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1.
Proteins ; 92(3): 411-417, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37909765

RESUMEN

A progressive aggregation of misfolded proteins is a hallmark of numerous pathologies including diabetes Type 2, Alzheimer's disease, and Parkinson's disease. As a result, highly toxic protein aggregates, which are known as amyloid fibrils, are formed. A growing body of evidence suggests that phospholipids can uniquely alter the secondary structure and toxicity of amyloid aggregates. However, the role of phosphatidic acid (PA), a unique lipid that is responsible for cell signaling and activation of lipid-gated ion channels, in the aggregation of amyloidogenic proteins remains unclear. In this study, we investigate the role of the length and degree of unsaturation of fatty acids (FAs) in PA in the structure and toxicity of lysozyme fibrils formed in the presence of this lipid. We found that both the length and saturation of FAs in PA uniquely altered the secondary structure of lysozyme fibrils. However, these structural differences in PA caused very little if any changes in the morphology of lysozyme fibrils. We also utilized cell toxicity assays to determine the extent to which the length and degree of unsaturation of FAs in PA altered the toxicity of lysozyme fibrils. We found that amyloid fibrils formed in the presence of PA with C18:0 FAs exerted significantly higher cell toxicity compared to the aggregates formed in the presence of PA with C16:0 and C18:1 FAs. These results demonstrated that PA can be an important player in the onset and spread of amyloidogenic diseases.


Asunto(s)
Muramidasa , Ácidos Fosfatidicos , Muramidasa/química , Amiloide/química , Estructura Secundaria de Proteína , Proteínas Amiloidogénicas
2.
Glia ; 72(8): 1374-1391, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38587131

RESUMEN

Oligodendrocytes and astrocytes are metabolically coupled to neuronal compartments. Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters. However, lactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions. Here we show that mice with a cell type-specific disruption of both Ldha and Ldhb genes in oligodendrocytes lack a pathological phenotype that would be indicative of oligodendroglial dysfunctions or lack of axonal metabolic support. Indeed, when combining immunohistochemical, electron microscopical, and in situ hybridization analyses in adult mice, we found that the vast majority of mature oligodendrocytes lack detectable expression of LDH. Even in neurodegenerative disease models and in mice under metabolic stress LDH was not increased. In contrast, at early development and in the remyelinating brain, LDHA was readily detectable in immature oligodendrocytes. Interestingly, by immunoelectron microscopy LDHA was particularly enriched at gap junctions formed between adjacent astrocytes and at junctions between astrocytes and oligodendrocytes. Our data suggest that oligodendrocytes metabolize lactate during development and remyelination. In contrast, for metabolic support of axons mature oligodendrocytes may export their own glycolysis products as pyruvate rather than lactate. Lacking LDH, these oligodendrocytes can also "funnel" lactate through their "myelinic" channels between gap junction-coupled astrocytes and axons without metabolizing it. We suggest a working model, in which the unequal cellular distribution of LDH in white matter tracts facilitates a rapid and efficient transport of glycolysis products among glial and axonal compartments.


Asunto(s)
Axones , Glucólisis , L-Lactato Deshidrogenasa , Oligodendroglía , Animales , Oligodendroglía/metabolismo , Axones/metabolismo , L-Lactato Deshidrogenasa/metabolismo , L-Lactato Deshidrogenasa/genética , Glucólisis/fisiología , Ratones , Regulación hacia Abajo/fisiología , Ratones Endogámicos C57BL , Lactato Deshidrogenasa 5/metabolismo , Astrocitos/metabolismo , Astrocitos/ultraestructura , Ratones Transgénicos , Isoenzimas/metabolismo , Isoenzimas/genética , Uniones Comunicantes/metabolismo , Uniones Comunicantes/ultraestructura , Ratones Noqueados
3.
Small ; 20(19): e2307308, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38126576

RESUMEN

Reaction kinetics can be improved by the enhanced electrical contact between different components growing symbiotically. But so far, due to the necessity for material synthesis conditions match, the component structures of cooperative growth are similar, and the materials are of the same type. The collaborative growth of high-reaction kinetics composite homogeneous core-shell heterostructure between various materials is innovatively proposed with different structures in one step. The NiCo-LDH and PPy successfully symbiotically grow on activated carbon fiber fabric in one step. The open channel structure of the NiCo-LDH nanosheets is preserved while PPy effectively wrapped around the NiCo-LDH. The well-defined nanostructure with abundant active sites and convenient ion diffusion paths is favorable for electrolyte entry into the entire nanoarrays. In addition, owing to the enhanced electronic interaction between different components through XPS analysis, the NiCo-LDH@PPy electrode shows outstanding reaction kinetics and structural stability. The as-synthesized NiCo-LDH@PPy exhibited excellent super-capacitive storage capabilities, robust capacitive activity, and good rate survival. Furthermore, an asymmetric supercapacitor (ASC) device made of NiCo-LDH@PPy and activated carbon (AC) is able to maintain a long cycle life while achieving high power and energy densities.

4.
Small ; 20(28): e2311431, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38366284

RESUMEN

Renewable electricity-driven seawater splitting presents a green, effective, and promising strategy for building hydrogen (H2)-based energy systems (e.g., storing wind power as H2), especially in many coastal cities. The abundance of Cl- in seawater, however, will cause severe corrosion of anode catalyst during the seawater electrolysis, and thus affect the long-term stability of the catalyst. Herein, seawater oxidation performances of NiFe layered double hydroxides (LDH), a classic oxygen (O2) evolution material, can be boosted by employing tungstate (WO4 2-) as the intercalated guest. Notably, insertion of WO4 2- to LDH layers upgrades the reaction kinetics and selectivity, attaining higher current densities with ≈100% O2 generation efficiency in alkaline seawater. Moreover, after a 350 h test at 1000 mA cm-2, only trace active chlorine can be detected in the electrolyte. Additionally, O2 evolution follows lattice oxygen mechanism on NiFe LDH with intercalated WO4 2-.

5.
Small ; 20(26): e2310112, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38221688

RESUMEN

The development of effective oxygen evolution reaction (OER) and urea oxidation reaction (UOR) on heterostructure electrocatalysts with specific interfaces and characteristics provides a distinctive character. In this study, heterostructure nanocubes (NCs) comprising inner cobalt oxysulfide (CoOS) NCs and outer CoFe (CF) layered double hydroxide (LDH) are developed using a hydrothermal methodology. During the sulfidation process, the divalent sulfur ions (S2-) are released from the breakdown of the sulfur source and react with the Co-precursors on the surface leading to the transformation of CoOH nanorods into CoOS nanocubes. Further, X-ray photoelectron spectroscopy (XPS) and X-ray absorption spectroscopy (XAS) analyses reveal that the interactions at the interface of the CF@CoOS NCs significantly altered the electronic structure, thus enhancing the electrocatalytic performance. The optimal catalysts exhibited effective OER and UOR activities, the attained potentials are 1.51 and 1.36 V. This remarkable performance is attributable to the induction of electron transfer from the CoFe LDH to CoOS, which reduces the energy barrier of the intermediates for the OER and UOR. Furthermore, an alkaline water and urea two-cell electrolyzer assembled using CF@CoOS-2 NCs and Pt/C as the anode and cathode requires a cell voltage of 1.63 and 1.56 V along with a durability performance.

6.
Small ; 20(13): e2307294, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37963858

RESUMEN

The pursuit of stable and efficient electrocatalysts toward seawater oxidation is of great interest, yet it poses considerable challenges. Herein, the utilization of Cr-doped CoFe-layered double hydroxide nanosheet array is reported on nickel-foam (Cr-CoFe-LDH/NF) as an efficient electrocatalyst for oxygen evolution reaction in alkaline seawater. The Cr-CoFe-LDH/NF catalyst can achieve current densities of 500 and 1000 mA cm -2 with remarkably low overpotentials of only 334 and 369 mV, respectively. Furthermore, it maintains at least 100 h stability when operated at 500 mA cm-2.

7.
Small ; 20(16): e2307797, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032156

RESUMEN

The rational design of inexpensive metal electrocatalysts with exciting catalytic activity for overall water splitting (OWS) remains a significant challenge. Heterostructures of NiFe layered double hydroxides (NiFe-LDHs) with abundant oxygen defects and tunable electronic properties have garnered considerable attention. Here, a self-supporting heterostructured catalyst (named MoO3/NiFe-NF) is synthesized via a hydrothermal method to grow NiFe-LDH with oxygen vacancies (OV) in situ on inexpensive nickel foam (NF). Subsequently, MoO3 is anchored and grown on the surface of NiFe-LDH by electrodeposition. The obtained catalysts achieved outstanding oxygen/hydrogen evolution reaction (OER/HER, 212 mV/85 mV@10 mA cm-2) performance in 1 m KOH. Additionally, when MoO3/NiFe-NF is utilized as the cathode and anode in OWS, a current density of 10 mA cm-2 can be obtained as an ultralow battery voltage of 1.43 V, a significantly lower value compared to the commercial electrolyzer incorporating Pt/C and IrO2 electrode materials. Finally, density functional theory (DFT) calculations and advanced spectroscopy technology are conducted to reveal the effects of heterojunctions and OV on the internal electronic structure of the electrical catalysts. Mainly, the present study provides a novel tactic for the rational design of remarkable, low-cost NiFe-LDH electrocatalysts with heterostructures for OWS.

8.
Small ; : e2401315, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747008

RESUMEN

Battery-type electrode materials with high capacity, wide potential windows, and good cyclic stability are crucial to breaking through energy storage limitations and achieving high energy density. Herein, a novel 2D-on-2D Al-doped NiCo layered double hydroxide (NiCoAlx LDH) nanosheet arrays with high-mass-loading are grown on a carbon cloth (CC) substrate via a two-step hydro/solvothermal deposition strategy, and the effect of Al doping is employed to modify the deposition behavior, hierarchical morphology, phase stability, and multi-metallic synergistic effect. The optimized NiCoAl0.1 LDH electrode exhibits capacities of 5.43, 6.52, and 7.25 C cm-2 (9.87, 10.88, and 11.15 F cm-2) under 0-0.55, 0-0.60, and 0-0.65 V potential windows, respectively, illustrating clearly the importance of the wide potential window. The differentiated deposition strategy reduces the leaching level of Al3+ cations in alkaline solutions, ensuring excellent cyclic performance (108% capacity retention after 40 000 cycles). The as-assembled NiCoAl0.1 LDH//activated carbon cloth (ACC) hybrid supercapacitor delivers 3.11 C cm-2 at 0-2.0 V, a large energy density of 0.84 mWh cm-2 at a power density of 10.00 mW cm-2, and excellent cyclic stability with ≈135% capacity retention after 150 000 cycles.

9.
Small ; 20(31): e2400139, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38497843

RESUMEN

The oxygen evolution reaction (OER) performance of NiCo LDH electrocatalysts can be improved through fluorine doping. The roles of Ni and Co active sites in such catalysts remain ambiguous and controversial. In addressing the issue, this study draws upon the molecular orbital theory and proposes the active center competitive mechanism between Ni and Co. The doped F-atoms can directly impact the valence state of metal atoms or exert an indirect influence through the dehydrogenation, thereby modulating the active center. As the F-atoms are progressively aggregate, the eg orbitals of Ni and Co transition from e2 g to e1 g, and subsequently to e0 g. The corresponding valence state elevates from +2 to +3, and then to +4, signifying an initial increase followed by a subsequent decrease in the electrocatalytic performance. Furthermore, a series of F-NiCo LDH catalysts are synthesized to verify the eg orbital occupancy analysis, and the catalytic OER overpotentials are 303, 243, 240, and 246 mV at the current density of 10 mA cm-2, respectively, which coincides well with the theoretical prediction. This investigation not only provides novel mechanistic insights into the transition and competition of Ni and Co in F-NiCo LDH catalysts but also establishes a foundation for the design of high-performance catalysts.

10.
Small ; 20(8): e2306382, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37828635

RESUMEN

Amelioration of nickel-cobalt layered double hydroxides (NiCo-LDH) with a high specific theoretical capacitance is of great desire for high-power supercapacitors. Herein, a molybdenum (Mo) doping strategy is proposed to improve the charge-storage performance of NiCo-LDH nanosheets growing on carbon cloth (CC) via a rapid microwave process. The regulation of the electronic structure and oxygen vacancy of the LDH is consolidated by the density functional theory (DFT) calculation, which demonstrates that Mo doping narrows the band gap, reduces the formation energy of hydroxyl vacancies, and promotes ionic and charge transfer as well as electrolyte adsorption on the electrode surface. The optimal Mo-doped NiCo-LDH electrode (MoNiCo-LDH-0.05/CC) has an amazing specific capacity of 471.1 mA h g-1 at 1 A g-1 , and excellent capacity retention of 84.8% at 32 A g-1 , far superior to NiCo-LDH/CC (258.3 mA h g-1 and 76.4%). The constructed hybrid supercapacitor delivers an energy density of 103.3 W h kg-1 at a power density of 750 W kg-1 and retains the cycle retention of 85.2% after 5000 cycles. Two assembled devices in series can drive thirty LED lamps, revealing a potential application prospect of the rationally synthesized MoNiCo-LDH/CC as an energy-storage electrode material.

11.
Small ; 20(26): e2309689, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38258384

RESUMEN

Developing efficient water-splitting electrocatalysts to accelerate the slow oxygen evolution reaction (OER) kinetics is urgently desired for hydrogen production. Herein, ultralow phosphorus (P)-doped NiFe LDH (NiFePx LDH) with mild compressive strain is synthesized as an efficient OER electrocatalyst. Remarkably, NiFePx LDH with the phosphorus mass ratio of 0.32 wt.% and compressive strain ratio of 2.53% (denoted as NiFeP0.32 LDH) exhibits extraordinary OER activity with an overpotential as low as 210 mV, which is superior to that of commercial IrO2 and other reported P-based OER electrocatalysts. Both experimental performance and density function theory (DFT) calculation demonstrate that the doping of P atoms can generate covalent Fe─P coordination bonds and lattice distortion, thus resulting in the consequent depletion of electrons around the Fe active center and the downward shift of the d-band center, which can lead to a weaker adsorption ability of *O intermediate to improve the catalytic performance of NiFeP0.32 LDH for OER. This work provides novel insights into the distinctive coordinated configuration of P in NiFePx LDH, which can result in superior catalytic performance for OER.

12.
Small ; 20(26): e2311047, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38269475

RESUMEN

Anion exchange membrane water electrolysis (AEMWE) is an attractive method for green hydrogen production. It allows the use of non-platinum group metal catalysts and can achieve performance comparable to proton exchange membrane water electrolyzers due to recent technological advances. While current systems already show high performances with available materials, research gaps remain in understanding electrode durability and degradation behavior. In this study, the performance and degradation tracking of a Ni3Fe-LDH-based single-cell is implemented and investigated through the correlation of electrochemical data using chemical and physical characterization methods. A performance stability of 1000 h, with a degradation rate of 84 µV h-1 at 1 A cm-2 is achieved, presenting the Ni3Fe-LDH-based cell as a stable and cost-attractive AEMWE system. The results show that the conductivity of the formed Ni-Fe-phase is one key to obtaining high electrolyzer performance and that, despite Fe leaching, change in anion-conducting binder compound, and morphological changes inside the catalyst bulk, the Ni3Fe-LDH-based single-cells demonstrate high performance and durability. The work reveals the importance of longer stability tests and presents a holistic approach of electrochemical tracking and post-mortem analysis that offers a guideline for investigating electrode degradation behavior over extended measurement periods.

13.
J Transl Med ; 22(1): 474, 2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38764020

RESUMEN

BACKGROUND: The initiation of fibroblast growth factor 1 (FGF1) expression coincident with the decrease of FGF2 expression is a well-documented event in prostate cancer (PCa) progression. Lactate dehydrogenase A (LDHA) and LDHB are essential metabolic products that promote tumor growth. However, the relationship between FGF1/FGF2 and LDHA/B-mediated glycolysis in PCa progression is not reported. Thus, we aimed to explore whether FGF1/2 could regulate LDHA and LDHB to promote glycolysis and explored the involved signaling pathway in PCa progression. METHODS: In vitro studies used RT‒qPCR, Western blot, CCK-8 assays, and flow cytometry to analyze gene and protein expression, cell viability, apoptosis, and cell cycle in PCa cell lines. Glycolysis was assessed by measuring glucose consumption, lactate production, and extracellular acidification rate (ECAR). For in vivo studies, a xenograft mouse model of PCa was established and treated with an FGF pathway inhibitor, and tumor growth was monitored. RESULTS: FGF1, FGF2, and LDHA were expressed at high levels in PCa cells, while LDHB expression was low. FGF1/2 positively modulated LDHA and negatively modulated LDHB in PCa cells. The depletion of FGF1, FGF2, or LDHA reduced cell proliferation, induced cell cycle arrest, and inhibited glycolysis. LDHB overexpression showed similar inhibitory effect on PCa cells. Mechanistically, we found that FGF1/2 positively regulated STAT1 and STAT1 transcriptionally activated LDHA expression while suppressed LDHB expression. Furthermore, the treatment of an FGF pathway inhibitor suppressed PCa tumor growth in mice. CONCLUSION: The FGF pathway facilitates glycolysis by activating LDHA and suppressing LDHB in a STAT1-dependent manner in PCa.


Asunto(s)
Factores de Crecimiento de Fibroblastos , Glucólisis , L-Lactato Deshidrogenasa , Neoplasias de la Próstata , Factor de Transcripción STAT1 , Transducción de Señal , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/genética , Humanos , Animales , L-Lactato Deshidrogenasa/metabolismo , Línea Celular Tumoral , Factor de Transcripción STAT1/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Ratones Desnudos , Proliferación Celular , Ratones , Regulación Neoplásica de la Expresión Génica , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Apoptosis , Lactato Deshidrogenasa 5/metabolismo , Isoenzimas
14.
Oncology ; 102(1): 76-84, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37579734

RESUMEN

INTRODUCTION: Tumor burden is a frequently mentioned parameter; however, a commonly accepted definition is still lacking. METHODS: In this double-center prospective and retrospective study, 76 patients with unresectable stage III or stage IV melanoma treated with ipilimumab were included. We defined the baseline tumor burden (BTB) as the global sum of all metastases' longest diameters before treatment started and correlated the calculated BTB with disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and with the baseline levels of LDH, S100B, and sULPB2. RESULTS: BTB correlated significantly with DCR (p = 0.009), PFS (p = 0.002), OS (p = 0.032), and the occurrence of NRAS mutation (p = 0.006). BTB was also correlated to baseline serum levels of LDH (p = 0.011), S100B (p = 0.027), and SULBP (p < 0.0001). Multivariate analysis revealed that BPB and LDH were independently correlated with PFS and OS. With increasing BTB, disease control was less likely; no patient with a BTB >200 mm achieved disease control. For patients with brain metastasis, no correlation of BTB with DCR (p = 0.251), PFS (p = 0.059), or OS (p = 0.981) was observed. CONCLUSION: Calculated BTB is an independent prognostic factor for patients with metastatic melanoma treated with ipilimumab. Using calculated BTB as a definition of tumor burden may help increase comparability of outcome of therapies in future studies.


Asunto(s)
Melanoma , Humanos , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Ipilimumab/uso terapéutico , Carga Tumoral , Estudios Retrospectivos , Estudios Prospectivos
15.
Chemistry ; 30(6): e202303025, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-37902103

RESUMEN

In recent years, layered double hydroxides (LDH) nanosheets have garnered substantial attention as intriguing inorganic anionic layered clay materials. These nanosheets have captured the attention of researchers due to their unique physicochemical properties. This review aims to showcase the latest advancements in laboratory research concerning LDH nanosheets, with a specific emphasis on their methods of preparation. This review provides detailed insights into the factors influencing the anionic conductivity of LDH, along with delineating the applications of LDH nanosheets in the realm of energy conversion. Notably, the review highlights the crucial role of LDH nanosheets in the oxygen evolution reaction (OER), a vital process in water splitting and diverse electrochemical applications. The review emphasizes the significant potential of LDH nanosheets in enhancing supercapacitor technology, owing to their high surface area and exceptional charge storage capacity. Additionally, it elucidates the prospective application of LDH nanosheets as anion exchange membranes in anion exchange membrane fuel cells, potentially revolutionizing fuel cell performance through improved efficiency and stability facilitated by enhanced ion transport properties.

16.
Chemistry ; 30(22): e202304024, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38391394

RESUMEN

Formaldehyde is susceptible to illegal addition to foodstuffs to extend their shelf life due to its antimicrobial, preservative and bleaching properties. In this study, a self-supporting "nanosheet on nanosheet" arrays electrocatalyst with core-shell heterostructure was prepared in situ by coupling NiCo layer double hydroxide with 2D ZIF derived Co-nitrogen-doped porous carbon on carbon cloth (Co-N/C@NiCo-LDH NSAs/CC). Co-N/C nanosheet arrays act as a scaffold core with good electrical conductivity, providing more NiCo-LDH nucleation sites to avoid NiCo-LDH agglomeration, thus having fast mass/charge transfer performance. While the NiCo-LDH nanosheet arrays shell with high specific surface area provide more active sites for electrochemical reactions. As an electrocatalytic sensing electrode, Co-N/C@NiCo-LDH NSAs/CC has a wide linear range of 1 µM to 13 mM for formaldehyde detection, and the detection limit is 82 nM. Besides, the sensor has been applied to the detection of formaldehyde in food samples with satisfactory results.

17.
FASEB J ; 37(7): e22972, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37302013

RESUMEN

Docosahexaenoic (DHA) and arachidonic acids (ARA) are omega-3 and omega-6 long-chain polyunsaturated fatty acids (LCPUFAs). These molecules constitute a substantial portion of phospholipids in plasma membranes. Therefore, both DHA and ARA are essential diet components. Once consumed, DHA and ARA can interact with a large variety of biomolecules, including proteins such as insulin and α-synuclein (α-Syn). Under pathological conditions known as injection amyloidosis and Parkinson's disease, these proteins aggregate forming amyloid oligomers and fibrils, toxic species that exert high cell toxicity. In this study, we investigate the role of DHA and ARA in the aggregation properties of α-Syn and insulin. We found that the presence of both DHA and ARA at the equimolar concentrations strongly accelerated aggregation rates of α-Syn and insulin. Furthermore, LCPUFAs substantially altered the secondary structure of protein aggregates, whereas no noticeable changes in the fibril morphology were observed. Nanoscale Infrared analysis of α-Syn and insulin fibrils grown in the presence of both DHA and ARA revealed the presence of LCPUFAs in these aggregates. We also found that such LCPUFAs-rich α-Syn and insulin fibrils exerted significantly greater toxicities compared to the aggregates grown in the LCPUFAs-free environment. These findings show that interactions between amyloid-associated proteins and LCPUFAs can be the underlying molecular cause of neurodegenerative diseases.


Asunto(s)
Ácidos Grasos Omega-3 , Enfermedad de Parkinson , Humanos , alfa-Sinucleína/metabolismo , Insulina , Amiloide/toxicidad , Amiloide/química , Ácidos Grasos Insaturados , Proteínas Amiloidogénicas , Ácidos Araquidónicos
18.
Mol Pharm ; 21(3): 1334-1341, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38373398

RESUMEN

Parkinson's disease (PD) is a severe pathology that is caused by a progressive degeneration of dopaminergic neurons in substantia nigra pars compacta as well as other areas in the brain. These neurodegeneration processes are linked to the abrupt aggregation of α-synuclein (α-syn), a small protein that is abundant at presynaptic nerve termini, where it regulates cell vesicle trafficking. Due to the direct interactions of α-syn with cell membranes, a substantial amount of work was done over the past decade to understand the role of lipids in α-syn aggregation. However, the role of phosphatidic acid (PA), a negatively charged phospholipid with a small polar head, remains unclear. In this study, we examined the effect of PA large unilamellar vesicles (LUVs) on α-syn aggregation. We found that PA LUVs with 16:0, 18:0, and 18:1 FAs drastically reduced the toxicity of α-syn fibrils if were present in a 1:1 molar ratio with the protein. Our results also showed that the presence of these vehicles changed the rate of α-syn aggregation and altered the morphology and secondary structure of α-syn fibrils. These results indicate that PA LUVs can be used as a potential therapeutic strategy to reduce the toxicity of α-syn fibrils formed upon PD.


Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Liposomas Unilamelares/metabolismo , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas/metabolismo
19.
BMC Infect Dis ; 24(1): 685, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38982355

RESUMEN

BACKGROUND: Coronavirus disease (COVID-19) may lead to serious complications and increased mortality. The outcomes of patients who survive the early disease period are burdened with persistent long-term symptoms and increased long-term morbidity and mortality. The aim of our study was to determine which baseline parameters may provide the best prediction of early and long-term outcomes. METHODS: The study group comprised 141 patients hospitalized for COVID-19. Demographic data, clinical data and laboratory parameters were collected. The main study endpoints were defined as in-hospital mortality and 1-year mortality. The associations between the baseline data and the study endpoints were evaluated. Prediction models were created. RESULTS: The in-hospital mortality rate was 20.5% (n = 29). Compared with survivors, nonsurvivors were significantly older (p = 0.001) and presented comorbidities, including diabetes (0.027) and atrial fibrillation (p = 0.006). Assessment of baseline laboratory markers and time to early death revealed negative correlations between time to early death and higher IL-6 levels (p = 0.032; Spearman rho - 0.398) and lower lymphocyte counts (p = 0.018; Pearson r -0.438). The one-year mortality rate was 35.5% (n = 50). The 1-year nonsurvivor subgroup was older (p < 0.001) and had more patients with arterial hypertension (p = 0.009), diabetes (p = 0.023), atrial fibrillation (p = 0.046) and active malignancy (p = 0.024) than did the survivor subgroup. The model composed of diabetes and atrial fibrillation and IL-6 with lymphocyte count revealed the highest value for 1-year mortality risk prediction. CONCLUSIONS: Diabetes and atrial fibrillation, as clinical factors, and LDH, IL-6 and lymphocyte count, as laboratory determinants, are the best predictors of COVID-19 mortality risk.


Asunto(s)
COVID-19 , Mortalidad Hospitalaria , SARS-CoV-2 , Humanos , COVID-19/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Interleucina-6/sangre , Comorbilidad , Adulto , Recuento de Linfocitos
20.
Environ Sci Technol ; 58(19): 8597-8606, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38687950

RESUMEN

NiFe layered double hydroxides (NiFe-LDH) exhibited an outstanding performance and promising application potential for removing ozone. However, the effect of interlayer anions on ozone removal remains ambiguous. Here, a series of NiFe-LDH with different interlayer anions (F-, Cl-, Br-, NO3-, CO32-, and SO42-) were prepared to investigate the effect of the interlayer anion on ozone removal for the first time. It was found that the interlayer anions are a key factor affecting the water resistance of the NiFe-LDH catalyst under moist conditions. NiFe-LDH-CO32- exhibited the best water resistance, which was much better than that of NiFe-LDH containing other interlayer anions. The in situ DIRFTS demonstrates that the carbonates in the interlayer of NiFe-LDH-CO32- will undergo coordination changes through the interaction with water molecules under moist conditions, exposing new metal sites. As a result, the newly exposed metal sites could activate water molecules into hydroxyl groups that act as active sites for catalyzing ozone decomposition. This work provides a new insight into the interlayer anions of LDH, which is important for the design and development of LDH catalysts with excellent ozone removal properties.


Asunto(s)
Aniones , Hidróxidos , Ozono , Ozono/química , Hidróxidos/química , Catálisis , Aniones/química
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