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1.
J Chromatogr A ; 1735: 465347, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39244914

RESUMEN

Metal-organic frameworks (MOFs) are promising materials for sample pretreatment. The performance improvement of powdered MOFs is hindered by their aggregation and difficult recovery. To overcome these issues, a biodegradable lightweight spherical aerogel was used as a support for the in situ growth of copper-based MOFs (MOF-199). Furthermore, Fe3O4 nanoparticles were incorporated into the aerogel to achieve magnetic properties. Thus, hybrid aerogel spheres containing MOF-199 supported on magnetic oxidized cellulose nanofiber/carboxymethyl chitosan (MOF-199@mag-CNF/CMC) were fabricated. The effects of Fe3O4 loading amount and organic-ligand concentration on the properties (spherical geometry and mechanical strength) of the hybrid aerogel spheres were studied. Their potential application in the extraction of benzodiazepines (BZPs) from urine samples prior to liquid chromatography-mass spectrometry was evaluated. The highly dispersed MOF-199 crystals on the spherical aerogel effectively overcame the inherent structural shrinkage of the bare aerogel spheres; thus, the MOF-199@mag-CNF/CMC aerogel spheres were robust and could withstand repeated use for at least eight consecutive extraction cycles. Further, MOF-199@mag-CNF/CMC exhibited improved BZP extraction efficiency, which was 2.5-11.6 times higher than that of bare Cu2+@mag-CNF/CMC aerogel spheres, primarily due to additional π-π interaction and H-bonding as well as improved specific surface area. Parameters influencing the extraction and desorption processes were also comprehensively investigated. Under optimal conditions, this method provided a wide linear range of 0.1-10 µg/L (R2 > 0.995) and good precision (2.8-6.7% for intra-day; 1.9-7.8 % for inter-day). The limits of detection and quantification ranged from 0.02 to 0.11 µg/L and from 0.06 to 0.33 µg/L, respectively. The recoveries for the urine samples spiked with three concentrations of BZPs ranged from 73.9 % to 114.1 %. The proposed method is simple, sensitive and eco-friendly and can be used for the determination of BZPs from urine for clinical and forensic examinations.


Asunto(s)
Benzodiazepinas , Celulosa , Quitosano , Estructuras Metalorgánicas , Extracción en Fase Sólida , Extracción en Fase Sólida/métodos , Estructuras Metalorgánicas/química , Celulosa/química , Celulosa/análogos & derivados , Quitosano/química , Benzodiazepinas/orina , Benzodiazepinas/química , Benzodiazepinas/aislamiento & purificación , Humanos , Límite de Detección , Geles/química , Reproducibilidad de los Resultados
2.
Sci Rep ; 14(1): 19876, 2024 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191875

RESUMEN

Frataxin (FXN) is required for iron-sulfur cluster biogenesis, and its loss causes the early-onset neurodegenerative disease Friedreich ataxia (FRDA). Loss of FXN is a susceptibility factor in the development of diabetes, a common metabolic complication after myocardial hypertrophy in patients with FRDA. The underlying mechanism of FXN deficient-induced hyperglycemia in FRDA is, however, poorly understood. In this study, we confirmed that the FXN deficiency mouse model YG8R develops insulin resistance in elder individuals by disturbing lipid metabolic homeostasis in adipose tissues. Evaluation of lipolysis, lipogenesis, and fatty acid ß-oxidation showed that lipolysis is most severely affected in white adipose tissues. Consistently, FXN deficiency significantly decreased expression of lipolytic genes encoding adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) resulting in adipocyte enlargement and inflammation. Lipolysis induction by fasting or cold exposure remarkably upregulated FXN expression, though FXN deficiency lessened the competency of lipolysis compared with the control or wild type mice. Moreover, we found that the impairment of lipolysis was present at a young age, a few months earlier than hyperglycemia and insulin resistance. Forskolin, an activator of lipolysis, or pioglitazone, an agonist of PPARγ, improved insulin sensitivity in FXN-deficient adipocytes or mice. We uncovered the interplay between FXN expression and lipolysis and found that impairment of lipolysis, particularly the white adipocytes, is an early event, likely, as a primary cause for insulin resistance in FRDA patients at later age.


Asunto(s)
Adipocitos Blancos , Modelos Animales de Enfermedad , Frataxina , Ataxia de Friedreich , Resistencia a la Insulina , Proteínas de Unión a Hierro , Lipólisis , Animales , Ataxia de Friedreich/metabolismo , Ataxia de Friedreich/genética , Ataxia de Friedreich/patología , Ratones , Proteínas de Unión a Hierro/metabolismo , Proteínas de Unión a Hierro/genética , Adipocitos Blancos/metabolismo , Adipocitos Blancos/patología , Masculino , Lipasa/metabolismo , Lipasa/genética , Humanos
3.
Proc Natl Acad Sci U S A ; 121(31): e2321929121, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39047035

RESUMEN

Colorectal cancer and Crohn's disease patients develop pyogenic liver abscesses due to failures of immune cells to fight off bacterial infections. Here, we show that mice lacking iron regulatory protein 2 (Irp2), globally (Irp2-/-) or myeloid cell lineage (Lysozyme 2 promoter-driven, LysM)-specifically (Irp2ΔLysM), are highly susceptible to liver abscesses when the intestinal tissue was injured with dextran sodium sulfate treatment. Further studies demonstrated that Irp2 is required for lysosomal acidification and biogenesis, both of which are crucial for bacterial clearance. In Irp2-deficient liver tissue or macrophages, the nuclear location of transcription factor EB (Tfeb) was remarkably reduced, leading to the downregulation of Tfeb target genes that encode critical components for lysosomal biogenesis. Tfeb mislocalization was reversed by hypoxia-inducible factor 2 inhibitor PT2385 and, independently, through inhibition of lactic acid production. These experimental findings were confirmed clinically in patients with Crohn's disease and through bioinformatic searches in databases from Crohn's disease or ulcerative colitis biopsies showing loss of IRP2 and transcription factor EB (TFEB)-dependent lysosomal gene expression. Overall, our study highlights a mechanism whereby Irp2 supports nuclear translocation of Tfeb and lysosomal function, preserving macrophage antimicrobial activity and protecting the liver against invading bacteria during intestinal inflammation.


Asunto(s)
Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Enfermedad de Crohn , Proteína 2 Reguladora de Hierro , Lisosomas , Macrófagos , Animales , Lisosomas/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Ratones , Humanos , Enfermedad de Crohn/inmunología , Enfermedad de Crohn/metabolismo , Proteína 2 Reguladora de Hierro/metabolismo , Proteína 2 Reguladora de Hierro/genética , Ratones Noqueados , Ratones Endogámicos C57BL , Hígado/metabolismo , Hígado/inmunología , Hígado/patología
4.
J Hazard Mater ; 477: 135290, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39047563

RESUMEN

The rapid expansion of fast fashion has significantly increased microplastic fiber (MPF) release during laundry practices, accounting for approximately one-third of primary microplastics entering the ocean. Currently, a significant gap exists in global-scale research on the release of MPFs from washing textiles. This study introduces an innovative empirical model to assess the spatial distribution of MPF emissions. The model estimates an annual global emission of 5.69 million tons of MPFs from laundry. Of this total, machine washing accounts for the majority (93.7 %), with hand washing contributing the remaining 6.3 %. As the primary source of MPF pollution, Asia's emissions reach 3.71 million tons, far exceeding those of North America (1.18 million tons) and Europe (0.45 million tons). The primary issue is that wastewater management efficiency varies significantly worldwide. In Asia, there is persistently high discharge of MPFs into natural waters, and the removal efficiency of wastewater treatment plants is still comparatively low. In contrast, the United States and many European countries exhibit better MPF retention. The global nature of this challenge mandates international collaboration for comprehensive environmental conservation. Our study provides the first high-resolution global distribution map of MPF emissions and discharge into natural waters, establishing a data foundation for global and regional management of microplastics originating from household laundry sources.

5.
J Chromatogr A ; 1727: 464993, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38759462

RESUMEN

Anabolic steroids and ß-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 µg/L for methyltestosterone and trenbolone, and 0.02-5 µg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 µg/L. The limits of quantification were 0.02-0.40 µg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.


Asunto(s)
Anabolizantes , Límite de Detección , Nanopartículas de Magnetita , Polietilenglicoles , Humanos , Polietilenglicoles/química , Anabolizantes/orina , Anabolizantes/aislamiento & purificación , Nanopartículas de Magnetita/química , Doping en los Deportes , Adsorción , Reproducibilidad de los Resultados , Extracción en Fase Sólida/métodos , Dióxido de Silicio/química
6.
Environ Res ; 251(Pt 2): 118670, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38493849

RESUMEN

The surfactant-enhanced bioremediation (SEBR) of organic-contaminated soil is a promising soil remediation technology, in which surfactants not only mobilize pollutants, but also alter the mobility of bacteria. However, the bacterial response and underlying mechanisms remain unclear. In this study, the effects and mechanisms of action of a selected nonionic surfactant (Tween 80) on Pseudomonas aeruginosa transport in soil and quartz sand were investigated. The results showed that bacterial migration in both quartz sand and soil was significantly enhanced with increasing Tween 80 concentration, and the greatest migration occurred at a critical micelle concentration (CMC) of 4 for quartz sand and 30 for soil, with increases of 185.2% and 27.3%, respectively. The experimental results and theoretical analysis indicated that Tween 80-facilitated bacterial migration could be mainly attributed to competition for soil/sand surface sorption sites between Tween 80 and bacteria. The prior sorption of Tween 80 onto sand/soil could diminish the available sorption sites for P. aeruginosa, resulting in significant decreases in deposition parameters (70.8% and 33.3% decrease in KD in sand and soil systems, respectively), thereby increasing bacterial transport. In the bacterial post-sorption scenario, the subsequent injection of Tween 80 washed out 69.8% of the bacteria retained in the quartz sand owing to the competition of Tween 80 with pre-sorbed bacteria, as compared with almost no bacteria being eluted by NaCl solution. Several machine learning models have been employed to predict Tween 80-faciliated bacterial transport. The results showed that back-propagation neural network (BPNN)-based machine learning could predict the transport of P. aeruginosa through quartz sand with Tween 80 in-sample (2 CMC) and out-of-sample (10 CMC) with errors of 0.79% and 3.77%, respectively. This study sheds light on the full understanding of SEBR from the viewpoint of degrader facilitation.


Asunto(s)
Biodegradación Ambiental , Aprendizaje Automático , Polisorbatos , Pseudomonas aeruginosa , Tensoactivos , Polisorbatos/química , Tensoactivos/química , Pseudomonas aeruginosa/efectos de los fármacos , Microbiología del Suelo , Porosidad , Contaminantes del Suelo/química
7.
Chemosphere ; 352: 141399, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38331263

RESUMEN

Layered double hydroxides (LDHs) have been recognized to have great potential for the treatment of heavy metals in wastewater and soil through various mechanisms. Isomorphic substitution is an important mechanism for the sorption of heavy metal cations with LDH reconstruction and highly stable product formation. However, sorption performance, structure-related relationships, and, more importantly, stability are still poorly understood. In this study, a series of LDHs with different structures were synthesized to evaluate their cadmium (Cd) sorption performance and stability concerning the isomorphic substitution mechanism. Divalent cation types in the LDH lattice determined the Cd sorption capacity as well as the isomorphic substitution possibility, following the order of hydroxide solubility of divalent cations (MII): Ca2+>Mg2+>(Cd2+) > Ni2+>Zn2+. In addition, CaAl-LDH exhibited a super-high Cd sorption capacity of 625.0 mg g-1. Cd sorption by LDHs with different interlayer anion types and divalent/trivalent cation molar ratios varied due to crystallite size-related MII release through cation-exchange/isomorphic substitution. Coexisting cations (e.g., Zn2+, Ni2+, Mg2+) influence the sorption performance of MII-LDH mainly through isomorphic substitution mechanism, largely depending on the solubility of MII(OH)2 with a trend of stable product formation. Furthermore, Mg2.9Cd0.1AlCl-LDH was fabricated, and limited Cd dissolution without destruction of the LDH structure was observed under various conditions. For example, only 7.69%, 2.16% and 0.96% of Cd was released from as-prepared Mg2.9Cd0.1AlCl-LDH in NaCl solution (0.02 mol L-1, pH 5), soil extract, and soil matrix, respectively. The very low leaching of Cd from Cd-containing LDHs indicated the high stability of LDH-sorbed Cd via isomorphic substitution and feasible practical application in Cd sequestration in wastewater treatment and soil remediation.


Asunto(s)
Cadmio , Metales Pesados , Cationes Bivalentes , Cationes , Hidróxidos/química , Suelo
8.
Blood ; 143(21): 2145-2151, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38364110

RESUMEN

ABSTRACT: Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin-labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI-measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.


Asunto(s)
Anemia de Células Falciformes , Circulación Cerebrovascular , Oxígeno , Humanos , Anemia de Células Falciformes/sangre , Niño , Adolescente , Masculino , Femenino , Oxígeno/sangre , Oxígeno/metabolismo , Preescolar , Imagen por Resonancia Magnética/métodos , Pirazinas/uso terapéutico , Pirazinas/administración & dosificación , Proyectos Piloto , Benzaldehídos/uso terapéutico , Benzaldehídos/farmacología , Benzaldehídos/administración & dosificación , Espectroscopía Infrarroja Corta/métodos , Pirazoles
9.
J Biol Chem ; 300(2): 105612, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38159858

RESUMEN

NCOA4 is a selective cargo receptor for ferritinophagy, the autophagic turnover of ferritin (FTH), a process critical for regulating intracellular iron bioavailability. However, how ferritinophagy flux is controlled through NCOA4 in iron-dependent processes needs to be better understood. Here, we show that the C-terminal FTH-binding domain of NCOA4 harbors a [3Fe-4S]-binding site with a stoichiometry of approximately one labile [3Fe-4S] cluster per NCOA4 monomer. By analyzing the interaction between NCOA4 and HERC2 ubiquitin ligase or NCOA4 and FTH, we demonstrate that NCOA4 regulates ferritinophagy by sensing the intracellular iron-sulfur cluster levels. Under iron-repletion conditions, HERC2 recognizes and recruits holo-NCOA4 as a substrate for polyubiquitination and degradation, favoring ferritin iron storage. Under iron-depletion conditions, NCOA4 exists in the form of apo-protein and binds ferritin to promote the occurrence of ferritinophagy and release iron. Thus, we identify an iron-sulfur cluster [3Fe-4S] as a critical cofactor in determining the fate of NCOA4 in favoring iron storage in ferritin or iron release via ferritinophagy and provide a dual mechanism for selective interaction between HERC2 and [3Fe-4S]-NCOA4 for proteasomal degradation or between ferritin and apo-NCOA4 for ferritinophagy in the control of iron homeostasis.


Asunto(s)
Homeostasis , Hierro , Coactivadores de Receptor Nuclear , Autofagia , Ferritinas/metabolismo , Hierro/química , Hierro/metabolismo , Coactivadores de Receptor Nuclear/genética , Coactivadores de Receptor Nuclear/metabolismo , Azufre/química , Azufre/metabolismo , Humanos , Animales , Ratones , Dominios Proteicos , Línea Celular , Células Cultivadas , Ubiquitina-Proteína Ligasas/metabolismo , Estabilidad Proteica , Complejo de la Endopetidasa Proteasomal/metabolismo
10.
J Biomed Opt ; 28(12): 126005, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38107767

RESUMEN

Significance: Although multilayer analytical models have been proposed to enhance brain sensitivity of diffuse correlation spectroscopy (DCS) measurements of cerebral blood flow, the traditional homogeneous model remains dominant in clinical applications. Rigorous in vivo comparison of these analytical models is lacking. Aim: We compare the performance of different analytical models to estimate a cerebral blood flow index (CBFi) with DCS in adults. Approach: Resting-state data were obtained on a cohort of 20 adult patients with subarachnoid hemorrhage. Data at 1 and 2.5 cm source-detector separations were analyzed with the homogenous, two-layer, and three-layer models to estimate scalp blood flow index and CBFi. The performance of each model was quantified via fitting convergence, fit stability, brain-to-scalp flow ratio (BSR), and correlation with transcranial Doppler ultrasound (TCD) measurements of cerebral blood flow velocity in the middle cerebral artery (MCA). Results: The homogeneous model has the highest pass rate (100%), lowest coefficient of variation (CV) at rest (median [IQR] at 1 Hz of 0.18 [0.13, 0.22]), and most significant correlation with MCA blood flow velocities (Rs=0.59, p=0.010) compared with both the two- and three-layer models. The multilayer model pass rate was significantly correlated with extracerebral layer thicknesses. Discarding datasets with non-physiological BSRs increased the correlation between DCS measured CBFi and TCD measured MCA velocities for all models. Conclusions: We found that the homogeneous model has the highest pass rate, lowest CV at rest, and most significant correlation with MCA blood flow velocities. Results from the multilayer models should be taken with caution because they suffer from lower pass rates and higher coefficients of variation at rest and can converge to non-physiological values for CBFi. Future work is needed to validate these models in vivo, and novel approaches are merited to improve the performance of the multimodel models.


Asunto(s)
Encéfalo , Hemorragia Subaracnoidea , Adulto , Humanos , Encéfalo/irrigación sanguínea , Hemodinámica , Velocidad del Flujo Sanguíneo/fisiología , Análisis Espectral , Circulación Cerebrovascular/fisiología
11.
Langmuir ; 39(44): 15808-15816, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37885070

RESUMEN

Although core-shell microparticles with a hard core and soft shell are often used to fabricate photonic crystal films, they are rarely applied to construct steady amorphous colloidal array (ACA) patterns. In this work, a series of monodisperse core-shell microparticles with a polystyrene (PS) core and poly(methyl methacrylate-butyl acrylate) (P(MMA-BA)) shell have been successfully synthesized, and the glass transition temperatures (Tg) of the shell layer have been well regulated. The synthesized core-shell microparticles were then used to fabricate ACA patterns via a convenient infiltration-driven assembly method. The results showed that the Tg of the shell significantly affected the microstructure of the amorphous colloidal arrays (ACAs). During the assembly process, the microparticles quickly contacted each other and the lower-Tg shells could merge with each other to form a continuous film. In this situation, the PS core was embedded and ranked in the P(MMA-BA) film, and both the refractive index contrast and order degree of the colloidal array became relatively low, resulting in a poor structural color. However, when the Tg of the shell layer was moderately high, a short-range ordered array was prepared via infiltration-driven assembly, thereby displaying a bright structural color. More importantly, the shell layers could merge with each other to some extent after short-time heating, resulting in fine mechanical stability. In brief, this study provides a facile and environmental approach to construct steady ACA patterns, which is promising in printing and painting industries.

12.
Elife ; 122023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-37561022

RESUMEN

Postmenopausal atherosclerosis (AS) has been attributed to estrogen deficiency. However, the beneficial effect of hormone replacement therapy (HRT) is lost in late postmenopausal women with atherogenesis. We asked whether aging-related iron accumulation affects estrogen receptor α (ERα) expression, thus explaining HRT inefficacy. A negative correlation has been observed between aging-related systemic iron deposition and ERα expression in postmenopausal AS patients. In an ovariectomized Apoe-/- mouse model, estradiol treatment had contrasting effects on ERα expression in early versus late postmenopausal mice. ERα expression was inhibited by iron treatment in cell culture and iron-overloaded mice. Combined treatment with estradiol and iron further decreased ERα expression, and the latter effect was mediated by iron-regulated E3 ligase Mdm2. In line with these observations, cellular cholesterol efflux was reduced, and endothelial homeostasis was disrupted. Consequently, AS was aggravated. Accordingly, systemic iron chelation attenuated estradiol-triggered progressive AS in late postmenopausal mice. Thus, iron and estradiol together downregulate ERα through Mdm2-mediated proteolysis, providing a potential explanation for failures of HRT in late postmenopausal subjects with aging-related iron accumulation. This study suggests that immediate HRT after menopause, along with appropriate iron chelation, might provide benefits from AS.


Asunto(s)
Aterosclerosis , Receptor alfa de Estrógeno , Humanos , Femenino , Ratones , Animales , Receptor alfa de Estrógeno/genética , Posmenopausia , Terapia de Reemplazo de Estrógeno , Aterosclerosis/metabolismo , Estradiol , Terapia de Reemplazo de Hormonas , Quelantes del Hierro
13.
Biomed Opt Express ; 14(7): 3635-3653, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37497521

RESUMEN

Microvascular cerebral blood flow exhibits pulsatility at the cardiac frequency that carries valuable information about cerebrovascular health. This study used diffuse correlation spectroscopy to quantify normative features of these waveforms in a cohort of thirty healthy adults. We demonstrate they are sensitive to changes in vascular tone, as indicated by pronounced morphological changes with hypercapnia. Further, we observe significant sex-based differences in waveform morphology, with females exhibiting higher flow, greater area-under-the-curve, and lower pulsatility. Finally, we quantify normative values for cerebral critical closing pressure, i.e., the minimum pressure required to maintain flow in a given vascular region.

14.
Cell Biosci ; 13(1): 87, 2023 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-37179385

RESUMEN

BACKGROUND: Ferroptosis is a unique cell death, dependent on iron and phospholipid peroxidation, involved in massive processes of physiopathology. Tremendous attention has been caught in oncology, particularly for those therapy-resistant cancers in the mesenchymal state prone to metastasis due to their exquisite vulnerability to ferroptosis. Therefore, a therapeutical ferroptosis inducer is now underway to be exploited. RESULTS: A natural compound, hinokitiol (hino), has been considered to be an iron chelator. We have a novel finding that hino complexed with iron to form Fe(hino)3 can function as a ferroptosis inducer in vitro. The efficiency, compared with the same concentration of iron, increases nearly 1000 folds. Other iron chelators, ferroptosis inhibitors, or antioxidants can inhibit Fe(hino)3-induced ferroptosis. The complex Fe(hino)3 efficacy is further confirmed in orthotopic triple-negative breast cancer (TNBC) tumor models that Fe(hino)3 significantly boosted lipid peroxidation to induce ferroptosis and significantly reduced the sizes of TNBC cell-derived tumors. The drug's safety was also evaluated, and no detrimental side effects were found with the tested dosage. CONCLUSIONS: When entering cells, the chelated iron by hinokitiol as a complex Fe(hino)3 is proposed to be redox-active to vigorously promote the production of free radicals via the Fenton reaction. Thus, Fe(hino)3 is a ferroptosis inducer and, therapeutically, exhibits anti-TNBC activity.

15.
Inflammopharmacology ; 31(4): 1993-2005, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37155118

RESUMEN

Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and antioxidant activities. However, there is no evidence whether oridonin have a protective effect on atherosclerosis. This study focused on the effects of oridonin on oxidative stress and inflammation generated from atherosclerosis. The therapeutic effect on atherosclerosis was evaluated by intraperitoneal injection of oridonin in a high-fat fed ApoE-/- mouse model. We isolated mouse peritoneal macrophages and detected the effect of oridonin on oxidized low-density lipoprotein-induced lipid deposition. Oil red O staining, Masson's staining, dihydroethidium fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR were used to evaluate the effect on atherosclerosis and explore the mechanisms. Oridonin treatment significantly alleviated the progression of atherosclerosis, reduced macrophage infiltration and stabilized plaques. Oridonin could significantly inhibit inflammation associated with NLRP3 activation. Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that oridonin could prevent the formation of foam cells by increasing lipid efflux protein and reducing lipid uptake protein in macrophages. Oridonin has a protective effect on atherosclerosis in ApoE-/- mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore, oridonin may be a potential therapeutic agent for atherosclerosis.


Asunto(s)
Aterosclerosis , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Noqueados , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Inflamación/tratamiento farmacológico , Apolipoproteínas E , Apolipoproteínas/uso terapéutico , Ratones Endogámicos C57BL
16.
Neurophotonics ; 10(1): 015010, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37006324

RESUMEN

Significance: Diffuse correlation spectroscopy (DCS) is an emerging optical modality for non-invasive assessment of an index of regional cerebral blood flow. By the nature of this noninvasive measurement, light must pass through extracerebral layers (i.e., skull, scalp, and cerebral spinal fluid) before detection at the tissue surface. To minimize the contribution of these extracerebral layers to the measured signal, an analytical model has been developed that treats the head as a series of three parallel and infinitely extending slabs (mimicking scalp, skull, and brain). The three-layer model has been shown to provide a significant improvement in cerebral blood flow estimation over the typically used model that treats the head as a bulk homogenous medium. However, the three-layer model is still a gross oversimplification of the head geometry that ignores head curvature, the presence of cerebrospinal fluid (CSF), and heterogeneity in layer thickness. Aim: Determine the influence of oversimplifying the head geometry on cerebral blood flow estimated with the three-layer model. Approach: Data were simulated with Monte Carlo in a four-layer slab medium and a three-layer sphere medium to isolate the influence of CSF and curvature, respectively. Additionally, simulations were performed on magnetic resonance imaging (MRI) head templates spanning a wide-range of ages. Simulated data were fit to both the homogenous and three-layer model for CBF. Finally, to mitigate the errors in potential CBF estimation due to the difficulty in defining layer thickness, we investigated an approach to identify an equivalent, "optimized" thickness via a pressure modulation. Results: Both head curvature and failing to account for CSF lead to significant errors in the estimation of CBF. However, the effect of curvature and CSF on relative changes in CBF is minimal. Further, we found that CBF was underestimated in all MRI-templates, although the magnitude of these underestimations was highly influenced by small variations in the source and detector optode positioning. The optimized thickness obtained from pressure modulation did not improve estimation accuracy of CBF, although it did significantly improve the estimation accuracy of relative changes in CBF. Conclusions: In sum, these findings suggest that the three-layer model holds promise for improving estimation of relative changes in cerebral blood flow; however, estimations of absolute cerebral blood flow with the approach should be viewed with caution given that it is difficult to account for appreciable sources of error, such as curvature and CSF.

17.
Environ Pollut ; 327: 121593, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37030599

RESUMEN

Eradication of heavy metals and dyes simultaneously from wastewater is urgently needed to safeguard public and environmental health. In this study, magnetic porous biochar derived from wasted Myriophyllum aquaticum (MPMaB) was synthesized by KOH-activation and co-precipitation method to treat chromate and rhodamine B (RhB)-bearing wastewater. The KOH activation significantly improved the pore structure of biochar with a high specific surface area of 937.1 m2 g-1. The sorption performance of MPMaB for Cr(VI) and RhB in single and co-solutes conditions was evaluated. In single system, a pH-dependent sorption pattern for Cr(VI) by MPMaB was revealed and the estimated sorption capability reached 175.4 mg g-1, whereas the Langmuir-based sorption capacity of RhB was 175.4 mg g-1 pH-independently. MPMaB partially transformed Cr(VI) to less toxic Cr(III) (approximately 59.3%). Synergistic sorption of Cr(VI) with the coexistence of RhB was observed, where synergistic effect ranged from 119% to 527% depending on pH. For example, the sorption capacity of Cr(VI) on MPMaB, at pH 2, augmented from 175.4 mg g-1 (single system) to 208.3 mg g-1 (binary system). Preferential sorption of Cr(VI) was found and was further confirmed by the post-sorption of Cr(VI) (or RhB) by MPMaB pre-sorbed with RhB (or chromate). Chromate sorption mechanisms mainly include electrostatic interactions and complexation, while the sorption of RhB is ascribed to π-π interactions, pore filling and hydrogen bonding. Additionally, MPMaB showed excellent reusability and maintained high removal efficiency after 5 cycles. In short, MPMaB can efficiently treat chromium and dyes-containing wastewater as sustainable and environmentally friendly adsorbent.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Cromatos , Biomasa , Porosidad , Adsorción , Contaminantes Químicos del Agua/química , Cromo/química , Carbón Orgánico/química , Cinética , Fenómenos Magnéticos
18.
Antioxidants (Basel) ; 12(3)2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36978814

RESUMEN

BACKGROUND: Iron regulatory proteins (IRPs) maintain cellular iron homeostasis. Due to aberrant tissue-iron distribution, Irp2-deficient mice suffer microcytic anemia and neurodegeneration, while iron overload occurs in the liver and intestine. We previously found that Irp2 deficiency-induced Hif2 plays an important role in neurodegeneration. METHODS: To test the role of Hif2 in Irp2 deficiency-induced anemia, we used Irp2 global knockout mice. Following Hif2 inhibition, routine blood tests, iron availability in bone marrow, histological assays, and biochemical analysis were performed to assess anemia improvement and tissue iron distribution. RESULTS: We found that Hif2 inhibition improved anemia. The increased iron bioavailability for erythropoiesis was mainly derived from hepatic iron release, and secondly from enhanced intestinal absorption. We further demonstrate that nuclear receptor coactivator 4 (Ncoa4) was upregulated for iron release via the process of ferritinophagy. The released iron was utilized not only for intracellular Fe-S biogenesis but also for erythropoiesis after being exported from the liver to circulation. The hepatic iron export reduced hepcidin expression to further support iron absorption through the hepcidin-ferroportin axis to alleviate intestinal iron overload. CONCLUSION: Irp2 not only regulates cellular iron homeostasis but also tissue iron distribution by managing the involvement of Hif2-Ncoa4.

19.
Environ Sci Pollut Res Int ; 30(17): 50484-50495, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36795216

RESUMEN

The treatment and surfactant recovery of soil washing/flushing effluent containing high levels of surfactants and organic pollutants are critical for the surfactant-assisted remediation of soils and waste management due to their complexity and high-potential risks. Combination of waste activated sludge material (WASM) and a kinetic-based two-stage system design was introduced in this study as a novel strategy for the separation of phenanthrene and pyrene from Tween 80 solutions. The results showed that WASM can effectively sorb phenanthrene and pyrene with high affinities (Kd) of 2325.5 L·kg-1 and 9911.2 L·kg-1, respectively. This allowed a high-level recovery of Tween 80 of 90.47 ± 1.86%, with selectivity of up to 69.7. In addition, a two-stage design was constructed, and the results showed an improved reaction time (approximately 5% of equilibrium time in conventional single-stage process) and increased the separation levels of phenanthrene or pyrene from Tween 80 solutions. For instance, the minimal total operating time for the sorption of 99% pyrene from 1.0 g·L-1 Tween 80 was only 23.0 min in the two-stage process compared to that of 480 min with a 71.9% removal level in the single-stage system. Results indicated that the combination of low-cost waste WASH and two-stage design was a high-efficiency and time-saving way to recover surfactants from soil washing effluents.


Asunto(s)
Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Tensoactivos , Polisorbatos , Aguas del Alcantarillado , Hidrocarburos Policíclicos Aromáticos/análisis , Pirenos , Lipoproteínas , Suelo , Contaminantes del Suelo/análisis
20.
Langmuir ; 2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36621519

RESUMEN

Numerous cationic magnetic nanoparticles (MNPs) have previously been developed for demulsifying oil-in-water (O/W) emulsion, and results showed that the cationic MNPs could effectively flocculate and remove the negatively charged oil droplets via charge attraction; however, to the best of our knowledge, there are no research reports regarding the synergetic influence of both the positive charge density and interfacial activity of MNPs on the demulsification performance. In this study, three tertiary amine polymer-grafted MNPs, namely, poly(2-dimethylaminoethyl acrylate)-grafted MNPs (M-PDMAEA), poly(2-dimethylamino)ethyl methacrylate)-grafted MNPs (M-PDMAEMA), and poly(2-diethylaminoethyl methacrylate)-grafted MNPs (M-PDEAEMA), were synthesized and evaluated for their demulsification performance. Results demonstrated that a high positive charge density and superior interfacial activity of MNPs could cause partial oil droplet re-dispersion when excessive MNPs were introduced, leading to a lower magnetic separation efficiency and narrower demulsification window. Herein, a demulsification window is defined as a range of nanoparticle dosages in which the MNPs can effectively demulsify the O/W emulsion under certain conditions. For highly positively charged MNPs, their good interfacial activity could aggravate the formation of a narrower demulsification window. When tertiary amine polymer-grafted MNPs carried a lower positive charge density or weak interfacial activity, that is, M-PDMAEA at pH 4.0, M-PDMAEMA at pH 5.0-9.0, and M-PDEAEMA at pH 9.0-10.0, wide demulsification windows were observed. Additionally, a recycling experiment suggested that MNPs could maintain high demulsification efficiency up to at least five cycles, indicating their satisfactory recyclability. The three tertiary amine polymer-grafted MNPs can be potentially used for efficient demulsification from surfactant-free O/W emulsion in various pH ranges.

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