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1.
Eco Environ Health ; 3(2): 208-226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38655003

RESUMO

Nuclear isotopes, distinct atoms characterized by varying neutron counts, have profoundly influenced a myriad of sectors, spanning from medical diagnostics and therapeutic interventions to energy production and defense strategies. Their multifaceted applications have been celebrated for catalyzing revolutionary breakthroughs, yet these advancements simultaneously introduce intricate challenges that warrant thorough investigation. These challenges encompass safety protocols, potential environmental detriments, and the complex geopolitical landscape surrounding nuclear proliferation and disarmament. This comprehensive review embarks on a deep exploration of nuclear isotopes, elucidating their nuanced classifications, wide-ranging applications, intricate governing policies, and the multifaceted impacts of their unintended emissions or leaks. Furthermore, the study meticulously examines the cutting-edge remediation techniques currently employed to counteract nuclear contamination while projecting future innovations in this domain. By weaving together historical context, current applications, and forward-looking perspectives, this review offers a panoramic view of the nuclear isotope landscape. In conclusion, the significance of nuclear isotopes cannot be understated. As we stand at the crossroads of technological advancement and ethical responsibility, this review underscores the paramount importance of harnessing nuclear isotopes' potential in a manner that prioritizes safety, sustainability, and the greater good of humanity.

2.
J Environ Manage ; 344: 118496, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37384996

RESUMO

The effects of raw attapulgite clay and thermally modified attapulgite clay on the growth status of submerged plant Vallisneria Spiralis (V. spiralis) and the microenvironment of sediment were first explored. The results demonstrated that the attapulgite could effectively promote the development of V. spiralis and improve plant stress resistance by enhancing the activity of antioxidant enzymes. The 10% addition of attapulgite clay increased the biomass of V. spiralis by 27%∼174%, and the promoted rate of raw attapulgite clay was 2∼5 times of modified attapulgite clay. The attapulgite increased redox potential in sediment (P < 0.05) and provided proper niches for organism propagation, further promoting the degradation of organic matter and nutrient metabolism in sediment. The value of Shannon, Chao, and Ace was 9.98, 4865.15, 5029.08 in the 10% modified attapulgite group, and 10.12, 4856.85, 4947.78 in the 20% raw attapulgite group, respectively, indicating that the attapulgite could increase the microbial diversity and abundance in sediment. Additionally, the nutrient elements, such as Ca, Na, S, Mg, K, Zn, and Mo, that dissolved from attapulgite may also promote the V. spiralis growth. This study provided an environment-friendly approach to facilitating submerged macrophyte restoration in the eutrophic lake ecosystem.


Assuntos
Ecossistema , Hydrocharitaceae , Argila , Biomassa , Compostos de Magnésio , Hydrocharitaceae/metabolismo , Lagos
3.
BMC Plant Biol ; 23(1): 279, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37231351

RESUMO

BACKGROUND: The myeloblastosis (MYB) superfamily is the largest transcription factor family in plants that play diverse roles during stress responses. However, the biotic stress-responsive MYB transcription factors of the grapevine have not been systematically studied. In China, grapevine berries are often infected with the grapevine berry inner necrosis virus (GINV), which eventually reduces the nutritional quality and commodity value. RESULTS: The present study identified and characterized 265 VvMYB or VvMYB-related genes of the "Crimson seedless" grapevine. Based on DNA-binding domain analysis, these VvMYB proteins were classified into four subfamilies, including MYB-related, 2R-MYB, 3R-MYB, and 4R-MYB. Phylogenetic analysis divided the MYB transcription factors into 26 subgroups. Overexpression of VvMYB58 suppressed GINV abundance in the grapevine. Further qPCR indicated that among 41 randomly selected VvMYB genes, 12 were induced during GINV infection, while 28 were downregulated. These findings suggest that VvMYB genes actively regulate defense response in the grapevine. CONCLUSION: A deeper understanding of the MYB TFs engaged in GINV defense response will help devise better management strategies. The present study also provides a foundation for further research on the functions of the MYB transcription factors.


Assuntos
Fatores de Transcrição , Vitis , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Frutas/genética , Frutas/metabolismo , Vitis/metabolismo , Filogenia , Necrose/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
J Environ Manage ; 332: 117373, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36708598

RESUMO

Oil-based drill cutting ash (OBDCA) was treated by alkali melting-hydrothermal method and used as novel adsorbent (AM-HT-OBDCA) for the recovery of phosphorus (P) in water body. The experiment parameter for preparation of AM-HT-OBDCA was optimized, including alkali melting ratio (MOBDCA: MNaOH), alkali melting temperature and hydrothermal temperature. The adsorption process of phosphorus on AM-HT-OBDCA was fit well with the pseudo-second-order model and the Langmuir model. The calculated theoretic adsorption capacity of phosphorus on AM-HT-OBDCA was 62.9 mg/g. The adsorption behavior was spontaneous and endothermic. The effect of pH value and interfering ions on the adsorption of phosphorus in AM-HT-OBDCA was investigated. The main existing form of adsorbed phosphorus on AM-HT-OBDCA was sodium hydroxide extraction form phosphorus (NaOH-P), including iron form phosphorus (Fe-P) and aluminum form phosphorus (Al-P). Precipitation and ligand exchange were the main mechanisms of phosphorus adsorption on AM-HT-OBDCA. The AM-HT-OBDCA used for phosphorus adsorption (AM-HT-OBDCA-P) could be further utilized as fertilizer to promote plant growth. The results of this study provide fundamental data and evaluation support for resource utilization of OBDCA. These results will also provide a reference for the adsorption and recovery utilization of phosphorus using solid waste-based adsorbent.


Assuntos
Álcalis , Poluentes Químicos da Água , Hidróxido de Sódio , Adsorção , Fósforo , Ferro , Poluentes Químicos da Água/análise , Cinética
5.
Open Life Sci ; 17(1): 1296-1308, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36249531

RESUMO

Somatic embryogenesis receptor-like kinases (SERKs), a subfamily of receptor-like kinases, play important roles in response to abiotic stresses in addition to apomictic reproductive development in numerous plant species. The purpose of the present work was to determine if an ortholog of the SERK gene is present in the Diospyros lotus genome, isolate it and analyze its expression during embryogeny and abiotic stress. An ortholog of the SERK gene was isolated from the D. lotus genome, and designated as DlSERK1. The physical and chemical properties, protein structure, and evolutionary relationship of the DlSERK1 protein were analyzed by bioinformatics methods, and the expression of DlSERK1 gene during embryonic development and under low-temperature, salt, and drought stresses was examined through real-time quantitative PCR analysis. DlSERK1 contained 1,881 bp open reading frame encoding 626 amino acids, with a molecular mass of 69.18 kDa and pI of 5.34. DlSERK1 had strong hydrophilic property, signal peptide cleavage sites, and two transmembrane regions, indicating that DlSERK1 is a secretory protein. The secondary structure of DlSERK1 was consistent with the tertiary structure, both of which were dominated by random curls and alpha-helices. DlSERK1 had the typical structure of SERK proteins, and harbored multiple phosphorylation and glycosylation sites. Quantitative analysis showed that DlSERK1 was expressed during the embryonic development period, and the highest expression level was at 10 days post-flowering. The DlSERK1 expression level was down-regulated under low-temperature stress and up-regulated under drought and salt stresses. Our study showed that DlSERK1 was expressed in embryo development and could respond to low-temperature, drought, and salt stresses, which lays a foundation for further research on the function of SERK1 in the apomixis growth and development of environmental adaptation in D. lotus.

6.
Sci Total Environ ; 846: 157505, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-35870592

RESUMO

We investigated the long-term effects (6 years) of sediment improvement and submerged plant restoration of a subtropical shallow urban lake, Hangzhou West Lake China. To reveal the lake ecosystems variations, we analyzed the sediment properties, submerged macrophyte characteristics, sediment microorganisms, and benthic macroinvertebrate communities from 2015 to 2020. The ecological restoration project decreased sediment TP and OM, increased submerged macrophyte biomass and sediment microbial diversity, and improved the benthic macroinvertebrate communities in the restored area. The sediment TP decreased from 2.94 mg/g in 2015 to 1.33 mg/g in 2020. The sediment OM of the restored area decreased from 27.44 % in 2015 to 8.08 % in 2020. Principal component analysis (PCA) confirmed that the restoration improved the sediment conditions, making it suitable for the growth of submerged macrophytes, and then sped up the restoration and reconstruction of the lake ecosystem. These results have significant implications on the ecological management of shallow lakes.


Assuntos
Ecossistema , Lagos , Biomassa , China , Estudos Longitudinais , Plantas
7.
J Environ Sci (China) ; 118: 130-139, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35305761

RESUMO

Ecological restoration is one of the hot technologies for the reconstruction of eutrophic lake ecosystems in which the restoration and propagation of submerged plants is the key and difficult step. In this paper, the effect of vermiculite on the growth process of Vallisneria spiralis and sediment microenvironment were investigated, aiming to provide a theoretical basis for the application of vermiculite in aquatic ecological restoration. Results of growth indexes demonstrated that 5% and 10% vermiculite treatment groups statistically promote the growth of Vallisneria spiralis compared to the control. Meanwhile, the results of ecophysiological indexes showed that photosynthetic pigment, soluble sugar content, superoxide dismutase (SOD), and catalase (CAT) activity of 5% and 10% group were increased compared with the control while the malondialdehyde (MDA) content exhibited the opposite result (p < 0.05), which illustrated that vermiculite can improve the resistance of plants and delay the aging process of Vallisneria spiralis. In addition, result of PCA (Principal Component Analysis) demonstrated 5% and 10% group has improved the sediment physical conditions and create more ecological niche for microorganisms directly, and then promoted the growth of plants. The dissolution results showed that vermiculite can dissolve the constant and trace elements needed for plant growth. Furthermore, the addition of vermiculite increased the diversity of microorganisms in the sediments, and promoted the increase of plant growth-promoting bacteria and phosphorus-degrading bacteria. This study could provide a technique reference for the further application of vermiculite in the field of ecological restoration.


Assuntos
Ecossistema , Hydrocharitaceae , Silicatos de Alumínio , Lagos
8.
Chemosphere ; 298: 134236, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35288180

RESUMO

The diffusive gradients in thin films (DGT) technique was applied to determine the mechanism by which bentonite improves the eutrophic lake sediment microenvironment and enhances submerged plant growth. The migration dynamics of N, P, S, and other nutrient elements were established for each sediment layer and the remediation effects of bentonite and submerged plants on sediments were evaluated. Submerged plant growth in the bentonite group was superior to that of the Control. At harvest time, the growth of Vallisneria spiralis and Hydrilla verticillata was optimal on a substrate consisting of five parts eutrophic lake sediment to one part modified bentonite (MB5/1). Bentonite addition to the sediment was conducive to rhizosphere microorganism proliferation. Microbial abundance was highest under the MB5/1 treatment whilst microbial diversity was highest under the RB1/1 (equal parts raw bentonite and eutrophic lake sediment) treatment. Bentonite addition to the sediment may facilitate the transformation of nutrients to bioavailable states. The TP content of the bentonite treatment was 22.47%-46.70% lower than that of the Control. Nevertheless, the bentonite treatment had higher bioavailable phosphorus (BIP) content than the control. The results of this study provide theoretical and empirical references for the use of a combination of modified bentonite and submerged plants to remediate eutrophic lake sediment microenvironments.


Assuntos
Hydrocharitaceae , Poluentes Químicos da Água , Bentonita/química , Sedimentos Geológicos/química , Lagos/química , Fósforo/química , Poluentes Químicos da Água/análise
9.
Microorganisms ; 10(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35208904

RESUMO

Leaf microorganism communities play significant roles in the process of plant growth, but the microbiome profiling of crop leaves is still a relatively new research area. Here, we used 16S rDNA sequencing to profile the microbiomes of 78 primary dried tobacco leaf samples from 26 locations in eight Chinese provinces. Our analyses revealed that the national leaf microbial communities contain 4473 operational taxonomic units (OTU) representing 1234 species, but there is a small, national core microbiome with only 14 OTU representing nine species. The function of this core microbiome is related to processes including nitrogen fixation, detoxification of diverse pollutants, and heavy-metal reduction. The leaf microorganism communities are obviously affected by local environments but did not exhibit obvious relationships to single ecological factors (e.g., temperature, precipitation). Our findings enhance the understanding of microbial diversity of tobacco leaves, which could be utilized for a variety of bioprocess, agricultural, and environmental detoxification applications.

11.
Environ Sci Pollut Res Int ; 29(17): 25939-25951, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34850346

RESUMO

Modified maifanite (MMF) was prepared by the synthesized method with sulfuric acid treatment and high-temperature calcination and evaluated as an effective adsorption material to remove the nutrient salt in waste watery. Compared with the raw maifanite (RMF), the MMF exhibited a higher adsorption capacity and higher removal efficiency. The results showed that the adsorption rates of total phosphorus (TP), total nitrogen (TN), ammonia nitrogen (NH3-N), nitrate-nitrogen (NOx-N), and chemical oxygen demand (COD) by MMF were 86.7%, 44.9%, 29.1%, 19.8%, and 11.9%, respectively, and compared to RMF, the average adsorption capacity of these nutrients by MMF increased by 20.5 mg/kg, 126.2 mg/kg, 61.9 mg/kg, 117.18 mg/kg, and 86.9 mg/kg, respectively. MMF maintained the basic structure and composition of maifanite, while having a rougher and looser surface, more irregular pores, wider gaps, and more active materials such as oxidizing Fe. This study suggests that MMF can be further applied to treat domestic sewage and eutrophic water.


Assuntos
Fósforo , Esgotos , Adsorção , Nitrogênio/análise , Nutrientes , Eliminação de Resíduos Líquidos/métodos
12.
J BUON ; 26(3): 1183, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34269000

RESUMO

The Editors of JBUON issue an Expression of Concern to 'Antiproliferative activities of auraptenol against drugresistant human prostate carcinoma cells are mediated via programmed cell death, endogenous ROS production, and targeting the JNK/p38 MAPK signal pathways', by Yunli Liu, Xuedong Li, Zhaoyan Chen, Yunhui Chan; JBUON 2020;25(1):454-459; PMID: 32277668. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.


Assuntos
Carcinoma , Preparações Farmacêuticas , Apoptose , Cumarínicos , Humanos , Masculino , Próstata/metabolismo , Espécies Reativas de Oxigênio , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
J Environ Manage ; 287: 112308, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33706092

RESUMO

The effects of clay mineral bentonite on the growth process of submerged macrophyte V. spiralis and sediment microenvironment were investigated in the study for the first time, aiming to determine whether it is suitable for application in the field of ecological restoration. The growth index, and physiological and biochemical index of V. spiralis in the experiments were measured once a month, and the changes of rhizosphere microorganisms and physicochemical properties of sediments were also studied at the same time. The results demonstrated that bentonite can effectively promote the growth of V. spiralis. The treatment groups of RB1/1 and MB1/5 (the mass ratios of bentonite to sediment were 1/1 and 1/5, respectively.) showed the best V. spiralis growth promotion rates which were 18.78%, and 11.79%, respectively. The highest microbial diversity and abundance existed in group of RB10 (the mass ratio of sediment to bentonite was 10/1), in which the OTUs, Shannon, Chao and Ace were 1521.0, 5.20, 1712.26, and 1686.31, respectively. Bentonite was conducive to the propagation of rhizosphere microorganisms, and further changed the physical and chemical properties of the sediment microenvironment. The nutrient elements dissolved from bentonite may be one of the main reasons that promoted the growth of V. spiralis. The purpose of this result is to prove that bentonite can be further applied as sediment improver and growing media in ecological restoration projects in eutrophic shallow lakes.


Assuntos
Bentonita , Sedimentos Geológicos , Lagos , Minerais , Fósforo , Rizosfera
14.
J Hazard Mater ; 403: 123956, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33265000

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic derivatives are organic pollutants that pose a serious health risk to human beings. In this study, a newly isolated Pseudomonas brassicacearum strain MPDS could effectively degrade PAHs and heterocyclic derivatives, including naphthalene, fluorene, dibenzofuran (DBF) and dibenzothiophene (DBT). Notably, strain MPDS is able to degrade fluorene, DBF and DBT uniquely via a lateral dioxygenation pathway, while most reported strains degrade fluorene, DBF and DBT via an angular dioxygenation pathway or co-metabolize them via a lateral dioxygenation pathway. Strain MPDS completely degraded 50 mg naphthalene (in 50 mL medium) in 84 h, and OD600 reached 1.0-1.1; while, it stabilized at OD600 0.5-0.6 with 5 mg fluorene or DBF or DBT. Meanwhile, 65.7% DBF and 32.1% DBT were degraded in 96 h, and 40.3% fluorene was degraded in 72 h, respectively. Through genomic and transcriptomic analyses, and comparative genomic analysis with another DBF degradation strain, relevant gene clusters were predicted, and a naphthalene-degrading gene cluster was identified. This study provides understanding of degradation of PAHs and their heterocyclic derivatives, as well as new insights into the lateral dioxygenation pathway of relevant contaminants.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Policíclicos Aromáticos , Biodegradação Ambiental , Humanos , Pseudomonas/genética
15.
Environ Pollut ; 267: 115380, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32892006

RESUMO

The effects of maifanite on the physiological and phytochemical process of submerged macrophytes Hydrilla verticillate (H.verticillata) were investigated for the first time in the study. The growth index: plant biomass, root length, plant height and leaf spacing, and physiological and phytochemical indexes: chlorophyll, soluble protein, malondialdehyde (MDA), peroxidase (POD), superoxide dismutase (SOD) content and vitality of the roots of H.verticillata were tested. The results found that maifanite can significantly promote the growth of H.verticillata. The modified maifanite were more conducive to plant growth compared with the raw maifanite, and the MM1 group had the best growth promoting effect. The physiological and phytochemical indexes showed that maifanite can delay the aging process of H.verticillata (P < 0.05). The possible reasons for promoting H.verticillata growth were that maifanite can provide excellent propagation conditions for plant rhizosphere microorganisms, contains abundant major and microelements, and improve the sediment microenvironment. This study may provide a technique for the further application of maifanite in the field of ecological restoration.


Assuntos
Hydrocharitaceae , Biomassa , Clorofila , Minerais , Silicatos
16.
J BUON ; 25(1): 454-459, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32277668

RESUMO

PURPOSE: Prostate cancer is considered to be one of the most common cancers in men and as such there is a pressing need for finding new therapeutic agents to treat this disease. Therefore, the main purpose of the current research work was to study the anticancer effects of a naturally occurring coumarin- Auraptenol- against drug-resistant human prostate cancer cells and evaluate its effects on programmed cell death, reactive oxygen species (ROS) production, and JNK/p38 MAPK signalling pathway. METHODS: Cell proliferation was examined by CCK8 cell viability assay. Apoptosis-related studies were checked by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) and Hoechst staining, as well as flow cytometry using annexin V/propidium iodide (PI) assay. Western blot was used to study the effects of Auraptenol on apoptosis-related protein expressions including Bax, Bcl-2, as well as JNK/p38 MAPK signalling pathway. ROS production was evaluated by flow cytometry. RESULTS: The results showed that Auraptenol caused significant reduction in the viability of the human LNCaP prostate carcinoma cells in a dose-dependent manner, exhibiting an IC50 of 25 µM in cancer cells and IC50 of 100 µM in normal PNT2 cells. The AO/EB staining assay showed that Auraptenol inhibited the viability of cancer cells via induction of apoptotic cell death, which was associated with increase in Bax and decrease in Bcl-2 levels. Hoechst staining results also confirmed that Auraptenol induced programmed cell death. The apoptotic cells increased from 0.8% in the control to 32.5% in the study group at 50 µM concentration of Auraptenol. Auraptenol also induced an increase in ROS production in a dose-dependent manner. Finally, this molecule blocked the JNK/p38 MAPK signal pathway concentration-dependently in human prostate cancer cells. CONCLUSION: In conclusion, the current study indicates that this molecule could be developed as a potential anticancer drug against human prostate carcinoma provided further studies are carried out.


Assuntos
Apoptose/efeitos dos fármacos , Cumarínicos/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias da Próstata/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Cumarínicos/farmacologia , Humanos , Masculino , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismo
17.
IEEE Trans Cybern ; 49(9): 3255-3267, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29994284

RESUMO

In this paper, a time-scale-dependent coupling scheme for two-time-scale nonlinear complex networks is proposed. According to this scheme, the inner coupling matrices are related to the fast dynamics of individual subsystems, but are no longer time-scale-independent. Designing time-scale-dependent inner coupling matrices is motivated by the fact that the difference of time scales is an essential feature of modular architecture of two-time-scale systems. Under the novel coupling framework, the previous assumption on individual two-time-scale subsystems that the fast dynamics must be exponentially stable can be removed. The idea of time-scale separation is employed to analyze the stability of synchronization error systems via weighted ε -dependent Lyapunov functions. For a given upper bound of the singular perturbation parameter ε , it is proved that the exponential decay rate of the synchronization error can be guaranteed to be independent of the value of ε . In this way, criteria for local and global exponential synchronization are established. The allowable upper bound of ε such that the synchronizability of the considered two-time-scale network is retained can be obtained by solving a set of ε -dependent matrix inequalities. Finally, the efficiency of the proposed time-scale-dependent coupling strategy is demonstrated through numerical simulations.

18.
Biochem Pharmacol ; 156: 78-85, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30086287

RESUMO

Dipeptidyl peptidase-IV (DPP4) is a cell surface serine peptidase widely expressed in the brain. Recent studies suggest that DPP4 contributes to the development of febrile seizures (FS); however, the underlying mechanism is still unclear. Thus, we investigated the role of DPP4 in the progression of FS at the molecular and electrophysiological levels using FS models in vivo and in vitro. Herein, we found that both the mRNA and protein levels of DPP4 were upregulated in the FS model. Administration of the pharmacological DPP4 inhibitor sitagliptin suppressed the hyperthermia-induced neuronal excitability as determined via whole-cell patch-clamp recordings in vitro. Interestingly, sitagliptin administration activated the glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) pathway by increasing the expression of GLP-1 and GLP-1R in a rat model of FS. Moreover, administration of the GLP-1R inhibitor exendin9-39 increased seizure severity, and sitagliptin reversed the effect, as shown in the electroencephalogram (EEG) and patch-clamp results in a rat model of FS. Furthermore, the GLP-1R-mediated reduction in GABAergic transmission was enhanced by sitagliptin and DPP4 knockdown through increasing miniature inhibitory post-synaptic currents (mIPSCs) in vitro accompanied by increased synaptic release of GABA in vivo. Taken together, our results demonstrate a role of DPP4 in regulating GABAergic transmission via the GLP-1/GLP-1R pathway. These findings indicated that DPP4 may represent a novel therapeutic strategy and target for FS.


Assuntos
Dipeptidil Peptidase 4/metabolismo , Peptídeo 1 Semelhante ao Glucagon/fisiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/fisiologia , Convulsões Febris/metabolismo , Animais , Inibidores da Dipeptidil Peptidase IV/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/citologia , Masculino , Neurturina/efeitos dos fármacos , Neurturina/fisiologia , Interferência de RNA , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fosfato de Sitagliptina/farmacologia
19.
Exp Neurol ; 307: 90-98, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29885296

RESUMO

Epilepsy is a common neurological disorder with a complex etiology. Our previous study demonstrated that dipeptidyl peptidase IV (DPP4) may be associated with the pathogenesis of epilepsy. However, whether the DPP4 inhibitor sitagliptin has an anticonvulsant effect and the underlying mechanism remain to be elucidated. In this study, we determined that sitagliptin remarkably attenuated the severity of seizures in a pentylenetetrazole (PTZ)-induced rat model. In addition, sitagliptin decreased epileptiform activity measured by electroencephalography (EEG) recordings and patch-clamp methods. Interestingly, sitagliptin pretreatment downregulated the RAGE-JAK2/STAT3 pathway and decreased the expression of CXCL4 and CXCR3. Moreover, CXCR3 knockdown decreased the expression of RAGE, JAK2 and STAT3 in cultured neurons, which suggests that CXCR3 is upstream of the RAGE-JAK2/STAT3 pathway. Altogether, our present data suggest that sitagliptin has an anticonvulsant effect, which might act via downregulation of the CXCL4/CXCR3 axis, followed by a decrease in RAGE and JAK2/STAT3 expression. Considering these effects, sitagliptin could be considered as a novel potential anticonvulsant drug.


Assuntos
Anticonvulsivantes/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptores CXCR3/metabolismo , Convulsões/metabolismo , Fosfato de Sitagliptina/uso terapêutico , Animais , Anticonvulsivantes/farmacologia , Inibidores da Dipeptidil Peptidase IV/farmacologia , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Receptores CXCR3/antagonistas & inibidores , Convulsões/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fosfato de Sitagliptina/farmacologia
20.
Mol Med Rep ; 11(4): 2717-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25482028

RESUMO

Smad4 has recently been identified as a tumor suppressor gene in a variety of cancers, yet the role of Smad4 in renal cell carcinoma (RCC) remained to be elusive. Therefore, the aim of the present study was to explore the function of Smad4 in RCC. The expression of Smad4 reduced the growth rate of RCC. The levels of Smad4 and forkhead box protein H1 (FOXH1) mRNA were reduced, while the levels of estrogen receptor were increased in RCC cells compared with those in human renal epithelial cells (P<0.01). Western blot analysis showed an identical trend among the three molecules. Glutathione S­transferase pull­down and immunoprecipitation assays proved the interaction between Smad4 and FOXH1. An immunofluorescence assay revealed that Smad4 and FOXH1 were colocalized in the nuclei of RCC cells. Smad4 interacts with Smad2 and migrates into the nucleus, where it interacts with FOXH1 to repress the protein expression of estrogen receptor. These results indicate that Smad4 acts as a tumor suppressor by activating FOXH1, and then suppressing the expression of estrogen receptor, in addition to tumor migration and invasion. Hence, Smad4 should be investigated as a potential target for the treatment for RCC.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Fatores de Transcrição Forkhead/genética , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteína Smad4/metabolismo , Ativação Transcricional , Adulto , Idoso , Carcinoma de Células Renais/patologia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ligação Proteica , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Fatores de Risco , Proteína Smad4/genética , Transfecção
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