RESUMO
Despite active clinical trials on the use of Oleandrin alone or in combination with other drugs for the treatment of solid tumors, the potential synergistic effect of Oleandrin with radiotherapy remains unknown. This study reveals a new mechanism by which Oleandrin targets ATM and ATR kinase-mediated radiosensitization in lung cancer. Various assays, including clonogenic, Comet, immunofluorescence staining, apoptosis and Cell cycle assays, were conducted to evaluate the impact of oleandrin on radiation-induced double-strand break repair and cell cycle distribution. Western blot analysis was utilized to investigate alterations in signal transduction pathways related to double-strand break repair. The efficacy and toxicity of the combined therapy were assessed in a preclinical xenotransplantation model. Functionally, Oleandrin weakens the DNA damage repair ability and enhances the radiation sensitivity of lung cells. Mechanistically, Oleandrin inhibits ATM and ATR kinase activities, blocking the transmission of ATM-CHK2 and ATR-CHK1 cell cycle checkpoint signaling axes. This accelerates the passage of tumor cells through the G2 phase after radiotherapy, substantially facilitating the rapid entry of large numbers of inadequately repaired cells into mitosis and ultimately triggering mitotic catastrophe. The combined treatment of Oleandrin and radiotherapy demonstrated superior inhibition of tumor proliferation compared to either treatment alone. Our findings highlight Oleandrin as a novel and effective inhibitor of ATM and ATR kinase, offering new possibilities for the development of clinical radiosensitizing adjuvants.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Cardenolídeos , Dano ao DNA , Neoplasias Pulmonares , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Animais , Cardenolídeos/farmacologia , Dano ao DNA/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Tolerância a Radiação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Reparo do DNA/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células A549RESUMO
Root-knot nematodes (Meloidogyne spp.) are soilborne pathogens that infect vegetable crops and cause major economic losses worldwide annually. Therefore, there is an urgent need for novel nematicides or biological control agents to reduce the damage caused by root-knot nematodes. In this study, we tested efficacy of the Bacillus cereus strain Bc-cm103, isolated from the rhizoplane of Cucumis metuliferus, against Meloidogyne incognita. Strain Bc-cm103 fermentation broth caused 100% mortality of the nematode second-stage juveniles within 12 h and decreased the egg hatching rate by 40.06% within 72 h compared with sterile water. Confocal laser-scanning microscopy revealed that strain Bc-cm103 formed a biofilm on cucumber (C. sativus) roots, which protected the roots from the infection of M. incognita. Additionally, strain Bc-cm103 activated the defense-responsive genes PR1, PR2, LOX1, and CTR1 in cucumber. Furthermore, strain Bc-cm103 significantly reduced the appearance of root galls in pot, split-root, and field tests. These results indicated that B. cereus strain Bc-cm103 had a strong suppressive effect on M. incognita and therefore could be used as a potential biocontrol agent against this pathogen.
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Solanum lycopersicum , Tylenchoidea , Animais , Antinematódeos , Bacillus cereus , Agentes de Controle BiológicoRESUMO
Bacillus cereus strain Bc-cm103 shows nematicidal activity and, therefore, has been used as a biological control agent to control the root-knot nematode Meloidogyne incognita. However, it remains unknown whether volatile organic compounds (VOCs) produced by B. cereus strain Bc-cm103 are effective in biocontrol against M. incognita. Therefore, in this study, we investigated the activity of Bc-cm103 VOCs against M. incognita. The B. cereus strain Bc-cm103 significantly repelled the second-stage juveniles (J2s) of M. incognita. In vitro evaluation of VOCs produced by the fermentation of Bc-cm103 in a three-compartment Petri dish revealed the mortality rates of M. incognita J2s as 90.8% at 24 h and 97.2% at 48 h. Additionally, evaluation of the ability of Bc-cm103 VOCs to suppress M. incognita infection in a double-layered pot test showed that root galls on cucumber roots decreased by 46.1%. Furthermore, 21 VOCs were identified from strain Bc-cm103 by solid-phase microextraction gas chromatography-mass spectrometry, including alkanes, alkenes, esters, and sulfides. Among them, dimethyl disulfide (30.63%) and S-methyl ester butanethioic acid (30.29%) were reported to have strong nematicidal activity. Together, these results suggest that B. cereus strain Bc-cm103 exhibits fumigation activity against M. incognita.
Assuntos
Solanum lycopersicum , Tylenchoidea , Compostos Orgânicos Voláteis , Animais , Bacillus cereus , Fumigação , Compostos Orgânicos Voláteis/farmacologiaRESUMO
Discriminating the maturity levels of tobacco leaf with in-situ measurement can effectively reduce loss rate and quality decline due to misjudgment of the maturity levels of tobacco leaf. In the meantime, the regular way we use to determine the maturity levels of tobacco, which is depend on tobacco leaf age and judgment of tobacco grower, lacks of objectivity. So this paper proposed a method to identify maturity levels of tobacco leaf by using spectral feature parameters combined with the method of support vector machine (SVM). In this paper, a total of 351 tobacco leaf samples collected in 5 maturity levels including immature (M1), unripe (M2), mature (M3), ripe (M4), and mellow (M5) determined by experts were scanned by field spectroscope(ASD FieldSpec3) with in-situ measurement for getting their reflectance spectrum. Through spectral analysis we found that the spectrum of tobacco leaf with different levels of maturity can be distinguished in visible band but not easily be distinguished in near-infrared band, so we use the tobacco leaf spectrum in visible band as the sensitive bands to analyze and model. To find the most suitable input variables for modeling, we use continuous spectrum (350~780 nm), feature band (496~719 nm) and spectral feature parameters (the reflectance of green peak, location of green peak, first order differential value of red-edge and blue-edge, red-edge and blue-edge area, location of red-edge and blue-edge) in visible region as the input variables, and using these three kinds of input variables in the method of SVM to establish a discriminant model for identifying maturity levels of tobacco leaf. The result shows that, the model using spectral feature parameters gains the accuracy rate of 98.85%. While the accuracy rates of other two models were 90.80% and 93.10%, respectively. The conclusion was drawn that using spectral feature parameters in visible spectrum as the input variables in SVM can improve the model performance. It is feasible to use this method to identify maturity level of tobacco leaf with in-situ measurement.
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Fast and non-destructive measurements of tobacco leaf pigment contents by spectroscopy in situ in the field has great significance in production guidance for nutrient diagnosis and growth monitoring of tobacco in vegetative growth stage, and it is also very important for the quality evaluation of tobacco leaves in mature stage. The purpose of this study is to estimate the chlorophyll and carotenoid contents of tobacco leaves using tobacco leaf spectrum collected in the field. Reflectance spectrum of tobacco leaves in vegetative growth stage and mature stage were collected in situ in the field and the pigment contents of tobacco leaf samples were measured in this study, taking the tobacco leaf samples collected in each and both stages as modeling sets respectively, and using the methods of support vector machine (SVM) and spectral indice to establish the pigment content estimation models, and then compare the prediction performance of the models built by different methods. The study results indicated that the difference of estimation performance by each stage or mixed stages is not significant. For chlorophyll content, SVM and spectral indice modeling methods can both have a well estimation performance, while for carotenoid content, SVM modeling method has a better estimation performance than spectral indice. The coefficient of determination and the root mean square error of SVM model for estimating tobacco leaf chlorophyll content by each stage were 0.867 6 and 0.014 7, while the coefficient of determination and the root mean square error of SVM model for estimating tobacco leaf chlorophyll content by mixed stages were 0.898 6 and 0.012 3; The coefficient of determination and the root mean square error for estimating tobacco leaf carotenoid content by each stage were 0.861 4 and 0.002 5, while the coefficient of determination and the root mean square error of SVM model for estimating tobacco leaf carotenoid content by mixed stages were 0.839 9 and 0.002 5. The innovation point of this study is that on the basis of support vector machine and spectral indice, models established by each stage and mixed stages for estimating the pigment contents of tobacco leaf samples can provide scientific basis and technical support for quality control of tobacco leaf production in field and the ensurance of tobacco leaf recovery quality.
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Carotenoides/análise , Clorofila/análise , Nicotiana , Folhas de Planta/química , Modelos Teóricos , Análise Espectral , Máquina de Vetores de SuporteRESUMO
To establish the quantitative relationship between soil spectrum and the concentration of available nitrogen, phosphorus and potassium in soil, the critical procedures of a new analysis method were examined, involving spectral preprocessing, wavebands selection and adoption of regression methods. As a result, a soil spectral analysis model was built using VIS/NIRS bands, with multiplicative scatter correction and first-derivative for spectral preprocessing, and local nonlinear regression method (Local regression method of BP neural network). The coefficients of correlation between the chemically determined and the modeled available nitrogen, phosphorus and potassium for predicted samples were 0.90, 0.82 and 0.94, respectively. It is proved that the prediction of local regression method of BP neural network has better accuracy and stability than that of global regression methods. In addition, the estimation accuracy of soil available nitrogen, phosphorus and potassium was increased by 40.63%, 28.64% and 28.64%, respectively. Thus, the quantitative analysis model established by the local regression method of BP neural network could be used to estimate the concentration of available nitrogen, phosphorus and potassium rapidly. It is innovative for using local nonlinear method to improve the stability and reliability of the soil spectrum model for nutrient diagnosis, which provides technical support for dynamic monitoring and process control for the soil nutrient under different growth stages of field-growing crops.
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Nitrogênio/análise , Fósforo/análise , Potássio/análise , Solo/química , Modelos Teóricos , Redes Neurais de Computação , Reprodutibilidade dos Testes , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Proteins interact with each other to fulfill their functions. The importance of weak protein-protein interactions has been increasingly recognized. However, owing to technical difficulties, ultra-weak interactions remain to be characterized. Phosphorylation can take place via a K(D)≈25â mM interaction between two bacterial enzymes. Using paramagnetic NMR spectroscopy and with the introduction of a novel Gd(III)-based probe, we determined the structure of the resulting complex to atomic resolution. The structure accounts for the mechanism of phosphoryl transfer between the two enzymes and demonstrates the physical basis for their ultra-weak interaction. Further, molecular dynamics (MD) simulations suggest that the complex has a lifetime in the micro- to millisecond regimen. Hence such interaction is termed a fleeting interaction. From mathematical modeling, we propose that an ultra-weak fleeting interaction enables rapid flux of phosphoryl signal, providing a high effective protein concentration.
Assuntos
Proteínas/química , Simulação de Dinâmica Molecular , Ressonância Magnética Nuclear Biomolecular , Fosforilação , Transdução de SinaisRESUMO
The purpose of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on dextran sulfate sodium (DSS)-induced colitis in mice. The present data demonstrated that oral administration of Fx (50 and 200 mg/kg body weight/day) for 36 days significantly alleviated the severity of colitis in DSS-treated mice, as evidenced by attenuating body weight loss, bloody stool, diarrhea, shortened colon length, colonic epithelium distortion, a thin mucus layer, goblet cell depletion, damaged crypts, and extensive infiltration of inflammatory cells in the colonic mucosa. Additionally, Fx notably relieved DSS-induced intestinal epithelial barrier dysfunction via maintaining the tight junction function and preventing excessive apoptosis of colonic epithelial cells. Moreover, Fx effectively diminished colonic inflammation and oxidative stress in DSS-treated mice, and its mechanisms might be due to blunting the activation of NF-κB and NLRP3 inflammasome signaling pathways. Furthermore, Fx also modulates DSS-induced gut microbiota dysbiosis via recovering the richness and diversity of gut microbiota and reshaping the structure of gut microbiota, such as increasing the Firmicutes and Bacteroidota (F/B) ratio and elevating the relative abundance of some potential beneficial bacteria, including Lactobacillaceae and Lachnospiraceae. Overall, Fx might be developed as a promising functional ingredient to prevent colitis and maintain intestinal homeostasis.
Assuntos
Colite , Microbioma Gastrointestinal , Xantofilas , Camundongos , Animais , Sulfato de Dextrana/efeitos adversos , Disbiose/induzido quimicamente , Disbiose/tratamento farmacológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colo/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
Largemouth bass (Micropterus salmoides) has emerged as a significant economic fish species, with a rise in Aeromonas veronii infections in farming. However, research on adjuvants for vaccines against A. veronii in largemouth bass remains scarce. In present study, recombinant largemouth bass IL-1ß (LbIL-1ß) was expressed to explore its adjuvant effect on the A. veronii inactivated vaccine. Following vaccination with recombinant LbIL-1ß (rLbIL-1ß) and the inactivated A. veronii, higher serum SOD levels and lysozyme activities were observed in largemouth bass from inactivated A. veronii + rLbIL-1ß vaccinated group. Furthermore, it was discovered that rLbIL-1ß was able to boost the serum-specific antibody levels induced by the inactivated A. veronii. The qRT-PCR analysis revealed that rLbIL-1ß also enhanced the expression of IgM, CD4, and MHC II in largemouth bass triggered by the inactivated A. veronii. After challenged with live A. veronii, the outcomes demonstrated that the relative percentage survival (RPS) for largemouth bass resulting from the inactivated A. veronii in combination with rLbIL-1ß was 76.67 %, surpassing the RPS of 60 % in the inactivated A. veronii group. Collectively, these findings indicate that rLbIL-1ß enhances the protective effect of the A. veronii inactivated vaccine on largemouth bass, showcasing potential as an adjuvant for further development.
Assuntos
Adjuvantes Imunológicos , Aeromonas veronii , Vacinas Bacterianas , Bass , Doenças dos Peixes , Interleucina-1beta , Vacinas de Produtos Inativados , Animais , Aeromonas veronii/imunologia , Vacinas Bacterianas/imunologia , Bass/imunologia , Bass/microbiologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Infecções por Bactérias Gram-Negativas/prevenção & controle , Vacinação , Vacinas de Produtos Inativados/imunologiaRESUMO
The aim of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on lipopolysaccharide (LPS)-induced intestinal barrier injury in mice. Our results demonstrated that the oral administration of Fx (50 and 200 mg per kg body weight per day) for consecutive 7 days significantly alleviated the severity of LPS-induced intestinal barrier injury in mice, as evidenced by attenuating body weight loss, improving intestinal permeability, and ameliorating intestinal morphological damage such as reduction in the ratio of the villus length to the crypt depth (V/C), intestinal epithelium distortion, goblet cell depletion, and low mucin 2 (MUC2) expression. Fx also significantly mitigated LPS-induced excessive apoptosis of intestinal epithelial cells (IECs) and curbed the decrease of tight junction proteins including claudin-1, occludin, and zonula occludens-1 in the ileum and colon. Additionally, Fx effectively alleviated LPS-induced extensive infiltration of macrophages and neutrophils into the intestinal mucosa, the overproduction of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1beta (IL-1ß) and IL-6, and gasdermin D (GSDMD)-mediated pyroptosis of IECs. The underlying mechanisms might be associated with inhibiting the activation of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathways. Moreover, Fx also notably restrained intestinal reactive oxygen species (ROS), malondialdehyde and protein carbonylation levels in LPS-treated mice, and it might be mediated by activating the nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway. Overall, these findings indicated that Fx might be developed as a potential effective dietary supplement to prevent intestinal barrier injury.
Assuntos
Mucosa Intestinal , Lipopolissacarídeos , Xantofilas , Animais , Camundongos , Xantofilas/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Lipopolissacarídeos/efeitos adversos , Masculino , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Permeabilidade , Camundongos Endogâmicos C57BL , Proteínas de Junções Íntimas/metabolismo , Citocinas/metabolismoRESUMO
The microbiological transformation of the triterpene nigranoic acid (3,4-secocycloarta-4(28),24(Z)-diene-3,26-dioic acid) (1) to 3,4-secocycloarta-4(28),17(20),24(Z)-triene-7ß-hydroxy-16ß,26-lactone-3-oic acid (2) and 3,4-secocycloarta-4(28),17(20)(Z),24(Z)-triene-7ß-hydroxy-16ß-methoxy-3,26-dioic acid (3) by the freshwater fungus Dictyosporium heptasporum YMF1.01213 has been demonstrated. The structures of the biotransformation products were determined by spectroscopic and MS analyses. Compound 2, characterized by the presence of a formed C-16/C-26 ester bridge, provided a novel nine-membered lactone ring structural skeleton for 3,4-secocycloartane triterpenoid derivatives. In addition, Compounds 1-3 exhibited weak anti-HIV activity in vitro. Compounds 2 and 3 were reported for the first time as natural product derivatives.
Assuntos
Fármacos Anti-HIV/metabolismo , Fungos/metabolismo , Triterpenos/metabolismo , Fármacos Anti-HIV/química , Biotransformação , Água Doce/microbiologia , Humanos , Ressonância Magnética Nuclear Biomolecular , Triterpenos/química , Triterpenos/farmacologiaRESUMO
OBJECTIVE: To observe the impact of adenosine A1 receptor stimulation on extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathways on angiotensin II (AngII) stimulated cardiomyocytes of neonatal rats in vitro. METHODS: Cardiomyocytes of neonatal rats were cultured in vitro. Cardiomyocytes hypertrophy was induced by AngII (0.1 µmol/L). The antihypertrophic effect of adenosine A1 receptor stimulation via adenosine A1 receptor agonist R-PIA (1 µmol/L) was observed in the presence or absence of ERK1/2 inhibitor 1, 4-Diamino-2, 3-dicyano-1, 4-bis(o-aminophenylmercapto) butadiene (U0126) 1 µmol/L, PKC inhibitor Ro-31-8220 (50 nmol/L), and pertussis toxin (PTX, 5 mg/L). The total protein content was assayed by the method of Lowry. The expression of mRNA of atrial natriuretic peptide (ANP) was determined by RT-PCR. [Ca(2+)]i was measured by confocal microscope using Fluo-3/AM as fluorescent indicator. The relative expression of ERK1/2 was determined by Western blot. RESULTS: Compared with normal control group, AngII induced significant cardiomyocyte hypertrophy. Compared with AngII group, R-PIA significantly inhibited AngII-induced increase of the protein content, cardiomyocytes volume and expression of ERK1/2, calcium ion fluorescence intensity, similar as U0126 and Ro-31-8220. The inhibitory effects on AngII induced cardiomyocytes hypertrophy of R-PIA were lost when preincubated with PTX. CONCLUSION: Adenosine A1 receptor can inhibit AngII induced cardiomyocyte hypertrophy through downregulating ERK signal pathways and reducing intracellular Ca(2+).
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Agonistas do Receptor A1 de Adenosina/farmacologia , Angiotensina II/farmacologia , Sistema de Sinalização das MAP Quinases , Miócitos Cardíacos/efeitos dos fármacos , Receptor A1 de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Células Cultivadas , Feminino , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Ratos Sprague-Dawley , Receptor A1 de Adenosina/efeitos dos fármacosRESUMO
The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.
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Antioxidantes , Óleos de Peixe , Antioxidantes/farmacologia , Óleos de Peixe/química , Ácido Eicosapentaenoico , Ácidos Graxos , Suplementos Nutricionais , Ácidos Docosa-HexaenoicosRESUMO
SCOPE: Skeletal muscle atrophy is a critical feature of cancer-associated cachexia (CAC) and it is responsible for poor quality of life and high mortality in cancer patients. The previous study demonstrates that eicosapentaenoic acid-enriched phospholipids (EPA-PL) prevent body weight loss in a mouse model of CAC. However, the role of EPA-PL on cancer-induced skeletal muscle atrophy remains unclear. METHODS AND RESULTS: In the present study, a Lewis lung carcinoma (LLC) mouse model is established, then the effect and underlying mechanism of EPA-PL on skeletal muscle atrophy in LLC-bearing mice are investigated. The results reveal that EPA-PL treatment significantly attenuates skeletal muscle atrophy in LLC-bearing mice, as evidenced by suppressing the reductions of skeletal muscle mass, myofiber cross-sectional area, and grip strength. Besides, the study finds that EPA-PL alleviated cancer-induced skeletal muscle atrophy via balancing muscle protein degradation and synthesis, inhibiting type I oxidative muscle fibers atrophy, and promoting mitochondrial function. Furthermore, the results also indicate that EPA-PL may counteract skeletal muscle atrophy in LLC mouse model via a sirtuin 1-dependent mechanism. CONCLUSION: These findings provide evidence that EPA-PL may be beneficial as a nutritional supplement for prevention and treatment of cancer-induced skeletal muscle atrophy.
Assuntos
Carcinoma Pulmonar de Lewis , Camundongos , Animais , Carcinoma Pulmonar de Lewis/complicações , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Fosfolipídeos/metabolismo , Qualidade de Vida , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/prevenção & controle , Modelos Animais de Doenças , Músculo Esquelético/metabolismoRESUMO
A general comparison of fundamental distinctions between the FeO(2+) and FeS(2+) complexes in an identical cyanide or isocyanide ligand environment for methane hydroxylation has been probed computationally in this work in a series of hypothetical [Fe(IV)(X)(CN)5](3-), [Fe(IV)(X)(NC)5](3-), (X = O, S) complexes. We have detailed an analysis of the geometric and electronic structures using density functional theory calculations. In addition, their σ- and π-mechanisms in C-H bond activation process have been described with the aid of the schematic molecular orbital diagram. From our theoretical results, it is shown that (a) the iron(IV)-sulfido complex apparently is able to hydroxylate C-H bond of methane as good as the iron(IV)-oxo species, (b) the O-CN, S-CN complexes have an inherent preference for the low-spin state, while for the case of O-NC and S-NC in which S = 1 and S = 2 states are relatively close in energy, (c) each of the d block electron orbital plays an important role, which is not just spectator electron, and (d) in comparison to the cyanide and isocyanide ligand environment, we can see that the FeS(2+) species prefer the cyanide ligand environment, while the FeO(2+) species favor the isocyanide ligand environment. In addition, a remarkably good correlation of the σ-/π-mechanism for hydrogen abstraction from methane with the gap between the Fe-dz2 (α) and C-H (α) pair as well as the Fe-dxz/yz (ß) and C-H (ß) pair has been found.
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Objective: Our study aimed to investigate the effects of computer-assisted cognitive remediation therapy (CCRT) on cognitive function, social function and quality of life in patients with vascular dementia (VD). Methods: Ninety-eight patients with VD were treated with CCRT in four 45-minute sessions per week over a course of 40 sessions to exercise four cognitive functions, including flexibility, working memory, plan execution and social cognition. The Mini-Mental State Examination (MMSE), Social Disability Screening Schedule (SDSS), Personal and Social Performance Scale (PSP), and Generic Quality of Life Inventory-74 (GQOL-74) were used to assess before and after treatment. Results: (1) The scores of orientation (5.60 ± 1.35), calculation (2.20 ± 0.79), verbal ability (7.10 ± 0.36), spatial ability (0.78 ± 0.42), immediate memory (2.42 ± 0.53), short-term memory (1.17 ± 0.78) and MMSE (23.36 ± 2.98) were all improved after treatment (P < 0.05) compared with those before treatment; (2) The scores of SDSS, PSP and Activities of Daily Living (ADL) after treatment were 8.23 ± 0.94, 81.36 ± 14.23, and 32.7 ± 12.1, and all of which improved (P < 0.05); (3) The scores of physical health were 68.24 ± 7.44, mental health were 69.75 ± 7.15, social function were 69.08 ± 7.43, material life were 37.46 ± 4.85 and the total score were 230.79 ± 9.56, all of which improved (P < 0.05). Conclusion: For patients with VD, CCRT can improve their cognitive function, social function, daily life ability and quality of life.
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Objective: To examine the bactericidal effects of three different states of medical ozone (liquid, gas, and oil) against drug-resistant strains of common bacteria on burn wounds, which could as a clinical reference. Methods: Three multidrug-resistant strains of methicillin-resistant Staphylococcus aureus, pan-resistant Pseudomonas aeruginosa, and ESBLs Klebsiella pneumoniae were identified from burn wounds. The colonies of the three varieties of bacteria were each carried out using the pour plate method prior to the start of the experiment. Then, depending on the state of ozone, different treatment procedures are applied. Group of ozone gas: in a closed glass jar, the bacterial liquid was injected into a single layer of sterile gauze, and the ozone gas concentration was held at 50 g/mL. The bacterial liquid was diluted and combined directly with ozone water in the ozone water group. Ozone is a type of oil: after the emulsifier was added to the oil group. The gas, water, and oil groups were rapidly neutralized and counted again after 5, 10, and 30 minutes. Results: Ozone gas and oil groups totally eliminated multidrug resistant bacteria in the above study within 30 minutes. (2) At 5 and 10 minutes, the difference in bactericidal effect between ozone gas group and ozone water and oil group was statistically significant (P<0.05), and there was no significant difference between ozone water and oil groups (P>0.05); at the time of 30 minutes, the effects of bactericidal effect between ozone water group and ozone gas and oil had no significance (P> 0.05). Conclusion: Ozone has the ability to kill bacteria, depending on the treatment time, different ozone types should be chosen for sterilization and disinfection in clinical application.
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Intestinal barrier dysfunction has emerged as a potential contributor to the development of several severe diseases. Herein, the effect and underlying mechanism of DHA-enriched phospholipids (DHA-PL) and EPA-enriched phospholipids (EPA-PL) on protecting against lipopolysaccharide (LPS)-induced intestinal barrier injury were elucidated. C57BL/6J male mice were fed an AIN-93G diet containing 1% DHA-PL or EPA-PL for 4 weeks and then were intraperitoneally injected with LPS (10 mg/kg) to cause intestinal barrier injury. The results manifested that DHA-PL and EPA-PL pretreatment balanced apoptosis and autophagy in intestinal epithelial cells and maintained intestinal tight junction integrity. Our findings also demonstrated that cotreatment with EX-527, a sirtuin 1 specific inhibitor, hindered the role of DHA-PL and EPA-PL against LPS-evoked intestinal barrier injury through reversing the inhibitory action of them on NF-κB and MAPKs activation as well as their potentiating actions on Nrf2 nuclear translocation. Overall, DHA-PL and EPA-PL alleviated LPS-mediated intestinal barrier injury via inactivation of the NF-κB and MAPKs pathways as well as activating the Nrf2 antioxidant pathway via up-regulating sirtuin 1.
Assuntos
Ácido Eicosapentaenoico , Lipopolissacarídeos , Animais , Ácidos Docosa-Hexaenoicos/farmacologia , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfolipídeos , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Acute liver injury is a life-threatening syndrome that often results from the actions of viruses, drugs and toxins. Herein, the protective effect and potential mechanism of krill oil (KO), a novel natural product rich in long-chain n-3 polyunsaturated fatty acids bound to phospholipids and astaxanthin, on lipopolysaccharide (LPS)-evoked acute liver injury in mice were investigated. Male C57BL/6J mice were administered intragastrically with 400 mg kg-1 KO or fish oil (FO) once per day for 28 consecutive days prior to LPS exposure (10 mg kg-1, intraperitoneally injected). The results revealed that KO pretreatment significantly ameliorated LPS-evoked hepatic dysfunction indicated by reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and attenuated hepatic histopathological damage. KO pretreatment also mitigated LPS-induced hepatic oxidative stress, as evidenced by decreased malondialdehyde (MDA) contents, elevated glutathione (GSH) levels, and elevated catalase (CAT) and superoxide dismutase (SOD) activities. Additionally, LPS-evoked overproduction of pro-inflammatory mediators in serum and the liver was inhibited by KO pretreatment. Furthermore, KO pretreatment suppressed LPS-induced activation of the hepatic toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway. Interestingly, the hepatoprotective effect of KO was superior to that of FO. Collectively, the current findings suggest that KO protects against LPS-evoked acute liver injury via inhibition of oxidative stress and inflammation.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Euphausiacea , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Euphausiacea/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/toxicidade , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse OxidativoRESUMO
Some chronic diseases such as cancer-associated cachexia (CAC) and obesity are associated with the overproduction of tumor necrosis factor-alpha (TNF-α) that stimulates excess lipolysis in adipocytes. Our previous studies have shown that docosahexaenoic acid-enriched phospholipids (DHA-PL) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) ameliorated CAC and obesity-related metabolic disorders. To identify the molecular mechanisms involved, we examined the impact and the associated signaling pathways of DHA-PL and EPA-PL on TNF-α-induced lipolysis in 3T3-L1 adipocytes. The present results revealed that DHA-PL and EPA-PL inhibited the TNF-α-induced increase of glycerol release and protected lipid droplets. In addition, DHA-PL and EPA-PL increased DHA and EPA contents in the phospholipid fraction of adipocytes, respectively. Moreover, DHA-PL and EPA-PL enhanced sirtuin 1 (SIRT1) deacetylase activity and its protein expression. By activating SIRT1, DHA-PL and EPA-PL upregulated the G0/G1 switch gene 2 protein level to inhibit adipose triglyceride lipase activity, activate AMP-activated protein kinase to reverse the downregulation of perilipin expression and phosphorylation of hormone-sensitive lipase (HSL) at Ser565 and prevent the phosphorylation of HSL at Ser660. Furthermore, DHA-PL and EPA-PL improved glucose uptake and glucose transporter type 4 translocation to the plasma membrane in TNF-α-treated adipocytes. Thus, it was concluded that DHA-PL and EPA-PL inhibit TNF-α-induced lipolysis in 3T3-L1 adipocytes by activating the SIRT1 pathways.