo-ß-lactamases (MBLs), which have one or two zinc ions (Zn2+) on the active site and are resistant to common inhibitors of serine ß-lactamases, such as clavulanic acid, sulbactam, tazobactam, and avibactam. Therefore, the design of inhibitors against MBLs has been directed toward various compounds, with groups such as nitrogen, thiols, and metal-binding carboxylates, or compounds such as bicyclic boronates that mimic hydrolysis intermediates. Other compounds, such as dipicolinic acid and aspergillomarasmin A, have also been shown to inhibit MBLs by chelating Zn2+. In fact, recent inhibitors are based on Zn2+ chelation, which is an important factor in the mechanism of action of most MBL inhibitors. Therefore, in this review, we analyzed the current strategies for the design and mechanism of action of metal-ion-binding inhibitors that combat MDR bacteria.


Asunto(s)
Zinc , Inhibidores de beta-Lactamasas , beta-Lactamasas , Inhibidores de beta-Lactamasas/química , Inhibidores de beta-Lactamasas/farmacología , beta-Lactamasas/metabolismo , beta-Lactamasas/química , Zinc/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Metales/química , Bacterias/efectos de los fármacos , Bacterias/enzimología
4.
Adv Neurobiol ; 37: 83-121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39207688

RESUMEN

Microglial cells are the most receptive cells in the central nervous system (CNS), expressing several classes of receptors reflecting their immune heritage and newly acquired neural specialisation. Microglia possess, depending on the particular context, receptors to neurotransmitters and neuromodulators as well as immunocompetent receptors. This rich complement allows microglial cells to monitor the functional status of the nervous system, contribute actively to the regulation of neural activity and plasticity and homeostasis, and guard against pathogens as well as other challenges to the CNS's integrity and function.


Asunto(s)
Microglía , Microglía/metabolismo , Humanos , Animales , Sistema Nervioso Central/metabolismo , Plasticidad Neuronal/fisiología
5.
Environ Sci Pollut Res Int ; 31(38): 50857-50873, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39098971

RESUMEN

In this study, four Brazilian clays (Bofe, Verde-lodo, commercial Fluidgel, and expanded commercial vermiculite) were evaluated for their adsorptive capacity and removal percentage in relation to different toxic metals (Ni2+, Cd2+, Zn2+, and Cu2+). The best results were obtained by expanded vermiculite, with cadmium removal reaching values of 95%. The most promising clay was modified by the sodification process, and the metal cadmium was used to evaluate the ion exchange process. The clays expanded vermiculite (EV) and VNa-sodified vermiculite were evaluated by equilibrium study at 25, 35, and 45 °C. At 25 °C, EV obtained a maximum adsorption capacity of 0.368 mmol/g and sodified vermiculite 0.480 mmol/g, which represents an improvement of 30.4% in modified clay capacity. At 45 °C, the sodified vermiculite reached 0.970 mmol/g adsorption capacity. The Langmuir, Redlich-Peterson Freundlich, and Dubinin-Raduskevich models were adjusted to the results. Langmuir provided the best fit among the models. The thermodynamic quantities (ΔS, ΔH, and ΔG) demonstrated that the process is spontaneous and endothermic and the metal is captured by physisorption and chemisorption in the studied temperature range. For the ion exchange equilibrium, the binary Langmuir and binary Langmuir-Freundlich models were adjusted to the expanded vermiculite and sodified vermiculite isotherms, respectively. Both models were predictive. Thermal analysis indicated good heat resistance even after material modification. The apparent and real densities demonstrated that after each treatment or contamination, the clayey material undergoes contraction in its structure. An improved efficiency of the adsorbent was found after sodification.


Asunto(s)
Silicatos de Aluminio , Arcilla , Termodinámica , Adsorción , Arcilla/química , Brasil , Intercambio Iónico , Silicatos de Aluminio/química , Contaminantes Químicos del Agua/química , Metales/química
6.
J Mech Behav Biomed Mater ; 158: 106678, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096683

RESUMEN

OBJECTIVE: Analyze the effects of the functionalization of pre-functionalized GIC particles with chlorhexidine on the physicochemical properties and antimicrobial activity. MATERIALS AND METHODS: Four groups were prepared: (1) GIC (Bioglass R - Biodinamica) - control group; (2) GIC-CHX 1%: Group containing 1% pre-reacted CHX particles; (3) GIC-CHX 2.5%: Group containing 2.5% pre-reacted CHX particles; (4) GIC-CHX 5%: Group containing 5% pre-reacted CHX particles. Hourglass-shaped specimens (10 mm × 2 mm x 1 mm) were fabricated for mechanical tests including cohesive strength (n = 12), modulus of elasticity (n = 12) and microhardness (n = 10). Discs (10 mm × 2 mm) were prepared for the analysis of Ca+2, PO4- and F- ions release (n = 3), and roughness (n = 12). To evaluate the setting time, a Gilmore needle was used according to ISO 9917-1:2016. Disk-shaped specimens (5 × 1mm) were manufactured and subjected to bacterial activity (n = 9) (Streptococcus mutans ATCC 159). RESULTS: Modulus, roughness, setting time and ions release (Ca+2, PO4-, and F-) there were no statistically significant differences among the groups (p > 0.05). The setting time did not change with the incorporation of CHX. The GIC-CHX 2.5% and GIC-CHX 5% groups exhibited superior antibacterial activity compared to the control group and GIC-CHX 1% (p < 0.001). The GIC-CHX 5% group showed the highest microhardness values (p < 0.041), cohesive strength (p < 0.009) when compared to the control group. CONCLUSION: The pre-reacted CHX in GICs was able to confer antimicrobial activity, improve cohesive strength, microhardness, and did not impair ion release, setting time, and roughness.


Asunto(s)
Clorhexidina , Cementos de Ionómero Vítreo , Ensayo de Materiales , Clorhexidina/química , Clorhexidina/farmacología , Cementos de Ionómero Vítreo/química , Cementos de Ionómero Vítreo/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Streptococcus mutans/efectos de los fármacos , Dureza , Fenómenos Mecánicos , Propiedades de Superficie , Fenómenos Químicos , Antibacterianos/farmacología , Antibacterianos/química
7.
Front Cell Dev Biol ; 12: 1414935, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108834

RESUMEN

Ion channels are integral membrane proteins mediating ion flow in response to changes in their environment. Among the different types of ion channels reported to date, the super-family of TRP channels stands out since its members have been linked to many pathophysiological processes. The family comprises 6 subfamilies and 28 members in mammals, which are widely distributed throughout most tissues and organs and have an important role in several aspects of cellular physiology. It has been evidenced that abnormal expression, post-translational modifications, and channel trafficking are associated with several pathologies, such as cancer, cardiovascular disease, diabetes, and brain disorders, among others. In this review, we present an updated summary of the mechanisms involved in the subcellular trafficking of TRP channels, with a special emphasis on whether different post-translational modifications and naturally occurring mutagenesis affect both expression and trafficking. Additionally, we describe how such changes have been associated with the development and progress of diverse pathologies associated with the gain or loss of functional phenotypes. The study of these processes will not only contribute to a better understanding the role of TRP channels in the different tissues but will also present novel possible therapeutic targets in diseases where their activity is dysregulated.

8.
Chempluschem ; : e202400486, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196606

RESUMEN

Photo-switchable coatings for lithium ion batteries (LIB) can offer the possibility to control the diffusion processes from the electrode materials to the electrolyte and thus, for example, reducing the energy loss in the fully charged state. Fulgide derivatives, as known photo-switches, are investigated concerning their use as coating for vanadium pentoxide, a potential cathode material for LIB. With the help of Density Functional Theory calculations, two fulgide derivatives are characterized with respect to their photophysics, their aggregation behaviour on the cathode material and the ability to form self-assembled monolayers (SAM). Furthermore, the two states of the photo-switchable coating are tested with respect to lithium diffusion from the cathode material, passing the SAM and entering the electrolyte. We found a difference for the energy barriers depending on the state of the photo-switch, preferring its closed form. This behaviour can be used to prevent the loss of charge in batteries of portable devices.

9.
Cell Mol Life Sci ; 81(1): 337, 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39120784

RESUMEN

The α9α10 nicotinic cholinergic receptor (nAChR) is a ligand-gated pentameric cation-permeable ion channel that mediates synaptic transmission between descending efferent neurons and mechanosensory inner ear hair cells. When expressed in heterologous systems, α9 and α10 subunits can assemble into functional homomeric α9 and heteromeric α9α10 receptors. One of the differential properties between these nAChRs is the modulation of their ACh-evoked responses by extracellular calcium (Ca2+). While α9 nAChRs responses are blocked by Ca2+, ACh-evoked currents through α9α10 nAChRs are potentiated by Ca2+ in the micromolar range and blocked at millimolar concentrations. Using chimeric and mutant subunits, together with electrophysiological recordings under two-electrode voltage-clamp, we show that the TM2-TM3 loop of the rat α10 subunit contains key structural determinants responsible for the potentiation of the α9α10 nAChR by extracellular Ca2+. Moreover, molecular dynamics simulations reveal that the TM2-TM3 loop of α10 does not contribute to the Ca2+ potentiation phenotype through the formation of novel Ca2+ binding sites not present in the α9 receptor. These results suggest that the TM2-TM3 loop of α10 might act as a control element that facilitates the intramolecular rearrangements that follow ACh-evoked α9α10 nAChRs gating in response to local and transient changes of extracellular Ca2+ concentration. This finding might pave the way for the future rational design of drugs that target α9α10 nAChRs as otoprotectants.


Asunto(s)
Calcio , Receptores Nicotínicos , Animales , Ratas , Acetilcolina/metabolismo , Acetilcolina/farmacología , Secuencia de Aminoácidos , Sitios de Unión , Calcio/metabolismo , Simulación de Dinámica Molecular , Técnicas de Placa-Clamp , Subunidades de Proteína/metabolismo , Subunidades de Proteína/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/química , Xenopus laevis
10.
Front Pharmacol ; 15: 1408156, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119605

RESUMEN

One of the reasons to suggest olive oil consumption for a healthy life is its potential to induce robust lipidomic remodeling through membrane modification by dietary lipids. This remodeling might, in turn, modulate essential lipid-protein interactions while maintaining accurate transmembrane protein/domain orientation. Oleic acid, the primary compound in olive oil, has been suggested as a modulator of ion channel function. In this study, we explored whether this lipid could rescue the trafficking of mutated transmembrane proteins. In our initial approach, we supplemented the cell culture medium of HEK-293 cells expressing cyclic nucleotide channels tagged using green fluorescent protein (CNG-GFP) with olive oil or oleic acid. In addition to wild-type channels, we also expressed R272Q and R278W mutant channels, two non-functional intracellularly retained channels related to retinopathies. We used fluorescence microscopy and patch-clamp in the inside-out configuration to assess changes in the cell localization and function of the tested channels. Our results demonstrated that olive oil and oleic acid facilitated the transport of cyclic nucleotide-gated R272Q mutant channels towards the plasma membrane, rendering them electrophysiologically functional. Thus, our findings reveal a novel property of olive oil as a membrane protein traffic inductor.

11.
Br J Pharmacol ; 181(22): 4546-4570, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39081110

RESUMEN

BACKGROUND AND PURPOSE: Gastrointestinal tumours overexpress voltage-gated calcium (CaV3) channels (CaV3.1, 3.2 and 3.3). CaV3 channels regulate cell growth and apoptosis colorectal cancer. Gossypol, a polyphenolic aldehyde found in the cotton plant, has anti-tumour properties and inhibits CaV3 currents. A systematic study was performed on gossypol blocking mechanism on CaV3 channels and its potential anticancer effects in colon cancer cells, which express CaV3 isoforms. EXPERIMENTAL APPROACH: Transcripts for CaV3 proteins were analysed in gastrointestinal cancers using public repositories and in human colorectal cancer cell lines HCT116, SW480 and SW620. The gossypol blocking mechanism on CaV3 channels was investigated by combining heterologous expression systems and patch-clamp experiments. The anti-tumoural properties of gossypol were estimated by cell proliferation, viability and cell cycle assays. Ca2+ dynamics were evaluated with cytosolic and endoplasmic reticulum (ER) Ca2+ indicators. KEY RESULTS: High levels of CaV3 transcripts correlate with poor prognosis in gastrointestinal cancers. Gossypol blockade of CaV3 isoforms is concentration- and use-dependent interacting with the closed, activated and inactivated conformations of CaV3 channels. Gossypol and CaV3 channels down-regulation inhibit colorectal cancer cell proliferation by arresting cell cycles at the G0/G1 and G2/M phases, respectively. CaV3 channels underlie the vectorial Ca2+ uptake by endoplasmic reticulum in colorectal cancer cells. CONCLUSION AND IMPLICATIONS: Gossypol differentially blocked CaV3 channel and its anticancer activity was correlated with high levels of CaV3.1 and CaV3.2 in colorectal cancer cells. The CaV3 regulates cell proliferation and Ca2+ dynamics in colorectal cancer cells. Understanding this blocking mechanism maybe improve cancer therapies.


Asunto(s)
Bloqueadores de los Canales de Calcio , Canales de Calcio Tipo T , Proliferación Celular , Neoplasias del Colon , Gosipol , Humanos , Gosipol/farmacología , Gosipol/análogos & derivados , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Proliferación Celular/efectos de los fármacos , Canales de Calcio Tipo T/metabolismo , Canales de Calcio Tipo T/genética , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Calcio/metabolismo , Línea Celular Tumoral , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Antineoplásicos/farmacología
12.
Dent Mater ; 40(10): 1507-1514, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39048463

RESUMEN

OBJECTIVE: To evaluate experimental dimethacrylate-based materials containing calcium orthophosphates or calcium silicate particles in terms of their optical, mechanical and Ca2+ release behaviour. METHODS: Dicalcium phosphate dihydrate (DCPD), hydroxyapatite (HAp), beta-tricalcium phosphate (ß-TCP) or calcium silicate (CaSi) particles were added to a photocurable BisGMA/TEGDMA resin (1:1 in mols) at a 30 vol% fraction. Materials containing silanized or non-silanized barium glass particles were used as controls. Degree of conversion (DC) at the top and base of 2-mm thick specimens was determined by ATR-FTIR spectroscopy (n = 5). Translucency parameter (TP) and transmittance (%T) were determined using a spectrophotometer (n = 3). Biaxial flexural strength (BFS) and flexural modulus (FM) were determined by biaxial flexural testing after 24 h storage in water (n = 10). Ca2+ release in water was determined during 28 days by inductively coupled plasma optical emission spectrometry (n = 3). Statistical analysis was performed using ANOVA/Tukey test (DC: two-way; TP, %T; BFS and FM: one-way; Ca2+ release: repeated measures two-way, α = 5 %). RESULTS: CaSi and ß-TCP particles drastically reduced DC at 2 mm, TP and %T (p < 0.001). Compared to both controls, all Ca2+-releasing materials presented lower BFS (p < 0.001) and only the material with DCPD showed significantly lower FM (p < 0.05). The material containing CaSi presented the highest Ca2+ release, while among materials formulated with calcium orthophosphates the use of DCPD resulted in the highest release (p < 0.001). SIGNIFICANCE: CaSi particles allowed the highest Ca2+ release. Notwithstanding, the use of DCPD resulted in a material with the best compromise between optical behaviour, DC, strength and Ca2+ release.


Asunto(s)
Compuestos de Calcio , Fosfatos de Calcio , Ensayo de Materiales , Silicatos , Silicatos/química , Compuestos de Calcio/química , Fosfatos de Calcio/química , Espectroscopía Infrarroja por Transformada de Fourier , Durapatita/química , Resistencia Flexional , Ácidos Polimetacrílicos/química , Polietilenglicoles/química , Bisfenol A Glicidil Metacrilato/química , Resinas Compuestas/química , Vidrio/química , Calcio/química , Espectrofotometría , Fenómenos Químicos , Dióxido de Silicio , Compuestos de Bario
13.
Polymers (Basel) ; 16(14)2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39065309

RESUMEN

Additive manufacturing (AM), commonly known as 3D printing, allows for the manufacturing of complex systems that are not possible using traditional manufacturing methods. Nevertheless, some disadvantages are attributed to AM technologies. One of the most often referred to is the defects of the produced components, particularly the porosity. One approach to solving this problem is to consider it as a non-problem, i.e., taking advantage of the defects. Commercially, LAY-FOMM®60 polymer was successfully used in AM through a material extrusion process. This filament is a blend of two polymers, one of them soluble in water, allowing, after its removal from the printed components, the increase in porosity. The defects produced were exploited to evaluate the metallic ion removal capacity of manufactured components using non-potable tap water. Two experimental setups, continuous and ultrasound-assisted methods, were compared, concerning their water cleaning capacity. Results revealed that continuous setup presented the highest metallic ion removal capacity (>80%) for the following three studied metallic ions: iron, copper, and zinc. High water swelling capacity (~80%) and the increase in porosity of 3D-printed parts played a significant role in the ion sorption capacity. The developed strategy could be considered a custom and affordable alternative to designing complex filtration/separation systems for environmental and wastewater treatment applications.

14.
Pharmaceuticals (Basel) ; 17(7)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-39065722

RESUMEN

Mefloquine (MQ) is an antimalarial medication prescribed to treat or malaria prevention.. When taken by children, vomiting usually occurs, and new doses of medication frequently need to be taken. So, developing pediatric medicines using taste-masked antimalarial drug complexes is mandatory for the success of mefloquine administration. The hypothesis that binding mefloquine to an ion-exchange resin (R) could circumvent the drug's bitter taste problem was proposed, and solid-state 13C cross-polarization magic angle spinning (CPMAS) NMR was able to follow MQ-R mixtures through chemical shift and relaxation measurements. The nature of MQ-R complex formation could then be determined. Impedimetric electronic tongue equipment also verified the resinate taste-masking efficiency in vitro. Variations in chemical shifts and structure dynamics measured by proton relaxation properties (e.g., T1ρH) were used as probes to follow the extension of mixing and specific interactions that would be present in MQ-R. A significant decrease in T1ρH values was observed for MQ carbons in MQ-R complexes, compared to the ones in MQ (from 100-200 ms in MQ to 20-50 ms in an MQ-R complex). The results evidenced that the cationic resin interacts strongly with mefloquine molecules in the formulation of a 1:1 ratio complex. Thus, 13C CPMAS NMR allowed the confirmation of the presence of a binding between mefloquine and polacrilin in the MQ-R formulation studied.

15.
Acta Crystallogr C Struct Chem ; 80(Pt 8): 349-356, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38984908

RESUMEN

The synthesis, crystal structure and magnetic properties of an oxamate-containing erbium(III) complex, namely, tetrabutylammonium aqua[N-(2,4,6-trimethylphenyl)oxamato]erbium(III)-dimethyl sulfoxide-water (1/3/1.5), (C16H36N)[Er(C11H12NO3)4(H2O)]·3C2H6OS·1.5H2O or n-Bu4N[Er(Htmpa)4(H2O)]·3DMSO·1.5H2O (1), are reported. The crystal structure of 1 reveals the occurrence of an erbium(III) ion, which is surrounded by four N-phenyl-substituted oxamate ligands and one water molecule in a nine-coordinated environment, together with one tetrabutylammonium cation acting as a counter-ion, and one water and three dimethyl sulfoxide (DMSO) molecules of crystallization. Variable-temperature static (dc) and dynamic (ac) magnetic measurements were carried out for this mononuclear complex, revealing that it behaves as a field-induced single-ion magnet (SIM) below 5.0 K.

16.
Function (Oxf) ; 5(5)2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-38984987

RESUMEN

Polycystic kidney disease (PKD), a disease characterized by the enlargement of the kidney through cystic growth is the fourth leading cause of end-stage kidney disease world-wide. Transient receptor potential Vanilloid 4 (TRPV4), a calcium-permeable TRP, channel participates in kidney cell physiology and since TRPV4 forms complexes with another channel whose malfunction is associated to PKD, TRPP2 (or PKD2), we sought to determine whether patients with PKD, exhibit previously unknown mutations in TRPV4. Here, we report the presence of mutations in the TRPV4 gene in patients diagnosed with PKD and determine that they produce gain-of-function (GOF). Mutations in the sequence of the TRPV4 gene have been associated to a broad spectrum of neuropathies and skeletal dysplasias but not PKD, and their biophysical effects on channel function have not been elucidated. We identified and examined the functional behavior of a novel E6K mutant and of the previously known S94L and A217S mutant TRVP4 channels. The A217S mutation has been associated to mixed neuropathy and/or skeletal dysplasia phenotypes, however, the PKD carriers of these variants had not been diagnosed with these reported clinical manifestations. The presence of certain mutations in TRPV4 may influence the progression and severity of PKD through GOF mechanisms. PKD patients carrying TRVP4 mutations are putatively more likely to require dialysis or renal transplant as compared to those without these mutations.


Asunto(s)
Enfermedades Renales Poliquísticas , Canales Catiónicos TRPV , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo , Humanos , Enfermedades Renales Poliquísticas/genética , Enfermedades Renales Poliquísticas/patología , Mutación , Femenino , Masculino , Células HEK293 , Mutación con Ganancia de Función , Canales Catiónicos TRPP/genética , Adulto
17.
Methods Mol Biol ; 2796: 97-103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38856897

RESUMEN

The development of cell-based fluorescent assays has resulted in an incredible tool for searching new ion channels' modulators with a biophysical and clinical profile. Among all the ion channels, potassium (K+)-permeable channels represent the most diverse and relevant for cell function, making them attractive targets for drug discovery. Some of the cell-based assays for K+ channels take advantage of a thallium-sensitive dye whose fluorescence increased upon the binding of thallium (Tl+), an ion able to move through K+ channels. We optimize the FLIPR Potassium Assay Kit based on thallium influx to measure the Kv10.1 activity.


Asunto(s)
Talio , Talio/metabolismo , Humanos , Colorantes Fluorescentes/química , Células HEK293 , Fluorescencia , Canales de Potasio Éter-A-Go-Go
18.
Ecotoxicology ; 33(7): 683-696, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38861073

RESUMEN

Silver nanoparticles (AgNPs) are among the most produced nanomaterials in the world and are incorporated into several products due to their biocide and physicochemical properties. Since freshwater bodies are AgNPs main final sink, several consequences for biota are expected to occur. With the hypothesis that AgNPs can interact with environmental factors, we analyzed their ecotoxicity in combination with humic acids and algae. In addition to the specific AgNPs behavior in the media, we analyzed the mortality, growth, and phototactic behavior of Chydorus eurynotus (Cladocera) as response variables. While algae promoted Ag+ release, humic acids reduced it by adsorption, and their combination resulted in an intermediated Ag+ release. AgNPs affected C. eurynotus survival and growth, but algae and humic acids reduced AgNPs lethality, especially when combined. The humic acids mitigated AgNP effects in C. eurynotus growth, and both factors improved its phototactic behavior. It is essential to deepen the study of the isolated and combined influences of environmental factors on the ecotoxicity of nanoparticles to achieve accurate predictions under realistic exposure scenarios.


Asunto(s)
Cladóceros , Sustancias Húmicas , Nanopartículas del Metal , Plata , Contaminantes Químicos del Agua , Plata/toxicidad , Nanopartículas del Metal/toxicidad , Animales , Contaminantes Químicos del Agua/toxicidad , Cladóceros/efectos de los fármacos , Cladóceros/fisiología
19.
ACS Nano ; 18(28): 18572-18583, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38941562

RESUMEN

Solid-state nanochannels (SSNs) have emerged as promising platforms for controlling ionic transport at the nanoscale. SSNs are highly versatile, and this feature can be enhanced through their combination with porous materials such as Metal-Organic Frameworks (MOF). By selection of specific building blocks and experimental conditions, different MOF architectures can be obtained, and this can influence the ionic transport properties through the nanochannel. Herein, we study the effects of confined synthesis of Zr-based UiO-66 MOF on the ion transport properties of single bullet-shaped poly(ethylene terephthalate) (PET) nanochannels. We have found that emerging textural properties from the MOF phase play a determinant role in controlling ionic transport through the nanochannel. We demonstrate that a transition from ion current saturation regimes to diode-like regimes can be obtained by employing different synthetic approaches, namely, counterdiffusion synthesis, where MOF precursors are kept separate and forced to diffuse through the nanochannel, and one-pot synthesis, where both precursors are placed at both ends of the channel. Also, by considering the dependence of the charge state of the UiO-66 MOF on the protonation degree, pH changes offered a mechanism to tune the iontronic output (and selectivity) among different regimes, including anion-driven rectification, cation-driven rectification, ion current saturation, and ohmic behavior. Furthermore, Poisson-Nernst-Planck (PNP) simulations were employed to rationalize the different iontronic outputs observed experimentally for membranes modified by different methods. Our results demonstrate a straightforward tool to synthesize MOF-based SSN membranes with tunable ion transport regimes.

20.
Dent J (Basel) ; 12(6)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38920859

RESUMEN

BACKGROUND: To compare the clinical effectiveness of ion-releasing restorations (IRR) vs. composite resin (CR) in dental restorations. METHODS: A systematic search was carried out from articles published until January 2024, in the biomedical databases: PubMed, Cochrane Library, Scielo, Scopus, Web of Science and Google Scholar. Randomized clinical trials were included, with a follow-up time greater than or equal to 1 year, without time and language limits and which reported the clinical effect of IRR compared to CR in dental restorations. The RoB 2.0 tool was used to assess the risk of bias of the included studies and the GRADEPro GDT tool was used to assess the quality of evidence and the strength of recommendation of the results. RESULTS: The search yielded a total of 1109 articles. After excluding those that did not meet the selection criteria, 29 articles remained for the quantitative synthesis. The analysis found no statistically significant difference when comparing the dental restorations with IRRs or CRs. CONCLUSION: The literature reviewed suggests that there are no differences between the IRRs and CRs in dental restorations.

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