RESUMEN
Nitrous oxide (N2 O) was previously deemed as a potent greenhouse gas but is actually an untapped energy source, which can accumulate during the microbial denitrification of nitric oxide (NO). Compared with the organic electron donor required in heterotrophic denitrification, elemental sulfur (S0 ) is a promising electron donor alternative due to its cheap cost and low biomass yield in sulfur-driven autotrophic denitrification. However, no effort has been made to test N2 O recovery from sulfur-driven denitrification of NO so far. Therefore, in this study, batch and continuous experiments were carried out to investigate the NO removal performance and N2 O recovery potential via sulfur-driven NO-based denitrification under various Fe(II)EDTA-NO concentrations. Efficient energy recovery was achieved, as up to 35.5%-40.9% of NO was converted to N2 O under various NO concentrations. N2 O recovery from Fe(II)EDTA-NO could be enhanced by the low bioavailability of sulfur and the acid environment caused by sulfur oxidation. The NO reductase (NOR) and N2 O reductase (N2 OR) were inhibited distinctively at relatively low NO levels, leading to efficient N2 O accumulation, but were suppressed irreversibly at NO level beyond 15 mM in continuous experiments. Such results indicated that the regulation of NO at a relatively low level would benefit the system stability and NO removal capacity during long-term system operation. The continuous operation of the sulfur-driven Fe(II)EDTA-NO-based denitrification reduced the overall microbial diversity but enriched several key microbial community. Thauera, Thermomonas, and Arenimonas that are able to carry out sulfur-driven autotrophic denitrification became the dominant organisms with their relative abundance increased from 25.8% to 68.3%, collectively.
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Desnitrificación/fisiología , Microbiota , Óxido Nítrico , Óxido Nitroso , Azufre/metabolismo , Procesos Autotróficos/fisiología , Microbiota/genética , Microbiota/fisiología , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Óxido Nitroso/análisis , Óxido Nitroso/metabolismoRESUMEN
Chemical absorption-biological reduction based on Fe(II)EDTA is a promising technology to remove nitric oxide (NO) from flue gases. However, limited effort has been made to enable direct energy recovery from NO through production of nitrous oxide (N2O) as a potential renewable energy rather than greenhouse gas. In this work, the enhanced energy recovery in the form of N2O via biological NO reduction was investigated by conducting short-term and long-term experiments at different Fe(II)EDTA-NO and organic carbon levels. The results showed both NO reductase and N2O reductase were inhibited at Fe(II)EDTA-NO concentration up to 20 mM, with the latter being inhibited more significantly, thus facilitating N2O accumulation. Furthermore, N2O accumulation was enhanced under carbon-limiting conditions because of electron competition during short-term experiments. Up to 47.5% of NO-N could be converted to gaseous N2O-N, representing efficient N2O recovery. Fe(II)EDTA-NO reduced microbial diversity and altered the community structure toward Fe(II)EDTA-NO-reducing bacteria-dominated culture during long-term experiments. The most abundant bacterial genus Pseudomonas, which was able to resist the toxicity of Fe(II)EDTA-NO, was significantly enriched, with its relative abundance increased from 1.0 to 70.3%, suggesting Pseudomonas could be the typical microbe for the energy recovery technology in NO-based denitrification.
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Óxido Nítrico , Óxido Nitroso , Carbono , Desnitrificación , GasesRESUMEN
BACKGROUND: Resistant starch (RS) has health benefits and can be used as a functional ingredient in various food products. Kansas hard red winter (HRW) wheat is conventionally used for bread making and this is attributed to its strong gluten network. To develop Asian white salted noodles with a high RS content, HRW wheat flour was partially replaced with cross-linked phosphorylated RS4 wheat starch. Vital wheat gluten or wheat protein isolate was added to compensate for textural changes due to the addition of RS. RESULTS: The maximum recommended level of RS4 starch to replace HRW wheat flour was 40%. The substitution of 10-40 parts of RS4 for flour did not change hardness in cooked noodles but it did reduce their extensibility, cohesiveness, and springiness, which was probably due to the non-swelling properties of RS4. At 40 parts of RS4 replacement, supplementation of 2-8 parts of vital wheat gluten or wheat protein isolate in the composite flour notably enhanced the hardness and extensibility of cooked noodles, whereas cohesiveness and springiness were minimally affected. Supplemental vital wheat gluten produced a thicker protein network than endogenous protein or added wheat protein isolate, giving cooked noodles greater breaking force and distance. CONCLUSION: RS4 could be used as a functional ingredient to replace up to 40% of hard wheat flour for making Asian noodles while maintaining their hardness after cooking. The extensibility of cooked noodles with high RS4 could be noticeably enhanced by supplementation with vital wheat gluten in the composite flour (RS/flour = 40/60). © 2020 Society of Chemical Industry.
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Harina/análisis , Manipulación de Alimentos/métodos , Almidón/química , Triticum/química , Pan/análisis , Culinaria , Glútenes/química , Dureza , Fosforilación , Triticum/clasificaciónRESUMEN
Colon cancer is one of the most life-threatening malignancies worldwide. Long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is a cancer-associated biomarker involved in the metastasis and prognosis of several cancers. However, whether and how HOTAIR affects colon cancer progression is still unclear. Consequently, we used RNA interference to knock down HOTAIR to explore its effects on human colon cancer cells. The dual luciferase reporter gene assay was initially used for testify the regulating relationship between lncRNA HOTAIR and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). We determined the expressions of HOTAIR, IGF2BP2, E-cadherin, and vimentin. Meanwhile, cell growth, cycle and apoptosis, migration, and invasion were assayed. LoVo cells were transplanted into nude mice, and tumor formation and microvessel density were evaluated. LncRNA HOTAIR positively regulated IGF2BP2. Besides, the expressions of HOTAIR and E-cadherin and the apoptosis were increased, while the expressions of IGF2BP2 and vimentin, the growth, invasion and migration of LoVo cells, the average tumor weight, and microvessel density value were decreased. Of importance, overexpressed IGF2BP2 could reverse the above impacts. Taken together, the current study indicates that silencing of HOTAIR could inhibit the invasion, proliferation, and migration, and promote apoptosis of colon cancer LoVo cells through suppressing IGF2BP2 and the epithelial-mesenchymal transition.
RESUMEN
BACKGROUND: Glutathione S-transferase omega 1 (GSTO1), as a member of the glutathione S-transferase (GST) family genes, has been discovered to be up-regulated in several cancer cell lines which exhibited strong aggressiveness. However, the function of GSTO1 on cutaneous malignant melanoma (CMM) has not been illuminated. METHODS: Outcome of expression level and prognosis of GSTO1 were obtained from Oncomine and TCGA database. The specific effects of GSTO1 on the characteristics and regulatory mechanism of CMM cells were demonstrated by cell counting kit-8, colony formation, flow cytometry, and transwell assays in vitro. Western blot was employed to analyze the expression of proliferating cell nuclear antigen (PCNA), p53 and epithelial-to-mesenchymal (EMT) related proteins. RESULTS: We observed that GSTO1 was up-regulated in CMM samples when compared with the corresponding controls. Moreover, patients in CMM with high expression of GSTO1 were more likely to have a poor prognosis. Through in vitro experiments, silenced GSTO1 resulted in inhibition of CMM cells growth and aggressiveness, increased cell apoptosis, and blocked cell cycle. Finally, the expression of PCNA, p53 and EMT-related proteins were changed due to reduction of GSTO1. CONCLUSIONS: To sum up, our outcomes exhibited that weakening GSTO1 reduced the proliferation and mobility of CMM cells, increased the apoptosis ability of CMM cells, and arrested cell cycle at G1 phase, which can be achieved by affecting the expression of PCNA, p53 and the EMT process. This discovery provided a new perspective for elucidating the mechanism of CMM, and offered theoretical support for searching clinical therapeutic targets in the future.
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Glutatión Transferasa/metabolismo , Melanoma/metabolismo , Neoplasias Cutáneas/metabolismo , Apoptosis/fisiología , Ciclo Celular/fisiología , Línea Celular , Línea Celular Tumoral , Proliferación Celular/fisiología , Transición Epitelial-Mesenquimal/fisiología , Humanos , Melanoma/patología , Pronóstico , Antígeno Nuclear de Célula en Proliferación/metabolismo , Neoplasias Cutáneas/patología , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/fisiología , Melanoma Cutáneo MalignoRESUMEN
This study aims to investigate the effects of glucose transport l (Glut1) gene on proliferation, differentiation, and apoptosis of colorectal cancer (CRC) cells by regulating the TGF-ß/PI3K-AKT-mTOR signaling pathway. Immunohistochemistry was conducted to detect the positive Glut1 expression. Normal human CRC epithelial cells (CCD-18Co) and CRC cell line HCT116 were grouped into the control, blank, negative control (NC), and shGlut1-1 groups. RT-qPCR and Western blotting were performed to detect the expressions of Glut1, TGF-ß1, PI3K, AKT, PTEN, mTOR, Bcl-2, and Bax. Protein expression of phosphorylated-PI3K (p-PI3K), p-S473-AKT, p-S389-S6K1, p-T70-4EBP1, Cleaved caspase-3 and Cleaved-PARP were detected. MTT assay, flow cytometry, and colony formation assay were performed in order to detect cell viability, cell cycle, and apoptosis, respectively. The positive expression rate of Glut1 in CRC tissues was 75% ± 8%, while in the adjacent normal tissues it was 0%. In comparison to adjacent normal tissues, CRC tissues had increased Glut1, TGF-ß1, PI3K, AKT, mTOR, and Bcl-2 expressions, and p-PI3K, p-S473-AKT, p-S389-S6K1, and p-T70-4EBP1 expressions; and decreased PTEN, Bax, Cleaved caspase-3, and Cleaved-PARP expressions. In comparison with the blank and NC groups, cells in the shGlut1-1 group showed decreased Glut1, TGF-ß1, PI3K, AKT, mTOR, and Bcl-2 expressions, and p-PI3K, p-S473-AKT, p-S389-S6K1, and p-T70-4EBP1 expressions; and increased PTEN, Bax, Cleaved caspase-3, and Cleaved-PARP expressions, along with more arrested cells in C0/C1 phase than in S phase and slower cell growth. These results suggested that silencing the Glut1 gene inhibited proliferation and promoted apoptosis of CRC cells by inactivating TGF-ß/PI3K-AKT-mTOR signaling pathway.
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Neoplasias Colorrectales/genética , Silenciador del Gen , Transportador de Glucosa de Tipo 1/genética , Transducción de Señal , Apoptosis , Diferenciación Celular , Línea Celular , Proliferación Celular , Supervivencia Celular , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Objective To explore the expressions of inhibitors of DNA binding-1 (Id-1) and matrix metalloproteinase-9 (MMP-9) in colorectal carcinoma tissues and its correlation with microvessel density (MVD). Methods The expressions of Id-1 and MMP-9 as well as CD34-labelled MVD in colorectal adenocarcinoma tissues (n=50) and normal adjacent tissues (n=50) were examined by immunohistochemistry. Results The positive expressions of Id-1 and MMP-9 were seen in 72.00% (36/50) and 78.00%(39/50) of colorectal adenocarcinoma tissues,which were significantly higher than those [24.00%(12/50) and 28.00% (14/50)] in normal adjacent tissues (P=0.000). The MVD value (17.22±2.08) in colorectal adenocarcinoma tissues was significantly higher than that (5.36±2.17) in normal adjacent tissues (P=0.000). The expressions of Id-1 and MMP-9 and MVD were significantly correlated with serosa invasion,TNM stage,carcinoembryonic antigen(+),lymph node metastasis,vascular invasion,and liver metastasis (all P<0.05) but not with the patient's age,gender,tumor size,and differentiation degree (all P>0.05). The MVD value with Id-1 and MMP-9 positive expression were significantly higher than those with Id-1 and MMP-9 negative expression (all P=0.000). The expression of Id-1 in colorectal adenocarcinoma tissues showed significantly positive correlation with that of MMP-9 (r=0.429,P=0.000). Cox multivariate analysis showed that Id-1 and MMP-9 expressions were independent prognostic factors for colorectal carcinoma. Conclusions The high expressions of Id-1 and MMP-9 have high correlations with the development and progression of colorectal adenocarcinoma and have positive correlation with MVD. Both of them may be involved in the microvascular generation and the invasion and hematogenous metastasis of colorectal carcinoma.
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Adenocarcinoma/metabolismo , Neoplasias Colorrectales/metabolismo , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Neovascularización Patológica , Adenocarcinoma/irrigación sanguínea , Neoplasias Colorrectales/irrigación sanguínea , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Neoplasias Hepáticas , Metástasis Linfática , Microcirculación , MicrovasosRESUMEN
BACKGROUND: Acute liver failure (ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats. METHODS: All rats were randomly divided into control, model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+ D-galactosamine+lipopolysaccharide. After induction of ALF, the rats in the treatment group received sodium butyrate (500 mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1 (HMGB1), liver function parameters, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were measured. The expression of HMGB1 and nuclear factor-kappa B (NF-kappaB) p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed. RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1, TNF-alpha and IFN-gamma were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group (P<0.05). Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-kappaB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF (P<0.05). CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.
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Ácido Butírico/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Fallo Hepático Agudo/prevención & control , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Animales , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Galactosamina , Proteína HMGB1/sangre , Mediadores de Inflamación/sangre , Interferón gamma/sangre , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Lipopolisacáridos , Hígado/metabolismo , Hígado/ultraestructura , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/patología , Permeabilidad , Ratas Wistar , Albúmina Sérica , Albúmina Sérica Humana , Factores de Tiempo , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.
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Linfocitos T CD4-Positivos/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Productos Finales de Glicación Avanzada/farmacología , Células TH1/efectos de los fármacos , Células Th17/efectos de los fármacos , Adulto , Animales , Western Blotting , Linfocitos T CD4-Positivos/metabolismo , Bovinos , Células Cultivadas , Glucosa/farmacología , Células HEK293 , Humanos , Interferón gamma/metabolismo , Interleucina-17/metabolismo , PPAR gamma/agonistas , PPAR gamma/genética , PPAR gamma/metabolismo , Prostaglandina D2/análogos & derivados , Prostaglandina D2/farmacología , Interferencia de ARN , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/genética , Receptores Inmunológicos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Albúmina Sérica Bovina/farmacología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Células TH1/metabolismo , Células Th17/metabolismoRESUMEN
Cadmium (Cd) and sulfamethoxazole (SMX) frequently coexist in farmlands, yet their synergistic toxicological impacts on terrestrial invertebrates remain unexplored. In this study, earthworms were exposed to artificial soils percolated with Cd (5 mg/kg), SMX (5 mg/kg) or combination of them for 7 days, followed by a 12-day elimination phase in uncontaminated soil. The uptake of Cd and SMX by the earthworms, along with their subcellular distribution, was meticulously analyzed. Additionally, a suite of biomarkers-including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and weight loss-were evaluated to assess the health status of the earthworms and the toxicological effects of the Cd and SMX mixture. Notably, the cotreatment with Cd and SMX resulted in a significantly higher weight loss in Eisenia fetida (41.25 %) compared to exposure to Cd alone (26.84 %). Moreover, the cotreatment group exhibited substantially higher concentrations of Cd in the total internal body, fraction C (cytosol), and fraction E (tissue fragments and cell membranes) in Eisenia fetida compared to Cd alone counterparts. The combined exposure also significantly elevated the SMX levels in the total body and fraction C compared with the SMX-only treated earthworms. Additionally, Eisenia fetida subjected to the combined treatment showed markedly increased activities of SOD, CAT, and MDA compared to those treated with Cd alone. The effect addition indices (EAIs), ranging from 1.00 to 2.23, unequivocally demonstrated a synergistic effect of the combined treatments. Interestingly, relocating the earthworms to clean soil did not mitigate the observed adverse effects. These findings underscore the increased risk posed by the Cd-SMX complex to terrestrial invertebrates in agricultural areas.
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Biomarcadores , Cadmio , Oligoquetos , Contaminantes del Suelo , Sulfametoxazol , Oligoquetos/efectos de los fármacos , Oligoquetos/fisiología , Animales , Sulfametoxazol/toxicidad , Cadmio/toxicidad , Contaminantes del Suelo/toxicidad , Biomarcadores/metabolismo , Malondialdehído/metabolismo , Superóxido Dismutasa/metabolismo , Catalasa/metabolismoRESUMEN
OBJECTIVE: High-mobility group box-1 (HMGB1) is identified as an extracellularly released mediator of inflammation. In this study, specific monoclonal anti-HMGB1 antibody was administered to rats with acute on chronic liver failure (ACLF) in order to evaluate the therapeutic efficacy of HMGB1 blockade. METHODS: All animals were randomly divided into control group, model group and anti-HMGB1 antibody group. The changes in liver histology and apoptosis of liver tissue were detected by H&E staining and TUNEL assay, respectively. The serum levels of alanine aminotransferase (ALT), endotoxin, HMGB1, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were examined. The hepatic levels of HMGB1, caspase3, Toll-like receptor 4 (TLR4) and p65 subunit of NF-κB (P65) were also determined. RESULTS: Changes in liver pathology and liver cell apoptosis were greatly attenuated in the anti-HMGB1 antibody group compared with the model group. The serum levels of ALT, endotoxin, TNF-α, IFN-γ and HMGB1 were also decreased in the anti-HMGB1 antibody group. Furthermore, the hepatic levels of HMGB1, TLR4, caspase3 and P65 were also down-regulated by HMGB1 blockade. CONCLUSION: Blockade of HMGB1 can confer a protective effect against ACLF in rats, even 24 h after induction of ACLF. The protective effect of HMGB1 blockade is associated with interactions of HMGB1 with the TLR4 signaling pathway and cytokine production.
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Anticuerpos Monoclonales/uso terapéutico , Proteína HMGB1/antagonistas & inhibidores , Fallo Hepático/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Alanina Transaminasa/sangre , Animales , Anticuerpos Monoclonales/farmacología , Antígeno CD24 , Proteína HMGB1/inmunología , Proteína HMGB1/metabolismo , Interferón gamma/sangre , Lipopolisacáridos , Fallo Hepático/metabolismo , Masculino , Sustancias Protectoras/farmacología , Ratas , Ratas Wistar , Receptor Toll-Like 4/metabolismo , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/sangreRESUMEN
BACKGROUND: The tumor-draining lymph node (TDLN) is the critical and initial site of the immune decision made between activation and tolerance to tumor antigens. Tumor-reactive lymphadenopathy in TDLN has been observed for decades, but the profiles of immune regulation in these nodes remain unclear. MATERIALS AND METHODS: Both regulatory T cells (Tregs) and effector T cells were examined using 6 × 10(5) Hepa1-6 hepatocellular carcinoma cells implanted in footpads of syngeneic C57BL/6J mice, which formed TDLN. FOXP3(+) Tregs and CD8(+) T cells in TDLN were detected by immunohistochemical staining. The frequency of CD4(+)FOXP3(+) T cells and FOXP3 mRNA expression were determined by flow cytometry and real-time quantitative polymerase chain reaction. The interferon γ secretion ability of CD8(+) T cells in TDLN was measured by enzyme-linked immunospot technique. RESULTS: There was significant expansion of Tregs and CD8(+) T cells in the tumor-draining popliteal lymph node compared with nondraining popliteal lymph node and spleen in the same mouse. Tregs were diffusely distributed in the CD8(+) T cell compartment. The CD8(+) T cells primed in TDLN showed a strong ability of interferon γ secretion via in vitro stimulation. CONCLUSIONS: These findings support the notion that Tregs suppress CD8(+) T cells by secreting cytokines such as transforming growth factor ß and interleukin 10, but do not make CD8(+) T cells lose function in the TDLN. Deletion of Tregs at the secondary lymphoid organs could be crucial for the establishment of a tumor-specific immunotherapy.
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Linfocitos T CD8-positivos/patología , Carcinoma Hepatocelular/patología , Interferón gamma/metabolismo , Neoplasias Hepáticas/patología , Ganglios Linfáticos/patología , Linfocitos T Reguladores/patología , Animales , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/metabolismo , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Tolerancia Inmunológica , Interleucina-10/metabolismo , Neoplasias Hepáticas/metabolismo , Ganglios Linfáticos/metabolismo , Ratones , Ratones Endogámicos C57BL , Linfocitos T Reguladores/metabolismo , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Previous studies have shown that betaine prevents alcohol-induced liver injury and improves liver function. The purpose of this study was to investigate the hepatoprotective effects of betaine on nonalcoholic fatty liver disease (NAFLD) and to observe changes of HMGB1/TLR4 signaling. METHODS: Thirty rats were randomly divided into control, model, and betaine groups. The rats in the model and betaine groups were fed a high-fat diet for 12 weeks to induce an animal model of NAFLD. The rats in the betaine group were then intragastrically administered betaine solution at a dose of 400 mg/kg per day for four weeks. Liver histology was examined. Serum levels of ALT, AST, TC, TG, HDL-C, LDL-C, FFA, HMGB1, NF-κB, TLR4, and tHcy were determined and intrahepatic TC, TG, and Hcy levels were assayed. mRNA expression and protein levels of HMGB1, NF-κB, and TLR4 in liver tissue were also determined. RESULTS: Compared with the control group, rats in the model group developed severe liver injury, accompanied by significant increases in serum levels of ALT, AST, TC, TG, LDL-C, FFA, HMGB1, NF-κB, and TLR4, intrahepatic TC, TG, and Hcy content, histological scores for steatosis, inflammation, and necrosis, and mRNA expression and protein levels of HMGB1, NF-κB, and TLR4, and a significant decrease in serum HDL-C (P < 0.05). Compared with the model group, all these indicators were significantly improved by administration of betaine (P < 0.05). CONCLUSIONS: Betaine effectively protects against high-fat-diet-induced NAFLD and improves liver function; the mechanism is probably related to inhibition of HMGB1/TLR4 signaling pathways.
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Betaína/farmacología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Grasas de la Dieta/efectos adversos , Regulación de la Expresión Génica/fisiología , Dominios HMG-Box/fisiología , Receptor Toll-Like 4/metabolismo , Animales , Citocinas/genética , Citocinas/metabolismo , Hígado Graso/prevención & control , Femenino , Dominios HMG-Box/genética , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico , Ratas , Ratas Sprague-Dawley , Organismos Libres de Patógenos Específicos , Receptor Toll-Like 4/genética , Aumento de PesoRESUMEN
BACKGROUND: The pathogenesis and progression of acute liver failure (ALF) are closely associated with intestinal endotoxemia because of the high permeability of the intestinal wall. Treatment with ethyl pyruvate (EP) has been shown to protect liver failure effectively. The current study aimed to explore the relationship between proinflammatory cytokines and intestinal permeability, and to investigate whether EP administration might prevent the release of multiple proinflammatory cytokines and decrease intestinal permeability and therefore, protect the liver from injury. METHODS: The ALF model was induced by D-galactosamine in rats. The rats were randomly divided into control (saline, i.p.), model (D-galactosamine, 1.2 g/kg, i.p.), prevention [EP injection (40 mg/kg) 2 hours ahead of D-galactosamine] and treatment groups (EP injection 2 hours after D-galactosamine). Samples were obtained at 12 and 24 hours after ALF induction, respectively. The histology of liver and intestinal tissue was assessed. Serum alanine aminotransferase, endotoxin, D(-)-lactate, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and high mobility group box-1 (HMGB1) were evaluated. The survival of rats was also recorded. RESULTS: The rats in model group showed severe damage to liver tissue and intestinal mucosa 12 and 24 hours after ALF induction. EP significantly improved liver or intestinal injury. In addition, serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels were significantly increased in the model group compared with the control group. There was a positive correlation between intestinal permeability and proinflammatory cytokines. EP significantly reduced serum endotoxin, D(-)-lactate, DAO, TNF-alpha, IFN-gamma and HMGB1 levels. The median survival time was significantly prolonged in both prevention and treatment groups (126 and 120 hours compared with 54 hours in the model group). CONCLUSIONS: EP has protective and therapeutic effects on intestinal mucosa. EP decreases intestinal permeability, and inhibits the release of multiple proinflammatory cytokines in rats with ALF.
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Antiinflamatorios/farmacología , Traslocación Bacteriana/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Endotoxinas/sangre , Galactosamina , Mediadores de Inflamación/sangre , Mucosa Intestinal/efectos de los fármacos , Fallo Hepático Agudo/tratamiento farmacológico , Piruvatos/farmacología , Animales , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/microbiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citoprotección , Modelos Animales de Enfermedad , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Hígado/efectos de los fármacos , Hígado/patología , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/inmunología , Fallo Hepático Agudo/microbiología , Fallo Hepático Agudo/patología , Masculino , Permeabilidad , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Cisplatin is one of the most widely used chemical drugs for anticancer treatment. Recent studies have focused on the ability of cisplatin to retain the high mobility group box 1 (HMGB1) protein in cisplatin-DNA adducts, thereby preventing its release from the nucleus. Because HMGB1 is a powerful inflammatory mediator in many diseases, the aim of this study is to evaluate the therapeutic effect of cisplatin acute liver failure. In this study, low-dose cisplatin was administered to treat PMA-induced macrophage-like cells induced by PMA and rats with acute liver failure. We found that cell viability and liver injury were greatly improved by cisplatin treatment. The extracellular levels of HMGB1, TNF-α and IFN-γ were also significantly decreased by the administration of cisplatin. During inflammation, nuclear HMGB1 translocates from the nucleus to the cytoplasm. The administration of cisplatin reduced the cytoplasmic levels of HMGB1 and increased nuclear HMGB1 levels in vitro and in vivo. In conclusion, cisplatin can protect against acute liver failure by retaining HMGB1 in the nucleus and preventing its release into the extracellular milieu.
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Núcleo Celular/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Citoprotección/efectos de los fármacos , Proteína HMGB1/metabolismo , Fallo Hepático Agudo/tratamiento farmacológico , Alanina Transaminasa/sangre , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Núcleo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Citocinas/biosíntesis , Fallo Hepático Agudo/sangre , Fallo Hepático Agudo/enzimología , Fallo Hepático Agudo/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratas Wistar , Análisis de Supervivencia , Factores de TiempoRESUMEN
To reclaim nitrous oxide (N2O) as an energy resource economically, this study developed an autotrophic denitrification-based system with thiosulfate (S2O32-) and nitric oxide (NO) as electron donor and acceptor, respectively. NO from flue gases is absorbed on Fe(II)EDTA to overcome its low solubility in liquid phase by forming Fe(II)EDTA-NO. Short-term batch tests and long-term continuous experiments were conducted to investigate the N2O production profile and NO conversion efficiency from thiosulfate-based denitrification under varied Fe (II)EDTA-NO conditions (5-20 mM). Up to 39% of NO was converted to gaseous N2O at 20 mM Fe(II)EDTA-NO amid batch test due to the inhibition of key enzymatic activities by NO and the acidic conditions following thiosulfate oxidation. Higher Fe(II)EDTA-NO levels induced lower enzymatic activities with N2OR being suppressed harder than NOR. Microbial diversity was reduced in the continuous thiosulfate-driven Fe(II)EDTA-NO-based denitrification system. NO-resistant bacteria and sulfide-tolerant denitrifiers were enriched, facilitating NO conversion to N2O thereafter.
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Desnitrificación , Tiosulfatos , Procesos Autotróficos , Reactores Biológicos , Electrones , Óxido Nítrico , Óxido NitrosoRESUMEN
INTRODUCTION: Chronic hepatitis B (CHB) virus (HBV) infection has emerged as a global health burden affecting nearly 292 million people. Tenofovir alafenamide (TAF) is an effective treatment for CHB patients. However, the detailed mechanism underlying the antiviral activity of TAF remains unclear. METHODS: In this study, we investigated the antiviral effect of exosomes derived from the serum of CHB patients treated with TAF (Exo-serum) and TAF-treated macrophages (MP) (Exo-MP(TAF)). RESULTS: RNAseq analysis was also performed to determine the associated long non-coding RNAs (lncRNAs). The results demonstrated that both Exo-serum and Exo-MP(TAF) could be taken up by HepAD38 cells and exhibited potent antiviral activities, as manifested by significantly downregulating the levels of hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and covalently closed circular DNA. The antiviral effect of Exo-serum was more potent than those of TAF treatment alone. RNAseq analysis revealed that lncRNA HOTTIP was upregulated significantly in Exo-serum. Further, lncRNA HOTTIP knockdown reversed the antiviral effect of Exo-MP(TAF) on HepAD38 cells, whereas lncRNA HOTTIP knockdown exerted the opposite roles. DISCUSSION: Taken together, these results suggest that exosomal lncRNA HOTTIP is essential for the antiviral activity of TAF and provide a novel understanding of the exosome-mediated mechanism underlying HBV infection.
RESUMEN
A number of thrips species are among the most significant agricultural pests globally. Use of repellent intercrop plants is one of the key components in plant-based 'push-pull' strategies to manage pest populations. In this study, the behavioral responses of three thrips species, Frankliniella occidentalis (Pergande), Frankliniella intonsa (Trybom), and Thrips palmi Karny (Thysanoptera: Thripidae) to Rosmarinus officinalis were investigated in Y-tube olfactometer bioassays and cage experiments. In addition, the major volatile compounds from rosemary were identified and the effect of the individual compounds on thrips behavior was evaluated. Females and males of the three thrips species were significantly repelled by the volatiles from cut rosemary leaves. The presence of rosemary plants significantly reduced settlement of females of the three thrips species and eggs laid by F. occidentalis females on target host plants. In total, 47 compounds were identified in the volatiles collected from the cut leaves of rosemary plants. The responses of the three thrips species to 10 major volatile compounds showed significant differences. However, α-pinene, the most abundant volatile, was repellent to F. occidentalis and F. intonsa. Eucalyptol, the second most abundant volatile, showed significant repellent activity to all the three thrips species. Our findings showed that rosemary is a promising repellent plant against the three thrips pests we tested, which could be a good candidate for 'push' plants in plant-based 'push-pull' strategies. The identified volatile compounds that accounted for the repellent activity could be developed as repellents for sustainable thrips management.
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Repelentes de Insectos , Lamiaceae , Lamiales , Rosmarinus , Thysanoptera , Animales , Femenino , MasculinoRESUMEN
Due to the environmental risks caused by microplastics, understanding the sources and characteristics of microplastics and cutting off their routes into the environment are crucial. However, so far, studies on microplastics in the landfill leachate system (a major pathway of microplastics into the environment) are still limited, especially for tiny particles <50 µm that might have higher risks to the environment. This study investigated the microplastics in landfill leachate and in leachate treatment works, with a size detection limit down to 10 µm. The results showed that the microplastics particle and mass concentrations in the untreated leachate were 235.4 ± 17.1 item/L and 11.4 ± 0.8 µg/L, respectively, with tiny particles (<50 µm) accounting for over 50%. Overall, 27 polymeric materials were detected in leachate samples, with polyethylene and polypropylene being the most abundant in the untreated leachate. The neutral buoyancy of microplastics (average density: 0.94 g/cm3), together with irregular shapes, suggested they may be difficult to be removed by sedimentation. Further exploring the fate of microplastics in leachate treatment works showed that the membrane treatment effectively reduced microplastics loading to 0.14% for particle and 0.01% for mass, but the average particle density rose. The differences in polymeric materials distribution at different sampling locations and the presence of membrane-related polymer in membrane treatment effluent suggested tiny microplastics could be generated and released from membrane systems. Moreover, this study discovered that the sludge dewatering liquor could contain a high amount of microplastics, and the estimated particle loading was about 3.6 times higher than that in dewatered sludge. This suggested a new approach to microplastics mitigation through separating microplastics from the sludge dewatering liquor before its recirculation.
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Microplásticos , Contaminantes Químicos del Agua , Plásticos , Aguas del Alcantarillado , Contaminantes Químicos del Agua/análisisRESUMEN
Intercropping of aromatic plants provides an environmentally benign route to reducing pest damage in agroecosystems. However, the effect of intercropping on natural enemies, another element which may be vital to the success of an integrated pest management approach, varies in different intercropping systems. Rosemary, Rosmarinus officinalis L. (Lamiaceae), has been reported to be repellent to many insect species. In this study, the impact of sweet pepper/rosemary intercropping on pest population suppression was evaluated under greenhouse conditions and the effect of rosemary intercropping on natural enemy population dynamics was investigated. The results showed that intercropping rosemary with sweet pepper significantly reduced the population densities of three major pest species on sweet pepper, Frankliniella intonsa, Myzus persicae, and Bemisia tabaci, but did not affect the population densities of their natural enemies, the predatory bug, Orius sauteri, or parasitoid, Encarsia formosa. Significant pest population suppression with no adverse effect on released natural enemy populations in the sweet pepper/rosemary intercropping system suggests this could be an approach for integrated pest management of greenhouse-cultivated sweet pepper. Our results highlight the potential of the integration of alternative pest control strategies to optimize sustainable pest control.