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1.
BMC Plant Biol ; 24(1): 433, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773359

RESUMO

BACKGROUND: Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). RESULTS: Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. CONCLUSION: This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars.


Assuntos
Brassica napus , Congelamento , Proteínas de Plantas , Brassica napus/genética , Brassica napus/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Família Multigênica , Genoma de Planta , Resposta ao Choque Frio/genética
2.
Front Neurol ; 15: 1353305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38721122

RESUMO

Alpha rhythm slowing is an important electroencephalogram(EEG) feature associated with (AD). This study aims to understand the correlation between alpha band deceleration and molecular changes from the perspective of neural computing. Considering the effect of Aß amyloid deposition on the inhibitory changes in the thalamic, a thalamic cortical model coupled with Aß amyloid is established. The results show that Aß amyloid deposition may induce neurotoxicity in thalamic reticular nucleus neurons, which results in inhibitory changes in the thalamus and slows the alpha rhythm of EEG output from the thalamus. In order to understand the pathogenesis more intuitively, some numerical simulations are provided to illustrate the obtained theories. This research is helpful to understand the pathogenesis of AD, so as to provide theoretical basis for the intervention and control of the disease.

3.
Heliyon ; 10(7): e28246, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38689981

RESUMO

The drill-blasting method is a commonly used mining technique in open-pit mines, and the peak particle velocity (PPV) caused by blasting vibrations is an important indicator for evaluating the rationality of blasting mining design parameters. To develop an effective PPV prediction model, a parameter self-optimizing RUN-XGBoost prediction model is implemented using the Runge-Kutta optimization algorithm (RUN) combined with extreme gradient boosting (XGBoost). The factors affecting the prediction of PPV, including maximum explosive (ME), total explosive (TE), blast center distance (BCD), blast hole depth (BHD), and height difference between the measurement location and the blast location (DH), are selected as the influencing indicators. 188 pieces of blasting operation data were measured at the RK open pit copper-cobalt mine. Then, the RUN-XGBoost prediction model for PPV is studied and compared with the Sadovsky empirical formula, traditional XGBoost model, PSO-XGBoost model, and some traditional machine learning models (Ridge, LASSO, SVM, and SVR) using R2, RMSE, VAF, MAE, and MBE as evaluation indicators for model prediction results. Finally, the Shapley Additive Explanations (SHAP) method is used to evaluate the contribution of different influencing indicators to the PPV prediction results. The results show that the RUN-XGBoost prediction model is significantly better than other machine learning models and the Sadovsky empirical formula in the prediction of PPV, further demonstrating that the RUN-XGBoost prediction model can handle the nonlinear features of multiple factors and provide a reliable, simple, and effective PPV prediction model, forming a rapid prediction and evaluation method for blasting vibrations in open-pit mining.

4.
J Sci Food Agric ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591364

RESUMO

Monascus pigments (MPs) have been used as natural food pigments for many years. There is a high demand for Monascus red pigments (MRPs) to enhance color and for antibacterial and cancer prevention therapies in food and medicine. Most MRPs are not water soluble, and the yield of water-soluble MRPs is naturally low. On the other hand, water-soluble MRP is more cost effective for application in industrial mass production. Therefore, it is important to improve the yield of water-soluble MRPs. Environmental factors have a significant influence on the synthesis of water-soluble MRPs, which is crucial for the development of industrial production of water-soluble MRPs. This review introduces the biosynthetic pathways of water-soluble MRPs and summarizes the effects of environmental factors on the yield of water-soluble MRPs. Acetyl coenzyme A (acetyl-CoA) is a precursor for MPs synthesis. Carbon and nitrogen sources and the carbon/nitrogen ratio can impact MP production by regulating the metabolic pathway of acetyl-CoA. Optimization of fermentation conditions to change the morphology of Monascus can stimulate the synthesis of MPs. The appropriate choice of nitrogen sources and pH values can promote the synthesis of MRPs from MPs. Additives such as metal ions and non-ionic surfactants can affect the fluidity of Monascus cell membrane and promote the transformation of MRPs into water-soluble MRPs. This review will lay the foundation for the industrial production of water-soluble MRPs. © 2024 Society of Chemical Industry.

5.
BMC Cancer ; 24(1): 548, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689248

RESUMO

PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.


Assuntos
Quimiorradioterapia Adjuvante , Estadiamento de Neoplasias , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/efeitos adversos , Adulto , Fatores de Risco , Idoso , Resultado do Tratamento , Histerectomia
6.
J Agric Food Chem ; 72(15): 8618-8631, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38569082

RESUMO

Daidzein (DAN) is an isoflavone, and it is often found in its natural form in soybean and food supplements. DAN has poor bioavailability owing to its extremely low water solubility and first-pass metabolism. Herein, we hypothesized that a bioactivatable natural amino acid-bearing carbamate prodrug strategy could increase the water solubility and metabolic stability of DAN. To test our hypothesis, nine amino acid prodrugs of DAN were designed and synthesized. Compared with DAN, the optimal prodrug (daidzein-4'-O-CO-N-isoleucine, D-4'-I) demonstrated enhanced water solubility and improved phase II metabolic stability and activation to DAN in plasma. In addition, unlike the passive transport of DAN, D-4'-I maintained high permeability via organic anion-transporting polypeptide 2B1 (OATP2B1)-mediated transport. Importantly, D-4'-I increased the oral bioavailability by 15.5-fold, reduced the gender difference, and extended the linear absorption capacity in the pharmacokinetics of DAN in rats. Furthermore, D-4'-I exhibited dose-dependent protection against liver injury. Thus, the natural amino acid-bearing carbamate prodrug strategy shows potential in increasing water solubility and improving phase II metabolic stability to enhance the oral bioavailability of DAN.


Assuntos
Isoflavonas , Pró-Fármacos , Animais , Ratos , Administração Oral , Aminoácidos/química , Disponibilidade Biológica , Carbamatos/química , Pró-Fármacos/química , Solubilidade , Água
7.
Neuropsychiatr Dis Treat ; 20: 523-533, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38469210

RESUMO

Background: The 4-hydroxysesamin (4-HS, a di-tetrahydrofuran lignin) is a modified sesamin that was prepared in the laboratory. This preclinical study was designed to preliminarily investigate the neuroprotective properties of 4-HS. Methods: In vitro, neuronal injury and inflammation were simulated by oxygen-glucose deprivation and lipopolysaccharide (LPS) exposure in mouse hippocampal neuronal HT22 cell line, and treated with 4-HS and/or metformin (MET, MAPK pathway activator for exploring mechanism). CCK-8, flow cytometry, and enzyme-linked immunosorbent assay were performed to evaluate cell viability, apoptosis, and inflammation. Apoptosis- and pathway-related proteins were detected by Western blotting. Middle cerebral artery occlusion (MCAO) was constructed as a stroke model and treated with 4-HS for in vivo confirmation. Histological staining was used for in vivo evaluation of 4-HS properties. Results: The 4-HS showed similar anti-inflammatory activity to sesamin but did not affect the cell viability of HT22 cells. In vitro, 4-HS improved the cell viability, ameliorated neuronal apoptosis, along with the reversion of apoptotic proteins (Bax, cleaved-caspase 3/9, Bcl-2) expression and inflammatory cytokines (IL-6, TNF-α, IL-10) in LPS-treated HT22 cells. The 4-HS suppressed the phosphorylation of ERK, JNK, and p38 but the addition of MET reversed 4-HS-induced changes of phenotype and protein expression in LPS-treated cells. In vivo, 4-HS showed apparent improvement in cerebral infarction, brain tissue morphology, neuronal architecture, apoptosis, and inflammation of MCAO mice, and also showed inhibiting effects on the phosphorylation of ERK, JNK, and p38, confirming in vivo results. Conclusion: In this first pre-clinical study on 4-HS, we preliminarily demonstrated the neuroprotective properties of 4-HS both in cell and animal models, and proposed that the underlying mechanism might be associated with the MAPK pathway.

8.
Epilepsy Res ; 201: 107338, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38447234

RESUMO

BACKGROUND: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammatory pathway is implicated in the development of epilepsy and can be suppressed by the activation of the silent information regulator 1 (SIRT1). However, the expression and correlation of the NLRP3 pathway and SIRT1 in drug-resistant epilepsy (DRE) remain unknown. METHODS: This study evaluated the histopathology of the cerebral cortex from nine patients with DRE and eight patients with cavernous haemangioma undergoing surgical treatment. It analysed the expression of the NLRP3, interleukin-1ß (IL-1ß), caspase-1 and SIRT1 using immunohistochemistry. Additionally, the contents of NLRP3, caspase-1, IL-1ß and SIRT1 in the serum samples of the included study participants were determined using ELISA method. The correlation between the NLRP3 pathway and the SIRT1 was assessed using Spearman's correlation analysis. RESULTS: The expression of NLRP3, caspase-1 and IL-1ß in the cerebral cortex of patients with DRE was elevated, with the NLRP3 expression being negatively correlated with the SIRT1 expression. Furthermore, IL-1ß in serum was upregulated in patients with DRE. The correlation between the content of serum SIRT1 and NLRP3, caspase-1 and IL-1ß in patients with DRE was not significant. Notably, serum caspase-1 levels were obviously higher in patients with bilateral hippocampal sclerosis than in patients with unilateral hippocampal sclerosis. CONCLUSIONS: The current results indicate that the expression of the NLRP3/caspase-1/IL-1ß pathway is significantly upregulated in patients with DRE and that it is partially correlated with the SIRT1 expression. This study is important for understanding the pathophysiology of DRE and developing new treatment strategies for it.


Assuntos
Esclerose Hipocampal , Inflamassomos , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR , Domínio Pirina , Sirtuína 1/metabolismo , Caspase 1/metabolismo , Interleucina-1beta/metabolismo
9.
Curr Treat Options Oncol ; 25(4): 434-452, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38517596

RESUMO

OPINION STATEMENT: The introduction of total mesorectal excision into the radical surgery of rectal cancer has significantly improved the oncological outcome with longer survival and lower local recurrence. Traditional treatment modalities of distal rectal cancer, relying on radical surgery, while effective, take their own set of risks, including surgical complications, potential damage to the anus, and surrounding structure owing to the pursuit of thorough resection. The progress of operating methods as well as the integration of systemic therapies and radiotherapy into the peri-operative period, particularly the exciting clinical complete response of patients after neoadjuvant treatment, have paved the way for organ preservation strategy. The non-inferiority oncological outcome of "watch and wait" compared with radical surgery underscores the potential of organ preservation not only to control local recurrence but also to reduce the need for treatments followed by structure destruction, hopefully improving the long-term quality of life. Radical radiotherapy provides another treatment option for patients unwilling or unable to undergo surgery. Organ preservation points out the direction of treatment for distal rectal cancer, while additional researches are needed to answer remaining questions about its optimal use.


Assuntos
Quimiorradioterapia , Neoplasias Retais , Humanos , Resultado do Tratamento , Preservação de Órgãos , Qualidade de Vida , Neoplasias Retais/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Conduta Expectante/métodos
10.
Sci Total Environ ; 926: 171822, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38521266

RESUMO

It holds significant practical importance to screen and investigate endophytic bacteria with salt-tolerant activity in rice for the development of relevant microbial agents. A total of 179 strains of endophytic bacteria were isolated from 24 samples of salt-tolerant rice seeds, with almost 95 % of these bacteria exhibiting tolerance to a salt content of 2 % (0.34 mol/L). Following the screening process, a bacterium named G9H01 was identified, which demonstrated a salt tolerance of up to 15 % (2.57 mol/L) and resistance to Magnaporthe oryzae, the causal agent of rice blast disease. Phylogenetic analysis confirmed G9H01 as a strain of Bacillus paralicheniformis. The complete genome of G9H01 was sequenced and assembled, revealing a considerable number of genes encoding proteins associated with salt tolerance. Further analysis indicated that G9H01 may alleviate salt stress in a high-salt environment through various mechanisms. These mechanisms include the utilization of proteins such as K+ transporters, antiporters, and Na+/H+ antiporters, which are involved in K+ absorption and Na+ excretion. G9H01 also demonstrated the ability to uptake and accumulate betaine, as well as secrete extracellular polysaccharides. Collectively, these findings suggest that Bacillus paralicheniformis G9H01 has potential as a biocontrol agent, capable of promoting rice growth under saline-alkali-tolerant conditions.


Assuntos
Ascomicetos , Bacillus , Oryza , Tolerância ao Sal , Álcalis , Filogenia , Bactérias/metabolismo , Antiporters/genética
11.
J Sep Sci ; 47(5): e2300746, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38471966

RESUMO

In this work, monodisperse and nano-porous poly(bismaleimide-co-divinylbenzene) microspheres with large specific surface area (427.6 m2 /g) and rich pore structure were prepared by one-pot self-stable precipitation polymerization of 2,2'-bis[4-(4-maleimidophenoxy) phenyl] propane and divinylbenzene. The prepared poly(bismaleimide-co-divinylbenzene) microspheres were employed as dispersive solid-phase extraction (DSPE) adsorbent for the extraction of triazine herbicides. Under optimized conditions, good linearities were obtained between the peak area and the concentration of triazine herbicides in the range of 1-400 µg/L (R2 ≥ 0.9987) with the limits of detection of 0.12-0.31 µg/L. Triazine herbicides were detected using the described approach in vegetable samples (i.e., cucumber, tomato, and maize) with recoveries of 93.6%-117.3% and relative standard deviations of 0.4%-3.5%. In addition, the recoveries of triazine herbicides remained above 80.7% after being used for nine DSPE cycles, showing excellent reusability of poly(bismaleimide-co-divinylbenzene) microspheres. The adsorption of poly(bismaleimide-co-divinylbenzene) microspheres toward triazine herbicides was a monolayer and chemical adsorption. The adsorption mechanism between triazine herbicides and adsorbents might be a combination of hydrogen bonding, electrostatic interaction, and π-π conjugation. The results confirmed the potential use of the poly(bismaleimide-co-divinylbenzene) microspheres-based DSPE coupled to the high-performance liquid chromatography method for the detection of triazine herbicide residues in vegetable samples.


Assuntos
Herbicidas , Verduras , Compostos de Vinila , Verduras/química , Cromatografia Líquida de Alta Pressão/métodos , Microesferas , Porosidade , Triazinas/análise , Extração em Fase Sólida/métodos , Herbicidas/análise , Limite de Detecção
12.
ACS Appl Mater Interfaces ; 16(11): 14026-14037, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38447136

RESUMO

With the rapid development of small-molecule electron acceptors, polymer electron donors are becoming more important than ever in organic photovoltaics, and there is still room for the currently available high-performance polymer donors. To further develop polymer donors with finely tunable structures to achieve better photovoltaic performances, random ternary copolymerization is a useful technique. Herein, by incorporating a new electron-withdrawing segment 2,3-bis(3-octyloxyphenyl)dithieno[3,2-f:2',3'-h]quinoxaline derivative (C12T-TQ) to PM6, a series of terpolymers were synthesized. It is worth noting that the introduction of the C12T-TQ unit can deepen the highest occupied molecular orbital energy levels of the resultant polymers. In addition, the polymer Z6 with a 10% C12T-TQ ratio possesses the highest film absorption coefficient (9.86 × 104 cm-1) among the four polymers. When blended with Y6, it exhibited superior miscibility and mutual crystallinity enhancement between Z6 and Y6, suppressed recombination, better exciton separation and charge collection characteristics, and faster hole transfer in the D-A interface. Consequently, the device of Z6:Y6 successfully achieved enhanced photovoltaic parameters and yielded an efficiency of 17.01%, higher than the 16.18% of the PM6:Y6 device, demonstrating the effectiveness of the meta-octyloxy-phenyl-modified dithieno[3,2-f:2',3'-h]quinoxaline moiety to build promising terpolymer donors for high-performance organic solar cells.

13.
Cell Biochem Biophys ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38411783

RESUMO

Breast cancer (BC) is a lethal disorder that threatens the life safety of the majority of females globally, with rising morbidity and mortality year by year. Doxorubicin is a cytotoxic anthracycline antibiotic that is widely used as one of the first-line chemotherapy agents for patients with BC. However, the efficacy of doxorubicin in the clinic is largely limited by its serious side effects and acquired drug resistance. Allicin (diallyl thiosulfinate), as the major component and key active compound present in freshly crushed garlic, has shown potential effects in suppressing chemotherapy resistance in various cancers. Our research aimed to explore the relationship between allicin and doxorubicin resistance in BC. To generate doxorubicin-resistant BC cell lines (MCF-7/DOX and MDA-MB-231/DOX), doxorubicin-sensitive parental cell lines MCF-7 and MDA-MB-231 were continuously exposed to stepwise increased concentrations of doxorubicin over a period of 6 months. CCK-8, colony formation, flow cytometry, RT-qPCR, and western blotting assays were performed to investigate the effects of allicin and/or doxorubicin treatment on the viability, proliferation and apoptosis and the expression of Nrf2, HO-1, phosphate AKT and AKT in doxorubicin-resistant BC cells. Our results showed that combined treatment of allicin with doxorubicin exhibited better effects on inhibiting the proliferation and enhancing the apoptosis of doxorubicin-resistant BC cells than treatment with allicin or doxorubicin alone. Mechanistically, allicin suppressed the levels of Nrf2, HO-1, and phosphate AKT in doxorubicin-resistant BC cells. Collectively, allicin improves the doxorubicin sensitivity of BC cells by inactivating the Nrf2/HO-1 signaling pathway.

14.
Chemosphere ; 352: 141336, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309599

RESUMO

In the pursuit of a safe, low-cost, and sustainable method for the reuse of landfill-mined-soil-like-fractions (LFMSFs), pot experiments were conducted using seven growth substrates consisting of LFMSFs, tea residue, and peat for the cultivation of Photinia × fraseri. Six of the substrates had 40 %:60 %, 60 %:40 %, and 80 %:20 % volume ratios of LFMSFs to tea residue or peat, and one substrate consisted entirely of LFMSFs. The physicochemical properties of the substrate, growth parameters of the plants, and heavy metal content in the different pots were determined after one year of growth. The results indicated that the physicochemical properties of the substrate, that was composed of a mixture of LFMSFs and tea residue showed a significant improvement in organic matter, nitrogen, phosphorus, and potassium. However, there was also an increase in the salt and heavy metal contents when compared with those of peat. The plant growth in the LFMSF and tea residue substrate was slightly lower than that in the LFMSF and peat mixture. Notably, the best plant growth and environmentally friendly effects were observed when LFMSFs were added at 40 %. Additionally, most of the heavy metals were primarily removed from the substrate through the leaves of the seedlings, with the heavy metal contents being relatively low. In conclusion, LFMSFs as a cultivation substrate, represent a practical approach for reutilization, which could contribute to the reduction of reliance on traditional resources.


Assuntos
Metais Pesados , Poluentes do Solo , Solo/química , Metais Pesados/análise , Poluentes do Solo/análise , Instalações de Eliminação de Resíduos , Chá
15.
Brain Res ; 1831: 148820, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38417653

RESUMO

Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified human astrocyte-specific genes and found 131 of these genes significantly differentially expressed in human temporal lobe epilepsy (TLE) datasets. Multiple astrocytic functions, such as cell adhesion, cell morphogenesis, actin filament-based process, apoptotic cell clearance and response to oxidative stress, were found to be promoted. Moreover, multiple altered astrocyte-specific genes were enriched in phagocytosis, perisynaptic astrocyte processes (PAPs), plasticity, and synaptic functions. Nine hub genes (ERBB2, GFAP, NOTCH2, ITGAV, ABCA1, AQP4, LRP1, GJA1, and YAP1) were identified by protein-protein interaction (PPI) network analysis. The correlation between the expression of these hub genes and seizure frequency, as well as epilepsy-related factors, including inflammatory mediators, complement factors, glutamate excitotoxicity and astrocyte reactivity, were analyzed. Additionally, upstream transcription factors of the hub genes were predicted. Finally, astrogliosis and the expression of the hub genes were validated in an epileptic rat model. Our findings reveal the various changes in astrocyte function associated with epilepsy and provide candidate astrocyte-specific genes that could be potential antiepileptogenic targets.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Ratos , Humanos , Animais , Epilepsia do Lobo Temporal/metabolismo , Astrócitos/metabolismo , Gliose/metabolismo , Convulsões/metabolismo , Epilepsia/metabolismo
16.
Medicine (Baltimore) ; 103(4): e37080, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277543

RESUMO

This study assessed oral health conditions and associated factors (including sociodemographic characteristics and self-reported oral health-related behaviors) among Chinese adolescents. This cross-sectional study enrolled 3840 adolescents aged 12 to 15 years from 12 middle schools in Foshan, Southeast China, in 2016, using multistage, stratified cluster sampling. Participants underwent a clinical oral examination and completed a questionnaire. The prevalence of dental caries, probe bleeding, and calculus was 37.6%, 46.2%, and 39.7%, respectively; the mean decayed/missed/filled teeth index was 0.86 ±â€…1.58. A mean of 2.09 ±â€…3.65 and 1.85 ±â€…3.52 teeth showed probe bleeding and calculus, respectively. Only 0.3% and 0.1% of adolescents aged 15 years had periodontal pockets (depth ≥ 4 mm) and attachment loss, respectively, which were most common in tooth positions 46 and 36 (Federation Dentaire International 2-digit system). Regarding oral health-related behavior, 49.1% of the participants failed to brush their teeth at least twice daily, 98.5% never or rarely used dental floss, and 58.7% reported middle-high frequency sugar consumption. Older age, female, administrative region, maternal education lower than university, brushing teeth less than twice daily, flossing less than once daily, and frequent sugar consumption were significant risk factors of caries. Older age, female, administrative region, brushing less than twice daily, and flossing less than once daily significantly increased periodontal risk. Despite the overall low prevalence of adverse dental conditions among adolescents in Foshan, their oral hygiene habits were undeveloped. Thus, their identified risk factors need close monitoring, and families, schools, communities, and the government should jointly promote adolescents' oral health.


Assuntos
Cálculos , Cárie Dentária , Humanos , Feminino , Adolescente , Criança , Saúde Bucal , Estudos Transversais , Cárie Dentária/epidemiologia , China/epidemiologia , Prevalência , Açúcares da Dieta
17.
BMC Pharmacol Toxicol ; 25(1): 1, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167102

RESUMO

A connection between diabetes and an increased risk of epilepsy has been suggested by observational studies. Animal studies have also shown that antihyperglycemic drugs can improve seizures. However, it is unclear whether antihyperglycemic drugs have a causal role in epilepsy in humans. To investigate this potential causal relationship, a Mendelian randomisation study was conducted using International League Against Epilepsy data as the discovery set and FinnGen data as the replication set. It was discovered that three antidiabetic drug target genes, ETFDH, CYP21A2 and CYP2D6, were involved in the occurrence of epilepsy. In particular, ETFDH was identified as a target gene in both the discovery set (inverse variance weighting [IVW], odds ratio [OR] = 1.018, 95% confidence interval [CI], 1.004-1.033, p = 0.009) and replication set (IVW, OR = 1.074, 95% CI, 1.034-1.114, p = 0.00016), and CYP21A2 was identified in the discovery set (IVW, OR = 1.029, 95% CI, 1.005-1.053, p = 0.016) and replication set (IVW, OR = 1.057, 95% CI, 1.001-1.116, p = 0.045) as having a causal association with an increased risk of epilepsy. Conversely, the CYP2D6 gene was found to be a protective factor for epilepsy in both the discovery set (IVW, OR = 0.0984, 95% CI, 0.969-0.998, p = 0.025) and replication set (IVW, OR = 0.977, 95% CI, 0.955-1.000, p = 0.046). A search of DrugBank revealed that metformin, an anti-glucose drug, is an inhibitor of the ETFDH gene and may have a potential therapeutic effect on epilepsy.


Assuntos
Epilepsia , Metformina , Animais , Humanos , Hipoglicemiantes/uso terapêutico , Citocromo P-450 CYP2D6 , Epilepsia/tratamento farmacológico , Epilepsia/genética , Convulsões , Esteroide 21-Hidroxilase
18.
Huan Jing Ke Xue ; 45(1): 459-469, 2024 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-38216495

RESUMO

Microplastic pollution is not only an environmental problem but also a social problem. Many studies have been conducted on the sources, abundance, and distribution of microplastics in the environment, but an understanding of human exposure levels and potential health risks remains very limited. Based on the bibliometric methods, the present review systematically summarized the exposure pathways of microplastics in humans, and then the characteristics and potential adverse impacts on human health were expounded upon. Available literature showed that microplastics in human bodies were mainly concentrated on sizes smaller than 50 µm, and polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) were the main polymers. Microplastics in environments entered human bodies mainly through food and respiratory pathways, then accumulated in lung and gastrointestinal tissues. Most importantly, small-sized microplastics could distribute in tissues and organs via the circulatory system. The results from lab-based toxicological experiments showed that microplastics not only posed threats to cell membrane integrity, immune stress, gut microbiota, and energy metabolism but also had potentially adverse impacts on the reproductive system. To further understand the health risks of microplastic pollution, it is necessary to promote research on the toxicological effects of microplastics as well as the inner mechanisms and also to establish risk assessment frameworks for evaluating microplastic pollution. These works are crucial to preventing the risks of microplastic pollution with scientific evidence.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Microplásticos/toxicidade , Plásticos/efeitos adversos , Monitoramento Ambiental , Poluentes Químicos da Água/análise , Poluição Ambiental
19.
Artigo em Inglês | MEDLINE | ID: mdl-38244428

RESUMO

An ultra-performance liquid chromatography-tandem mass spectrometry was developed to assay the concentration for the quantification of cycloicaritin and its carbamate prodrug (3-O-L-valyl carbamate prodrug of cycloicaritin) in the plasma of Sprague-Dawley rats. Analytes were separated on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 µm) after liquid-liquid extraction with methyl tert-butyl ether. Acetonitrile and water containing 0.1 % formic acid were the mobile phases of the method. Using electrospray ionization in the positive ion mode, the method was performed with a total run time of 2.60 min. The response of the experiments was linear over the concentration ranges from 1 to 250 ng/mL for cycloicaritin and 1-250 ng/mL for prodrug. The intra- and inter-day precision and accuracy were within the recommended limits of the FDA. The matrix effect that we observed met the criteria. The method was successfully applied to the pharmacokinetics of cycloicaritin and its carbamate prodrug in Sprague-Dawley rats.


Assuntos
Pró-Fármacos , Espectrometria de Massas em Tandem , Ratos , Animais , Espectrometria de Massas em Tandem/métodos , Ratos Sprague-Dawley , Valina , Carbamatos , Cromatografia Líquida , Espectrometria de Massa com Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes
20.
Nano Lett ; 24(5): 1729-1737, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38289279

RESUMO

Rechargeable hydrogen gas batteries, driven by hydrogen evolution and oxidation reactions (HER/HOR), are emerging grid-scale energy storage technologies owing to their low cost and superb cycle life. However, compared with aqueous electrolytes, the HER/HOR activities in nonaqueous electrolytes have rarely been studied. Here, for the first time, we develop a nonaqueous proton electrolyte (NAPE) for a high-performance hydrogen gas-proton battery for all-climate energy storage applications. The advanced nonaqueous hydrogen gas-proton battery (NAHPB) assembled with a representative V2(PO4)3 cathode and H2 anode in a NAPE exhibits a high discharge capacity of 165 mAh g-1 at 1 C at room temperature. It also efficiently operates under all-climate conditions (from -30 to +70 °C) with an excellent electrochemical performance. Our findings offer a new direction for designing nonaqueous proton batteries in a wide temperature range.

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