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1.
J Transl Med ; 21(1): 707, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37814294

RESUMO

BACKGROUND: Seizures are associated with a decrease in γ-aminobutyric type A acid receptors (GABAaRs) on the neuronal surface, which may be regulated by enhanced internalization of GABAaRs. When interactions between GABAaR subunit α-1 (GABRA1) and postsynaptic scaffold proteins are weakened, the α1-containing GABAaRs leave the postsynaptic membrane and are internalized. Previous evidence suggested that neuroplastin (NPTN) promotes the localization of GABRA1 on the postsynaptic membrane. However, the association between NPTN and GABRA1 in seizures and its effect on the internalization of α1-containing GABAaRs on the neuronal surface has not been studied before. METHODS: An in vitro seizure model was constructed using magnesium-free extracellular fluid, and an in vivo model of status epilepticus (SE) was constructed using pentylenetetrazole (PTZ). Additionally, in vitro and in vivo NPTN-overexpression models were constructed. Electrophysiological recordings and internalization assays were performed to evaluate the action potentials and miniature inhibitory postsynaptic currents of neurons, as well as the intracellular accumulation ratio of α1-containing GABAaRs in neurons. Western blot analysis was performed to detect the expression of GABRA1 and NPTN both in vitro and in vivo. Immunofluorescence co-localization analysis and co-immunoprecipitation were performed to evaluate the interaction between GABRA1 and NPTN. RESULTS: The expression of GABRA1 was found to be decreased on the neuronal surface both in vivo and in vitro seizure models. In the in vitro seizure model, α1-containing GABAaRs showed increased internalization. NPTN expression was found to be positively correlated with GABRA1 expression on the neuronal surface both in vivo and in vitro seizure models. In addition, NPTN overexpression alleviated seizures and NPTN was shown to bind to GABRA1 to form protein complexes that can be disrupted during seizures in both in vivo and in vitro models. Furthermore, NPTN was found to inhibit the internalization of α1-containing GABAaRs in the in vitro seizure model. CONCLUSION: Our findings provide evidence that NPTN may exert antiepileptic effects by binding to GABRA1 to inhibit the internalization of α1-containing GABAaRs.


Assuntos
Anticonvulsivantes , Receptores de GABA-A , Humanos , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/metabolismo , Proteínas de Transporte/metabolismo , Ácido gama-Aminobutírico/metabolismo , Neurônios , Receptores de GABA-A/metabolismo , Convulsões/metabolismo
2.
Arch Biochem Biophys ; 734: 109499, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36587827

RESUMO

Parvalbumin-expressing neurons are a type of inhibitory intermediate neuron that play an important role in terminating seizures. The aim of the present study was to use lentiviral construction and packaging technology to overexpress and silence the parvalbumin gene in pheochromocytoma (PC12) cells, and to evaluate how parvalbumin influences the metabolic pathway involving glutamate and γ-aminobutyric acid (GABA). In this work, Immunofluorescence staining was used to verify the differentiation of PC12 cells into neurons after adding nerve growth factor (NGF). Western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm lentivirus-mediated knockdown or overexpression of parvalbumin. Expression of parvalbumin, the 65-kDa GAD isoform (GAD65), and the 67-kDa GAD isoform (GAD67) in neuronal cells was examined at the mRNA and protein levels using qRT-PCR, western blotting and immunofluorescence staining, while intracellular glutamate and GABA levels were determined by high performance liquid chromatography (HPLC). We demonstrate that the expression of parvalbumin is associated with GAD65 and GAD67. Interestingly, overexpression of parvalbumin up-regulated GAD65 and GAD67, increased GABA concentration, and decreased glutamate concentration. Silencing of parvalbumin led to the opposite effects. Altogether, parvalbumin affected the expression of GAD65 and GAD67, thereby influencing the metabolic pathway involving glutamate and GABA.


Assuntos
Glutamato Descarboxilase , Ácido Glutâmico , Parvalbuminas , Animais , Ratos , Ácido gama-Aminobutírico/metabolismo , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Ácido Glutâmico/metabolismo , Redes e Vias Metabólicas , Neurônios/metabolismo , Parvalbuminas/metabolismo
3.
J Org Chem ; 88(4): 2393-2403, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36715636

RESUMO

A novel and convenient K2S2O8-mediated diiodo cyclization of 1,6-enynes for the facile synthesis of functionalized γ-lactam derivatives has been developed. This reaction features mild and transition-metal-free conditions, which offer a green and efficient entry to synthetically important γ-lactam scaffolds. Mechanistic studies suggest that iodide radicals initiate the cascade cyclic transformation.

4.
J Nat Prod ; 86(1): 18-23, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36607819

RESUMO

Lasiodiplodiapyrones A and B (1 and 2), two new preussomerin derivatives, possessing an unexpected 6-methyl-4H-furo[3,2-c]pyran-4-one moiety and a highly functionalized conjoint and complicated polycyclic ring system, along with two known congeners (3 and 4), were isolated from the fungus Lasiodiplodia pseudotheobromae. Their structures including absolute configurations were determined by spectroscopic analyses, Mosher's method, and ECD calculations. A biosynthetic pathway was proposed to explain the origin of lasiodiplodiapyrones A and B as well as their relationship with preussomerins. Compounds 1-4 showed suppressive effects on the production of NO with IC50 values of 4.8 ± 0.3, 8.5 ± 1.1, 5.9 ± 0.8, and 12.8 ± 1.3 µM, respectively.


Assuntos
Ascomicetos , Pironas , Estrutura Molecular , Ascomicetos/química , Piranos
5.
Org Biomol Chem ; 20(15): 3174-3182, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35347333

RESUMO

The thermal tetradehydro-Diels-Alder (TDDA) reaction for the synthesis of polysubstituted aromatic compounds remains underestimated probably due to the harsh conditions and multiproduct results. Herein, a mild intramolecular TDDA reaction of aryldiyne compounds is presented with linear naphthalenes only, exhibiting good functional group tolerance. The reaction is easy to operate and amenable to multigram-scale synthesis. From the preliminary work, it was found that the mild conditions may be the key to the completely linear product in the reactions.


Assuntos
Naftalenos , Reação de Cicloadição
6.
Langmuir ; 36(47): 14255-14267, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33206532

RESUMO

Electrocoalescence technology is an important method for the demulsification of crude oil emulsion, but its development is restricted by the short circuit caused by droplet chain formation. To reveal the formation mechanism of droplet chains, the electrocoalescence behaviors of two droplets and droplet clusters under pulsed direct current (DC) electric fields are experimentally studied. The two droplets usually successively undergo complete coalescence, partial coalescence, and noncoalescence as the electric field strength increases. The critical electric field strengths for complete coalescence under pulsed DC electric fields with different frequencies are obtained. The effects of the electric field waveform and frequency on the noncoalescence characteristics of two droplets and the stability of droplet chains are explored. The droplet chains under a high-frequency electric field are more stable and longer than those under a low-frequency electric field due to the reduction of the movement distance and the generation of daughter droplets from tip streaming. The reversal of the composition of electric forces due to charge transfer is the fundamental mechanism of noncoalescence of two droplets and chain formation in the emulsion under a pulsed DC electric field.

7.
J Clin Psychopharmacol ; 35(5): 517-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26280836

RESUMO

Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may contribute to methamphetamine dependence. We hypothesized that this polymorphism had a role in cognitive deficits in methamphetamine-dependent patients and in the relationship of serum BDNF with cognitive impairments. We conducted a case-control study by assessing 194 methamphetamine-dependent patients and 378 healthy volunteers without history of drug use on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We showed no significant differences in genotype and allele distributions between the methamphetamine-dependent patients and controls. Some aspects of cognitive function significantly differed in the 2 groups. The serum BDNF levels in methamphetamine-dependent patients were significantly higher than those of the healthy controls. In the patients, partial correlation analysis showed a significant positive correlation between serum BDNF and the delayed memory index score. The RBANS scores showed statistically significant BDNF level × genotype interaction. Further regression analyses showed a significant positive association between BDNF levels and the RBANS total score, immediate memory or attention index among Val homozygote patients, whereas a significant negative association of BDNF levels with the RBANS total score, visuospatial/constructional, or language index was found among Met/Val heterozygous patients. We demonstrated significant impairment on some aspects of cognitive function and increased BDNF levels in methamphetamine-dependent patients as well as genotypic differences in the relationships between BDNF levels and RBANS scores on the BDNF Val66Met polymorphism only in these patients.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Transtornos Cognitivos/genética , Metanfetamina/efeitos adversos , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Transtornos Cognitivos/etiologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Metanfetamina/administração & dosagem , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
8.
Langmuir ; 31(30): 8275-83, 2015 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-26138311

RESUMO

In this paper, the conical breakup of a water droplet suspended in oil under the alternating current (ac) electric field was experimentally studied with the help of a high-speed video camera. We observed three stages of transient oscillation of deformation characterized by deformation degree l* before the conical breakup that were described in detail. Then a theoretical model was developed to find out the dynamic mechanisms of that behavior. Despite a very small discrepancy, good agreement between model predictions and experimental observations of the evolution of the droplet deformation was observed, and the possible reasons for the discrepancy were discussed as well. Finally, the stresses on the interface were calculated with the theoretical model and their influence on the dynamic behavior before the breakup was obtained. The differences between the droplet breakup mode of ac and direct current electric field are also discussed in our paper.

9.
Compr Psychiatry ; 59: 62-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25764907

RESUMO

An increasing number of evidence showed that genetic factors might contribute to drug abuse vulnerability. Data from genetic scans in humans suggest that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be associated with substance abuse or dependence. To test the hypothesis that the BDNF gene polymorphism is involved in methamphetamine abuse, we compared three single nucleotide polymorphisms (SNPs, rs16917204, rs16917234, and rs2030324) of the BDNF gene in 200 methamphetamine abusers and 219 healthy individuals. We also considered the association of these polymorphisms with impulsivity in methamphetamine abusers using Barratt Impulsivity Scale-11(BIS-11) Chinese version. Individual SNP analysis showed no significant differences in genotype and allele distributions between the methamphetamine abusers and controls. Haplotype analysis of rs16917204-rs16917234-rs2030324 revealed that a major C-C-T haplotype was significantly associated a lower odds of methamphetamine abuse, even after Bonferroni correction. Within the methamphetamine-abuse group, subjects carrying the T allele of rs2030324 genotype had significantly higher motor impulsivity scores of BIS compared to those with the C/C genotype. Our findings suggest that the BDNF gene polymorphism may contribute to the impulsivity in methamphetamine abusers.


Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Fator Neurotrófico Derivado do Encéfalo/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Comportamento Impulsivo , Polimorfismo de Nucleotídeo Único/genética , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Genótipo , Humanos
10.
Environ Sci Pollut Res Int ; 31(14): 21189-21207, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38388978

RESUMO

Technological innovation is regarded as an important means to improve carbon efficiency. However, there is no consensus on this view. Meanwhile, few studies have considered how technological innovation affects carbon efficiency. To this end, this study investigates the influencing mechanism and effects of technological innovation on carbon emission efficiency from the perspectives of industrial restructuring and R&D element flow. It establishes the influencing and mechanism model and then deeply studies the impact and paths of technological innovation on carbon emission efficiency, using panel data from 30 provinces in 1999-2020. Results show that (1) technological innovation improves carbon emission efficiency. (2) Regional differences in the impact effects of technological innovation are evident, with a greater contribution to carbon emission efficiency in eastern region. (3) Innovation improves carbon efficiency through two paths: advanced industrial structure and industrial structure rationalization. (4) The moderating effect demonstrates that the technological innovation's influence is gradually enhanced with the interregional mobility of R&D personnel and capital. Hence, decision-makers should correctly guide the orderly flow of R&D factors and further improve the carbon emission reduction effect by increasing innovation support and helping optimize the industrial structure.


Assuntos
Carbono , Indústrias , Carbono/análise , Tecnologia , Invenções , Eficiência
11.
J Matern Fetal Neonatal Med ; 37(1): 2351196, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38735863

RESUMO

OBJECTIVE: Although early evidence shows that epilepsy can increase the risks of adverse pregnancy, some outcomes are still debatable. We performed a systematic review and meta-analysis to explore the effects of maternal and fetal adverse outcomes in pregnant women with epilepsy. METHODS: PubMed, Embase, Cochrane, and Web of Science were employed to collect studies that investigated the potential risk of obstetric complications during the antenatal, intrapartum, or postnatal period, as well as any neonatal complications. The search was conducted from inception to November 16, 2022. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included original studies. The odds ratio (OR) values were extracted after adjusting for confounders to measure the relationship between pregnant women with epilepsy and adverse maternal or fetal outcomes. The protocol for this systematic review is registered with PROSPERO ID CRD42023391539. RESULTS: Of 35 articles identified, there were 142,577 mothers with epilepsy and 34,381,373 mothers without epilepsy. Our study revealed a significant association between pregnant women with epilepsy (PWWE) and the incidence of cesarean section, preeclampsia/eclampsia, gestational hypertension, induction of labor, gestational diabetes and postpartum hemorrhage compared with those without epilepsy. Regarding newborns outcomes, PWWE versus those without epilepsy had increased odds of preterm birth, small for gestational age, low birth weight (<2500 g), and congenital malformations, fetal distress. The odds of operative vaginal delivery, newborn mortality, and Apgar (≤ 7) were similar between PWWE and healthy women. CONCLUSION: Pregnant women affected by epilepsy encounter a higher risk of adverse obstetric outcomes and fetal complications. Therefore, it is crucial to develop appropriate prevention and intervention strategies prior to or during pregnancy to minimize the negative impacts of epilepsy on maternal and fetal health.


Assuntos
Epilepsia , Complicações na Gravidez , Resultado da Gravidez , Humanos , Gravidez , Feminino , Epilepsia/epidemiologia , Epilepsia/complicações , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Recém-Nascido
12.
Sci Total Environ ; 927: 172311, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38599416

RESUMO

Flotation technology is widely utilized to remove emulsified oil droplets from Produced water. Organic acid adsorption on the oil droplet surface affects bubble attachment, reducing oil removal efficiency. This investigation exploited the principle of similar dissolution to synthesize condensate bubbles (CB). The surface properties of oil droplets and CB and air bubbles (AB) were appraised using FTIR, zeta potential, interfacial tension, and contact angle measurements. The research also investigated the effects of acetic acids (AA) on the adhesion of oil droplets to AB and CB along with the underlying mechanism via the Extended Derjaguin-Landau-Verwey-Overbeek (EDLVO) interaction theory and the Stefan-Reynolds model of liquid film thinning, integrated with adhesion times. Flotation efficiency and kinetic dissimilarities between AB and CB were also examined. The results indicated that CB exhibits superior lipophilic hydrophobicity compared to AB, reduced induction and spreading times upon oil droplet attachment, and maximized oil removal efficiency. Furthermore, CB could mitigate the impact of AA on adhesion. The interaction barriers between CB and oil droplets were minimal, and the thinning rate of the hydration film was quicker than in AB. The conventional first-order model proved effective in fitting the AB flotation, whereas a delay constant was applied to the model of the CB flotation rate.

13.
Front Pharmacol ; 15: 1336122, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405667

RESUMO

Background: Epilepsy is a prevalent neurological disease where neuroinflammation plays a significant role in epileptogenesis. Recent studies have suggested that Astragalus polysaccharides (APS) have anti-inflammatory properties, which make them a potential candidate for neuroprotection against central nervous system disease. Nevertheless, the extent of their effectiveness in treating epilepsy remains enigmatic. Therefore, our study aims to investigate the potential of APS to mitigate epileptogenesis and its comorbidities by exploring its underlying mechanism. Methods: Initially, we employed pentylenetetrazol-induced seizure mice to validate APS' effectiveness. Subsequently, we employed network pharmacology analysis to probe the possible targets and signaling pathways of APS in treating epilepsy. Ultimately, we verified the key targets and signaling pathways experimentally, predicting their mechanisms of action. Results: APS have been observed to disturb the acquisition process of kindling, leading to reduced seizure scores and a lower incidence of complete kindling. Moreover, APS has been found to improve cognitive impairments and prevent hippocampal neuronal damage during the pentylenetetrazole (PTZ)-kindling process. Subsequent network pharmacology analysis revealed that APS potentially exerted their anti-epileptic effects by targeting cytokine and toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathways. Finally, experimental findings showed that APS efficiently inhibited the activation of astrocytes and reduced the release of pro-inflammatory mediators, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). In addition, APS impeded the activation of the TLR4/NF-κB signaling cascade in a PTZ-induced kindling mouse model. Conclusion: The outcomes of our study suggest that APS exerts an impact on epileptogenesis and mitigates cognitive impairment by impeding neuroinflammatory processes. The mechanism underlying these observations may be attributed to the modulation of the TLR4/NF-κB signaling pathway, resulting in a reduction of the release of inflammatory mediators. These findings partially agree with the predictions derived from network pharmacology analyses. As such, APS represents a potentially innovative and encouraging adjunct therapeutic option for epileptogenesis and cognitive deficit.

14.
ACS Chem Neurosci ; 15(10): 1951-1966, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38696478

RESUMO

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.


Assuntos
Cálcio , Ácido Glutâmico , Ácido Caínico , Parvalbuminas , Estado Epiléptico , Ácido gama-Aminobutírico , Animais , Masculino , Camundongos , Cálcio/metabolismo , Modelos Animais de Doenças , Ácido gama-Aminobutírico/metabolismo , Glutamato Descarboxilase/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Camundongos Transgênicos , Parvalbuminas/metabolismo , Estado Epiléptico/metabolismo , Estado Epiléptico/induzido quimicamente
15.
Endocrinol Metab (Seoul) ; 39(1): 40-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38347707

RESUMO

Thyroid radiofrequency ablation and microwave ablation are widely adopted minimally invasive treatments for diverse thyroid conditions worldwide. Fundamental skills such as the trans-isthmic approach and the moving shot technique are crucial for performing thyroid ablation, and advanced techniques, including hydrodissection and vascular ablation, improve safety and efficacy and reduce complications. Given the learning curve associated with ultrasound-guided therapeutic procedures, operators need training and experience. While training models exist, limited attention has been given to ultrasound maneuvers in ablation needle manipulation. This article introduces two essential maneuvers, the zigzag moving technique and the alienate maneuver, while also reviewing the latest ultrasound techniques in thyroid ablation, contributing valuable insights into this evolving field.


Assuntos
Ablação por Radiofrequência , Nódulo da Glândula Tireoide , Humanos , Resultado do Tratamento , Nódulo da Glândula Tireoide/cirurgia , Ablação por Radiofrequência/métodos , Ultrassonografia
16.
J Phys Chem B ; 127(25): 5668-5675, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37311091

RESUMO

Electromagnetic synergy is a more effective physical method than a single AC electric field (ACEF) to enhance oil-water separation. However, the electrocoalescence behavior of droplets dispersed with salt ions in oil under the synergistic electromagnetic field (EMSF) still lacks research. Herein, the evolution coefficient of liquid bridge diameter (C1) characterizes the growth rate of the liquid bridge diameter, a series of Na2CO3-dispersed droplets with different ionic strengths were prepared, and C1 values of droplets under ACEF and EMSF were compared. Micro high-speed experiments revealed that C1 under ACEF is larger than C1 under EMSF. In particular, when σ = 100 µS·cm-1and E = 629.73 kV·m-1, C1 under the ACEF is 15% larger than C1 under EMSF. Additionally, the theory of ion enrichment is put forward, which explains the influence of salt ions on ζ potential and total surface potential in EMSF. This study provides guidance for designing high-performance devices by introducing electromagnetic synergy in water-in-oil emulsion treatment.

17.
Artigo em Inglês | MEDLINE | ID: mdl-37587811

RESUMO

BACKGROUND: Astragalus polysaccharides (APS), a group of bioactive compounds obtained from the natural source Astragalus membranaceus(AM), exhibits numerous pharmacological actions in the central nervous system, such as anti-inflammatory, antioxidant, and immunomodulatory properties. Despite the remarkable benefits, the effectiveness of APS in treating anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and the corresponding mechanism have yet to be fully understood. As such, this study aims to investigate the impact of APS on anti-NMDAR encephalitis and explore the potential molecular network mechanism. METHODS: The impact of APS intervention on mice with anti-NMDAR encephalitis was assessed, and the possible molecular network mechanism was investigated utilizing network pharmacology and bioinformatics techniques such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG),protein-protein interaction (PPI) network, and molecular docking. Enzyme-linked immunosorbent assay (ELISA) was applied to detect the expression of core target proteins. RESULTS: APS significantly ameliorated cognitive impairment and reduced susceptibility to PTZ-induced seizures in mice with anti-NMDAR encephalitis, confirming the beneficial effect of APS on anti-NMDAR encephalitis. Seventeen intersecting genes were identified between APS and anti-NMDAR encephalitis. GO and KEGG analyses revealed the characteristics of the intersecting gene networks. STRING interaction in the PPI network was applied to find crucial molecules. The results of molecular docking suggested that APS may regulate interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as potential targets in anti-NMDAR encephalitis. Furthermore, the levels of IL-1ß, IL-6, and TNF-α detected by ELISA in anti-NMDAR encephalitis mice were significantly downregulated in response to the administration of APS. CONCLUSION: The findings of this study demonstrate the significant role of APS in the treatment of anti-NMDAR encephalitis, as it effectively suppresses inflammatory cytokines. These results suggest that APS has the potential to be considered as a viable herbal medication for the treatment of anti-NMDAR encephalitis.

18.
Brain Sci ; 13(10)2023 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-37891861

RESUMO

OBJECTIVE: The structural covariance network (SCN) alterations in patients with temporal lobe epilepsy and comorbid sleep disorder (PWSD) remain poorly understood. This study aimed to investigate changes in SCNs using structural magnetic resonance imaging. METHODS: Thirty-four PWSD patients, thirty-three patients with temporal lobe epilepsy without sleep disorder (PWoSD), and seventeen healthy controls underwent high-resolution structural MRI imaging. Subsequently, SCNs were constructed based on gray matter volume and analyzed via graph-theoretical approaches. RESULTS: PWSD exhibited significantly increased clustering coefficients, shortest path lengths, transitivity, and local efficiency. In addition, various distributions and numbers of SCN hubs were identified in PWSD. Furthermore, PWSD networks were less robust to random and target attacks than those of healthy controls and PWoSD patients. CONCLUSION: This study identifies aberrant SCN changes in PWSD that may be related to the susceptibility of patients with epilepsy to sleep disorders.

19.
Endocr Relat Cancer ; 30(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902083

RESUMO

Ataxia telangiectasia and Rad3-related protein (ATR) is a critical component of the DNA damage response and a potential target in the treatment of cancers. An ATR inhibitor, BAY 1895344, was evaluated for its use in differentiated thyroid cancer (DTC) therapy. BAY 1895344 inhibited cell viability in four DTC cell lines (TPC1, K1, FTC-133, and FTC-238) in a dose-dependent manner. BAY 1895344 treatment arrested DTC cells in the G2/M phase, increased caspase-3 activity, and caused apoptosis. BAY 1895344 in combination with either sorafenib or lenvatinib showed mainly synergistic effects in four DTC cell lines. The combination of BAY 1895344 with dabrafenib plus trametinib revealed synergistic effects in K1 cells that harbor BRAFV600E. BAY 1895344 monotherapy retarded the growth of K1 and FTC-133 tumors in xenograft models. The combinations of BAY 1895344 plus lenvatinib and BAY 1895344 with dabrafenib plus trametinib were more effective than any single therapy in a K1 xenograft model. No appreciable toxicity appeared in animals treated with either a single therapy or a combination treatment. Our findings provide the rationale for the development of clinical trials of BAY 1895344 in the treatment of DTC.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Animais , Humanos , Neoplasias da Glândula Tireoide/patologia , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Sorafenibe/farmacologia , Adenocarcinoma/tratamento farmacológico , Proteínas Mutadas de Ataxia Telangiectasia
20.
Environ Sci Pollut Res Int ; 29(6): 8012-8025, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34837615

RESUMO

The 2010 Deepwater Horizon spill remains the largest catastrophic release of oil and gas into the deep sea. The irrupted oil and gas substantially impact a marine ecosystem, cause human injury, and have high societal opinions. Therefore, understanding the transport and dispersion of subsurface hydrocarbon provides an imperative substratum for the practical assessment and response of marine oil spill accidents. In this review, we summarize the major advances since the Deepwater Horizon accident, with emphasis on the observation and modeling of the droplet and the formation and dynamics of the plume. Additional complexity including more than the investigation of gas-saturated oil at high-pressure and the effect of Earth's rotation on near field plume is also outlined. We end with a few outlooks on key priorities for more precisely estimations on future oil spills.


Assuntos
Ecossistema , Poluição por Petróleo , Acidentes , Humanos , Hidrocarbonetos
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