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The utilization of lithium-sulfur battery is hindered by various challenges, including the "shuttle effect", limited sulfur utilization, and the sluggish conversion kinetics of lithium polysulfides (LiPSs). In the present work, a theoretical design for the viability of graphitic carbon nitride (g-C3N4) and phosphorus-doping graphitic carbon nitride substrates (P-g-C3N4) as promising host materials in a Li-S battery was conducted utilizing first-principles calculations. The PDOS shows that when the P atom is introduced, the 2p of the N atom is affected by the 2p orbital of the P atom, which increases the energy band of phosphorus-doping substrates. The energy bands of PC and Pi are 0.12 eV and 0.20 eV, respectively. When the lithium polysulfides are adsorbed on four substrates, the overall adsorption energy of PC is 48-77% higher than that of graphitic carbon nitride, in which the charge transfer of long-chain lithium polysulfides increase by more than 1.5-fold. It is found that there are powerful Li-N bonds between lithium polysulfides and P-g-C3N4 substrates. Compared with the graphitic carbon nitride monolayer, the anchoring effect of the LiPSs@P-g-C3N4 substrate is enhanced, which is beneficial for inhibiting the shuttle of high-order lithium polysulfides. Furthermore, the catalytic performance of the P-g-C3N4 substrate is assessed in terms of the S8 reduction pathway and the decomposition of Li2S; the decomposition energy barrier of the P-g-C3N4 substrate decrease by 10% to 18%. The calculated results show that P-g-C3N4 can promote the reduction of S8 molecules and Li-S bond cleavage within Li2S, thus improving the utilization of sulfur-active substances and the ability of rapid reaction kinetics. Therefore, the P-g-C3N4 substrates are a promising high-performance lithium-sulfur battery anchoring material.
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BACKGROUND: An increasing number of small nucleolar RNA host genes (SNHGs) have been revealed to be dysregulated in lung cancer tissues, and abnormal expression of SNHGs is significantly correlated with the prognosis of lung cancer. The purpose of this study was to conduct a meta-analysis to explore the correlation between the expression level of SNHGs and the prognosis of lung cancer. METHODS: A comprehensive search of six related databases was conducted to obtain relevant literature. Relevant information, such as overall survival (OS), progression-free survival (PFS), TNM stage, lymph node metastasis (LNM), and tumor size, was extracted. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled to evaluate the relationship between SNHG expression and the survival outcome of lung cancers. Sensitivity and publication bias analyses were performed to explore the stability and reliability of the overall results. RESULTS: Forty publications involving 2205 lung cancer patients were included in this meta-analysis. The pooled HR and 95% CI values indicated a significant positive association between high SNHG expression and poor OS (HR: 1.890, 95% CI: 1.595-2.185), disease-free survival (DFS) (HR: 2.31, 95% CI: 1.57-3.39) and progression-free survival (PFS) (HR: 2.01, 95% CI: 0.66-6.07). The pooled odds ratio (OR) and 95% CI values indicated that increased SNHG expression may be correlated with advanced TNM stage (OR: 1.509, 95% CI: 1.267-1.799), increase risk of distant lymph node metastasis (OR: 1.540, 95% CI: 1.298-1.828), and large tumor size (OR: 1.509, 95% CI: 1.245-1.829). Sensitivity analysis and publication bias results showed that each result had strong reliability and robustness, and there was no significant publication bias or other bias. CONCLUSION: Most SNHGs are upregulated in lung cancer tissues, and high expression of SNHGs predicts poor survival outcomes in lung cancer. SNHGs may be potential prognostic markers and promising therapeutic targets.
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Neoplasias Pulmonares , Neoplasias , RNA Longo não Codificante , Humanos , Neoplasias Pulmonares/genética , Metástase Linfática , Reprodutibilidade dos Testes , RNA Longo não Codificante/genética , RNA Longo não Codificante/análise , Neoplasias/patologia , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseRESUMO
The low cycle performance and low Coulomb efficiency of tin-based materials confine their large-scale commercial application for lithium-ion batteries. To overcome the shortage of volume expansion of pristine tin, Sn-Co alloy/rGO composites have been successfully synthesized by chemical reduction and sintering methods. The effects of sintering temperature on the composition, structure and electrochemical properties of Sn-Co alloy/rGO composites were investigated by experimental study and first-principles calculation. The results show that Sn-Co alloys are composed of a large number of CoSn and trace CoSn2 intermetallics, which are uniformly anchored on graphene nanosheets. The sintering treatment effectively improves the electrochemical performance, especially for the first Coulomb efficiency. The first charge capacity of Sn-Co alloy/rGO composites sintered at 450 °C is 675 mAh·g-1, and the corresponding Coulomb efficiency reaches 80.4%. This strategy provides a convenient approach to synthesizing tin-based materials for high-performance lithium-ion batteries.
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Pentagonal compounds, as a new family of 2D materials, have recently been extensively studied in the fields of electrocatalysis, photovoltaics, and thermoelectrics. Encouraged by the successful synthesis of pentagonal PdSe2, the thermoelectric properties of low-cost pentagonal NiX2 (X = S, Se, and Te) monolayers are theoretically predicted with the help of first-principles calculations and the semiclassical Boltzmann transport theory. The high dynamic and thermal stabilities of pentagonal NiX2 (X = S, Se, and Te) monolayers are confirmed according to the phonon dispersion spectrums and ab initio molecular dynamics (AIMD) simulations. Indirect semiconductor features with wide bandgaps of 2.44, 2.31, and 1.88 eV at the Heyd-Scuseria-Ernzerhof (HSE06) level are discovered for pentagonal NiS2, NiSe2, and NiTe2 monolayers. Combining the Boltzmann transport equation and deformation potential theory, the Seebeck coefficient, power factor, and thermoelectric figure of merit (ZT) of NiX2 (X = S, Se, and Te) monolayers are evaluated from 300 to 600 K. The strongly anisotropic ZT values are discovered, which are attributed to the significant differences in electrical and thermal transport along the x and y directions. In addition, low lattice thermal conductivities are observed at 600 K for the pentagonal NiTe2 monolayer, accompanying higher ZT values of 1.81 and 1.58 along the x and y directions. The predicted thermoelectric properties indicate that the low-cost pentagonal NiSe2 and NiTe2 monolayers are potential anisotropic thermoelectric materials with high performance.
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Alzheimer's disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD. However, the molecular mechanism of cannabidiol via TRPV2 in AD remains unknown. The present study investigated whether cannabidiol enhances the phagocytosis and clearance of microglial Aß via the TRPV2 channel. We used a human dataset, mouse primary neuron and microglia cultures, and AD model mice to evaluate TRPV2 expression and the ability of microglial amyloid-ß phagocytosis in vivo and in vitro. The results revealed that TRPV2 expression was reduced in the cortex and hippocampus of AD model mice and AD patients. Cannabidiol enhanced microglial amyloid-ß phagocytosis through TRPV2 activation, which increased the mRNA expression of the phagocytosis-related receptors, but knockdown of TRPV2 or Trem2 rescued the expression. TRPV2-mediated effects were also dependent on PDK1/Akt signaling, a pathway in which autophagy was indispensable. Furthermore, cannabidiol treatment successfully attenuated neuroinflammation while simultaneously improving mitochondrial function and ATP production via TRPV2 activation. Therefore, TRPV2 is proposed as a potential therapeutic target in AD, while CBD is a promising drug candidate for AD.
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Doença de Alzheimer , Canais de Cálcio , Canabidiol , Canais de Cátion TRPV , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Canais de Cálcio/genética , Canais de Cálcio/metabolismo , Canabidiol/farmacologia , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fagocitose , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
Carbonaceous materials with pores or bilayer spaces are a kind of potential host material to confine polyselenide diffusion and mitigate the shuttling effect. In the present work, a theoretical design of bilayer C2N (bi-C2N) as an efficient host material for lithium-selenium (Li-Se) batteries was explored by first-principles calculations. AA- and AB-stacking bilayer C2N could alleviate the dissolution of high-order polyselenides through a synergistic effect of physical confinement and strong Li-N bonds. Lithium polyselenides prefer to anchor on AA- and AB-stacking bilayer C2N instead of the commonly used electrolytes, showing their capabilities in suppressing the shuttle effect. Charge transfer occurs from Se8 and Li2Sen molecules (LiPSes) to AA- and AB-stacking bilayer C2N, giving rise to the formation of strong Li-N bonds. The AA- and AB-stacking LiPSes@C2N systems possess high electrical conductivities, which is beneficial for high electrochemical performance. In addition, the reversible conversion mechanisms of Li2Sen in the AA- and AB-stacking bilayer C2N are also investigated through the energy changes and decomposition reaction of the Li2Se molecule, and the results indicate that AA- and AB-stacking bilayer C2N facilitate the formation and decomposition of Li2Se by decreasing the active energy barriers and improving the selenium utilization rates. Our present work could shed some light on a possible strategy for designing highly efficient bilayer host materials for high performance Li-Se batteries.
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A new strategy of sodium ion batteries with the hybrid storage of Li and Na ions has attracted much attention in the field of large-scale energy storage. For revealing the mechanism of hybrid storage of Li and Na atoms in carbon materials, the lowest energy configuration, adsorption energy, differential charge density and density of states of LixNay clusters on graphene, as a structural unit of carbon materials, were calculated and investigated based on first principles density functional theory. The calculation results show that the deposition behavior of single Li or Na atoms on graphene is similar, and both are preferentially deposited at the hollow of graphene (H-site). The Li atom is deposited preferentially over the Na atom, and the deposition height of the Li atom is lower. When the total number of metal atoms x + y ≥ 3, LixNay clusters are deposited on graphene in the form of a stereotypical atomic cluster, in which the Li atom is usually at the bottom of the LixNay cluster, while the Na atom is usually at the top of the cluster. The electronic structure analysis shows that the electrons of the LixNay cluster are transferred to the anti-bonding π orbitals adjacent to graphene. The 2s orbitals of Li atoms and the 2s and 2p orbitals of Na atoms are hybridized with the 2p orbitals of C atoms. Therefore, the Li-C bonds or Na-C bonds formed between Li or Na atoms and C atoms of graphene are usually ionic bonds with partial covalent bond properties. Meanwhile, the Li-Li, Na-Na or Li-Na bonds formed inside LixNay clusters are usually multiple metal-metal bonds.
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Neuronostatin (NST) is an endogenous peptide hormone, it has the ability to improve oligomeric Aß (oAß)-induced cognitive impairments and increase blood glucose levels in mice. However, the relationship between NST and oAß regarding brain glucose metabolism has not yet been established. The present study defined the contributions of NST and oAß in the brain glucose metabolism in mice. It was found that i.c.v. co-administration of NST (3 nmol/mouse) and oAß (1 nmol/mouse) decreased the mRNA expressions of glucose-6-phosphate dehydrogenase and phosphofructokinase. The treatments were observed to reduce ATP production and the enzyme activities of glucose-6-phosphate dehydrogenase and hexokinase in both the cortex and hippocampus. Simultaneously, co-injection of NST and oAß inhibited the mRNA and protein expression of glucose transporters GLUT3 and GLUT1 in the cortex and hippocampus. NST promoted the oAß-induced decreased the cortical NeuN staining, while oAß increased the levels of NST in both the cortex and hippocampus. I.c.v. co-administration of NST and oAß led to increase the levels of GPR107 expression and the phosphorylation of PKA, Akt, PERK and eIF-2α in the cortex. These findings suggest that NST promoted oAß-induced dysfunctional glucose metabolism through the GPR107/PKA/Akt signaling pathway and PERK/eIF2α axis in the brain, which thus contributes to metabolic dysfunction and Alzheimer's disease (AD) pathophysiology.
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Peptídeos beta-Amiloides/farmacologia , Córtex Cerebral/metabolismo , Glucose/metabolismo , Hipocampo/metabolismo , Fragmentos de Peptídeos/farmacologia , Hormônios Peptídicos/farmacologia , Trifosfato de Adenosina/metabolismo , Peptídeos beta-Amiloides/química , Animais , Combinação de Medicamentos , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/metabolismo , Glucosefosfato Desidrogenase/metabolismo , Glicólise/efeitos dos fármacos , Hexoquinase/metabolismo , Masculino , Camundongos , Fragmentos de Peptídeos/química , Fosfofrutoquinases/metabolismo , Multimerização Proteica , Transdução de Sinais/fisiologiaRESUMO
Among the popular electrochemical energy storage devices, supercapacitors (SCs) have attracted much attention due to their long cycle life, fast charge and discharge, safety, and reliability. Transition metal oxides are one of the most widely used electrode materials in SCs because of the high specific capacitance. Among various transition metal oxides, Co3O4 and related composites are widely reported in SCs electrodes. In this review, we introduce the synthetic methods of Co3O4, including the hydrothermal/solvothermal method, sol-gel method, thermal decomposition, chemical precipitation, electrodeposition, chemical bath deposition, and the template method. The recent progress of Co3O4-containing electrode materials is summarized in detail, involving Co3O4/carbon, Co3O4/conducting polymer, and Co3O4/metal compound composites. Finally, the current challenges and outlook of Co3O4 and Co3O4-containing composites are put forward.
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Cobalto/química , Técnicas Eletroquímicas , Eletrodos , Óxidos/química , Capacitância Elétrica , Nanotubos de Carbono/química , Polímeros/químicaRESUMO
Lithium-sulfur batteries are very promising next-generation energy storage batteries due to their high theoretical specific capacity. However, the shuttle effect of lithium-sulfur batteries is one of the important bottlenecks that limits its rapid development. Herein, physical and chemical dual adsorption of lithium polysulfides are achieved by designing a novel framework structure consisting of MnO2, reduced graphene oxide (rGO), and carbon nanotubes (CNTs). The framework-structure composite of MnO2/rGO/CNTs is prepared by a simple hydrothermal method. The framework exhibits a uniform and abundant mesoporous structure (concentrating in ~12 nm). MnO2 is an α phase structure and the α-MnO2 also has a significant effect on the adsorption of lithium polysulfides. The rGO and CNTs provide a good physical adsorption interaction and good electronic conductivity for the dissolved polysulfides. As a result, the MnO2/rGO/CNTs/S cathode delivered a high initial capacity of 1201 mAh g-1 at 0.2 C. The average capacities were 916 mAh g-1, 736 mAh g-1, and 547 mAh g-1 at the current densities of 0.5 C, 1 C, and 2 C, respectively. In addition, when tested at 0.5 C, the MnO2/rGO/CNTs/S exhibited a high initial capacity of 1010 mAh g-1 and achieved 780 mAh g-1 after 200 cycles, with a low capacity decay rate of 0.11% per cycle. This framework-structure composite provides a simple way to improve the electrochemical performance of Li-S batteries.
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Fontes de Energia Elétrica , Grafite/química , Lítio/química , Compostos de Manganês/química , Estruturas Metalorgânicas/química , Nanotubos de Carbono/química , Enxofre/química , Eletroquímica , Eletrodos , Estruturas Metalorgânicas/ultraestrutura , Análise EspectralRESUMO
The desolvation effect of ions plays an important role in adjusting the capacity of supercapacitors and has attracted considerable attention after its discovery. Here, first-principles calculations were conducted to calculate the reaction energies of ions, water, and hydrated ions in bilayer graphene (BG) with different interlayer spacings (d) and to explore the desolvation behaviors of H+, Li+, Na+, and K+ ions. The calculated results showed that H+ can only exist in the state of H3O+ in AA-stacking BG, and desolvation exists only in the case of AB-stacking BG. The complete desolvation size for H+ ions in the AB-stacking system reached 5.6 Å, which was the largest desolvation size of the four ions studied. The critical desolvation sizes of Li+, Na+, and K+ in the BG layers of AA- and AB-stacking increased sharply as a consequence of the increasing ionic radius. However, the complete desolvation sizes of all three ions were in the range of 4-5 Å and with the increase in ionic radius, the complete desolvation sizes showed a reverse tendency. The complete desolvation size of Na+ in AB-stacking BG was slightly larger than that in AA-stacking BG. Further analysis presented that the ionic radii of H+, Li+, Na+, and K+ ions make a dominant contribution to the critical size of desolvation. Our present results provide useful information for improving the capacity of supercapacitors by precisely matching the pore structure and electrolyte through the adjustment of the pore structure of carbon materials.
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OBJECTIVE: The aim of this study was to investigate the effects of epigallocatechin-3-gallate on the proliferation and apoptosis of odontogenic keratocyst (OKC) keratinocytes in vitro. MATERIALS AND METHODS: Keratinocytes isolated from the epithelial lining of the OKC were cultured in keratinocyte serum-free medium and identified by CK10, CK14, pan-cytokeratin and vimentin immunofluorescence staining. The cells were exposed to EGCG at different concentrations, and proliferation inhibition was measured by cell counting kit 8 assay. Cell cycle and apoptosis were assessed by flow cytometry, and expression of the WNT signalling pathway-related proteins FZD3 and JNK3 was detected by quantitative real-time PCR and Western blotting. Human oral keratinocytes (HOKs) were used as the control. RESULTS: The OKC keratinocytes were successfully cultured. The primary cells were tile-like and expressed the epithelial biomarkers CK10, CK14 and pan-cytokeratin. Epigallocatechin-3-gallate inhibited cell proliferation in a dose- and time-dependent manner, arrested cell cycle in the G1 phase and induced apoptosis of OKC keratinocytes. FZD3 and JNK3 were overexpressed in OKC keratinocytes compared with HOKs and were downregulated by epigallocatechin-3-gallate treatment. CONCLUSION: Epigallocatechin-3-gallate inhibited proliferation and induced apoptosis in OKC keratinocytes, possibly by suppressing the WNT/JNK signalling pathway. It may thus be potentially used for OKC treatment.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Catequina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Catequina/farmacologia , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases , Cistos Odontogênicos , Via de Sinalização WntRESUMO
Lithium-sulfur (Li-S) batteries have attracted increasing attention due to their high theoretical capacity, being a promising candidate for portable electronics, electric vehicles and large-scale energy storage. The interactions of bilayer structured graphitic C3N4 (bi-C3N4) with S8, lithium polysulfides (LiPSs), 1,3-dioxolane, 1,2-dimethoxyethane and tetrahydrofuran ether-based solvents have been studied using first-principles calculations. It has been found that the (micropore-scale) interlayer of bi-C3N4 shows intimate contact and strong binding with S8 and LiPSs due to the formation of chemical Li-N bonds. The incorporation of soluble LiPSs by the wrinkled layers of bi-C3N4 with 5.5-7.2 Å interlayer pores can suppress the shuttling effect. The interlayer ultramicropores with interlayer distances of <4 Å can accommodate the small Li2S2 and Li2S molecules, and impede the irreversible reaction between the solvents and the LiPSs. The calculated energy gap of bi-C3N4 decreases to be narrow during lithiation. Our results can provide a guideline for promoting the electrochemical performance of microporous g-C3N4/sulfur composites for Li-S batteries.
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MicroRNAs (miRNAs) play several important roles in carcinogenesis, and the dysregulation of miRNAs is associated with cancer progression. Little is known about the role of miR-613 in ovarian cancer. In the present study, we demonstrate that miR-613 expression is downregulated in human ovarian cancer cell lines and tissues. Additionally, miR-613 overexpression suppressed ovarian cancer cell proliferation, colony formation, and invasion. Furthermore, KRAS was identified as a target of miR-613. Reintroducing KRAS rescued the inhibitory effects exerted by miR-613 on ovarian cancer cell proliferation and invasion. Taken together, our findings suggest that miR-613 functions as a candidate tumor suppressor miRNA in ovarian cancer by directly targeting KRAS. To the best of our knowledge, this is the first study to show that miR-613 affects the proliferation and invasion of ovarian cancer.
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MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Regiões 3' não Traduzidas , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Interferência de RNARESUMO
KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230-0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.
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Biomarcadores Tumorais/metabolismo , Carcinoma/metabolismo , Neoplasias Ovarianas/metabolismo , Proteínas Repressoras/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma/diagnóstico , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Proteínas Repressoras/genética , Proteína 28 com Motivo TripartidoRESUMO
This study investigates the protective effect of betanin against liver injury induced by carbon tetrachloride (CCl4) in common carp (Cyprinus carpio L.). The fish were treated with 1, 2, and 4 % betanin in fodder throughout the experiment. After 20 days of treatment, the fish were intraperitoneally injected with 20 % (v/v in peanut oil) CCl4 at a volume of 0.5 mL/kg body weight. The fish were killed 3 days after CCl4 intoxication, and then, histological and biochemical assays were performed. Results showed that CCl4-induced liver CYP2E1 activity, oxidative stress, and injury, as indicated by the depleted glycogen storage, increased serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) activities and liver histological damage. Compared with the CCl4 control group, the betanin-treated groups exhibited reduced CYP2E1 activity, decreased malondialdehyde level, increased liver antioxidative capacity (increased glutathione level and superoxide dismutase and catalase activities), increased liver glycogen storage, and reduced serum AST/ALT activities, with significant differences in the 2 and 4 % groups (p < 0.05). Histological assay further confirmed the protective effect of betanin. In conclusion, betanin attenuates CCl4-induced liver damage in common carp. Moreover, the inhibition of CYP2E1 activity and oxidative stress may have significant roles in the protective effect of betanin.
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Betacianinas/uso terapêutico , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Carpas , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocromo P-450 CYP2E1/metabolismo , Glicogênio/metabolismo , Fígado/enzimologia , Fígado/patologia , Estresse Oxidativo , Distribuição AleatóriaRESUMO
The widely used antibiotic metronidazole (MTZ) was investigated for its toxic effects on the innate immunity in common carp (Cyprinus carpio L.). The fish were exposed to MTZ at nominal concentrations of 0.1, 0.5, and 2.5 mg L(-1) in water for 30 days, followed by a 5-days of cleanout period, after which certain innate immunity parameters were measured. The results showed that under the tested concentrations, MTZ-exposed fish exhibited decline in several humoral and cellular parameters, including complement activity, lysozyme activity, bactericidal activity, total serum protein levels, total WBC count, and the respiratory burst activity of kidney leukocytes. Except for total serum proteins, all of these parameters showed a significant difference in the 2.5 mg L(-1) MTZ group compared to control group (p < 0.05). The results clearly support the contention that MTZ suppresses the innate immunity of common carp.
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Anti-Infecciosos/toxicidade , Carpas/imunologia , Imunidade Inata/efeitos dos fármacos , Metronidazol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Carpas/fisiologia , Rim/citologia , Rim/efeitos dos fármacos , Testes de ToxicidadeRESUMO
OBJECTIVE: To screen new agro-antibiotics, rare actinomycetes were isolated by improved separation methods from soil samples and the chemical structure of the antifungal active product was elucidated. METHODS: Dry heating method was used for soil samples pretreatment and the improved HV separation medium for rare actinomycetes separation; agar block rapid screening was used for the rapid evaluation of rare actinomycetes biological activity. For the identification of a strain numbered TJ430, morphology observation, cell chemical composition analysis, physiological and biochemical analysis, enzymology characteristics analysis, 16 S rDNA sequence analysis, and DNA hybridization method were used. Bioactive crude extract from fermentation was purified by column chromatography and preparative chromatography; infrared spectroscopy and high resolution mass spectrometry was used for structure elucidation of bioactive ingredient. RESULTS: A total of 570 rare actinomycetes strains were isolated. Antibacterial activity of rapid screen showed that the numbed TJ430 strain showed excellent anti oomycetes and broad-spectrum antifungal activity. Strain identification results show that the strain is a S. cavourensis. The molecular formulas of the effective ingredient is C40H66N3O11, molecular weight is 765. Amino, methyl, methylene, carbonyl, covalent bond, isopropyl and other chemical groups should contained in the molecular. CONCLUSION: The characterized antibacterial active ingredient has good development prospect.
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Antifúngicos/farmacologia , Microbiologia do Solo , Streptomyces/química , Streptomyces/metabolismo , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antifúngicos/metabolismo , Fungos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Filogenia , Streptomyces/genética , Streptomyces/isolamento & purificaçãoRESUMO
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, which is characterized by the accumulation and aggregation of amyloid in brain. Neuronostatin (NST) is an endogenous peptide hormone that participates in many fundamental neuronal processes. However, the metabolism and function of NST in neurons of AD mice are not known. In this study, by combining the structural analyses, primary cultures, knockout cells, and various assessments, the behavior, histopathology, brain-wide expression and cellular signaling pathways in the APP/PS1 mice were investigated. It was found that NST directly bound to GPR107, which was primarily expressed in neurons. NST modulated the neuronal survivability and neurite outgrowth induced by Aß via GPR107 in neurons. Intracerebroventricular (i.c.v.) administration of NST attenuated learning and memory abilities, reduced the synaptic protein levels of hippocampus, but improved amyloid plaques in the cortex and hippocampus of APP/PS1 mice. NST modulated glucose metabolism of hypothalamus-hippocampus-cortex axis in APP/PS1 mice and decreased ATP levels via the regulation of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) in response to Aß, suppressed energetic metabolism, and mitochondrial function in neurons via GPR107/protein kinase A (PKA) signaling pathway. In summary, our findings suggest that NST regulates neuronal function and brain energetic metabolism in AD mice via the GPR107/PKA signaling pathway, which can be a promising target for the treatment of AD.
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Doença de Alzheimer , Metabolismo Energético , Camundongos Transgênicos , Neurônios , Receptores Acoplados a Proteínas G , Animais , Doença de Alzheimer/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Camundongos , Hormônios Peptídicos/metabolismo , Hormônios Peptídicos/farmacologia , Camundongos Endogâmicos C57BL , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/fisiologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Peptídeos beta-Amiloides/metabolismo , Células Cultivadas , Masculino , Humanos , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismoRESUMO
Tirzepatide (LY3298176), a GLP-1 and GIP receptor agonist, is fatty-acid-modified and 39-amino acid linear peptide, which ameliorates learning and memory impairment in diabetic rats. However, the specific molecular mechanism remains unknown. In the present study, we investigated the role of tirzepatide in the neuroprotective effects in Alzheimer's disease (AD) model mice. Tirzepatide was administrated intraperitoneal (i.p.) APP/PS1 mice for 8 weeks with at 10 nmol/kg once-weekly, it significantly decreased the levels of GLP-1R, and GFAP protein expression and amyloid plaques in the cortex, it also lowered neuronal apoptosis induced by amyloid-ß (Aß), but did not affect the anxiety and cognitive function in APP/PS1 mice. Moreover, tirzepatide reduced the blood glucose levels and increased the mRNA expression of GLP-1R, SACF1, ATF4, Glu2A, and Glu2B in the hypothalamus of APP/PS1 mice. Tirzepatide increased the mRNA expression of glucose transporter 1, hexokinase, glucose-6-phosphate dehydrogenase, and phosphofructokinase in the cortex. Lastly, tirzepatide improved the energetic metabolism by regulated reactive oxygen species production and mitochondrial membrane potential caused by Aß, thereby decreasing mitochondrial function and ATP levels in astrocytes through GLP-1R. These results provide valuable insights into the mechanism of brain glucose metabolism and mitochondrial function of tirzepatide, presenting potential strategies for AD treatment.