RESUMEN
Diabetes leads to intestinal barrier dysfunction. 5-Hydroxytryptamine 4 receptor (5-HT4R) is distributed in the colonic mucosa, but little is known about the role of its activation in diabetes-evoked colonic barrier dysfunction. This study investigates whether activation of 5-HT4Rs on goblet cells (GCs) protects the colon from commensal bacterial translocation in diabetic mice. Expression of 5-HT4R detected inside the colonic epithelium by RNAscope in situ hybridization was further observed within the mucin 2 (MUC2)-immunoreactive GCs. In diabetic mice, neither 5-HT4R transcription nor protein levels were altered compared with those in nondiabetic mice. Bacterial translocation was characterized by 16S rRNA RNAscope in situ hybridization and manifested in both crypts and lamina propria of the colon in diabetic mice. Mucin production and MUC2 expression were significantly decreased in diabetic mice. Furthermore, the loss of mitochondrial cristae of GCs and the down-regulation of mitofilin, the core protein maintaining mitochondrial homeostasis, were observed in diabetic mice. Long-term treatment with 5-HT4R agonist in diabetic mice not only prevented bacterial penetration of the whole colonic mucosa but also promoted mucin production and MUC2 expression. Markedly, 5-HT4R agonist also restored the mitochondrial cristae of GCs and up-regulated mitofilin. However, co-administration of 5-HT4R antagonist abolished the effects of 5-HT4R agonist on diabetic mice. These findings indicate that 5-HT4R in colonic mucosa is an effective target for the treatment of diabetes-induced colonic mucous barrier dysfunction.
Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animales , Colon/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Ratones , Mucina 2/metabolismo , Mucinas/metabolismo , ARN Ribosómico 16S/metabolismo , Receptores de Serotonina 5-HT4/metabolismo , Serotonina/metabolismo , Serotonina/farmacologíaRESUMEN
Cyanobacteria fouling in ultrafiltration (UF) drinking water treatment poses a significant threat to the stability and sustainability of the process. Both phycocyanin found in cyanobacteria and the polymer membrane exhibit strong fluorescence, which could be readily detected using front-face excitation-emission matrix (FF-EEM) spectroscopy. In this study, FF-EEM was employed for the nondestructive and in situ characterization of algae fouling evolution in UF, while also analyzing fouling mechanisms and reversibility. The results indicated that phycocyanin fluorescence on the membrane surface showed a linear correlation with the specific algal cell count on the membrane surface before reaching saturation. As fouling progressed, membrane fluorescence decreased, which was associated with the extent of the surface coverage on the membrane. The plateau in membrane fluorescence indicated full coverage, coinciding with the cake filtration mechanism, cake compression, and deterioration of fouling reversibility. These findings highlight the promise of FF-EEM as a valuable tool for monitoring and evaluating fouling of cyanobacteria in UF systems.
Asunto(s)
Cianobacterias , Purificación del Agua , Ultrafiltración/métodos , Ficocianina , Membranas Artificiales , Filtración , Purificación del Agua/métodosRESUMEN
In this study, in situ pretreatments with ozone and Fe(II)/persulfate were employed to suppress membrane fouling during the filtration of algae-laden water and to improve the rejection of metabolites. Both ozonation and Fe(II)/persulfate pretreatments negatively impacted the cell integrity, especially ozonation. Fe(II)/persulfate pretreatment improved the removal of dissolved organic carbon and microcystin-LR, but ozonation resulted in a deterioration in the quality of the filtered water. This suggests that the Fe(II)/persulfate oxidation is selective for organic degradation over cell damage. With ozonation, 2-methylisoborneol and geosmin were detected in the filtered water, and the irreversible fouling increased. The intracellular organic release and generation of small organic compounds with ozonation may be the reason for the increased membrane fouling. Fe(II)/persulfate oxidation substantially mitigated the membrane-fouling resistance at concentrations over 0.2 mM compared to the membrane-fouling resistance without oxidation. The combined effect of oxidation and coagulation is likely the reason for the excellent fouling control with Fe(II)/persulfate pretreatment. Membrane fouling during the filtration of algae-laden water is successively governed by complete-blocking and cake-filtration mechanisms. Ozonation caused a shift in the initial major mechanism to intermediate blocking, and the Fe(II)/persulfate pretreatment (>0.2 mM) converted the dominant mechanism into single-standard blocking.
Asunto(s)
Ozono , Purificación del Agua , Compuestos Ferrosos , Membranas Artificiales , UltrafiltraciónRESUMEN
BACKGROUND: Several G-protein-coupled receptors (GPCRs) have been shown to be important signaling mediators between neurons and glia. In our previous screening for identification of nerve injury-associated GPCRs, G-protein-coupled receptor 84 (GPR84) mRNA showed the highest up-regulation by microglia after nerve injury. GPR84 is a pro-inflammatory receptor of macrophages in a neuropathic pain mouse model, yet its function in resident microglia in the central nervous system is poorly understood. METHODS: We used endogenous, natural, and surrogate agonists for GPR84 (capric acid, embelin, and 6-OAU, respectively) and examined their effect on mouse primary cultured microglia in vitro. RESULTS: 6-n-Octylaminouracil (6-OAU), embelin, and capric acid rapidly induced membrane ruffling and motility in cultured microglia obtained from C57BL/6 mice, although these agonists failed to promote microglial pro-inflammatory cytokine expression. Concomitantly, 6-OAU suppressed forskolin-induced increase of cAMP in cultured microglia. Pertussis toxin, an inhibitor of Gi-coupled signaling, completely suppressed 6-OAU-induced microglial membrane ruffling and motility. In contrast, no 6-OAU-induced microglial membrane ruffling and motility was observed in microglia from DBA/2 mice, a mouse strain that does not express functional GPR84 protein due to endogenous nonsense mutation of the GPR84 gene. CONCLUSIONS: GPR84 mediated signaling causes microglial motility and membrane ruffling but does not promote pro-inflammatory responses. As GPR84 is a known receptor for medium-chain fatty acids, those released from damaged brain cells may be involved in the enhancement of microglial motility through GPR84 after neuronal injury.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Microglía/efectos de los fármacos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/metabolismo , Animales , Animales Recién Nacidos , Benzoquinonas/farmacología , Células Cultivadas , Corteza Cerebral/citología , AMP Cíclico/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ácidos Decanoicos/farmacología , Eliminación de Gen , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Microglía/inmunología , Óxido Nítrico Sintasa de Tipo II/metabolismo , Toxina del Pertussis/farmacología , Receptores Acoplados a Proteínas G/genética , Transducción de Señal/efectos de los fármacos , Uracilo/farmacologíaRESUMEN
This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against amyloid beta (Aß25-35)-induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SH-SY5Y cells overexpressing SOD3 were generated by adenoviral vector-mediated infection and Aß25-35 was then added to the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes and calcium images were examined. Following Aß25-35 exposure, SOD3 overexpression promoted the survival of SH-SY5Y cells, decreased the production of ROS, decreased MDA and calcium levels, and decreased cytochrome c, caspase-3, caspase-9 and Bax gene expression. Furthermore, SOD3 overexpression increased the expression and activity of antioxidant enzyme genes and Bcl-2 expression. Together, our data demonstrate that SOD3 ameliorates Aß25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway. These data provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage.
Asunto(s)
Péptidos beta-Amiloides/toxicidad , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Superóxido Dismutasa/metabolismo , Apoptosis/efectos de los fármacos , Calcio/metabolismo , Línea Celular Tumoral , Humanos , Espacio Intracelular/metabolismo , Mitocondrias/efectos de los fármacos , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Olfactory ensheathing cells (OECs) are a type of glia from the mammalian olfactory system, with neuroprotective and regenerative properties. ß-Amyloid peptides are a major component of the senile plaques characteristic of the Alzheimer brain. The amyloid beta (Aß) precursor protein is cleaved to amyloid peptides, and Aß25-35 is regarded to be the functional domain of Aß, responsible for its neurotoxic properties. It has been reported that Aß25-35 triggers reactive oxygen species (ROS)-mediated oxidative damage, altering the structure and function of mitochondria, leading to the activation of the mitochondrial intrinsic apoptotic pathway. Our goal is to investigate the effects of OECs on the toxicity of aggregated Aß25-35, in human neuroblastoma SH-SY5Y cells. For such purpose, SH-SY5Y cells were incubated with Aß25-35 and OEC-conditioned medium (OECCM). OECCM promoted the cell viability and reduced the apoptosis, and decreased the intracellular ROS and the lipid peroxidation. In the presence of OECCM, mRNA and protein levels of antioxidant enzymes (SOD1 and SOD2) were upregulated. Concomitantly, OECCM decreased mRNA and the protein expression levels of cytochrome c, caspase-9, caspase-3, and Bax in SH-SY5Y cells, and increased mRNA and the protein expression level of Bcl-2. However, OECCM did not alter intracellular Ca2+ concentration in SH-SY5Y cells. Taken together, our data suggest that OECCM ameliorates Aß25-35-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial intrinsic pathway. These data provide new insights into the functional actions of OECCM on oxidative stress-induced cell damage.
Asunto(s)
Péptidos beta-Amiloides/toxicidad , Apoptosis/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Mitocondrias/metabolismo , Bulbo Olfatorio/citología , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Transducción de Señal/efectos de los fármacos , Animales , Calcio/metabolismo , Línea Celular Tumoral , Humanos , Mitocondrias/efectos de los fármacos , Oxidación-Reducción , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Bacterial quorum quenching (QQ) has been shown to be effective in controlling biofouling in membrane bioreactors (MBRs) for wastewater treatment. However, the encapsulation of a sufficient level of QQ bacteria is complicated and difficult. In plant research, gamma-caprolactone (GCL), which is structurally similar to the quorum signal, N-acyl homoserine lactone (AHL), was successfully used to specifically stimulate AHL-degrading bacteria (biostimulation) in hydroponic systems to control blackleg and soft rot diseases in potato. In this study, the feasibility of enriching QQ bacteria from activated sludge by GCL was examined, and the effect of biostimulation on biofouling control in MBR treating domestic wastewater was investigated. The results showed that after enrichment with GCL, activated sludge could effectively degrade AHLs, and a QQ gene (qsdA) was augmented. The proposed biostimulation QQ strategy, by introducing and continuously dosing GCL, could significantly increase QQ activity, decrease AHL, control the secretion of extracellular polymeric substances (EPS), and thus, effectively control biofouling in an MBR. This biostimulation QQ strategy provides a more convenient option for biofouling control in MBR applications. Biotechnol. Bioeng. 2016;113: 2624-2632. © 2016 Wiley Periodicals, Inc.
Asunto(s)
4-Butirolactona/farmacología , Fenómenos Fisiológicos Bacterianos/efectos de los fármacos , Incrustaciones Biológicas/prevención & control , Reactores Biológicos/microbiología , Percepción de Quorum/fisiología , Aguas Residuales/microbiología , Biodegradación Ambiental , Diseño de Equipo , Análisis de Falla de Equipo , Membranas Artificiales , Aguas del Alcantarillado/microbiología , Contaminantes Químicos del Agua/aislamiento & purificación , Contaminantes Químicos del Agua/metabolismo , Purificación del Agua/instrumentaciónRESUMEN
This study was designed to investigate the protective effects of extracellular superoxide dismutase (SOD3) against hydrogen peroxide (H2O2) induced damage in human neuroblastoma SH-SY5Y cells and to elucidate the mechanisms responsible for this beneficial effect. SOD3-overexpressing SH-SY5Y cells were generated by adenoviral vector-mediated infection, and H2O2 was then added into the cell culture system to establish an in vitro model of oxidative stress. Cell viability, the generation of intracellular reactive oxygen species (ROS), the expression and activity of antioxidant enzymes, the levels of lipid peroxidation malondialdehyde (MDA), the expression of mitochondrial apoptosis-related genes, and calcium imaging were examined. Following H2O2 exposure, the over-expression of SOD3 promoted the survival of SH-SY5Y cells; decreased the production of ROS, MDA levels, cytochrome C, caspase-3, caspase-9, and Bax gene expression, and calcium levels; and increased the expression and activity of antioxidant enzyme genes and the expression level of Bcl-2. Together, our data demonstrate that SOD3 ameliorates H2O2-induced oxidative damage in neuroblastoma SH-SY5Y cells by inhibiting the mitochondrial pathway and provide new insights into the functional actions of SOD3 on oxidative stress-induced cell damage.
Asunto(s)
Peróxido de Hidrógeno/toxicidad , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología , Superóxido Dismutasa/biosíntesis , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Humanos , Mitocondrias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Solid retention time (SRT) is one of the most important operational parameters in membrane bioreactor (MBR), which significantly influences membrane fouling. It is widely recognized that SRT mainly changes biomass characteristics, and then, influences membrane fouling. Effect of SRT on quorum sensing (QS) in MBR, which could also influence fouling by coordinating biofilm formation, has not been reported. In this study, fouling, QS, soluble microbial products (SMP), and extracellular polymer substances (EPS) in MBRs operated under SRTs of 4, 10, and 40 days were investigated. The results showed that as SRT increased, the abundance of quorum quenching (QQ) bacteria increased, the quorum signal degradation activity of activated sludge increased, the concentrations of signal molecules in MBR decreased, the excretion of SMP and EPS decreased, and thus membrane biofouling was alleviated. Therefore, besides altering the biomass physiochemical properties, SRT also changed the balance between QS and QQ in MBR, and in this way, influenced membrane biofouling.
Asunto(s)
Bacterias/crecimiento & desarrollo , Fenómenos Fisiológicos Bacterianos , Reactores Biológicos/microbiología , Membranas/microbiología , Percepción de Quorum , Factores de Tiempo , Purificación del AguaRESUMEN
BACKGROUND: Aluminum overload can cause severe brain injury and neurodegeneration. Previous studies suggest that prostacyclin synthase (PGIS) expression and prostacyclin receptor (IP) activation are beneficial for treatment of acute traumatic and ischemic brain injury. However, the potential value of PGIS/IP signaling pathway to chronic brain injury is still unclear. In this study, we investigated the change of PGIS/IP signaling pathway and the effect of beraprost sodium (BPS) on chronic brain injury in chronic aluminum-overload rats. METHODS: Rat model of chronic cerebral injury was established by chronic intragastric administration of aluminum gluconate(Al3+ 200 mg/kg per day,5d a week for 20 weeks). The methods of ELISA, qRT-PCR and Western blotting were used to detect the PGI2 level and the PGIS and IP mRNA and protein levels in hippocampi of chronic aluminum-overload rats, respectively. Rat hippocampal superoxide dismutase (SOD) activity and malondialdehyde (MDA) content also were measured. The effects of BPS (6, 12 and 24 µgâ kg(-1)) on brain injury in chronic aluminum-overload rats were evaluated. RESULTS: Compared with the control group, PGIS mRNA expression, PGI2 level, and the IP mRNA and protein expressions significantly increased in hippocampi of chronic aluminum-overload rats. Administration of BPS significantly improved spatial learning and memory function impairment and hippocampal neuron injury induced by chronic aluminum overload in rats. Meanwhile, administration of BPS resulted in a decrease of PGI2 level and downregulation of PGIS and IP expressions in a dose-dependent manner. Aluminum overload also caused a decrease of SOD activity and an increase of MDA content. Administration of BPS significantly blunted the decrease of SOD activity and the increase of MDA content induced by aluminum overload in rats. CONCLUSIONS: BPS has a significant neuroprotective effect on chronic brain injury induced by aluminum overload in rats. Remodeling the balance of PGIS/IP signaling pathway and inhibition of oxidative stress involve in the neuroprotective mechanism of BPS in aluminum-overload rats. The PGIS/IP signaling pathway is a potential therapeutic strategy for chronic brain injury patients.
Asunto(s)
Compuestos de Aluminio , Antiinflamatorios no Esteroideos/uso terapéutico , Daño Encefálico Crónico/inducido químicamente , Daño Encefálico Crónico/prevención & control , Epoprostenol/análogos & derivados , Fármacos Neuroprotectores/uso terapéutico , Aluminio/metabolismo , Animales , Sistema Enzimático del Citocromo P-450/metabolismo , Epoprostenol/biosíntesis , Epoprostenol/uso terapéutico , Gluconatos , Hipocampo/metabolismo , Hipocampo/patología , Oxidorreductasas Intramoleculares/metabolismo , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Trastornos de la Memoria/psicología , Proteínas del Tejido Nervioso/biosíntesis , Ratas , Ratas Sprague-Dawley , Receptores de Epoprostenol/efectos de los fármacos , Superóxido Dismutasa/metabolismoRESUMEN
Neurodegenerative diseases remain a significant unresolved societal burden afflicting millions of people worldwide. Neurons in the brain are highly sensitive to oxidative stress, which can be induced by metal toxicity. In this paper, a chronic aluminum overload-induced model of neurodegeneration was used to investigate whether metal ions (Al, Fe, Mn, Cu and Zn)-related oxidative stress was involved in neurodegenerative mechanism and to identify the protective action of meloxicam against rat hippocampal neuronal injury. The metal ion contents, activity of superoxide dismutase (SOD), and content of malondialdehyde (MDA) were detected. The results showed that the spatial learning and memory (SLM) function was significantly impaired in chronic aluminum overload rats. Considerable karyopycnosis was observed in hippocampal neurons. The SOD activity was weakened and the MDA content increased both significantly. In the hippocampus, Al, Fe, Mn, Cu, and Zn contents increased by 184.1%, 186.1%, 884.2%, 199.4% and 149.2%, respectively. Meloxicam administration (without Al) had no effect compared with the control group, while meloxicam treatment with aluminum exposure significantly protected rats from SLM function impairment, neuron death, lower SOD activity, higher MDA content and brain metal ion imbalance. Our findings suggest that the cerebral metal ion imbalance-related oxidative stress is involved in mechanism of cerebral injury and neurodegeneration induced by chronic Al overload in rats, and that meloxicam protects neurons by reducing metal ion imbalance-related oxidative stress.
Asunto(s)
Aluminio/toxicidad , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Tiazinas/uso terapéutico , Tiazoles/uso terapéutico , Animales , Hipocampo/metabolismo , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Meloxicam , Memoria/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Ratas , Superóxido Dismutasa/metabolismo , Tiazinas/farmacología , Tiazoles/farmacologíaRESUMEN
Recent evidence indicates that severe abnormalities in brain glucose/energy metabolism and insulin signaling have been documented to take a pivotal role in early sporadic Alzheimer's disease pathology. It has been reported that naringenin (NAR), derived from citrus aurantium, exhibits antioxidant potential and protects the brain against neurodegeneration. The current study was designed to further investigate the protective effect of the NAR on neurodegeneration in a rat model of AD induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ), and to determine whether this neuroprotective effect was associated with brain insulin signaling. Rats were injected bilaterally with ICV-STZ (3 mg/kg), while sham rats received the same volume of vehicle and then supplemented with NAR (25, 50 mg, 100 mg/kg, respectively) for 3 weeks. The ICV-STZ injected rats did not have elevated blood glucose levels. 21 days following ICV-STZ injection, rats treated with NAR had better learning and memory performance in the Morris water maze test compared with rats treated with saline. We demonstrated that NAR increased the mRNA expression of INS and INSR in cerebral cortex and hippocampus. In addition, NAR reversed ICV-STZ induced Tau hyper-phosphorylation in both hippocampus and cerebral cortex through downregulation of glycogen synthase kinase-3ß (GSK-3ß) activity, a key kinase in the insulin signaling. Brain levels of Abeta, which were elevated in ICV-STZ rats, were significantly reduced in NAR-treated rats via upregulation of insulin degrading enzyme. These effects were mediated by increased insulin and insulin receptors expression in the brain, suggesting that insulin sensitizer agents might have therapeutic efficacy in early AD.
Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Demencia/tratamiento farmacológico , Demencia/fisiopatología , Insulinas/metabolismo , Péptidos beta-Amiloides/metabolismo , Animales , Glucemia/efectos de los fármacos , Cognición/efectos de los fármacos , Cognición/fisiología , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Infusiones Intraventriculares , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Fragmentos de Péptidos/metabolismo , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Receptor de Insulina/metabolismo , Memoria Espacial/efectos de los fármacos , Memoria Espacial/fisiología , Estreptozocina , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. METHODS: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 µmol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 µmol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 µmol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and ß-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. RESULTS: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3ß and down-regulated the expression of ß-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of ß-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). CONCLUSIONS: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/ß-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.
Asunto(s)
Glioblastoma , Triterpenos Pentacíclicos , Vía de Señalización Wnt , Humanos , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , beta Catenina/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ligandos , Línea Celular Tumoral , Apoptosis , Factores de Necrosis Tumoral/farmacología , Proliferación Celular , Movimiento Celular , Transición Epitelial-MesenquimalRESUMEN
Urtica cannabina L. (UL) has been used clinically for centuries because of its anti-inflammatory properties. This study aimed to investigate the underlying mechanisms and anti-inflammatory effects of different UL concentrations in zebrafish. To elucidate UL's anti-inflammatory properties, two inflammation zebrafish models were designed 1) by severing the zebrafish's caudal fin to assess the repairing effect of UL on the tail inflammation, and 2) by inducing lipopolysaccharides (LPS)-mediated intestinal inflammation to assess the protective and reparative effects of UL on intestinal inflammation at the histological and genetic levels. Furthermore, the effect of UL on the LPS-induced intestinal flora changes was also assessed. After caudal fin resection, a scar formed on the tail of the zebrafish, and the area of the caudal fin increased by 1.30 times as much as that of the control group (P < 0.01). Moreover, this tail scar was alleviated after 10 mg/g UL supplementation but not after 30 mg/g UL dose. LPS decreased the feed intake and body weight of the zebrafish; however, these effects were reversed after 10 and 30 mg/g doses of UL. In addition, the LPS treatment also reduced the intestinal goblet cells by 49% in the zebrafish when compared with the control, which was significantly restored after 10 and 30 mg/g UL treatments. At the genetics level, the expression of the pro-inflammatory cytokine genes (TNF-α, IL6, and IL8) showed that 10 and 30 mg/g UL doses could rescue LPS-induced expression. The gut microbiota analysis revealed changes in the abundance of four major bacterial phyla in the 10 and 30 mg/g UL-treated groups, with an increased probiotic Bacteroidota and decreased pathogenic bacteria. These results indicate that UL strongly inhibits inflammation caused by caudal fin removal and LPS-induced inflammatory changes in the zebrafish intensity, suggesting that UL is a feed additive that could be developed to improve resistance to inflammation in livestock.
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Antiinflamatorios , Lipopolisacáridos , Pez Cebra , Animales , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Microbioma Gastrointestinal/efectos de los fármacos , Aditivos Alimentarios/farmacología , Alimentación Animal , Extractos Vegetales/farmacologíaRESUMEN
Slow dissolution/hydrolysis of insoluble/macromolecular organics and poor sludge filterability restrict the application potential of anaerobic membrane bioreactor (AnMBR). Bubble-free membrane microaeration was firstly proposed to overcome these obstacles in this study. The batch anaerobic digestion tests feeding insoluble starch and soluble peptone with and without microaeration showed that microaeration led to a 65.7-144.8% increase in methane production and increased critical flux of microfiltration membrane via driving the formation of large sludge flocs and the resultant improvement of sludge settleability. The metagenomic and bioinformatic analyses showed that microaeration significantly enriched the functional genes and bacteria for polysaccharide and protein hydrolysis, microaeration showed little negative effects on the functional genes involved in anaerobic metabolisms, and substrate transfer from starch to peptone significantly affected the functional genes and microbial community. This study demonstrates the dual synergism of microaeration to enhance the dissolution/hydrolysis/acidification of insoluble/macromolecular organics and sludge filterability for AnMBR application.
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Reactores Biológicos , Filtración , Membranas Artificiales , Aguas del Alcantarillado , Reactores Biológicos/microbiología , Aguas del Alcantarillado/microbiología , Anaerobiosis , Filtración/métodos , Metano/metabolismo , Hidrólisis , Almidón/metabolismoRESUMEN
OBJECTIVE: To investigate the effects of naringenin on the learning and memory ability of Alzheimer disease (AD) rats. METHODS: 30 male SD rats were randomly divided into control group (sham operation group), model group and naringenin group. AD model was established by injecting strepoztocin (3 mg/kg) twice into each of two intracerebroventriculas. Naringenin group were given intragastric administration of naringenin once a day for 3 weeks and the other two groups were given intragadtric administration of normal saline with the same dosage and time period. After 3 weeks, learning and memory ability in all the three groups were analyzed by Morris water maze, the activity of superoxide dismutase(SOD) and the content of malondialdehyde (MDA) of the rats' brain tissue was detected by chemical colorimetric determination. Observed the expressions of Abeta42 and Abeta40 by immunohistochemical method. The expression and degree of phosphorylation of tau protein was assayed by western blotting. RESULTS: 1. Compared with the sham operation group, the mean escape latency of the model group was significantly prolonged (P < 0.05) and the time that rats were in the platform quadrant was significantly shortened (P < 0.0.5). On the contrary, compared with the model group, the mean escape latency of naringenin group was significantly shortened (P < 0.05) and the time that rats were in the platform quadrant was significantly extended (P < 0.005). 2. The level of MDA in the model group, compared with the sham operation group group, was significantly increased (P < 0.05). Whereas, that of naringenin group, compared with the model group, was significantly decreased compared with the sham operation group (P < 0.05). The activity of SOD in the naringenin group was significantly increased comparing with the model group (P < 0.05). 3. The expressions of Abeta40 and Abeta42 in model group were obviously up-regulated. Instead, the expressions of Abeta40 and Abeta42 in the naringenin group were significantly down regulated. 4. There was no significant difference in the expression of tau protein among each groups. Nevertheless, the phosphorylation of tau protein in the model group was significantly enhanced than that in the control group (P < 0.05), and the phosphorylation of tau protein in the naringenin group was significantly reduced than that in the model group (P < 0.05). CONCLUSION: Naringenin can improve learning and memory ability of model rats with Alzheimer disease through the approach of oxidative stress.
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Enfermedad de Alzheimer/tratamiento farmacológico , Antioxidantes/farmacología , Encéfalo/efectos de los fármacos , Flavanonas/farmacología , Aprendizaje/efectos de los fármacos , Memoria/efectos de los fármacos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Antioxidantes/administración & dosificación , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Flavanonas/administración & dosificación , Masculino , Malondialdehído/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Rutaceae/química , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Proteínas tau/metabolismoRESUMEN
Ultrafiltration (UF) has been proven effective in removing algae during seasonal algal blooms, but the algal cells and the metabolites can induce severe membrane fouling, which undermines the performance and stability of the UF. Ultraviolet-activated sulfite with iron (UV/Fe(II)/S(IV)) could enable an oxidation-reduction coupling circulation and exert synergistic effects of moderate oxidation and coagulation, which would be highly preferred in fouling control. For the first time, the UV/Fe(II)/S(IV) was systematically investigated as a pretreatment of UF for treating Microcystis aeruginosa-laden water. The results showed that the UV/Fe(II)/S(IV) pretreatment significantly improved the removal of organic matter and alleviated membrane fouling. Specifically, the organic matter removal increased by 32.1% and 66.6% with UV/Fe(II)/S(IV) pretreatment for UF of extracellular organic matter (EOM) solution and algae-laden water, respectively, while the final normalized flux increased by 12.0-29.0%, and reversible fouling was mitigated by 35.3-72.5%. The oxysulfur radicals generated in the UV/S(IV) degraded the organic matter and ruptured the algal cells, and the low-molecular-weight organic matter generated in the oxidation penetrated the UF and deteriorated the effluent. The over-oxidation did not happen in the UV/Fe(II)/S(IV) pretreatment, which may be attributed to the cyclic redox Fe(II)/Fe(III) coagulation triggered by the Fe(II). The UV-activated sulfate radicals in the UV/Fe(II)/S(IV) enabled satisfactory organic removal and fouling control without over-oxidation and effluent deterioration. The UV/Fe(II)/S(IV) promoted the aggregation of algal foulants and postponed the shift of the fouling mechanisms from standard pore blocking to cake filtration. The UV/Fe(II)/S(IV) pretreatment proved effective in enhancing the UF for algae-laden water treatment.
RESUMEN
Resources recovery from landfill leachate (LFL) has been attracting growing attention instead of merely purifying the wastewater. An integrated two-stage membrane distillation (ITMD) was proposed to simultaneously purify LFL and recover ammonia in this study. The results showed that organics could be always effectively rejected by the ITMD regardless of varying feed pH, with COD removal higher than 99%. With feed pH increased from 8.64 to 12, the ammonia migration (50-100%) and capture (36-75%) in LFL were considerably enhanced, boosting the separated ammonia enrichment to 1.3-1.7 times due to the improved ammonium diffusion. However, the corresponding membrane flux of the first MD stage decreased from 13.7 to 10.5 L/m2·h. Elevating feed pH caused the deprotonation of NOM and its binding with inorganic ions, constituting a complex fouling layer on the membrane surface in the first MD stage. In contrast, the membrane permeability and fouling of the second MD were not affected by feed pH adjustment because only volatiles passed through the first MD. More importantly, it was estimated that ITMD could obtain high-quality water and recover high-purity ammonium from LFL with relatively low ammonium concentration at an input cost of $ 2-3/m3, which was very competitive with existing techniques. These results demonstrated that the ITMD can be a valuable candidate strategy for simultaneous water purification and nutrient recovery from landfill leachate.
Asunto(s)
Compuestos de Amonio , Contaminantes Químicos del Agua , Purificación del Agua , Amoníaco , Destilación , Agua , Purificación del Agua/métodos , Membranas ArtificialesRESUMEN
Background: During clinical practice, routine blood tests are commonly performed following pancreaticoduodenectomy (PD). However, the relationship between blood cell counts, inflammation-related indices, and postoperative complications remains unclear. Method: We conducted a retrospective study, including patients who underwent PD from October 2018 to July 2023 at the First Hospital of Chongqing Medical University, and compared baseline characteristics and clinical outcomes among different groups. Neutrophil count (NC), platelet count (PLT), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) were derived from postoperative blood test results. We investigated the association between these indicators and outcomes using multivariable logistic regression and restricted cubic spline analysis. The predictive performance of these indicators was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Result: A total of 232 patients were included in this study. Multivariate logistic regression and restricted cubic spline analysis showed that all indicators, except for PLT, were associated with clinical postoperative pancreatic fistula (POPF). SII, NLR, and NC were linked to surgical site infection (SSI), while SII, NLR, and PLR were correlated with CD3 complication. PLT levels were related to postoperative hemorrhage. SII (AUC: 0.729), NLR (AUC: 0.713), and NC (AUC: 0.706) effectively predicted clinical POPF. Conclusion: In patients undergoing PD, postoperative inflammation-related indices and blood cell counts are associated with various complications. NLR and PLT can serve as primary indicators post-surgery for monitoring complications.
Asunto(s)
Inflamación , Pancreaticoduodenectomía , Humanos , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos , Inflamación/etiología , Recuento de Linfocitos , Recuento de PlaquetasRESUMEN
Catalytic membrane can achieve sieving separation and advanced oxidation simultaneously, which can improve the effluent water quality while reducing membrane fouling. In this study, the catalytic membranes (M2+Al@AM) were fabricated by loading different binary layered metal oxides (M2+Al-LMO: MnAl-LMO, CuAl-LMO and CoAl-LMO) on alumina ceramic substrate membranes (AM) via vacuum filtration followed by calcination process. The performance of the catalytic membranes was investigated by filtering actual surface water. It was found that the presence of peroxymonosulfate (PMS) could mitigate membrane fouling effectively, as evidenced by the increase of normalized flux from 0.28 to 0.62 in CoAl@AM/PMS system, from 0.25 to 0.52 in CuAl@AM/PMS system, and from 0.22 to 0.31 in MnAl@AM/PMS system, respectively. Correspondingly, the CoAl@AM exhibited the highest removal for UV254, TOC and fluorescent components in the surface water, followed by CuAl@AM and MnAl@AM. Quenching effect of phenol and furfuryl alcohol proposed the surface-bound radicals and singlet oxygen were the major reactive oxygen species in the M2+Al@AM/PMS systems. Interface free energy calculations confirmed the in-situ PMS activation could enhance the repulsive interactions between NOM and the membranes, thus mitigating membrane fouling. This work provides an original but simple strategy for catalytic ceramic membrane preparation and new insights into the mechanism of membrane fouling mitigation in catalytic membrane system.