Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
1.
Mol Neurobiol ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842673

RESUMEN

Arachidonic acid (AA), an important polyunsaturated fatty acid in the brain, is hydrolyzed by a direct action of phospholipase A2 (PLA2) or through the combined action of phospholipase C and diacylglycerol lipase, and released into the cytoplasm. Various derivatives of AA can be synthesized mainly through the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (P450) enzyme pathways. AA and its metabolic enzymes and metabolites play important roles in a variety of neurophysiological activities. The abnormal metabolites and their catalytic enzymes in the AA cascade are related to the pathogenesis of various central nervous system (CNS) diseases, including epilepsy. Here, we systematically reviewed literatures in PubMed about the latest randomized controlled trials, animal studies and clinical studies concerning the known features of AA, its metabolic enzymes and metabolites, and their roles in epilepsy. The exclusion criteria include non-original studies and articles not in English.

3.
Adv Sci (Weinh) ; 11(13): e2308123, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38240582

RESUMEN

Fluoro- and chlorofluorocabons (FC/CFCs) are important refrigerants, solvents, and fluoropolymers in industry while being toxic and carrying high global warming potential. Detection and reclamation of FC/CFCs based on adsorption technology with highly selective adsorbents is important to labor safety and environmental protection. Herein, the study reports an integrated method to combine capture, separation, enrichment, and analysis of representative FC/CFCs (chlorodifluoromethane(R22) and 1,1,1,2-tetrafluoroethane (R134a)) by using the highly stable and porous Zr-MOF, DUT-67. Gas adsorption and breakthrough experiments demonstrate that DUT-67 has high R22/R134a uptake (124/116 cm3 g-1) and excellent R22/R134a/CO2 separation performance (IAST selectivities of R22/CO2 and R134a/CO2 ranging from 51.4 to 33.3, and 31.1 to 25.8), even in rather low concentration and humid conditions. A semi-quantitative analysis protocol is set up to analyze the low concentrations of R22/R134a based on the high selective R22/R134a adsorption ability, fast adsorption kinetics, water-resistant utility, facile regeneration, and excellent recyclability of DUT-67. In situ single-crystal X-ray diffraction, theoretical calculations, and in situ diffuse reflectance infrared Fourier transform spectra have been employed to understand the adsorption mechanism. This work may provide a potential adsorbent for purge and trap technique under room temperature, thus promoting the application of MOFs for VOCs sampling and quantitative analysis.

4.
ACS Appl Mater Interfaces ; 16(1): 847-852, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38153916

RESUMEN

Acetylene (C2H2) is widely used as a raw material for producing various downstream commodities in the petrochemical and electronic industry. Therefore, the acquisition of high-purity C2H2 from a C2H2/CO2 mixture produced by partial methane combustion or thermal hydrocarbon cracking is of great significance yet highly challenging due to their similar physical and chemical properties. Herein, we report an anionic metal-organic framework (MOF) named LIFM-210, which has Li+ cations in the pores and shows a higher adsorption affinity for C2H2 than CO2. LIFM-210 is constructed by a unique tetranuclear Ni(II) cluster acting as a 10-connected node and an organic ligand acting as a 5-connected node. Single-component adsorption and transient breakthrough experiments demonstrate the good C2H2 selective separation performance of LIFM-210. Theoretical calculations revealed that Li+ ions strongly prefer C2H2 to CO2 and are primary adsorption sites, playing vital roles in the selective separation of C2H2/CO2.

5.
World J Diabetes ; 14(11): 1585-1602, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38077806

RESUMEN

The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients' quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

6.
Psychon Bull Rev ; 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37803229

RESUMEN

Many mental processes are reactive - they are altered as a result of introspection and monitoring. It has been documented that soliciting trial-by-trial confidence ratings (CRs) reactively improves decision accuracy and lengthens response times (RTs), but the cognitive mechanisms underlying CR reactivity in decision-making remain unknown. The current study conducted two experiments and employed the drift-diffusion model (DDM) to explore why reporting confidence reactively alters the decision-making process. The results showed that CRs led to enhanced decision accuracy, longer RTs, and higher response thresholds. The findings are consistent with an increased conservatism hypothesis which asserts that soliciting CRs provokes feelings of uncertainty and makes individuals more cautious in their decision making.

7.
J Neuroinflammation ; 20(1): 247, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880726

RESUMEN

BACKGROUND: The astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive. METHODS: Here, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis. RESULTS: 4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure. CONCLUSIONS: Our results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.


Asunto(s)
Epilepsia del Lóbulo Temporal , Epilepsia , Factores de Transcripción NFI , Canales Catiónicos TRPV , Animales , Humanos , Ratones , 4-Aminopiridina/efectos adversos , Astrocitos/metabolismo , Encéfalo/metabolismo , Sistema Nervioso Central/metabolismo , Epilepsia/metabolismo , Epilepsia del Lóbulo Temporal/inducido químicamente , Epilepsia del Lóbulo Temporal/metabolismo , Factores de Transcripción NFI/genética , Factores de Transcripción NFI/metabolismo , Canales Catiónicos TRPV/metabolismo , Regulación hacia Arriba
8.
Sci Total Environ ; 901: 165921, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-37527718

RESUMEN

Microplastics (MPs) are abundant in aquaculture water, including in bioflocs aquaculture systems. Compared with other aquaculture systems, biofloc technology systems have the richest microbes and are beneficial to cultivated organisms. Therefore, this study provides a comprehensive assessment of the potential effects of MPs on aquaculture organisms in bioflocs systems. Here, Nile Tilapia (Oreochromis niloticus) were exposed to MPs (polystyrene; 32-40 µm diameter) with 0, 80 items/L (30 µg/L), and 800 items/L (300 µg/L) for 28 days in a bioflocs aquaculture system. The results showed that the MPs generally had no apparent effect on water quality, tilapia growth, or digestive enzyme activity. However, MPs accumulated the most in the liver (5.65 ± 0.74 µg/mg) and significantly increased the hepato-somatic index of tilapia and reduced the crude protein and lipid of tilapia muscle (p < 0.05). The levels of the antioxidant enzymes catalase and glutathione S-transferase increased significantly in response to MPs (p < 0.05). In contrast, MPs did not affect the content of glutathione, glutathione peroxidase, oxidized glutathione, and malondialdehyde, or the enzyme activity of Na+/K+-ATPase. Moreover, using an improved integrated biomarker response index, growth performance was found to be less responsive to MPs than to oxidative stress and digestive activity. Exposure to MPs did not significantly influence the microbial communities of the bioflocs and tilapia guts (p < 0.05). These results suggest that MPs barely affected tilapia in the bioflocs system. This study contributes to the evaluation of the ecological risk of MPs in aquaculture systems and a better understanding of the integrated response of cultivated vertebrates to MPs in biofloc technology systems.

9.
J Am Chem Soc ; 145(26): 14354-14364, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37348117

RESUMEN

Deep SO2 removal and recovery as industrial feedstock are of importance in flue-gas desulfurization and natural-gas purification, yet developing low-cost and scalable physisorbents with high efficiency and recyclability remains a challenge. Herein, we develop a viable synthetic protocol to produce DUT-67 with a controllable MOF structure, excellent crystallinity, adjustable shape/size, milli-to-kilogram scale, and consecutive production by recycling the solvent/modulator. Furthermore, simple HCl post-treatment affords depurated DUT-67-HCl featuring ultrahigh purity, excellent chemical stability, fully reversible SO2 uptake, high separation selectivity (SO2/CO2 and SO2/N2), greatly enhanced SO2 capture capacity, and good reusability. The SO2 binding mechanism has been elucidated by in situ X-ray diffraction/infrared spectroscopy and DFT/GCMC calculations. The single-step SO2 separation from a real quaternary N2/CO2/O2/SO2 flue gas containing trace SO2 is implementable under dry and 50% humid conditions, thus recovering 96% purity. This work may pave the way for future SO2 capture-and-recovery technology by pushing MOF syntheses toward economic cost, scale-up production, and improved physiochemical properties.

10.
Alzheimers Dement ; 19(11): 5074-5085, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37186161

RESUMEN

INTRODUCTION: The prevalence and risk factors for subjective cognitive decline (SCD) and its correlation with objective cognition decline (OCD) among community-dwelling older adults is inconsistent. METHODS: Older adults underwent neuropsychological and clinical evaluations to reach a consensus on diagnoses. RESULTS: This study included 7486 adults without mild cognitive impairment and dementia (mean age: 71.35 years [standard deviation = 5.40]). The sex-, age-, and residence-adjusted SCD prevalence was 58.33% overall (95% confidence interval: 58.29% to 58.37%), with higher rates of 61.25% and 59.87% in rural and female subgroups, respectively. SCD global and OCD language, SCD memory and OCD global, SCD and OCD memory, and SCD and OCD language were negatively correlated in fully adjusted models. Seven health and lifestyle factors were associated with an increased risk for SCD. DISCUSSION: SCD affected 58.33% of older adults and may indicate concurrent OCD, which should prompt the initiation of preventative intervention for dementia. HIGHLIGHTS: SCD affects 58.33% of older adults in China. SCD may indicate concurrent objective cognitive decline. Difficulty finding words and memory impairments may indicate a risk for AD. The presence of SCD may prompt preventative treatment initiation of MCI or dementia. Social network factors may be initial targets for the early prevention of SCD.


Asunto(s)
Disfunción Cognitiva , Demencia , Humanos , Femenino , Anciano , Estudios de Cohortes , Prevalencia , Vida Independiente , Disfunción Cognitiva/psicología , Cognición , Envejecimiento , Factores de Riesgo , Demencia/etiología , Pruebas Neuropsicológicas
11.
Sci Total Environ ; 866: 161362, 2023 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-36610618

RESUMEN

Biofloc technology, extensively used in intensive aquaculture systems, can prompt the formation of microbial aggregates. Microplastics (MPs) are detected abundantly in aquaculture waters. This study explored the effects of MPs on biofloc formation, microbial community composition and nitrogen transformation function in simulated biofloc aquaculture production systems. The formation process and settling performance of bioflocs were examined. High-throughput sequencing of 16S and 18S rRNA genes was used to investigate the microbial community compositions of bioflocs. Nitrogen dynamics were monitored and further explained from functional genes and microorganisms related to nitrogen transformation by metagenome sequencing. We found that the aggregates consisting of bioflocs and MPs were formed and the systems with MPs had relatively weak settling performance. No significant differences in bacterial diversity (p > 0.05) but significant differences in eukaryotic diversity (p < 0.05) were found between systems without and with MPs. Significant separations in the microbial communities of prokaryotes (p = 0.01) and eukaryotes (p = 0.01) between systems without and with MPs were observed. The peak concentration of nitrite nitrogen (NO2--N) in systems with MPs was lower than that in systems without MPs (pControl/MPs Low = 0.02 and pControl/MPs High = 0.03), probably due to the low abundance of hao and affiliated Alphaproteobacteria_bacterium_HGW-Alphaproteobacteria-1 and Alphaproteobacteria_bacterium, but the high abundance of nxrA and affiliated Alphaproteobacteria_bacterium_SYSU_XM001 and Hydrogenophaga_pseudoflava that related to nitrification. The low concentration of NO2--N in systems with MPs suggested that the presence of MPs might inhibit ammonia oxidation but promote nitrite oxidation by altering the microbial community structure and function. These results indicated that aggregates consisting of bioflocs and MPs could be formed in aquaculture water, and thus, inhibiting their settlement and altering nitrogen transformation function by affecting the microbial community composition.


Asunto(s)
Microbiota , Microplásticos , Plásticos , Nitrógeno , Dióxido de Nitrógeno , Acuicultura/métodos
12.
Oncogene ; 42(3): 169-183, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36385375

RESUMEN

Metadherin (MTDH) is a well-established oncogene in various cancers including Hepatocellular Carcinoma (HCC). However, the precise mechanism through which MTDH promotes cancer-related signaling pathways in HCC remains unknown. In this study, we identified DDX17 as a novel binding partner of MTDH. Furthermore, MTDH increased the protein level of DDX17 by inhibiting its ubiquitination. We confirmed that DDX17 was a novel oncogene, with dramatically upregulated expression in HCC tissues. The increased expression of DDX17 was closely associated with vascular invasion, TNM stage, BCLC stage, and poor prognosis. In vitro and in vivo tests demonstrated that DDX17, a downstream target of MTDH, played a crucial role in tumor initiation and progression. Mechanistically, DDX17 acted as a transcriptional regulator that interacted with Y-box binding protein 1 (YB1) in the nucleus, which in turn drove the binding of YB1 to its target epidermal growth factor receptor (EGFR) gene promoter to increase its transcription. This in turn increased expression of EGFR and the activation of the downstream MEK/pERK signaling pathway. Our results identify DDX17, stabilized by MTDH, as a powerful oncogene in HCC and suggest that the DDX17/YB1/EGFR axis contributes to tumorigenesis and metastasis of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Moléculas de Adhesión Celular/metabolismo , Transformación Celular Neoplásica/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Factores de Transcripción/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , ARN Helicasas DEAD-box/genética
13.
Mol Neurobiol ; 60(3): 1232-1249, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36434370

RESUMEN

Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel that can be activated by diverse stimuli, such as heat, mechanical force, hypo-osmolarity, and arachidonic acid metabolites. TRPV4 is widely expressed in the central nervous system (CNS) and participates in many significant physiological processes. However, accumulative evidence has suggested that deficiency, abnormal expression or distribution, and overactivation of TRPV4 are involved in pathological processes of multiple neurological diseases. Here, we review the latest studies concerning the known features of this channel, including its expression, structure, and its physiological and pathological roles in the CNS, proposing an emerging therapeutic strategy for CNS diseases.


Asunto(s)
Sistema Nervioso Central , Canales Catiónicos TRPV , Canales Catiónicos TRPV/metabolismo , Sistema Nervioso Central/metabolismo , Ácido Araquidónico/metabolismo , Calor
14.
Nutrients ; 14(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36296961

RESUMEN

Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular disease characterized by increased pulmonary vascular resistance, pulmonary vasoconstriction, and right ventricular hypertrophy. Recent developments in genomics and metabolomics have gradually revealed the roles of the gut microbiota (GM) and its metabolites in cardiovascular diseases. Accumulating evidence reveals that the GM plays important roles in the occurrence and development of PAH. Gut microbiota dysbiosis directly increases the gut permeability, thereby facilitating pathological bacterial translocation and allowing translocation of bacterial products such as lipopolysaccharides from the gut into circulation. This process aggravates pulmonary perivascular inflammation and exacerbates PAH development through the endothelial-mesenchymal transition. Additionally, a shift in the composition of PAH also affects the gut metabolites. Changes in gut metabolites, such as decreased short-chain fatty acids, increased trimethylamine N-oxide, and elevated serotonin, contribute to pulmonary perivascular inflammation and pulmonary vascular remodeling by activating several signaling pathways. Studies of the intestinal microbiota in treating pulmonary hypertension have strengthened linkages between the GM and PAH. Probiotic therapy and fecal microbiota transplantation may supplement existing PAH treatments. In this article, we provide new insight for diagnosing, preventing and treating PAH by adding to the current knowledge of the intestinal flora mechanisms and its metabolites efficacy involved in PAH.


Asunto(s)
Microbioma Gastrointestinal , Probióticos , Hipertensión Arterial Pulmonar , Humanos , Lipopolisacáridos , Serotonina , Disbiosis/microbiología , Ácidos Grasos Volátiles , Inflamación
15.
Front Oncol ; 12: 939564, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36248970

RESUMEN

There is a positive association between air pollution and lung cancer burden. This study aims to identify and examine lung cancer risks and mortality burdens associated with air pollutants, including PM10, NO2 and SO2, in seven eastern metropolises of China. The study population comprised a population from seven eastern metropolises of China. The yearly average values (YAV, µg/m3) of the PM10, NO2 and SO2 levels were extracted from China Statistical Yearbook (CSYB) for each selected city from 2006 to 2014. Data collected in the China Cancer Registry Annual Report (CCRAR) provide lung cancer incidence and mortality information. A two-level normal random intercept regression model was adopted to analyze the association between the lung cancer rates and individual air pollutant concentration within a five-year moving window of past exposure. The yearly average values of PM10, SO2 and NO2 significantly decreased from 2006 to 2014. Consistently, the male age-adjusted incidence rate (MAIR) and male age-adjusted mortality rate (MAMR) decreased significantly from 2006 to 2014.Air pollutants have a lag effect on lung cancer incidence and mortality for 2-3 years. NO2 has the significant association with MAIR (RR=1.57, 95% CI: 1.19-2.05, p=0.002), MAMR (RR=1.70, 95% CI: 1.32-2.18, p=0.0002) and female age-adjusted mortality rate (FAMR) (RR=1.27, 95% CI: 1.08-1.49, p=0.003). Our findings suggested that air pollutants may be related to the occurrence and mortality of lung cancer. NO2 was significantly associated with the risk of lung cancer, followed by SO2. Air pollutants have the strongest lag effect on the incidence and mortality of lung cancer within 2-3 years.

16.
ACS Appl Mater Interfaces ; 14(40): 45444-45450, 2022 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-36178410

RESUMEN

Adsorptive separation based on porous solid adsorbents has emerged as an excellent effective alternative to energy-intensive conventional separation methods in a low energy cost and high working capacity manner. However, there are few stable mesoporous metal-organic frameworks (MOFs) for efficient purification of methane from other light hydrocarbons in natural gas. Herein, we report a series of stable mesoporous MOFs, MIL-101-Cr/Fe/Fe-NH2, for efficient separation of CH4 and C3H8 from a ternary mixture CH4/C2H6/C3H8. Experimental results show that all three MOFs possess excellent thermal, acid/basic, and hydrothermal stability. Single-component adsorption suggested that they have high C3H8 adsorption capacity and commendable selectivity for C3H8 and C2H6 over CH4. Transient breakthrough experiments further certified the ability of direct separation of CH4 from simulated natural gas and indirect recovery of C3H8 from the packing column. Theoretical calculations illustrated that the van der Waals force proportional to the molecular weight is the key factor and that the structural integrity and defect can impact separation performances.

17.
ACS Appl Mater Interfaces ; 14(28): 32105-32111, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35791739

RESUMEN

A nitro-decorated microporous covalent organic framework, TpPa-NO2, has been synthesized in a gram scale with a one-pot reaction. It can effectively selectively separate C2H4 from a C2H2/C2H4/CO2 mixture and capture CO2 from CO2/N2 based on ideal adsorption solution theory calculations and transient breakthrough experiments. Theoretical calculations illustrated that the hydrogen atoms of imine bonds, carbonyl oxygen, and nitro group show high affinity toward C2H2 and CO2, playing vital roles in efficient separation.

18.
Cardiovasc Toxicol ; 22(9): 771-786, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35877038

RESUMEN

Cardiac remodelling is characterized by abnormal changes in the function and morphological properties such as diameter, mass, normal diameter of cavities, heart shape, fibrosis, thickening of vessels and heart layers, cardiomyopathy, infiltration of inflammatory cells, and some others. These damages are associated with damage to systolic and diastolic abnormalities, damage to ventricular function, and vascular remodelling, which may lead to heart failure and death. Exposure of the heart to radiation or anti-cancer drugs including chemotherapy drugs such as doxorubicin, receptor tyrosine kinase inhibitors (RTKIs) such as imatinib, and immune checkpoint inhibitors (ICIs) can induce several abnormal changes in the heart structure and function through the induction of inflammation and fibrosis, vascular remodelling, hypertrophy, and some others. This review aims to explain the basic mechanisms behind cardiac remodelling following cancer therapy by different anti-cancer modalities.


Asunto(s)
Insuficiencia Cardíaca , Neoplasias , Fibrosis , Humanos , Neoplasias/tratamiento farmacológico , Sístole , Remodelación Vascular , Remodelación Ventricular
19.
J Endod ; 48(6): 749-758, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35219748

RESUMEN

INTRODUCTION: Odontoblasts, terminally differentiated dentin-forming cells with their processes that penetrate into dentin, have been considered potential sensory cells. Current research suggests that odontoblasts sense external stimuli and transmit pain signals. PIEZO1, as a specific mechanically activated ion channel, may play an important role in mechanical transduction in odontoblasts. In this study, we devoted to investigating the functions and underlying molecular mechanisms of PIEZO1 ion channels in odontoblast mechanotransduction. METHODS: Human dental pulp stem cells were cultured in vitro and induced to differentiate into odontoblast-like cells (OLCs). The expression of PIEZO1 protein in pulp, dental pulp stem cells, and OLCs was detected by immunohistochemistry or immunofluorescence. The mechanical sensitivity of OLCs was detected by a constructed fluid shear stress model and examined by calcium fluorescence intensity. A single-cell mechanical stimulation model was used to detect the PIEZO1 electrophysiological properties of OLCs. Yoda1 (a PIEZO1-specific agonist), GsMTx4 (a PIEZO1 antagonist), and non-calcium ion extracellular solution were utilized to confirm PIEZO1 mechanotransduction in OLCs in both fluid shear stress and single-cell mechanical stimulation assays. The amount of ATP released by OLCs was measured under stimulation with Yoda1 and GsMTx4. Rat trigeminal ganglion neurons were cultured in vitro and detected by whole-cell patch-clamp recording under ATP stimulation. RESULTS: PIEZO1 ion channels were positively expressed in OLCs and odontoblastic bodies and processes but weakly expressed in dental pulp cells. After the treatment of OLCs with shearing stress or Yoda1, the fluorescence intensity of intracellular calcium ions increased rapidly but did not noticeably change after treatment with GsMTx4 or the non-calcium ion extracellular solution. When single-cell mechanical stimuli were applied to OLCs, the evoked inward currents were recorded by patch-clamp electrophysiology. The inward currents increased and current inactivation became slower after Yoda1 treatment, but these currents almost completely disappeared after the addition of GsMTx4. The amount of ATP released by OLCs increased significantly after Yoda1 stimulation, while GsMTx4 reversed the release of ATP. Whole-cell patch-clamp detection showed that ATP evoked slow inward currents and increased the frequency of action potentials of trigeminal ganglion neurons. CONCLUSIONS: Taken together, these findings indicated that odontoblasts evoked a fast inward current via PIEZO1 ion channels after the application of external mechanical stimuli and released ATP to transmit signals to adjacent cells. Thus, PIEZO1 ion channels in odontoblasts mediate mechanotransduction under various pathophysiological conditions in dentin.


Asunto(s)
Mecanotransducción Celular , Proteínas de la Membrana/metabolismo , Odontoblastos , Adenosina Trifosfato , Animales , Calcio/metabolismo , Canales Iónicos/metabolismo , Mecanotransducción Celular/fisiología , Odontoblastos/metabolismo , Ratas
20.
Neurotherapeutics ; 19(2): 660-681, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35182379

RESUMEN

Astrocytes are critical regulators of the immune/inflammatory response in several human central nervous system (CNS) diseases. Emerging evidence suggests that dysfunctional astrocytes are crucial players in seizures. The objective of this study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in 4-aminopyridine (4-AP)-induced seizures and the underlying mechanism. We also provide evidence for the role of Yes-associated protein (YAP) in seizures. 4-AP was administered to mice or primary cultured astrocytes. YAP-specific small interfering RNA (siRNA) was administered to primary cultured astrocytes. Mouse brain tissue and surgical specimens from epileptic patient brains were examined, and the results showed that TRPV4 was upregulated, while astrocytes were activated and polarized to the A1 phenotype. The levels of glial fibrillary acidic protein (GFAP), cytokine production, YAP, signal transducer activator of transcription 3 (STAT3), intracellular Ca2+([Ca2+]i) and the third component of complement (C3) were increased in 4-AP-induced mice and astrocytes. Perturbations in the immune microenvironment in the brain were balanced by TRPV4 inhibition or the manipulation of [Ca2+]i in astrocytes. Knocking down YAP with siRNA significantly inhibited 4-AP-induced pathological changes in astrocytes. Our study demonstrated that astrocytic TRPV4 activation promoted neuroinflammation through the TRPV4/Ca2+/YAP/STAT3 signaling pathway in mice with seizures. Astrocyte TRPV4 inhibition attenuated neuroinflammation, reduced neuronal injury, and improved neurobehavioral function. Targeting astrocytic TRPV4 activation may provide a promising therapeutic approach for managing epilepsy.


Asunto(s)
Astrocitos , Convulsiones , Canales Catiónicos TRPV , Animales , Astrocitos/metabolismo , Humanos , Ratones , Neuronas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Convulsiones/inducido químicamente , Convulsiones/genética , Convulsiones/metabolismo , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...