Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 77
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Cancer Immunol Immunother ; 73(4): 75, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38532108

RESUMEN

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.


Asunto(s)
Neoplasias , Neoplasias Gástricas , Animales , Humanos , Antígeno CD47 , Modelos Animales de Enfermedad , Inmunoterapia , Leucocitos Mononucleares/metabolismo , Recurrencia Local de Neoplasia , Fagocitosis , Factor A de Crecimiento Endotelial Vascular
2.
J Environ Manage ; 353: 120157, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38295639

RESUMEN

Nanoscale zerovalent iron (Fe0)-based materials have been demonstrated to be a effective method for the U(VI) removal. However, limited research has been conducted on the long-term immobilization efficiency and mechanism of Fe0-based materials for U(VI), which are essential for achieving safe handling and disposal of U(VI) on a large scale. In this study, the prepared carboxymethyl cellulose (CMC) and sulfurization dual stabilized Fe0 (CMC-Fe0/FeS) exhibited excellent long-term immobilization performances for U(VI) under both anoxic and oxic conditions, with the immobilization efficiencies were respectively reached over 98.0 % and 94.8 % after 180 days of aging. Most importantly, different from the immobilization mechanisms of the fresh CMC-Fe0/FeS for U(VI) (the adsorption effect of -COOH and -OH groups, coordination effect with sulfur species, as well as reduction effect of Fe0), the re-mobilized U(VI) were finally re-immobilized by the formed FeOOH and Fe3O4 on the aged CMC-Fe0/FeS. Under anoxic conditions, more Fe3O4 was produced, which may be the main reason for the long-term immobilization U(VI). Under oxic conditions, the production of Fe3O4 and FeOOH were relatively high, which both played significant roles in re-immobilizing U(VI) through surface complexation, reduction and incorporation effects.


Asunto(s)
Uranio , Carboximetilcelulosa de Sodio , Hierro , Adsorción
3.
Environ Geochem Health ; 46(7): 222, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849580

RESUMEN

In previous studies, iron-based nanomaterials, especially biochar (BC)-supported sulfidized nanoscale zero-valent iron (S-nZVI/BC), have been widely used for the remediation of soil contaminants. However, its potential risks to the soil ecological environment are still unknown. This study aims to explore the effects of 3% added S-nZVI/BC on soil environment and microorganisms during the remediation of Cd contaminated yellow-brown soil of paddy field. The results showed that after 49 d of incubation, S-nZVI/BC significantly reduced physiologically based extraction test (PBET) extractable Cd concentration (P < 0.05), and increased the immobilization efficiency of Cd by 16.51% and 17.43% compared with S-nZVI and nZVI/BC alone, respectively. Meanwhile, the application of S-nZVI/BC significantly increased soil urease and sucrase activities by 0.153 and 0.446 times, respectively (P < 0.05), improving the soil environmental quality and promoting the soil nitrogen cycle and carbon cycle. The results from the analysis of the 16S rRNA genes indicated that S-nZVI/BC treatment had a minimal effect on the bacterial community and did not appreciably alter the species of the original dominant bacterial phylum. Importantly, compared to other iron-based nanomaterials, incorporating S-nZVI/BC significantly increased the soil organic carbon (OC) content and decreased the excessive release of iron (P < 0.05). This study also found a significant negative correlation between OC content and Fe(II) content (P < 0.05). It might originate from the reducing effect of Fe-reducing bacteria, which consumed OC to promote the reduction of Fe(III). Accompanying this process, the redistribution of Cd and Fe mineral phases in the soil as well as the generation of secondary Fe(II) minerals facilitated Cd immobilization. Overall, S-nZVI/BC could effectively reduce the bioavailability of Cd, increase soil nutrients and enzyme activities, with less toxic impacts on the soil microorganisms.


Asunto(s)
Cadmio , Carbón Orgánico , Hierro , Microbiología del Suelo , Contaminantes del Suelo , Carbón Orgánico/química , Cadmio/química , Hierro/química , Oryza , Suelo/química , Bacterias/metabolismo , Restauración y Remediación Ambiental/métodos , ARN Ribosómico 16S , Biodegradación Ambiental
4.
Cardiovasc Diabetol ; 22(1): 142, 2023 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-37330498

RESUMEN

BACKGROUND: Biomarker of insulin resistance, namely triglyceride-glucose index, is potentially useful in identifying critically ill patients at high risk of hospital death. However, the TyG index might have variations over time during ICU stay. Hence, the purpose of the current research was to verify the associations between the dynamic change of the TyG index during the hospital stay and all-cause mortality. METHODS: The present retrospective cohort study was conducted using the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV) critical care dataset, which included data from 8835 patients with 13,674 TyG measurements. The primary endpoint was 1-year all-cause mortality. Secondary outcomes included in-hospital all-cause mortality, the need for mechanical ventilation during hospitalization, length of stay in the hospital. Cumulative curves were calculated using the Kaplan-Meier method. Propensity score matching was performed to reduce any potential baseline bias. Restricted cubic spline analysis was also employed to assess any potential non-linear associations. Cox proportional hazards analyses were performed to examine the association between the dynamic change of TyG index and mortality. RESULTS: The follow-up period identified a total of 3010 all-cause deaths (35.87%), of which 2477 (29.52%) occurred within the first year. The cumulative incidence of all-cause death increased with a higher quartile of the TyGVR, while there were no differences in the TyG index. Restricted cubic spline analysis revealed a nearly linear association between TyGVR and the risk of in-hospital all-cause mortality (P for non-linear = 0.449, P for overall = 0.004) as well as 1-year all-cause mortality (P for non-linear = 0.909, P for overall = 0.019). The area under the curve of all-cause mortality by various conventional severity of illness scores significantly improved with the addition of the TyG index and TyGVR. The results were basically consistent in subgroup analysis. CONCLUSIONS: Dynamic change of TyG during hospital stay is associated with in-hospital and 1-year all-cause mortality, and may be superior to the effect of baseline TyG index.


Asunto(s)
Enfermedad Crítica , Glucosa , Humanos , Tiempo de Internación , Estudios Retrospectivos , Triglicéridos , Glucemia , Factores de Riesgo , Biomarcadores
5.
Int J Mol Sci ; 24(14)2023 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-37510993

RESUMEN

Immunotherapies including adaptive immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have developed the treatment of cancer in clinic, and most of them focus on activating T cell immunity. Although these strategies have obtained unprecedented clinical responses, only limited subsets of cancer patients could receive long-term benefits, highlighting the demand for identifying novel targets for the new era of tumor immunotherapy. Innate immunity has been demonstrated to play a determinative role in the tumor microenvironment (TME) and influence the clinical outcomes of tumor patients. A thorough comprehension of the innate immune cells that infiltrate tumors would allow for the development of new therapeutics. In this review, we outline the role and mechanism of innate immunity in TME. Moreover, we discuss innate immunity-based cancer immunotherapy in basic and clinical studies. Finally, we summarize the challenges in sufficiently motivating innate immune responses and the corresponding strategies and measures to improve anti-tumor efficacy. This review could aid the comprehension of innate immunity and inspire the creation of brand-new immunotherapies for the treatment of cancer.


Asunto(s)
Neoplasias , Humanos , Neoplasias/patología , Inmunidad Innata , Inmunoterapia , Linfocitos T , Biología , Microambiente Tumoral
6.
Chem Soc Rev ; 48(20): 5266-5302, 2019 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-31468053

RESUMEN

As a newly emerging kind of porous material, covalent organic frameworks (COFs) have drawn much attention because of their fascinating structural features (e.g., divinable structure, adjustable porosity and total organic backbone). Since the seminal work of Yaghi and co-workers reported in 2005, the COF materials have shown superior potential in diverse applications, such as gas storage, adsorption, optoelectronics, catalysis, etc. Recently, COF materials have shown a new trend in sensing fields. This critical review briefly describes the synthesis routes for COF powders and thin films. What's more, the most fascinating and significant applications of COFs in sensing fields including explosive sensing, humidity sensing, pH detection, biosensing, gas sensing, metal ion sensing, and other substance sensing are summarized and highlighted. Finally, the major challenges and future trends of COFs with respect to their preparation and sensing applications are discussed.

7.
J Environ Manage ; 261: 109879, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32148248

RESUMEN

Heavy metal pollution, because of its high toxicity, non-biodegradability and biological enrichment, has been identified as a global aquatic ecosystems threat in recent decades. Due to the high efficiency, low cost, satisfactory recyclability, easy storage and separation, biosorbents have exhibited a promising prospect for heavy metals treatment in aqueous phase. This article comprehensively summarized different types of biosorbents derived from available low-cost raw materials such as agricultural and forestry wastes. The raw materials obtained are treated with conventional pretreatment or novel methods, which can greatly enhance the adsorption performance of the biosorbents. The suitable immobilization methods can not only further enhance the adsorption performance of the biosorbents, but also facilitate the process of separating the biosorbents from the wastewater. In addition, once biosorbents are put into large-scale use, the final disposal problems cannot be avoided. Therefore, it is necessary to review the currently accepted final disposal methods of biosorbents. Moreover, through the analysis of the adsorption and desorption mechanisms of biosorbents, it is not only beneficial to find the better methods to improve the adsorption performance of the biosorbents, but also better to explain the influencing factors of adsorption effect for biosorbents. Especially, different from many researches focused on biosorbents, this work highlighted the combination of biosorbents with catalytic technologies, which provided new ideas for the follow-up research direction of biosorbents. Finally, the purpose of this paper is to inject new impetus into the future development of biosorbents.


Asunto(s)
Metales Pesados , Contaminantes Químicos del Agua , Purificación del Agua , Adsorción , Ecosistema , Aguas Residuales
8.
J Environ Sci (China) ; 78: 267-275, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30665645

RESUMEN

Microplastics have caused great concern worldwide recently due to their ubiquitous presence within the marine environment. Up to now, most attention has been paid to their sources, distributions, measurement methods, and especially their eco-toxicological effects. With microplastics being increasingly detected in freshwater, it is urgently necessary to evaluate their behaviors during coagulation and ultrafiltration (UF) processes. Herein, the removal behavior of polyethylene (PE), which is easily suspended in water and is the main component of microplastics, was investigated with commonly used Fe-based salts. Results showed that although higher removal efficiency was induced for smaller PE particles, low PE removal efficiency (below 15%) was observed using the traditional coagulation process, and was little influenced by water characteristics. In comparison to solution pH, PAM addition played a more important role in increasing the removal efficiency, especially anionic PAM at high dosage (with efficiency up to 90.9%). The main reason was ascribed to the dense floc formation and high adsorption ability because of the positively charged Fe-based flocs under neutral conditions. For ultrafiltration, although PE particles could be completely rejected, slight membrane fouling was caused owing to their large particle size. The membrane flux decreased after coagulation; however, the membrane fouling was less severe than that induced by flocs alone due to the heterogeneous nature of the cake layer caused by PE, even at high dosages of Fe-based salts. Based on the behavior exhibited during coagulation and ultrafiltration, we believe these findings will have potential application in drinking water treatment.


Asunto(s)
Agua Potable/química , Plásticos/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Floculación , Hierro/química , Membranas Artificiales , Plásticos/análisis , Ultrafiltración/métodos , Contaminantes Químicos del Agua/análisis
9.
Crit Rev Biotechnol ; 38(5): 671-689, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29082760

RESUMEN

Endocrine-disrupting compounds (EDCs) can interfere with endocrine systems and bio-accumulate through the food chain and even decrease biodiversity in contaminated areas. This review discusses a critical overview of recent research progress in the biotransformation of EDCs (including polychlorinated biphenyl and nonylphenol, and suspected EDCs such as heavy metals and sulfonamide antibiotics) by white rot fungi (WRF) based on techniques with an emphasis on summarizing and analyzing fungal molecular, metabolic and genetic mechanisms. Not only intracellular metabolism which seems to perform essential roles in the ability of WRF to transform EDCs, but also advanced applications are deeply discussed. This review mainly reveals the removal pathway of heavy metal and antibiotic pollutants because the single pollution almost did not exist in a real environment while the combined pollution has become more serious and close to people's life. The trends in WRF technology and its related advanced applications which use the combined technology, including biocatalysis of WRF and adsorption of nanomaterials, to degrade EDCs have also been introduced. Furthermore, challenges and future research needs EDCs biotransformation by WRF are also discussed. This research, referring to metabolic mechanisms and the combined technology of WRF with nanomaterials, undoubtedly contributes to the applications of biotechnology. This review will be of great benefit to an understanding of the trends in biotechnology for the removal of EDCs.


Asunto(s)
Biodegradación Ambiental , Disruptores Endocrinos , Nanoestructuras/química , Phanerochaete , Biotecnología , Biotransformación , Disruptores Endocrinos/química , Disruptores Endocrinos/aislamiento & purificación , Disruptores Endocrinos/metabolismo , Metales Pesados/química , Metales Pesados/aislamiento & purificación , Metales Pesados/metabolismo , Phanerochaete/química , Phanerochaete/metabolismo , Phanerochaete/fisiología
10.
Kidney Blood Press Res ; 43(5): 1607-1622, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30347394

RESUMEN

BACKGROUND/AIMS: This experimental study aims to observe whether the protective effect of propofol against renal ischemia-reperfusion injury (IRI) in the rat interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43). METHODS: This study randomly divided male Sprague Dawley (SD) rats into an untreated control group, a sham-operated control group (sham group), an ischemia-reperfusion group (IR group), a propofol group (propofol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperfusion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the left kidney. Forty-five minutes after renal ischemia-reperfusion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting. RESULTS: The experimental study confirmed that the BUN and SCr of rats markedly increased after ischemia-reperfusion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by focal hemorrhages. Furthermore, the contraction activity of the renal interlobar artery greatly decreased, and the tension of the arteries in the renal lobe increased remarkably. After the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe after 24 h of ischemic reperfusion than after only 4 h. However, after pretreatment with propofol, regardless of whether ischemia-reperfusion was applied for 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all forms of renal damage were reversed. CONCLUSION: Our research suggests new ways for propofol to relieve ischemia-reperfusion injury by decreasing the abnormal expression of the gap junction protein Cx43. This study reveals a novel mechanism for the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI.


Asunto(s)
Conexina 43/metabolismo , Propofol/farmacología , Arteria Renal/lesiones , Daño por Reperfusión/prevención & control , Animales , Velocidad del Flujo Sanguíneo , Conexina 43/análisis , Conexina 43/efectos de los fármacos , Conexinas , Masculino , Oligopéptidos , Propofol/uso terapéutico , Ratas , Ratas Sprague-Dawley , Arteria Renal/química , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/patología , Vasoconstricción
11.
Ecotoxicol Environ Saf ; 153: 229-237, 2018 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-29453100

RESUMEN

Lead (Pb) is a highly toxic environmental pollutant, and could result in toxic effects on living organisms. The effects of 0, 100, 200, 500, 1000 and 2000 mg/kg of nZVI on plant growth, Pb accumulation and antioxidative responses of Lolium perenne were investigated. Results showed that the total Pb contents in L. perenne with the treatment of low concentrations of nZVI (100, 200 and 500 mg/kg) were higher than those in the non-nZVI treatments, and the highest Pb accumulation capacity of 1175.40 µg per pot was observed in L. perenne with the treatment of 100 mg/kg nZVI. However, the total Pb contents in L. perenne decreased at high concentrations of nZVI (1000 and 2000 mg/kg). This might be resulted from the decrease of photosynthetic chlorophyll content and the aggravated oxidative stress induced by the high concentration of nZVI, which caused the decrease of plant biomass and metal accumulation capacity in plant. Moreover, the sequential extraction experiments results showed that the lowest acid soluble fraction of Pb in the sediments was found in the treatment with 100 mg/kg of nZVI, indicating that 100 mg/kg was the optimum concentration for nZVI to assist the phytoremediation of Pb-polluted sediment. To conclude, these findings provide a promising method to remediate Pb-polluted sediment by nZVI assisted phytoremediation.


Asunto(s)
Sedimentos Geológicos/química , Hierro/química , Plomo/análisis , Lolium/efectos de los fármacos , Nanoestructuras/química , Contaminantes del Suelo/análisis , Antioxidantes/análisis , Biodegradación Ambiental , Biomasa , Relación Dosis-Respuesta a Droga , Lolium/química , Lolium/enzimología , Suelo/química
12.
Environ Sci Technol ; 51(19): 11308-11316, 2017 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-28850225

RESUMEN

Nanoparticles can be absorbed by plants, but their impacts on phytoremediation are not yet well understood. This study was carried out to determine the impacts of starch stabilized nanoscale zerovalent iron (S-nZVI) on the cadmium (Cd) accumulation and the oxidative stress in Boehmeria nivea (L.) Gaudich (ramie). Plants were cultivated in Cd-contaminated sediments amended with S-nZVI at 100, 500, and 1000 mg/kg, respectively. Results showed that S-nZVI promoted Cd accumulation in ramie seedlings. The subcellular distribution result showed that Cd content in cell wall of plants reduced, and its concentration in cell organelle and soluble fractions increased at S-nZVI treatments, indicating the promotion of Cd entering plant cells by S-nZVI. In addition, the 100 mg/kg S-nZVI alleviated the oxidative damage to ramie under Cd-stress, while 500 and 1000 mg/kg S-nZVI inhibited plant growth and aggravated the oxidative damage to plants. These findings demonstrate that nanoparticles at low concentration can improve the efficiency of phytoremediation. This study herein develops a promising novel technique by the combined use of nanotechnology and phytoremediation in the remediation of heavy metal contaminated sites.


Asunto(s)
Biodegradación Ambiental , Boehmeria , Cadmio , Hierro , Estrés Oxidativo
13.
J Sep Sci ; 39(3): 466-72, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26576511

RESUMEN

MaiLuoNing injection is a traditional Chinese medicine that used clinically since the 1950s in China. However, anaphylactic reactions, through the potentiation of mast cell degranulation, have been reported. In the present study, a rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization-ion trap-time of flight-mass spectrometry method was established for screening, analyzing, and identifying the potential anaphylactic components of MaiLuoNing injection. Harpagoside, a potential degranulator of rat basophilic leukemia-2H3 cells, was retained in rat basophilic leukemia-2H3 cell membrane chromatography. We aimed to evaluate the retained components to determine which of those were capable of inducing degranulation of basophilic leukemia cells. A ß-hexosaminidase assay revealed that harpagoside can induce rat basophilic leukemia-2H3 cell degranulation in a dose-dependent manner. BLBA/c mice also exhibit passive cutaneous anaphylaxis in response to harpagoside. These results indicate that rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization ion trap time-of-flight mass spectrometry is effective in screening for the anaphylactic components of MaiLuoNing injection.


Asunto(s)
Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/uso terapéutico , Leucemia Basofílica Aguda/patología , Espectrometría de Masa por Ionización de Electrospray/métodos , Animales , Línea Celular , Ratas
14.
J Neuroinflammation ; 12: 9, 2015 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-25595674

RESUMEN

BACKGROUND: Accumulating evidence suggests that neuroinflammation plays an important role in the progression of Parkinson's disease (PD). Excessively activated microglia produce several pro-inflammatory enzymes and pro-inflammatory cytokines, leading to damage to surrounding neurons and eventually inducing neurodegeneration. Therefore, the inhibition of microglial overactivation may be a potential therapeutic strategy to prevent the further progression of PD. ß-Hydroxybutyric acid (BHBA) has been shown to suppress lipopolysaccharide (LPS)-induced inflammation in BV-2 cells and to protect dopaminergic neurons in previous studies, but the underlying mechanisms remain unclear. Thus, in this study, we further investigated this mechanism in LPS-induced in vivo and in vitro PD models. METHODS: For the in vitro experiments, primary mesencephalic neuron-glia cultures were pretreated with BHBA and stimulated with LPS. [(3)H]dopamine (DA) uptake, tyrosine hydroxylase-immunoreactive (TH-ir) neurons and morphological analysis were evaluated and analyzed in primary mesencephalic neuron-glia cultures. In vivo, microglial activation and the injury of dopaminergic neurons were induced by LPS intranigral injection, and the effects of BHBA treatment on microglial activation and the survival ratio and function of dopaminergic neurons were investigated. Four our in vitro mechanistic experiment, primary microglial cells were pretreated with BHBA and stimulated with LPS; the cells were then assessed for the responses of pro-inflammatory enzymes and pro-inflammatory cytokines, and the NF-κB signaling pathway was evaluated and analyzed. RESULTS: We found that BHBA concentration-dependently attenuated the LPS-induced decrease in [(3)H]DA uptake and loss of TH-ir neurons in the primary mesencephalic neuron/glia mixed culture. BHBA treatment significantly improved the motor dysfunction of the PD model rats induced by intranigral injection of LPS, and this beneficial effect of BHBA was attributed to the inhibition of microglial overactivation and the protection of dopaminergic neurons in the substantia nigra (SN). Our in vitro mechanistic study revealed that the inhibitory effect of BHBA on microglia was mediated by G-protein-coupled receptor 109A (GPR109A) and involved the NF-κB signaling pathway, causing the inhibition of pro-inflammatory enzyme (iNOS and COX-2) and pro-inflammatory cytokine (TNF-α, IL-1ß, and IL-6) production. CONCLUSIONS: In conclusion, the present study supports the effectiveness of BHBA in protecting dopaminergic neurons against inflammatory challenge.


Asunto(s)
Ácido 3-Hidroxibutírico/uso terapéutico , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/etiología , Enfermedad de Parkinson/complicaciones , Receptores Acoplados a Proteínas G/metabolismo , Receptores Nicotínicos/metabolismo , Animales , Proteínas de Unión al Calcio/metabolismo , Células Cultivadas , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Embrión de Mamíferos , Regulación de la Expresión Génica/efectos de los fármacos , Lipopolisacáridos/toxicidad , Masculino , Mesencéfalo/citología , Proteínas de Microfilamentos/metabolismo , Neuroglía/efectos de los fármacos , Neuronas/efectos de los fármacos , Enfermedad de Parkinson/etiología , Ratas , Ratas Wistar , Receptores Acoplados a Proteínas G/genética , Receptores Nicotínicos/genética , Transducción de Señal/efectos de los fármacos , Conducta Estereotipada/efectos de los fármacos
15.
Mediators Inflamm ; 2014: 983401, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24803746

RESUMEN

ß-Hydroxybutyric acid (BHBA) has neuroprotective effects, but the underlying molecular mechanisms are unclear. Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The current study investigates the potential mechanisms whereby BHBA affects the expression of potentially proinflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). The results showed that BHBA significantly reduced LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1ß, and IL-6. Blocking of GPR109A by PTX resulted in a loss of this anti-inflammatory effect in BV-2 cells. Western blot analysis showed that BHBA reduced LPS-induced degradation of IκB-α and translocation of NF-κB, while no effect was observed on MAPKs phosphorylation. All results imply that BHBA significantly reduces levels of proinflammatory enzymes and proinflammatory cytokines by inhibition of the NF-κB signaling pathway but not MAPKs pathways, and GPR109A is essential to this function. Overall, these data suggest that BHBA has a potential as neuroprotective drug candidate in neurodegenerative diseases.


Asunto(s)
Ácido 3-Hidroxibutírico/farmacología , Inflamación/inducido químicamente , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Animales , Línea Celular , Proteínas I-kappa B/metabolismo , Ratones , Inhibidor NF-kappaB alfa , FN-kappa B , Transducción de Señal/efectos de los fármacos
16.
Biosens Bioelectron ; 255: 116270, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38588628

RESUMEN

Hepatocellular carcinoma (HCC), as one of the most lethal cancers, significantly impacts human health. Attempts in this area tends to develop novel technologies with sensitive and multiplexed detection properties for early diagnosis. Here, we present novel hydrogel photonic crystal (PhC) barcodes with tyramine deposition amplified enzyme-linked immunosorbent assay (ELISA) for highly sensitive and multiplexed HCC biomarker screening. Because of the abundant amino groups of acrylic acid (AA) component, the constructed hydrogel PhC barcodes with inverse opal structure could facilitate the loading of antibody probes for subsequent detection of tumor markers. By integrating tyramine deposition amplified ELISA on the barcode, the detection signal of tumor markers has been enhanced. Based on these features, it is demonstrated that the hydrogel PhC barcodes with tyramine deposition amplified ELISA could realize highly sensitive and multiplexed detection of HCC-related biomarkers. It was found that this method is flexible, sensitive and accurate, suitable for multivariate analysis of low abundance tumor markers and future cancer diagnosis. These features make the newly developed PhC barcodes an innovation platform, which possesses tremendous potential for practical application of low abundance targets.


Asunto(s)
Técnicas Biosensibles , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Hidrogeles/química , Carcinoma Hepatocelular/diagnóstico , Técnicas Biosensibles/métodos , Neoplasias Hepáticas/diagnóstico , Biomarcadores de Tumor , Ensayo de Inmunoadsorción Enzimática , Tiramina
17.
Animals (Basel) ; 14(8)2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38672375

RESUMEN

A pig inventory is a crucial component of achieving precise and large-scale farming. In complex pigsty environments, due to pigs' stress reactions and frequent obstructions, it is challenging to count them accurately and automatically. This difficulty contrasts with most current deep learning studies, which rely on overhead views or static images for counting. This research proposes a video-based dynamic counting method, combining YOLOv7 with DeepSORT. By utilizing the YOLOv7 network structure and optimizing the second and third 3 × 3 convolution operations in the head network ELAN-W with PConv, the model reduces the computational demand and improves the inference speed without sacrificing accuracy. To ensure that the network acquires accurate position perception information at oblique angles and extracts rich semantic information, we introduce the coordinate attention (CA) mechanism before the three re-referentialization paths (REPConv) in the head network, enhancing robustness in complex scenarios. Experimental results show that, compared to the original model, the improved model increases the mAP by 3.24, 0.05, and 1.00 percentage points for oblique, overhead, and all pig counting datasets, respectively, while reducing the computational cost by 3.6 GFLOPS. The enhanced YOLOv7 outperforms YOLOv5, YOLOv4, YOLOv3, Faster RCNN, and SSD in target detection with mAP improvements of 2.07, 5.20, 2.16, 7.05, and 19.73 percentage points, respectively. In dynamic counting experiments, the improved YOLOv7 combined with DeepSORT was tested on videos with total pig counts of 144, 201, 285, and 295, yielding errors of -3, -3, -4, and -26, respectively, with an average accuracy of 96.58% and an FPS of 22. This demonstrates the model's capability of performing the real-time counting of pigs in various scenes, providing valuable data and references for automated pig counting research.

18.
Front Cardiovasc Med ; 11: 1373480, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38911515

RESUMEN

Background: Previous studies have indicated a strong link between blood metabolites and hypertension, however the causality of metabolites and hypertension is unknown. Methods: Two-sample Mendelian randomization (MR) analysis was performed to assess the causal relationship between 486 blood metabolites and essential hypertension (EHT). Blood metabolite GWAS data was utilized as the exposure, with EHT GWAS data as the outcome. To further verify the results, another different source of EHT GWAS data was repeatedly analyzed. The major MR analytic approach used to determine causality was inverse variance weighted (IVW), with MR-Egger, Weighted Median, and MR-PRESSO models serving as supplements. We used the Cochran Q test to examine heterogeneity. Horizontal pleiotropy was examined using MR-Egger intercept and MR-PRESSO global test. The MR Steiger test confirmed the causal relationship between blood metabolites and EHT. Results: In this study, nine blood metabolites associated with EHT were preliminarily identified by MR analysis, including four known metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid, creatine, hexadecanedioate) and five unknown metabolites. Then another source of EHT GWAS data was repeatedly analyzed for further verification, and two overlapped metabolites (N-acetylornithine, X-12510-2-aminooctanoic acid) were found. There was a negative correlation between N-acetylornithine and EHT (OR = 0.987, 95% CI = 0.980-0.993, P = 1.01 × 10-4), Cochran's Q test suggested there was no heterogeneity (Q = 31.7586, P = 0.1331), MR-Egger intercept and MR-PRESSO global test suggested there was no horizontal pleiotropy (P > 0.05), Leave-one-out analysis indicated that no single single-nucleotide polymorphism (SNP) had a significant effect on the results, and MR Steiger test confirmed that the direction of causality was correct (P < 0.001). There was a negative correlation between X-12510-2-aminooctanoic acid and EHT (OR = 0.982, 95% CI = 0.972-0.993, P = 0.0017), and there was no evidence of heterogeneity or pleiotropy in multiple sensitivity analyses. Conclusion: The study discovered some blood metabolites causally linked to EHT, which might lead to new understandings of the pathophysiology of hypertension.

19.
Environ Sci Pollut Res Int ; 31(7): 10950-10966, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38214863

RESUMEN

The pollution of antibiotics, specifically ciprofloxacin (CIP), has emerged as a significant issue in the aquatic environment. Advanced oxidation processes (AOPs) are capable of achieving stable and efficient removal of antibiotics from wastewater. In this work, biochar-supported sulfidized nanoscale zero-valent iron (S-nZVI/BC) was adopted to activate persulfate (PS) for the degradation of CIP. The impacts of different influencing factors such as S/Fe molar ratios, BC/S-nZVI mass ratios, PS concentration, S-nZVI/BC dosage, CIP concentration, initial pH, coexisting anions, and humic acid on CIP degradation efficiency were explored by batch experiments. The results demonstrated that the highest degradation ability of S-nZVI/BC was achieved when the S/Fe molar ratio was 0.07 and the BC/S-nZVI mass ratio was 1:1. Under the experimental conditions with 0.6 g/L S-nZVI/BC, 2 mmol/L PS, and 10 mg/L CIP, the degradation rate reached 97.45% after 90 min. The S-nZVI/BC + PS system showed significant degradation in the pH range from 3 to 9. The coexisting anions affected the CIP degradation efficiency in the following order: CO32- > NO3- > SO42- > Cl-. The radical quenching experiments and electron paramagnetic resonance (EPR) revealed that oxidative species, including SO4•-, HO•, •O2-, and 1O2, all contribute to the degradation of CIP, in which •O2- plays a particularly prominent role. Furthermore, the probable degradation pathway of CIP was explored according to the 12 degradation intermediates identified by LC-MS. This study provides a new idea for the activation method of PS and presents a new approach for the treatment of aqueous antibiotics with highly catalytic active nanomaterials.


Asunto(s)
Carbón Orgánico , Ciprofloxacina , Contaminantes Químicos del Agua , Hierro , Contaminantes Químicos del Agua/análisis , Antibacterianos , Agua
20.
Water Res ; 253: 121309, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38367381

RESUMEN

Antibiotics and antibiotic resistance genetic pollution have become a global environmental and health concern recently, with frequent detection in various environmental media. Therefore, finding ways to control antibiotics and antibiotic resistance genes (ARGs) is urgently needed. Nano zero-valent iron (nZVI) has shown a positive effect on antibiotics degradation and restraining ARGs, making it a promising solution for controlling antibiotics and ARGs. However, given the current increasingly fragmented research focus and results, a comprehensive review is still lacking. In this work, we first introduce the origin and transmission of antibiotics and ARGs in various environmental media, and then discuss the affecting factors during the degradation of antibiotics and the control of ARGs by nZVI and modified nZVI, including pH, nZVI dose, and oxidant concentration, etc. Then, the mechanisms of antibiotic and ARGs removal promoted by nZVI are also summarized. In general, the mechanism of antibiotic degradation by nZVI mainly includes adsorption and reduction, while promoting the biodegradation of antibiotics by affecting the microbial community. nZVI can also be combined with persulfates to degrade antibiotics through advanced oxidation processes. For the control of ARGs, nZVI not only changes the microbial community structure, but also affects the proliferation of ARGs through affecting the fate of mobile genetic elements (MGEs). Finally, some new ideas on the application of nZVI in the treatment of antibiotic resistance are proposed. This paper provides a reference for research and application in this field.


Asunto(s)
Antibacterianos , Contaminantes Químicos del Agua , Antibacterianos/farmacología , Hierro/química , Oxidación-Reducción , Farmacorresistencia Microbiana/genética , Adsorción , Contaminantes Químicos del Agua/química
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA