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The remediation of volatile chlorinated hydrocarbons in the quasi-vadose zone has become a significant challenge. We applied an integrated approach to assess the biodegradability of trichloroethylene to identify the biotransformation mechanism. The formation of the functional zone biochemical layer was assessed by analyzing the distribution of landfill gas, physical and chemical properties of cover soil, spatial-temporal variations of micro-ecology, biodegradability of landfill cover soil and distributional difference metabolic pathway. Real-time online monitoring showed that trichloroethylene continuously undergoes anaerobic dichlorination and simultaneous aerobic/anaerobic conversion-aerobic co-metabolic degradation on the vertical gradient of the landfill cover system and reduction in trans-1,2-dichloroethylene in the anoxic zone but not 1,1-dichloroethylene. PCR and diversity sequencing revealed the abundance and spatial distribution of known dichlorination-related genes within the landfill cover, with 6.61 ± 0.25 × 104-6.78 ± 0.09 × 106 and 1.17 ± 0.78 × 103-7.82 ± 0.07 × 105 copies per g/soil of pmoA and tceA, respectively. In addition, dominant bacteria and diversity were significantly linked with physicochemical factors, and Mesorhizobium, Pseudoxanthomonas and Gemmatimonas were responsible for biodegradation in the aerobic, anoxic and anaerobic zones. Metagenome sequencing identified 6 degradation pathways of trichloroethylene that may occur in the landfill cover; the main pathway was incomplete dechlorination accompanied by cometabolic degradation. These results indicate that the anoxic zone is important for trichloroethylene degradation.
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Tricloroetileno , Tricloroetileno/química , Multiómica , Biodegradación Ambiental , Instalaciones de Eliminación de Residuos , Bacterias/genética , Bacterias/metabolismo , Suelo , Reacción en Cadena de la Polimerasa , TecnologíaRESUMEN
River sediment is vital in containing water pollution and strengthening water remediation. This paper has conducted a study on the microecological health assessment of the sediment and water body of Guixi River in Dianjiang, Chongqing, China, using metagenomics sequencing and microbial biological integrity index (M-IBI) technology. The analysis of physical and chemical characteristics shows that the concentration of TN varies from 2.62 to 9.76 mg/L in each sampling section, and the eutrophication of the water body is relatively severe. The proportion of Cyanobacteria in the sampling section at the sink entrance is higher than that of other sites, where there are outbreaks of water blooms and potential hazards to human health. The dominant functions of each site include carbon metabolism, TCA cycle, and pyruvate metabolism. In addition, the main virulence factors and antibiotic resistance genes in sediment are Type IV pili (VF0082), LOS (CVF494), MymA operon (CVF649), and macrolide resistance genes macB, tetracyclic tetA (58), and novA. Correlation analysis of environmental factors and microorganisms was also performed, and it was discovered that Thiothrix and Acidovorax had obvious gene expression in the nitrogen metabolism pathway, and the Guixi River Basin had a self-purification capacity. Finally, based on the microecological composition of sediment and physical and chemical characteristics of the water body, the health assessment was carried out, indicating that the main pollution area was Dianjiang Middle School and the watershed near the sewage treatment plant. The findings should theoretically support an in-depth assessment of the water environment's microecological health.
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Monitoreo del Ambiente , Metagenómica , Ríos , Contaminantes Químicos del Agua , China , Contaminantes Químicos del Agua/análisis , Farmacorresistencia Bacteriana , Genes Bacterianos , HumanosRESUMEN
BACKGROUND: Interleukin 17 (IL-17) plays an important role in the pathogenesis of autoimmune diseases and might be associated with IgA nephropathy (IgAN). This study aimed to investigate the effect of IL-17 on autoimmune pathogenesis in IgA nephropathy. METHODS: DAKIKI cells were cultured and stimulated with IL-17 to perform dose-dependent and time-dependent experiments. Cell proliferation was examined by cell counting and the Cell Counting Kit-8 (CCK-8) assay. The IgA concentration and the degree of galactosylation in the supernatant were tested using ELISA and a helix aspersa (HAA) lectin binding assay, respectively. To study the mechanism of O-glycosylation, cells were stimulated with IL-17, lipopolysaccharide (LPS) or 5-azacytidine (5-AZA) + IL-17 for 48 h, and the levels of C1GALT1 and its molecular chaperone Cosmc were measured by western blot and real-time PCR. RESULTS: The cell counting and CCK-8 results suggested that B lymphocyte proliferation increased significantly with increased IL-17 concentration. IL-17 affected the quantity of IgA1 and its glycosylation status. HAA revealed that IL-17 promoted IgA1 underglycosylation. Mechanistically, the expression of C1GALT1 and Cosmc was significantly lower in cells stimulated by IL-17 or LPS than in the 5-AZA + IL-17 or the control group. CONCLUSIONS: Our results suggested that IL-17 stimulates B lymphocyte to promote B-cell proliferation, which leads to increased IgA1 production in vitro accompanied by underglycosylation of IgA1. The molecular mechanism for the IgA1 underglycosylation induced by IL-17 was similar to that of LPS; however, 5-AZA inhibited IgA1 underglycosylation. IL-17 might participate in IgAN pathogenesis by influencing the production and glycosylation of IgA1 in B-cells.
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Linfocitos B/fisiología , Galactosiltransferasas/metabolismo , Glomerulonefritis por IGA/inmunología , Inmunoglobulina A/metabolismo , Interleucina-17/metabolismo , Azacitidina/farmacología , Linfocitos B/inmunología , Recuento de Células , Línea Celular Tumoral , Proliferación Celular , Ensayo de Inmunoadsorción Enzimática , Glicosilación , Humanos , Inmunoglobulina A/inmunología , Interleucina-17/inmunología , Lipopolisacáridos/farmacología , Chaperonas Moleculares/metabolismo , Regulación hacia ArribaRESUMEN
OBJECTIVE: To explore the effects of Telmisartan on IKCa1 potassium channel after T-lymphocyte activation and proliferation in peripheral blood of hypertensive patients in Xinjiang Kazakh. METHODS: Peripheral blood T cells in vitro culture were isolated from 30 Xinjiang Kazakh outpatients without antihypertensive drug therapy. They were randomly selected from our hypertension clinic from August 2012 to December 2012. The proliferated T lymphocytes were divided into control, telmisartan and TRAM-34 groups. After culturing for 0, 24, 48 h after corresponding treatments, the patch-clamp technique was employed to record the electrophysiological changes of IKCa1 potassium channel of T lymphocytes. RESULTS: Under different treatment conditions, the IKCa1 potassium channel showed different electrophysiological changes. Pairwise comparison was made among the groups on the same time. For the telmisartan group, IKCa1 potassium channel peak current, peak current density of intervention 24 h and 48 h were significantly reduced compared with the control group (24 h:(835 ± 117)vs(1 471 ± 255) pA, (213 ± 61) vs (388 ± 129) pA/pF; 48 h:(631 ± 142) vs (1 555 ± 383) pA, (155 ± 54) vs (388 ± 114) pA/pF, all P < 0.01) . And the blocking rates of 0 h, 24 h and 48 h of telmisartan on IKCa1 potassium channel were 6.8%, 45.1% and 60.1% respectively. CONCLUSION: Telmisartan can block the IKCa1 potassium channel of T lymphocytes in peripheral blood of hypertensive patients in Xinjiang Kazakh. It suggests that telmisartan may play an anti-inflammatory effect by blocking the IKCa1 potassium channels of T lymphocyte activation.
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Bencimidazoles/farmacología , Benzoatos/farmacología , Hipertensión/fisiopatología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/efectos de los fármacos , Activación de Linfocitos , Células Cultivadas , Femenino , Humanos , Hipertensión/sangre , Hipertensión/etnología , Masculino , Persona de Mediana Edad , Linfocitos T/citología , TelmisartánRESUMEN
BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) were reported to protect from hypoxia-induced oxidative stress in coronary endothelial cells (CECs) after acute myocardial infarction (AMI). Nrf2 shows a protective effect in hypoxia-induced CECs after AMI. Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in angiogenesis after AMI. AIM: To explore the protective effect of ACEIs and the involved mechanisms under hypoxia challenge. METHODS: Human coronary endothelial cells (HCAECs) were used to establish hypoxia-induced oxidative stress injury in vitro. Flow cytometry was used to evaluate the protective effect of ACEI on hypoxia conditions.ET-1, NO, ROS, and VEGF were detected by ELISA. HO-1, Nrf2, and Keap-1, the pivotal member in the Nrf2 signaling pathway, eNOS and PLVAP were detected in HEAECs treated with ACEI by immunofluorescence, qPCR, and western blotting. RESULTS: The hypoxia ACEI or Nrf2 agonist groups showed higher cell viability compared with the hypoxia control group at 24 (61.75±1.16 or 61.23±0.59 vs. 44.24±0.58, both Pâ<â0.05) and 48âh (41.85±1.19 or 59.64±1.13 vs. 22.98±0.25, both Pâ<â0.05). ACEI decreased the levels of ET-1 and ROS under hypoxia challenge at 24 and 48âh (all Pâ<â0.05); ACEI increased the VEGF and NO levels (all Pâ<â0.05). ACEI promoted the expression level of eNOS, HO-1, Nrf2 and PLVAP but inhibited Keap-1 expression at the mRNA and protein levels (all Pâ<â0.05). Blockade of the Nrf2 signaling pathway significantly decreased the expression level of PLVAP. CONCLUSION: ACEI protects hypoxia-treated HEAECs by activating the Nrf2 signaling pathway and upregulating the expression of PLVAP.
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Inhibidores de la Enzima Convertidora de Angiotensina , Vasos Coronarios , Células Endoteliales , Factor 2 Relacionado con NF-E2 , Transducción de Señal , Humanos , Factor 2 Relacionado con NF-E2/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Transducción de Señal/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Vasos Coronarios/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Células CultivadasRESUMEN
Porcine epidemic diarrhea virus (PEDV) remains one of the major causative microorganisms of viral diarrhea in piglets worldwide, with no approved drugs for treatment. We identified a natural molecule, flavonol, which is widely found in tea, vegetables and herbs. Subsequently, the antiviral activity of compound flavonol was evaluated in Vero cells and IPEC-J2 cells, and its anti-PEDV mechanism was analyzed by molecular docking and molecular dynamics. The results showed that flavonol could effectively inhibit viral progeny production, RNA synthesis and protein expression of PEDV strains in a dose-dependent manner. When flavonol was added simultaneously with viral infection in Vero cells, it demonstrated potent anti-PEDV activity by affecting the viral attachment and internalization phases. Similarly, in IPEC-J2 cells, flavonol effectively inhibited PEDV infection at different stages of infection, except for the release phase. Moreover, flavonol mainly interacts with PEDV Mpro through hydrogen bonds and hydrophobic forces, and the complex formed by it has high stability. Importantly, flavonol also showed broad-spectrum activity against other porcine enteric coronaviruses such as TGEV and PDCoV in vitro. These findings suggest that flavonol may exert antiviral effects by interacting with viral Mpro, thereby affecting viral replication. This means that flavonol is expected to become a potential drug to prevent or treat porcine enteric coronavirus.
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Antivirales , Flavonoles , Virus de la Diarrea Epidémica Porcina , Replicación Viral , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Animales , Antivirales/farmacología , Antivirales/química , Flavonoles/farmacología , Chlorocebus aethiops , Porcinos , Células Vero , Replicación Viral/efectos de los fármacos , Simulación del Acoplamiento Molecular , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/tratamiento farmacológico , Internalización del Virus/efectos de los fármacos , Enfermedades de los Porcinos/virología , Enfermedades de los Porcinos/tratamiento farmacológico , Línea Celular , Simulación de Dinámica Molecular , Acoplamiento Viral/efectos de los fármacosRESUMEN
Recent epidemiological studies have discovered that a lot of cases of porcine epidemic diarrhea virus (PEDV) infection are frequently accompanied by porcine kobuvirus (PKV) infection, suggesting a potential relationship between the two viruses in the development of diarrhea. To investigate the impact of PKV on PEDV pathogenicity and the number of intestinal lymphocytes, piglets were infected with PKV or PEDV or co-infected with both viruses. Our findings demonstrate that co-infected piglets exhibit more severe symptoms, acute gastroenteritis, and higher PEDV replication compared to those infected with PEDV alone. Notably, PKV alone does not cause significant intestinal damage but enhances PEDV's pathogenicity and alters the number of intestinal lymphocytes. These results underscore the complexity of viral interactions in swine diseases and highlight the need for comprehensive diagnostic and treatment strategies addressing co-infections.
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Coinfección , Infecciones por Coronavirus , Intestinos , Kobuvirus , Linfocitos , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Virus de la Diarrea Epidémica Porcina/patogenicidad , Virus de la Diarrea Epidémica Porcina/fisiología , Porcinos , Enfermedades de los Porcinos/virología , Coinfección/virología , Coinfección/veterinaria , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Linfocitos/virología , Kobuvirus/patogenicidad , Kobuvirus/genética , Intestinos/virología , Diarrea/virología , Diarrea/veterinaria , Replicación Viral , Gastroenteritis/virología , Gastroenteritis/veterinaria , Infecciones por Picornaviridae/veterinaria , Infecciones por Picornaviridae/virologíaRESUMEN
The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6mmol/L), high glucose groups (10, 20, and 30mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p<0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p<0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p<0.05). The present results support the hypothesis that high glucose may activate NF-κB inflammatory signaling through IκBα sumoylation and ubiquitination.
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Glucosa/administración & dosificación , Proteínas I-kappa B/metabolismo , Células Mesangiales/metabolismo , FN-kappa B/fisiología , Animales , Quimiocina CCL2/biosíntesis , Nefropatías Diabéticas/etiología , Glucosa/farmacología , Inhibidor NF-kappaB alfa , Ratas , Proteína SUMO-1/metabolismo , Transducción de Señal/efectos de los fármacos , Sumoilación/efectos de los fármacos , Factor de Transcripción ReIA/biosíntesisRESUMEN
OBJECTIVE: To observe the current changes of voltage-dependent potassium channel (Kv1.3 potassium channel) and calcium-activated potassium channel (IKCa1 potassium channel) in peripheral blood T-lymphocyte derived from hypertensive patients of Xinjiang Kazakh. METHODS: Twenty randomly selected untreated Kazakh hypertensive patients and 20 Kazakh healthy subjects from Xinjiang were included in this study. T-lymphocytes were isolated from peripheral blood with magnetic cell sorting, the whole-cell currents of Kv1.3 and IKCa1 potassium channels were recorded with patch-clamp technique. RESULTS: (1) The current density of Kv1.3 potassium channel was significantly higher in the hypertensive group [(280 ± 74) pA/pF (n = 39)] than that in the control group [(179 ± 51) pA/pF (n = 38), P < 0.01], while the membrane capacitance was similar between the two groups. (2) The current density of IKCa1 potassium channel was also significantly higher in the hypertensive group [(198 ± 44) pA/pF (n = 28)] than that in the control group [(124 ± 43) pA/pF (n = 26), P < 0.01], while the membrane capacitance was also similar between the two groups. CONCLUSIONS: The T-lymphocytes Kv1.3 potassium channel and IKCa1 potassium channel current densities are higher in hypertensive patients in Xinjiang Kazakh suggesting a potential role of Kv1.3 and IKCa1 potassium channels activation in the pathophysiology of hypertension.
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Hipertensión/fisiopatología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/fisiología , Canal de Potasio Kv1.3/fisiología , Linfocitos T/fisiología , Adulto , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This study aimed to evaluate the correlation between microecology of sediments and water as well as their spatial-temporal variations in Changshou Lake. The results demonstrated that microecology in the lake exhibits spatiotemporal heterogeneity, and microbial diversity of sediments was significantly higher than that of water body. Further, it was found that there was statistically insignificant positive correlation between microecology of sediments and that of water body. PCoA and community structure analysis revealed that the predominant phyla which exhibited significant spatial differences in sediments were Proteobacteria, Actinobacteria and Planctomycetes. While, the distribution of dominant bacteria Actinobacteria and Verrucomicrobia in water body showed significant seasonal differences. Microbial networks analysis indicated that there was a cooperative symbiotic relationship between lake microbial communities. Notably, the same bacterial genus had no significant positive correlation in sediment and water, which suggested that bacteria transport between sediment-water interface does not influence the microecological functions of lake water.
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Bacterias , Agua , Estaciones del Año , Bacterias/genética , Lagos/química , China , Sedimentos Geológicos/química , ARN Ribosómico 16SRESUMEN
OBJECTIVE: To investigate the effect of PDGFRα+ stromal cells derived SCF on hematopoiesis of adult mice. METHODS: Pdgfrα-CreER; R26-tdTomato mice model was constructed, and the proportion and distribution of PDGFRα+ cells in the liver, spleen, lung, kidney and bone marrow were analyzed by flow cytometry and confocal microscopy. Then the Pdgfrα-CreER; Scf flox/flox mice model was further constructed, the Scf in PDGFRα+ was knocked out specifically, the effect of Scf-knocked out in PDGFRα+ stromal cells in the propitiation of HSPCs in the bone marrow was analyzed by flow cytometry. The effect of SCF on the proportion on number of peripheral blood cells in mice was analyzed by whole blood analyzer. RESULTS: After Scf was knocked out in PDGFRα+ stromal cells, the propitiation and number of LKS- cell, LKS+ cell, HSC, MPP1, MKP, PreGM, PreMegE, and CFU-E in the bone marrow of mice was decreased, as well as in the number of red blood cells and hemoglobin concentration of peripheral blood. However, Scf knocked out from PDGFRα+ cells showed no effect on the hematopoiesis in spleen. CONCLUSION: specific knocked out of Scf in PDGFRα+ stromal cells in adult mice can decrease the proportion of HSPCs in the bone marrow and the number of red blood cells in peripheral blood, and finally lead to anemia in mice.
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Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Factor de Células Madre , Animales , Médula Ósea , Células de la Médula Ósea , Hematopoyesis , RatonesRESUMEN
Intercropping is an ancient agricultural practice that provides a possible pathway for sustainable increases in crop yields. Here, we determine how competition with wheat affects nutrient uptake (nitrogen and phosphorus) and leaf traits, such as photosynthetic rate, in maize. In a field experiment, maize was planted as a sole crop, in three different intercrop configurations with wheat (a replacement intercrop and two add-row intercrops), and as a skip-row system with one out of each three maize rows omitted. Nitrogen and phosphorus uptake were determined at flowering and maturity. Specific leaf area, leaf nitrogen concentration, chlorophyll content and photosynthetic rate of the ear leaf were determined at flowering. Nitrogen and phosphorus concentrations were significantly lower in intercropped maize than in sole maize and skip-row maize at flowering, but these differences were smaller at maturity. At flowering, specific leaf area was significantly greater in intercrops than in skip-row maize. Leaf nitrogen concentration was significantly lower in add-row intercrops than in sole maize, skip-row maize or maize in the replacement intercrop. Leaf chlorophyll content was highest in sole and skip-row maize, intermediate in maize in the replacement intercrop and lowest in maize grown in add-row intercrops. On the contrary, photosynthetic rate was significantly higher in the replacement intercrop than in sole maize, skip-row maize and the intercrop with an additional maize row. The findings indicate that competition with intercropped wheat severely constrained nutrient uptake in maize, while photosynthetic rate of the ear leaf was not negatively affected. Possible mechanisms for higher photosynthesis rate at lower leaf nitrogen content in intercropped maize are discussed.
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Two new alpha-tetralone (=3,4-dihydronaphthalen-1(2H)-one) derivatives, berchemiaside A and B (1 and 2, resp.), and one new flavonoid, quercetin-3-O-(2-acetyl-alpha-L-arabinofuranoside (3), together with ten known flavonoids compounds, eriodictyol (4), aromadendrin (5), trans-dihydroquercetin (6), cis-dihydroquercetin (7), kaempferol (8), kaempferol-3-O-alpha-L-arabinofuranoside (9), quercetin (10), quercetin-3-O-alpha-L-arabinofuranoside or avicularin (11), quercetin 3'-methyl ether, 3-O-alpha-L-arabinofuranoside (12), and maesopsin (13), were isolated from the bark of Berchemia floribunda. Their structures were determined by various NMR techniques and chemical studies. Compounds 3-13 were tested for their cytotoxic activity against human leukemia cells. Among them, kaempferol (8) and maesopsin (13) showed significant inhibitory activities against human leukemia cells CCRF-CEM and its multidrug-resistant sub-line, CEM/ADR5000, with IC(50) values of 14.0, 5.3, 10.2, and 12.3 microM, respectively.
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Rhamnaceae/química , Tetralonas/química , Tetralonas/toxicidad , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Corteza de la Planta/químicaRESUMEN
One novel neolignan (tetracentronsine; 1), one new indole alkaloid (=3-(2-hydroxyethyl)-1H-indole-5-O-beta-D-glucopyranoside; 2), and two new phenol derivatives, 3-{2-[(beta-glucopyranosyl)oxy]-4,5-(methylenedioxy)phenyl}propanoic acid (3) and methyl 3-{2-[(beta-glucopyranosyl)oxy]-4,5-(methylenedioxy)phenyl}propanoate (4), together with six known compounds were isolated from the stem bark of Tetracentron sinense. Their structures were determined by spectral analysis, including 1D- and 2D-NMR, and MS analyses. These compounds were tested for their cytotoxic activity against human leukaemia cells in vitro. Among them, compound 2, (E)-3-(4-hydroxyphenyl)-N-[2-(4-hydroxyphenyl)ethyl]prop-2-enamide (5), and maslinic acid (6) showed significant inhibitory activities against human leukaemia cells CCRF-CEM and its multidrug-resistant sub-line, CEM/ADR5000, with IC50 values in a range of 7.1 to 29.7 microM.
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Antineoplásicos Fitogénicos , Glicósidos , Magnoliopsida/química , Plantas Medicinales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Glicósidos/química , Glicósidos/aislamiento & purificación , Glicósidos/farmacología , Humanos , Estructura Molecular , Corteza de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Relación Estructura-ActividadRESUMEN
BACKGROUND AND AIM: Increasing evidence indicates that chronic inflammation is a direct or indirect manifestation of hypertension. Potassium channels are thought to be critical for lymphocyte activation, which suggests that hypertension may be an inflammatory disease initiated at the ion channel level. METHODS: This study investigated changes in interleukin (IL)-6, IL-17, and transforming growth factor beta (TGF-b1) expression in the blood of Kazakh hypertensive patients in Northwest China using ELISA technology. Whole-cell patch clamp technology was used to evaluate current changes associated with Kv1.3 and KCa3.1 in peripheral blood T lymphocytes of hypertensive patients, and to investigate current changes induced by telmisartan. We also investigated the effects of telmisartan on expression of Kv1.3 and KCa3.1 at mRNA and protein levels in peripheral blood T lymphocytes using real-time polymerase chain reaction and Western blot analysis. RESULTS: Expression of IL-6, IL-17 and TGF-b1 in the blood of Kazakh hypertensive patients in Northwest China was significantly higher than in healthy controls (p < 0.05). The current mediated by Kv1.3 and KCa3.1 and the corresponding expression at mRNA and protein levels in T lymphocytes were also higher in these hypertensive patients than in controls (p < 0.05). Telmisartan intervention for 24 h and 48 h inhibited the current and expression of Kv1.3 and KCa3.1 at mRNA and protein levels (p < 0.05). CONCLUSIONS: These results indicated that the increase in functional Kv1.3 and KCa3.1 channels expressed in T lymphocytes of Kazakh patients with hypertension was blocked by telmisartan, resulting in a reduced inflammatory response. These results provide theoretical support for the treatment of hypertension at the cellular ion channel level.
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Bencimidazoles/farmacología , Benzoatos/farmacología , Hipertensión/metabolismo , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/antagonistas & inhibidores , Canal de Potasio Kv1.3/antagonistas & inhibidores , Linfocitos T/metabolismo , Antihipertensivos/farmacología , China , Citocinas/sangre , Femenino , Expresión Génica , Humanos , Hipertensión/sangre , Hipertensión/tratamiento farmacológico , Hipertensión/etnología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/genética , Kazajstán/etnología , Canal de Potasio Kv1.3/genética , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Bloqueadores de los Canales de Potasio/farmacología , Linfocitos T/efectos de los fármacos , TelmisartánRESUMEN
While inflammation is considered a central component in the development in diabetic nephropathy, the mechanism remains unclear. The NLRP3 inflammasome acts as both a sensor and a regulator of the inflammatory response. The NLRP3 inflammasome responds to exogenous and endogenous danger signals, resulting in cleavage of procaspase-1 and activation of cytokines IL-1ß, IL-18, and IL-33, ultimately triggering an inflammatory cascade reaction. This study observed the expression of NLRP3 inflammasome signaling stimulated by high glucose, lipopolysaccharide, and reactive oxygen species (ROS) inhibitor N-acetyl-L-cysteine in glomerular mesangial cells, aiming to elucidate the mechanism by which the NLRP3 inflammasome signaling pathway may contribute to diabetic nephropathy. We found that the expression of thioredoxin-interacting protein (TXNIP), NLRP3, and IL-1ß was observed by immunohistochemistry in vivo. Simultaneously, the mRNA and protein levels of TXNIP, NLRP3, procaspase-1, and IL-1ß were significantly induced by high glucose concentration and lipopolysaccharide in a dose-dependent and time-dependent manner in vitro. This induction by both high glucose and lipopolysaccharide was significantly inhibited by N-acetyl-L-cysteine. Our results firstly reveal that high glucose and lipopolysaccharide activate ROS/TXNIP/ NLRP3/IL-1ß inflammasome signaling in glomerular mesangial cells, suggesting a mechanism by which inflammation may contribute to the development of diabetic nephropathy.
Asunto(s)
Glucemia/análisis , Proteínas Portadoras/metabolismo , Inflamasomas/metabolismo , Células Mesangiales/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/sangre , Acetilcisteína/farmacología , Animales , Caspasa 1/metabolismo , Proteínas de Ciclo Celular , Glucosa/metabolismo , Inmunohistoquímica , Inflamación , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Masculino , Distribución Aleatoria , Ratas , Especies Reactivas de Oxígeno , Transducción de SeñalRESUMEN
OBJECTIVE: To explore the efficacy of Ruiyun procedure for hemorrhoids (RPH) combined with Xiaozhiling injection in the treatment of hemorrhoids complicated with human immunodeficiency virus (HIV) infection and its influence on cellular immune function. METHODS: Clinical data of 76 hemorrhoid patients, including 36 positive HIV and 40 negative HIV, undergoing RPH combined with Xiaozhiling injections in our center from January 2010 to December 2012 were retrospectively analyzed. Clinical efficacy and cellular immune function preoperative day 1, postoperative day 7, 30 were compared between positive and negative groups. RESULTS: Recurrence rates of positive group and negative group postoperative 6 months were 22.2% (8/36) and 22.5% (9/40), postoperative 1 year were 30.6% (11/36) and 30.0% (12/40) without significant differences (all P>0.05). Morbidity of postoperative complication was also not significantly different between two groups (P>0.05). According to HIV classification, peripheral lymph cell ratio, CD4 count, CD4/CD8, white blood cell count and neutrophil ratio were not significantly different between preoperative day 1 and postoperative day 7 in both groups (all P>0.05). Decreasing velocity and amplitude of CD4 in both groups from high to low was HIV III, HIV II, HIV I, HIV-, while after 30 days the increase of CD4 from high to low was HIV-, HIV I, HIV II, HIV III, which were significantly different as compared to postoperative day 7 (all P<0.05). CONCLUSIONS: RPH combined with Xiaozhiling injection in the treatment of hemorrhoids complicated with HIV infection is effective and safe. Postoperative inhibited cellular immune function can recover quickly.
Asunto(s)
Infecciones por VIH/complicaciones , Hemorroides/tratamiento farmacológico , Recuento de Linfocito CD4 , Hemorroides/cirugía , Humanos , Complicaciones Posoperatorias , Recurrencia , Estudios RetrospectivosRESUMEN
Recent studies have shown that sumoylation is a posttranslational modification involved in regulation of the transforming growth factor-ß (TGF-ß) signaling pathway, which plays a critical role in renal fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of TGF-ß signaling in DN is still unclear. In the present study, we investigated the expression of SUMO (SUMO1 and SUMO2/3) and Smad4 and the interaction between SUMO and Smad4 in cultured rat mesangial cells induced by high glucose. We found that SUMO1 and SUMO2/3 expression was significantly increased in the high glucose groups compared to the normal group (P < 0.05). Smad4 and fibronectin (FN) levels were also increased in the high glucose groups in a dose-dependent manner. Coimmunoprecipitation and confocal laser scanning revealed that Smad4 interacted and colocalized with SUMO2/3, but not with SUMO1 in mesangial cells. Sumoylation (SUMO2/3) of Smad4 under high glucose condition was strongly enhanced compared to normal control (P < 0.05). These results suggest that high glucose may activate TGF- ß/Smad signaling through sumoylation of Samd4 by SUMO2/3 in mesangial cells.
Asunto(s)
Glucosa/farmacología , Células Mesangiales/metabolismo , Proteína Smad4/metabolismo , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/metabolismo , Sumoilación/efectos de los fármacos , Animales , Línea Celular , Fibronectinas/genética , Fibronectinas/metabolismo , Regulación de la Expresión Génica , Células Mesangiales/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina/genéticaRESUMEN
Transforming growth factor-ß (TGF-ß) has been shown to be involved in diabetic nephropathy (DN). The SnoN protein can regulate TGF-ß signaling through interaction with Smad proteins. Recent studies have shown that SnoN is mainly degraded by the ubiquitin-proteasome pathway. However, the role of SnoN in the regulation of TGF- ß/Smad signaling in DN is still unclear. In this study, diabetic rats were randomly divided into a diabetic control group (DC group) and a proteasome inhibitor (MG132) diabetes therapy group (DT group). Kidney damage parameters and the expression of SnoN, Smurf2, and TGF-ß were observed. Simultaneously, we cultured rat glomerular mesangial cells (GMCs) stimulated with high glucose, and SnoN and Arkadia expression were measured. Results demonstrated that 24-hour urine protein, ACR, BUN, and the expression of Smurf2 and TGF- ß were significantly increased (P < 0.05), whereas SnoN was significantly decreased in the DC group (P < 0.05). However, these changes diminished after treatment with MG132. SnoN expression in GMCs decreased significantly (P < 0.05), but Arkadia expression gradually increased due to high glucose stimulation (P < 0.05), which could be almost completely reversed by MG132 (P < 0.05). The present results support the hypothesis that MG132 may alleviate kidney damage by inhibiting SnoN degradation and TGF-ß activation, suggesting that the ubiquitin-proteasome pathway may become a new therapeutic target for DN.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Leupeptinas/farmacología , Leupeptinas/uso terapéutico , Proteínas del Tejido Nervioso/metabolismo , Inhibidores de Proteasoma/farmacología , Inhibidores de Proteasoma/uso terapéutico , Proteolisis/efectos de los fármacos , Factores de Transcripción/metabolismo , Animales , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/fisiopatología , Regulación hacia Abajo/efectos de los fármacos , Glucosa/toxicidad , Pruebas de Función Renal , Glomérulos Renales/patología , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Células Mesangiales/patología , Proteinuria/complicaciones , Proteinuria/patología , Proteinuria/fisiopatología , Ratas Wistar , Estreptozocina , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Potato-sunflower intercropping is a prevailing cropping system in the agricultural and pastoral ecotone in China. To precisely simulate the crop phenology in the intercropping system is of significance for the assessment and optimization of intercropping systems. In this paper, the simulation model for the development stages of sunflower and potato in monoculture and intercropping was established, based on the crop's physiological development time, and validated with the field experimental data from 2010 to 2011. A good fitness was observed between the simulated and observed values of the crop's development stages. The root mean square error (RMSE) of the development stages from sowing to emergence, emergence to flowering, flowering to mature, and from sowing to mature was 1.2, 2.9, 2.4 and 2.6 d, respectively, with the prediction error lower than 5%. The model was strong on mechanistic, explanation and adaptability, and could be applied as a good tool in the researches of crop growth and development.