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Zeolite synthesis under acidic conditions has always presented a challenge. In this study, we successfully prepared series of ZSM-5 zeolite nanosheets (Z-5-SCA-X) over a broad pH range (4 to 13) without the need for additional supplements. This achievement was realized through aggregation crystallization of ZSM-5 zeolite subcrystal (Z-5-SC) with highly short-range ordering and ultrasmall size extracted from the synthetic system of ZSM-5 zeolite. Furthermore, the crystallization behavior of Z-5-SC was investigated, revealing its non-classical crystallization process under mildly alkaline and acidic conditions (pH<10), and the combination of classical and non-classical processes under strongly alkaline conditions (pH≥10). What's particularly intriguing is that, the silanol nest content in the resultant Z-5-SCA-X samples appears to be dependent on the pH values during the Z-5-SC crystallization process rather than its crystallinity. Finally, the results of the furfuryl alcohol etherification reaction demonstrate that reducing the concentration of silanol nests significantly enhances the catalytic performance of the Z-5-SCA-X zeolite. The ability to synthesize zeolite in neutral and acidic environments without the additional mineralizing agents not only broadens the current view of traditional zeolite synthesis but also provides a new approach to control the silanol nest content of zeolite catalysts.
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In this study, an amorphous silica reinforced, phosphoric-crosslinked chitosan foam (P-CTS@SixOy) was prepared. The introduction of amorphous silica not only increased the affinity of the adsorbent for uranium, but also improved the stability of the material. The number of active sites of P-CTS@SixOy was increased by the introduction of phosphate groups. The material exhibited excellent uranium adsorption performance with the removal capacity and efficiency of 850.5 mg g-1 and 98.1 %, respectively. After regenerations, the morphology of P-CTS@SixOy still maintained, and the uranium adsorption efficiency remained above 90 %, manifesting the excellent cycle performance of P-CTS@SixOy. In the dynamic adsorption experiment, P-CTS@SixOy successfully concentrated the volume of uranium-containing solution, and exhibited excellent uranium adsorption performance. The analysis of kinetics, isotherms, and thermodynamics manifested that the uranium adsorption behavior of P-CTS@SixOy was a spontaneous, endothermic, monolayer chemical adsorption process. X-ray photoelectron spectroscopy, Scanning Electron Microscope, and Fourier Transform Infrared Spectrometer were used to characterized the P-CTS@SixOy before and after adsorption, which demonstrated that the main interaction mechanism between uranium and P-CTS@SixOy was the complexation. These studies indicated the huge application prospect of P-CTS@SixOy in the treatment of large-scale uranium-containing wastewater.
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Quitosana , Urânio , Urânio/química , Quitosana/química , Adsorção , Dióxido de Silício/química , Águas Residuárias , Cinética , Espectroscopia de Infravermelho com Transformada de Fourier , Concentração de Íons de HidrogênioRESUMO
Brain diseases present a significant obstacle to both global health and economic progress, owing to their elusive pathogenesis and the limited effectiveness of pharmaceutical interventions. Phototherapy has emerged as a promising non-invasive therapeutic modality for addressing age-related brain disorders, including stroke, Alzheimer's disease (AD), and Parkinson's disease (PD), among others. This review examines the recent progressions in phototherapeutic interventions. Firstly, the article elucidates the various wavelengths of visible light that possess the capability to penetrate the skin and skull, as well as the pathways of light stimulation, encompassing the eyes, skin, veins, and skull. Secondly, it deliberates on the molecular mechanisms of visible light on photosensitive proteins, within the context of brain disorders and other molecular pathways of light modulation. Lastly, the practical application of phototherapy in diverse clinical neurological disorders is indicated. Additionally, this review presents novel approaches that combine phototherapy and pharmacological interventions. Moreover, it outlines the limitations of phototherapeutics and proposes innovative strategies to improve the treatment of cerebral disorders.
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Doença de Alzheimer , Doença de Parkinson , Humanos , Fototerapia , Pele , Doença de Parkinson/patologia , Doença de Alzheimer/patologiaRESUMO
ABSTRACT: M1 macrophage-mediated inflammation is critical in sepsis. We previously found the protective role of astragaloside intravenous (AS-IV) in sepsis-associated gut impairment, whose specific mechanism remains unknown. Gut microbiota modulates gut homeostatic balance to avoid excessive inflammation. Here, we aimed to investigate effects of AS-IV on gut macrophages polarization and potential roles of gut microbiota and short chain fatty acids (SCFAs) in septic gut damage. Mice were pretreated by AS-IV gavage for 7 days before cecal ligation and puncture. M1 polarization of gut lamina propria macrophages (LpMs) was promoted by cecal ligation and puncture, accompanied by abnormal cytokines release and intestinal barrier dysfunction. NLRP3 inflammasome was activated in M1 LpMs. 16S rRNA sequencing demonstrated gut microbiota imbalance. The levels of acetate, propionate, and butyrate in fecal samples decreased. Notably, AS-IV reversed LpMs M1/M2 polarization, lightened gut inflammation and barrier injury, reduced NLRP3 inflammasome expression in LpMs, restored the diversity of gut microbiome, and increased butyrate levels. Similarly, these benefits were mimicked by fecal microbiota transplantation or exogenous butyrate supplementation. In Caco-2 and THP-1 cocultured model, LPS and interferon γ caused THP-1 M1 polarization, Caco-2 barrier impairment, abnormal cytokines release, and high NLRP3 inflammasome expression in THP-1 cells, all of which were mitigated by butyrate administration. However, these protective effects of butyrate were abrogated by NLRP3 gene overexpression in THP-1. In conclusion, AS-IV can ameliorate sepsis-induced gut inflammation and barrier dysfunction by modulating M1/M2 polarization of gut macrophages, whose underlying mechanism may be restoring gut microbiome and SCFA to restrain NLRP3 inflammasome activation.
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Microbioma Gastrointestinal , Saponinas , Sepse , Triterpenos , Humanos , Animais , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Células CACO-2 , RNA Ribossômico 16S/metabolismo , Ácidos Graxos Voláteis/metabolismo , Butiratos/metabolismo , Inflamação/metabolismo , Macrófagos/metabolismo , Sepse/metabolismo , Citocinas/metabolismoRESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) has been used in inpatient, outpatient, and emergency patients in Western countries and is an important evaluation tool in medicine. In China, the application of CGA to multiple single diseases has achieved satisfactory intervention effects. OBJECTIVE: To explore the effect of CGA on postoperative quality of life (QoL), psychological state, neurological recovery, and self-efficacy in patients with cerebral hemorrhage. METHODS: In this randomized controlled trial, a total of 133 postoperative patients with cerebral hemorrhage who were treated and nursed in our hospital between March 2019 and March 2021 were randomly assigned to a control group (68 patients) and an observation group (65 patients). The control group was given a general comprehensive care intervention. The observation group was evaluated using an electronic medical record-based CGA system that assessed patient prognosis and was given individualized interventions based on the CGA findings. The postoperative QoL, psychological state, neurological recovery, and self-efficacy of the two groups were compared. RESULTS: After the intervention, self-decompression, self-decision-making, and positive attitudes of the observation group were higher than those of the control group. However, the National Institute of Health Stroke Scale score of the observation group was lower than that of the control group, the Self-rating anxiety scale and self-rating depression scale scores of the observation group were lower than those of the control group, and the social support score was significantly higher in the observation group than in the control group. After the intervention, the mental vitality, social interaction, emotional restriction, and mental status scores of the observation group were significantly higher than those of the control group. CONCLUSION: Comprehensive evaluation of patients with cerebral hemorrhage based on a CGA, targeting the individual factors that affect the prognosis of patients, and formulating and implementing individualized nursing intervention programs based on the CGA results can effectively relieve the symptoms of cerebral hemorrhage, reduce anxiety and depression, and improve the QoL of patients with cerebral hemorrhage.
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With deepening application of nuclear power technology, the problem of water ecological environment pollution caused by uranium (U(VI)) is becoming increasingly serious. Photoreduction separation of U(VI) on photocatalysts is considered as an effective strategy to solve uranium pollution. In this work, a novel ternary dual Z-scheme AgVO3-InVO4/g-C3N4 heterojunction (Z-AIGH) nanocomposite with high surface area (73.45 m2 g-1, Z-AIGH2) was designed. The batch adsorption experiment in dark environment showed that Z-AIGH2 nanocomposite had an excellent U(VI) adsorption performance. As for photocatalytic experiments, Z-AIGH2 exhibited a rapid photocatalytic response for separating U(VI) without any organic sacrifice agents. The U(VI) separation rate on Z-AIGH2 nanocomposite was over 98.7% after only 20.0 min visible light irradiation (T = 298 K, CU(â ¥) = 10.0 mg L-1, m/V = 0.1 g L-1 and pH = 7.0). Z-AIGH2 nanocomposite also showed good selectivity and cycle stability. The U(VI) removal rate of Z-AIGH2 nanocomposite after fifth cycles was about 96.1% (T = 298 K, CU(â ¥) = 10.0 mg L-1, m/V = 0.1 g L-1 and pH = 7.0). High photocatalytic activity of Z-AIGH2 for U(VI) was attributed to the construction of ternary dual Z-scheme heterojunction structure and ant nest-like hole structure. Based on above results, Z-AIGH2 nanocomposite had great potential for water environment renovation.
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Nanocompostos , Urânio , Luz , Poluição da Água , ÁguaRESUMO
Ultrasound could effectively change molecular structure of proteins, polysaccharides, and their interactions, and was used to treat the peanut protein isolate-high methoxy pectin (PPI-HMP) complexes in this study. Effects of different ultrasound parameters, PPI-HMP mixing ratio (40:1-5:2), and pH (2.0-8.0) on the PPI-HMP interactions were investigated. Turbidity, solution appearance, and Zeta-potential analysis revealed an electrostatic interaction between PPI and HMP from pH 2.0 to pH 6.0. Ultrasound changed the tertiary structure conformation of PPI according to the surface hydrophobicity analysis. Increased ultrasound power density and pH broke the hydrogen bonds between the complexes according to Fourier transform infrared spectroscopy analysis. Apparent viscosity and confocal laser scanning microscopy analysis showed that appropriate ultrasound treatment (5.43 W/cm3, 25 min, 25 °C) reduced the viscosity of the complexes, and enhanced the electrostatic and hydrophobic interactions between PPI and HMP. These findings will contribute to the application of PPI-HMP complexes in the food industry.
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Arachis , Pectinas , Pectinas/química , Arachis/metabolismo , Biopolímeros , Polissacarídeos/química , Concentração de Íons de HidrogênioRESUMO
Notopterygium incisum Ting ex H. T. Chang (N. incisum) is a precious Chinese traditional medicine distributed in high-altitude regions of southwest China. The aim of this study was to investigate the composition, antibacterial activity, and cytotoxicity of essential oil from aerial parts of N. incisum. N. incisum essential oil (NI-EO) was extracted by hydro-distillation, and gas chromatography/mass spectrometry (GC-MS) analysis showed that the major components of NI-EO were D-limonene (18.42%) and γ-terpinene (15.03%). The antibacterial activity and mechanism study showed that the diameters of inhibition zone (DIZs) of NI-EO against E. coli and S. aureus were 14.63 and 11.25 mm and the minimum inhibitory concentrations were 3.75 and 7.5 µL/mL, respectively. NI-EO not only caused intracellular biomacromolecule leakage and cell deformation by destroying bacterial cell wall integrity and cell membrane permeability, but also degraded the mature biofilm. The low toxicity of NI-EO was demonstrated in an assay on bovine mammary epithelial cells. These results implied that NI-EO was mainly composed of monoterpenes and sesquiterpenes and had excellent antibacterial activity and showed low levels of cytotoxicity. It is expected to be applied as a natural antibacterial agent in the future.
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Óleos Voláteis , Animais , Bovinos , Óleos Voláteis/farmacologia , Escherichia coli , Staphylococcus aureus , Antibacterianos/toxicidade , Componentes Aéreos da PlantaRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment on inflammatory response in ven-tilator-induced lung injury (VILI) mice, so as to explore the underlying mechanism of EA pretreatment on prevention of VILI. METHODS: C57BL/6 mice were randomly divided into sham-operation group, model group, EA group and sham-acupoint groupï¼with 8 mice in each group. The VILI model was established by ventilation with high tidal volume. Mice in the EA group and sham-acupoint group were given EA at "Zusanli" (ST36)and "Feishu"(BL13) or non-acupoints (located at 1-2 cm on both sides of the tail root of the proximal trunk) before mechanical ventilation, 30 min each time, once a day for 5 days. Arterial blood was collec-ted for blood gas analysis, the total protein content in bronchoalveolar lavage fluid (BALF) was detected by BCA method. The contents of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in BALF were detected by ELISA. Lung injury score was determined after HE staining. The protein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and Caspase-1 in lung tissue was detected by Western blot. RESULTS: Compared with the sham-operation group, the arterial partial pressure of oxygen and oxygenation index were decreased(P<0.05), the levels of total protein, IL-1ß and IL-18 in BALF, the W/D value and the pathological injury score of lung tissue and the protein expression levels of NLRP3, Caspase-1 and ASC were increased(P<0.05)in the model group. Following the interventions, the above mentioned increased or decreased indicators were reversed(P<0.05) in the EA group rather than in the sham-acupoint group. CONCLUSION: EA pretreatment of ST36 and BL13 can reduce the damage of lung tissue caused by mechanical ventilation, which may be related to its effect in reducing the expression of NLPR3 inflammasome related proteins, reducing the activation of inflammasome, and thereby reducing the inflammatory response.
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Eletroacupuntura , Lesão Pulmonar Induzida por Ventilação Mecânica , Camundongos , Animais , Inflamassomos/genética , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18 , Camundongos Endogâmicos C57BL , Pulmão/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/genética , Lesão Pulmonar Induzida por Ventilação Mecânica/terapia , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Caspase 1RESUMO
Objective: This study aimed to evaluate the effect of electroacupuncture preconditioning on regional cerebral oxygen saturation (rSO2) levels in elderly patients with diabetes. Methods: Forty patients undergoing elective diabetic foot surgery were enrolled in this study. All patients were aged 65 years and above and weighed 45-75 kg. All were characterized as class II or III according to the American Society of Anesthesiologists' physical status classification system. Patients were divided randomly into an electroacupuncture group (group E) and a control group (group C); both groups comprised 20 patients. In group E, the DU20 (Baihui), DU24 (Shenting), and EX-HN1 (Sishencong) acupoints were selected for electroacupuncture 30 min prior to administering anesthesia, while in group C, patients underwent routine anesthesia without electroacupuncture. The patients in both groups were anesthetized using a sciatic nerve block. The number of cases with increased or decreased regional oxygen saturation (rSO2) compared with the baseline as well as rSO2 variability in the two groups were recorded and compared. Results: There was no significant difference in the preoperative rSO2 values between the two groups (54.4 ± 4.8 (L), 53.9 ± 5.2 (R) [group C] vs 54.1 ± 5.2 (L), 54.5 ± 4.6 (R)[group E]). Compared with group C, the rSO2 in group E increased (50.3 ± 3.9 [group C] vs 58.4 ± 3.2[group E]), and this difference was statistically significant (P < 0.001). Conclusion: Electroacupuncture stimulation can increase rSO2 levels in patients with diabetes. Clinical Registration Number: ChiCTR2100048783 (http://www.chictr.org.cn).
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OBJECTIVES: To evaluate the effect of echinacoside (ECH) on cognitive dysfunction in post cerebral stroke model rats. METHODS: The post stroke cognitive impairment rat model was created by occlusion of the transient middle cerebral artery (MCAO). The rats were randomly divided into 3 groups by a random number table: the sham group (sham operation), the MCAO group (received operation for focal cerebral ischemia), and the ECH group (received operation for focal cerebral ischemia and ECH 50 mg/kg per day), with 6 rats in each group. The infarct volume and spatial learning were evaluated by triphenyl tetrazolium chloride staining and Morris water maze. The expression of α7nAChR in the hippocampus was detected by immunohistochemistry. The contents of acetylcholine (ACh), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), activities of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and catalase (CAT) were evaluated by enzyme linked immunosorbent assay. The neural apoptosis and autophagy were determined by TUNEL staining and LC3 staining, respectively. RESULTS: ECH significantly lessened the brain infarct volume and ameliorated neurological deficit in infarct volume and water content (both P<0.01). Compared with MCAO rats, administration of ECH revealed shorter escape latency and long retention time at 7, 14 and 28 days (all P<0.01), increased the α7nAChR protein expression, ACh content, and ChAT activity, and decreased AChE activity in MCAO rats (all P<0.01). ECH significantly decreased MDA content and increased the GSH content, SOD, and CAT activities compared with MCAO rats (all P<0.05). ECH suppressed neuronal apoptosis by reducing TUNEL-positive cells and also enhanced autophagy in MCAO rats (all P<0.01). CONCLUSION: ECH treatment helped improve cognitive impairment by attenuating neurological damage and enhancing autophagy in MCAO rats.
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Isquemia Encefálica , Disfunção Cognitiva , Fármacos Neuroprotetores , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Acetilcolinesterase , Animais , Autofagia , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Disfunção Cognitiva/complicações , Disfunção Cognitiva/tratamento farmacológico , Glutationa/metabolismo , Glicosídeos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Superóxido Dismutase/metabolismo , Receptor Nicotínico de Acetilcolina alfa7RESUMO
In this work, three kinds of biochars (PMBC-H2O, PMBC-PP and PMBC-HP) with excellent adsorption performance were obtained by carbonizing pig manure pre-treated with different agents. These biochars had the ordered mesoporous structures and possessed abundant active functional groups on their surface. The adsorption behaviors of the biochars towards UVI under various conditions were evaluated by batch experiment. The results showed that KMnO4 and H2O2 could enormously improve the adsorption performance of PMBC to UVI. After KMnO4 and H2O2 pretreatment, the maximum adsorption capacities of PMBC-PP (979.3 mg/g) and PMBC-HP (661.7 mg/g) were about 2.6 and 1.8 times higher than that of PMBC-H2O (369.9 mg/g), respectively, which was much higher than previously reported biochar-based materials. Obviously, KMnO4 pretreatment leaded to a higher enhancement than that of H2O2. The removal mechanism of UVI on PMBC-PP was discussed in-depth. The interaction between UVI species and PMBC-PP was mainly ascribed to the abundant active sites on the surface of PMBC-PP. In a word, conversion of pig manure pre-treated with KMnO4 into biochar not only demonstrates that PMBC-PP has great potential in the treatment of actual uranium-containing wastewater, but also provides a method for the rational utilization of pig manure to reduce the pollution.
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Esterco , Urânio , Adsorção , Animais , Carvão Vegetal , Peróxido de Hidrogênio , Suínos , Águas ResiduáriasRESUMO
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.
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Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Avaliação Pré-Clínica de Medicamentos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/uso terapêutico , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/genética , COVID-19 , Vacinas contra COVID-19 , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Feminino , Cobaias , Imunogenicidade da Vacina , Macaca fascicularis , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , Pneumonia Viral/virologia , Coelhos , Ratos , Ratos Wistar , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos , Células Vero , Vacinas Virais/efeitos adversosRESUMO
Geosmin (1) is a microbial terpene metabolite that is responsible for the typical smell of soil and causes an off-odor of food and water. Eudesmane sesquiterpenes are commonly found in plant essential oils. Here we describe the discovery of four geosmin-type metabolites, 7R-hydroxygeosmin (2), 3-oxogeosmin (3), 2R-hydroxy-7-oxogeosmin (4), 5-deoxy-7ß,9ß-dihydroxygeosmin (5), the plant-like eudesmanes 4ß,10α-eudesmane-5ß,11-diol (6) and (1S,5S,6S,7S,10S)-10α-eudesm-4(15)-ene-1α,6α-diol (7), and the known 1(10)E,5E-germacradiene-2,11-diol (8) from a bacterial endophyte (Streptomyces sp. JMRC:ST027706) of the mangrove plant Bruguiera gymnorrhiza. By means of NMR, MS, and ECD spectroscopy, all chemical structures as well as the absolute configurations for the new compounds were elucidated. Compounds 2-5 represent the first geosmin-related metabolites directly as bacterial natural products. The plant-derived eudesmane-5ß,11-diol (6) and (1S,5S,6S,7S,10S)-10α-eudesm-4(15)-ene-1α,6α-diol (7) are also now reported as bacterial products. The broad antimicrobial activities of 6 against a suite of fungal and bacterial pathogens including methicillin-resistant Staphylococcus aureus suggest that this terpene could be an important active principle of the medicinal plant Cymbopogon distans. The discovery of geosmin metabolites from one actinomycete indicated that these bacteria could possess enzymes for modifying geosmin and offer a possibility for bioremediation.
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Antibacterianos/isolamento & purificação , Endófitos/química , Naftóis/isolamento & purificação , Oxigênio/química , Rhizophoraceae/química , Sesquiterpenos de Eudesmano/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Naftóis/química , Naftóis/farmacologia , Sesquiterpenos de Eudesmano/química , Sesquiterpenos de Eudesmano/farmacologia , Análise Espectral/métodosRESUMO
Intestinal barrier dysfunction is a trigger for sepsis progression. NLRP3 inflammasome and RhoA contribute to sepsis and intestinal inflammation. The current study aimed to explore the effects of Astragaloside IV (AS-IV), a bioactive compound from Astragalus membranaceus, on sepsis-caused intestinal barrier dysfunction and whether NLRP3 inflammasome and RhoA are involved. Septic mice modeled by cecal ligation and puncture (CLP) operation were administered with 3 mg/kg AS-IV intravenously. AS-IV decreased mortality, cytokines release, I-FABP secretion, intestinal histological score and barrier permeability, and increased tight junction (TJ) expression in intestine in CLP model. Also, in Caco-2 cells subjected to lipopolysaccharide (LPS), 200 µg/mL AS-IV co-incubation reduced cytokines levels and enhanced in vitro gut barrier function without cytotoxicity. Subsequently, NLRP3 inflammasome and RhoA were highly activated both in intestinal tissue in vivo and in Caco-2 cells in vitro, both of which were significantly suppressed by AS-IV treatment. In addition, the benefits of AS-IV on Caco-2 monolayer barrier were largely counteracted by RhoA agonist CN03 and NLRP3 gene overexpression, respectively. Furthermore, LPS-induced NLRP3 inflammasome activation was abrogated by RhoA inhibitor C3 exoenzyme. However, NLRP3 knockdown by siRNA hardly affected RhoA activation in Caco-2 cells. These data suggest that AS-IV protects intestinal epithelium from sepsis-induced barrier dysfunction via inhibiting RhoA/NLRP3 inflammasome signal pathway.
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Medicamentos de Ervas Chinesas/administração & dosagem , Inflamassomos/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Saponinas/administração & dosagem , Sepse/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Triterpenos/administração & dosagem , ADP Ribose Transferases/farmacologia , Animais , Astragalus propinquus/química , Toxinas Botulínicas/farmacologia , Células CACO-2 , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Injeções Intravenosas , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Permeabilidade/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Sepse/complicações , Sepse/imunologia , Transdução de Sinais/imunologia , Proteína rhoA de Ligação ao GTP/agonistas , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy without effective treatment, and caused by the infection of Kaposi's sarcoma-associated herpesvirus (KSHV), predominantly in its latent form. Previously we showed that the SUMO2-interacting motif within the viral latency-associated nuclear antigen (LANASIM) is essential for establishment and maintenance of KSHV latency. Here, we developed a luciferase based live-cell reporter system to screen inhibitors selectively targeting the interaction between LANASIM and SUMO2. Cambogin, a bioactive natural product isolated from the Garcinia genus (a traditional herbal medicine used for cancer treatment), was obtained from the reporter system screening to efficiently inhibit the association of SUMO2 with LANASIM, in turn reducing the viral episome DNA copy number for establishment and maintenance of KSHV latent infection at a low concentration (nM). Importantly, Cambogin treatments not only specifically inhibited proliferation of KSHV-latently infected cells in vitro, but also induced regression of PEL tumors in a xenograft mouse model. This study has identified Cambogin as a novel therapeutic agent for treating PEL as well as eliminating persistent infection of oncogenic herpesvirus.
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Antineoplásicos/farmacologia , Linfoma de Efusão Primária/virologia , Terpenos/farmacologia , Latência Viral/efeitos dos fármacos , Animais , Antígenos Virais/efeitos dos fármacos , Antígenos Virais/metabolismo , Células HEK293 , Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8 , Humanos , Camundongos , Proteínas Nucleares/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Extratos Vegetais/farmacologia , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/efeitos dos fármacos , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Xin-Ji-Er-Kang (XJEK) is a Chinese herbal formula, which has been reported to exert effective protection against cardiovascular diseases, including hypertension and myocarditis. METHODS: Cultured human umbilical vascular endothelial cells (HUVECs) were treated with angiotensin II (Ang II) and different concentrations of aqueous layer extracts (AqE). Subsequently nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) expression levels were detected. In addition, fifty Kunming mice were randomized into control, Nω-nitro-L-arginine methyl ester (L-NAME), L-NAME+AqE, L-NAME+XJEK and L-NAME+fosinopril treatment groups. Following 8 weeks of treatment, the cardiac hemodynamic index was measured, relaxation of the aorta was examined and pathological changes were observed. Colorimetric analysis and enzyme linked immunosorbent assay (ELISA) were applied to determine the relevant indicators in plasma and cardiac tissues. RESULTS: The in vitro study results demonstrated that AqE could preserve endothelial function (NO, 21.05 ± 2.03 vs. 8.64 ± 0.59; eNOS, 1.08 ± 0.17 vs.0.73 ± 0.06). In addition, the in vivo results demonstrated that compared with the control group, treatment with AqE could enhance a high hemodynamic state (left ventricular systolic pressure, 116.76 ± 9.96 vs.114.5 ± 15.16), improve endothelial function (NO, 7.98 ± 9.64 vs. 1.66 ± 3.11; eNOS, 19.78 ± 3.18 vs.19.38 ± 3.85), suppress oxidative stress (OS) (superoxide dismutase, 178.17 ± 13.78 vs. 159.38 ± 18.86; malondialdehyde, 0.77 ± 0.13 vs.1.25 ± 0.36) and reverse cardiovascular remodeling. CONCLUSION: Polysaccharide from XJEK exerts protective effects against Ang II-induced injury in HUVECs and L-NAME-induced hypertension in mice and the underlying mechanism may be attributed to improving endothelial dysfunction, OS and the inflammation status in mice.
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Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Angiotensina II , Animais , Aorta/efeitos dos fármacos , Arginina/análogos & derivados , Arginina/sangue , Pressão Sanguínea/efeitos dos fármacos , Citocinas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipertensão/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Malondialdeído/sangue , Camundongos , Miocárdio/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Superóxido Dismutase/sangueRESUMO
The aim of the present study was to investigate the protective effects of curcumin and its effect on the methyl ethyl ketone/extracellular signal regulated kinase/cAMPresponse element binding protein (MEK/ERK/CREB) pathway. The study was conducted in vivo and in vitro as follows: In vivo: Focal cerebral ischemiareperfusion (IR) models of rats were made with the plugline method. Adult male SpragueDawley rats were divided into four groups: Sham operation control group, IR and curcumintreatment groups (100 mg/kg and IC, 300 mg/kg). The effects of curcumin on neurological deficit scores, brain water content and infarct volumes were identified. Transmission electron microscope was utilized to observe morphological changes of hippocampal neurons; hematoxylin and eosin staining was used to observe morphological changes of brain tissue; and the terminal deoxynucleotidyl transferase (TdT)mediated dUTP nick end labeling method detected neurons apoptosis of hippocampal CA1. Finally, western blot analysis detected the expression of phosphorylated (p)MEK, pERK, pCREB, Bcell lymphoma2 (Bcl2) and Bcl2 associated X protein (Bax). In vitro: An oxygenglucose deprivation/reoxygenation method was used on primary cultured astrocytes to make cerebral ischemiareperfusion models in vitro. Astrocytes were randomly divided into five groups: Normoxia, oxygenglucose deprivation/reoxygenation (OGD/Reoxy), OGD/Reoxy + curcumin (5, 10, 20 µmol/l). The cell viability and toxicity were assessed by MTT and lactate dehydrogenase release assay, and levels of pMEK, pERK and pCREB proteins were analyzed by the western blotting method. Curcumin was demonstrated to improve nerve damage symptoms and infarct volume, reduce brain water content, relieve neuronal apoptosis and also increase the expression of pMEK, pERK, pCREB, Bcl2 and reduce Bax levels in vivo and in vitro. In conclusion curcumin can mitigate focal cerebral ischemiareperfusion injuries and this effect may be carried out through the MEK/ERK/CREB pathway.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Curcumina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Isquemia Encefálica/complicações , Sobrevivência Celular/efeitos dos fármacos , Curcumina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Fármacos Neuroprotetores/farmacologia , Tamanho do Órgão/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/complicações , ÁguaRESUMO
BACKGROUND: Xin-Ji-Er-Kang (XJEK) shows protective effects on the myocardial ischemic diseases in our previous reports. We hypothesized that XJEK may exert preventing effects on L-NAME induced hypertensive mice by ameliorating oxidative stress (OS) and endothelial dysfunction (ED). METHODS: After treatment with XJEK for four weeks, cardiac function and cardiovascular pathology changes were evaluated. Then, endothelial-dependent vascular relaxation and serum NO, eNOS, AMDA, SOD, MDA content, and cardiac tissue eNOS expression were detected. RESULTS: The hypertensive mice displayed distinct cardiovascular remodeling including increased HW/BW index (4.7 ± 0.33 versus 5.2 ± 0.34), cross-section area, and collagen deposition. In addition, ED was found manifested by decreased serum NO (20.54 ± 8.05 versus 6.29 ± 2.33), eNOS (28.34 ± 2.36 versus 20.37 ± 2.30), content, and decreased eNOS expression in cardiac tissue and damaged endothelium-dependent diastolic function. Moreover, OS was detected confirmed by decreased SOD activity and increased MDA content in serum. However, treatment with XJEK for 4 wk could reverse cardiovascular remodeling (HW/BW index normalized from 5.2 ± 0.34 to 4.59 ± 0.25), ameliorate and preserve endothelial function (NO: 16.67 ± 7.24 versus 6.29 ± 2.33; eNOS: 16.67 ± 7.24 versus 6.29 ± 2.33), and suppress OS. CONCLUSION: XJEK has protective effects against cardiovascular remodeling in L-NAME induced hypertensive mice.