RESUMO
The widespread occurrence of organic antibiotic pollution in the environment and the associated harmful effects necessitate effective treatment method. Heterogeneous electro-Fenton (hetero-EF) has been regarded as one of the most promising techniques towards organic pollutant removal. However, the preparation of efficient cathode still remains challenging. Herein, a novel metal-organic framework (MOF)-derived Fe/Ni@C marigold-like nanosheets were fabricated successfully for the degradation of oxytetracycline (OTC) by serving as the hetero-EF cathode. The FeNi3@C (Fe/Ni molar ratio of 1:3) based hetero-EF system exhibited 8.2 times faster OTC removal rate than that of anodic oxidation and possessed many advantages such as excellent OTC degradation efficiency (95.4% within 90 min), broad environmental adaptability (satisfactory treatment performance for multiple antibiotics under various actual water matrixes), good stability and reusability, and significant toxicity reduction. The superior hetero-EF catalytic performance was mainly attributed to: 1) porous carbon and Ni existence were both conducive to the in-situ generation of H2O2 from dissolved O2; 2) the synergistic effects of bimetals together with electron transfer from the cathode promoted the regeneration of ≡ FeII/NiII, thereby accelerating the production of reactive oxygen species; 3) the unique nanosheet structure derived from the precursor two-dimensional Fe-Ni MOFs enhanced the accessibility of active sites. This work presented a promising hetero-EF cathode for the electrocatalytic treatment of antibiotic-containing wastewaters.
Assuntos
Estruturas Metalorgânicas , Oxitetraciclina , Poluentes Químicos da Água , Antibacterianos , Peróxido de Hidrogênio/química , Oxirredução , Eletrodos , Poluentes Químicos da Água/análiseRESUMO
The quality of rice, evaluated using multiple quality-related traits, is the main determinant of its market competitiveness. In this study, two japonica rice varieties with significant differences in quality-related traits were used as parents to construct two populations, BC3F2 and BC3F2:3, with Kongyu131 (KY131) as the recurrent parent. A genetic linkage map was constructed using the BC3F2 population based on 151 pairs of SSR/InDel polymorphic markers selected between the parents. Grain-shape-related traits (grain length GL, grain width GW, and length-to-width ratio LWR), chalkiness-related traits (white-core rate WCR, white-belly rate WBR, white-back rate BR, and chalkiness rate CR), and amylose content (AC) were investigated in the two populations in 2017 and 2018. Except for BR and CR, the traits showed similar characteristics with a normal distribution in both populations. Genetic linkage analysis was conducted for these quality-related traits, and a total of 37 QTLs were detected in the two populations. Further validation was performed on the newly identified QTLs with larger effects, and three grain shape QTLs and four chalkiness QTLs were successfully validated in different environments. One repeatedly validated QTL, qWCR3, was selected for fine mapping and was successfully narrowed down to a 100 kb region in which only two genes, LOC_0s03g45210 and LOC_0s03g45320, exhibited sequence variations between the parents. Furthermore, the variation of LOC_Os03g45210 leads to a frameshift mutation and premature protein termination. The results of this study provide a theoretical basis for positional cloning of the qWCR3 gene, thus offering new genetic resources for rice quality improvement.
Assuntos
Mapeamento Cromossômico , Ligação Genética , Oryza , Fenótipo , Locos de Características Quantitativas , Oryza/genética , Mapeamento Cromossômico/métodos , Grão Comestível/genética , Cromossomos de Plantas/genética , Genes de PlantasRESUMO
Grain size is a quantitative trait with a complex genetic mechanism, characterized by the combination of grain length (GL), grain width (GW), length to width ration (LWR), and grain thickness (GT). In this study, we conducted quantitative trait loci (QTL) analysis to investigate the genetic basis of grain size using BC1F2 and BC1F2:3 populations derived from two indica lines, Guangzhan 63-4S (GZ63-4S) and TGMS29 (core germplasm number W240). A total of twenty-four QTLs for grain size were identified, among which, three QTLs (qGW1, qGW7, and qGW12) controlling GL and two QTLs (qGW5 and qGL9) controlling GW were validated and subsequently fine mapped to regions ranging from 128 kb to 624 kb. Scanning electron microscopic (SEM) analysis and expression analysis revealed that qGW7 influences cell expansion, while qGL9 affects cell division. Conversely, qGW1, qGW5, and qGW12 promoted both cell division and expansion. Furthermore, negative correlations were observed between grain yield and quality for both qGW7 and qGW12. Nevertheless, qGW5 exhibited the potential to enhance quality without compromising yield. Importantly, we identified two promising QTLs, qGW1 and qGL9, which simultaneously improved both grain yield and quality. In summary, our results laid the foundation for cloning these five QTLs and provided valuable resources for breeding rice varieties with high yield and superior quality.
Assuntos
Mapeamento Cromossômico , Grão Comestível , Oryza , Locos de Características Quantitativas , Oryza/genética , Oryza/crescimento & desenvolvimento , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Fenótipo , Cromossomos de Plantas/genética , Sementes/genética , Sementes/crescimento & desenvolvimentoRESUMO
BACKGROUND Diabetes is related to higher risk of multiple cancers. This study aimed to explore the effect and mechanism of diabetes on liver metastasis of CRC. MATERIAL AND METHODS Overall and liver metastasis-free survival in diabetic and non-diabetic CRC patients were compared by Kaplan-Meier analysis. Expression of alphavß6 was detected by immunohistochemistry in clinical specimens. Effects of hyperglycemia on alphavß6 expression in colon cancer cells were assessed by western blot, real-time PCR, and flowcytometry. Effects of hyperglycemia on migration and invasion were demonstrated by Transwell assay. Expression and activity of MMP-9 and MMP-2 were determined by real-time PCR and gelatin zymography. Liver metastatic nodules were counted and b6 expression was detected by western blot in a liver metastasis mouse model. RESULTS CRC patients with diabetes had poorer overall and liver metastasis-free survival, and diabetes was associated with higher alphavß6 expression in CRC specimens. Hyperglycemia promoted the invasion and migration of colon cancer cells, and upregulated the expression and activity of MMP-9, which were attenuated by inhibition of alphavß6. Hyperglycemia upregulated the expression of ß6 and cell surface expression of avb6, which was reduced by ERK inhibitor. The in vitro results were confirmed in vivo in the mouse model. CONCLUSIONS Our study demonstrated the enhancing effect of hyperglycemia on liver metastasis of CRC, and showed that alphavß6 was involved in this process, suggesting that control of glucose levels and inhibition of alphavß6 can reduce the risk of liver metastasis in diabetic CRC patients.
Assuntos
Antígenos de Neoplasias/metabolismo , Neoplasias Colorretais/sangue , Hiperglicemia/metabolismo , Integrinas/metabolismo , Adulto , Animais , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Feminino , Expressão Gênica , Humanos , Hiperglicemia/patologia , Integrinas/genética , Neoplasias Hepáticas/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Metástase Neoplásica , RNA Longo não Codificante , Regulação para CimaRESUMO
NEW FINDINGS: What is the central question of this study? MiR-92b-3p was found to be reduced in a rat model of middle cerebral artery occlusion: what are the functions of miR-92b-3p in oxygen and glucose deprivation-reperfusion (OGD/R)? What is the main finding and its importance? MiR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammation caused by OGD/R via targeting TRAF3, suggesting that miR-92b-3p may serve as a potential therapeutic target in ischaemic stroke treatment. ABSTRACT: Stroke is the most common cause of human neurological disability. MiR-92b-3p has been shown to be decreased in a rat model of middle cerebral artery occlusion, but its effects in cerebral ischaemic insult are unknown. In this study, PC12 cells were exposed to oxygen and glucose deprivation-reperfusion (OGD/R) to establish cerebral ischaemic injury in vitro. Quantitative real time-PCR analysis demonstrated that OGD/R exposure led to down-regulation of miR-92b-3p and increased mRNA and protein levels of tumour necrosis factor receptor-associated factor 3 (TRAF3). Gain of miR-92b-3p expression facilitated cell survival; attenuated lactate dehydrogenase leakage, cell apoptosis, caspase 3 activity and cleaved-caspase 3 (c-caspase 3) expression; and decreased the Bax/Bcl-2 ratio. Furthermore, miR-92b-3p repressed mitochondrial membrane potential depolarization, reactive oxygen species production, cytochrome c protein expression, inflammatory cytokine production and the reduction of ATP content. MiR-92b-3p directly targeted the 3'-untranslated region of TRAF3 and decreased TRAF3 expression. Reinforced expression of TRAF3 partly abrogated the biological activity of miR-92b-3p during OGD/R. Hence, miR-92b-3p abated apoptosis, mitochondrial dysfunction and inflammatory responses induced by OGD/R by targeting TRAF3.
Assuntos
Apoptose/fisiologia , Glucose/metabolismo , Inflamação/metabolismo , MicroRNAs/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Fator 3 Associado a Receptor de TNF/metabolismo , Regiões 3' não Traduzidas/fisiologia , Animais , Isquemia Encefálica/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Regulação para Baixo/fisiologia , Neuroproteção/fisiologia , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Reperfusão/métodos , Acidente Vascular Cerebral/metabolismo , Regulação para Cima/fisiologiaRESUMO
BACKGROUND: Metabolic reprogramming, in which energetic metabolism changes from oxidative phosphorylation to glycolysis, is well-accepted as a hallmark of cancers including hepatocellular carcinoma (HCC). A growing body of evidence suggests the involvement of oncogenes and tumor suppressor genes in the control of metabolic reprogramming. In this study, we attempt to investigate whether loss of PTEN, a recognized tumor suppressor, drives metabolic reprogramming of HCC. METHODS: Cancerous liver tissues were surgically resected from 128 HCC patients, with 43 adjacent noncancerous liver tissues as control. Aerobic glycolysis (Warburg effect) was reflected by measurements of glucose uptake and lactate production, mitochondrial membrane potential collapse was observed by JC-1 staining, glycolytic rate and mitochondrial respiration were evaluated by determining glycolytic proton efflux rate (glycoPER) and oxygen consumption rate (OCR) in cultured human HHCC cells. RESULTS: Reciprocal expression of PTEN and PI3K was determined in cancer liver tissues. Overexpression of PTEN suppressed the Warburg effect, as evidenced by reductions in glucose uptake and lactate production, maintenance of mitochondrial function, and transformation of energetic metabolism from glycolysis to oxidative phosphorylation in cultured PTEN-negative HHCC cells. Importantly, 740 Y-P, a PI3K agonist that leads to activation of the PI3K pathway, partially abrogated the function of PTEN and reprogramed glucose metabolism in cultured HHCC cells. CONCLUSIONS: The discovery that loss of PTEN allows the tumor metabolic program has been a major advance in understanding the carcinogenesis of HCC. Video abstract Graphic abstract showing that loss of PTEN regulates the tumor metabolic program in hepatocellular carcinoma. Loss of PTEN leads to activation of the PI3K pathway enhances the Warburg effect, thereby promoting the development of hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Ácidos/metabolismo , Animais , Apoptose , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Respiração Celular , Regulação para Baixo , Espaço Extracelular/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Invasividade Neoplásica , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Efeito Warburg em OncologiaRESUMO
The presence and molecular characteristics of carbapenemase-producing Enterobacteriaceae (CPE) among meat products in China were investigated. A total of 110 carbapenem-resistant Enterobacteriaceae (CRE) isolates, including 94 Escherichia coli and 10 Klebsiella pneumoniae isolates, were identified from 105 of 794 (13.2%) samples. The positive rates markedly increased from 2016 (9.4%) to 2018 (22.2%). Only blaNDM genes were detected; 79.1% of blaNDM genes were carried by IncX3 plasmids. Routine monitoring of carbapenemase-producing Enterobacteriaceae in the animal food supply is highly recommended.
Assuntos
Carbapenêmicos/uso terapêutico , Escherichia coli/genética , Klebsiella pneumoniae/genética , Carne/microbiologia , Plasmídeos/genética , beta-Lactamases/genética , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , China , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/metabolismo , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodosRESUMO
BACKGROUND: The gut is becoming increasingly recognized as the source of various systemic diseases, and recently, it has been linked to bone metabolism via the so-called gut-bone axis. The microbiome and gut-derived mediators are thought to impact upon bone metabolism, and administration of probiotics has been shown to have beneficial effects in bone. The gut brush border enzyme intestinal alkaline phosphatase (IAP) plays an important role in controlling calcium absorption, inhibiting lipopolysaccharides, and other inflammatory mediators responsible for endotoxemia and appears to preserve the normal gut microbiota. Interestingly, IAP-deficient mice (AKP3-/-) also display a significant decrease in fecal Lactobacillus, the genus shown to be beneficial to bone. MATERIALS AND METHODS: IAP mRNA levels in mouse bone were measured using quantitative real-time polymerase chain reaction. Femurs of IAP-knockout (KO) and wild-type (WT) mice were analyzed by microcomputed tomography and histopathology. Serum levels of alkaline phosphatase, calcium, and phosphorus were measured. Target cell response upon exposure to serum from IAP-KO and WT mice was quantified using primary bone marrow macrophages. RESULTS: IAP was not significantly expressed in bones of WT or KO animals. IAP (alkaline phosphatase 3) expression in bone was vanishingly low compared to the duodenum (bone versus duodenum, 56.9 ± 17.7 versus 25,430.3 ± 10,884.5 relative expression, P = 0.01). Bone histology of younger IAP-KO and WT animals was indistinguishable, whereas older IAP-deficient mice showed a distinctly altered phenotype on histology and computed tomography scan. Younger KO mice did not display any abnormal levels in blood chemistry. Older IAP-KO animals showed an isolated increase in serum alkaline phosphatase levels reflecting an environment of active bone formation (IAP-WT versus IAP-KO, 80 ± 27.4 U/I versus 453 ± 107.5 U/I, P = 0.004). There was no significant difference in serum calcium or phosphorus levels between KO and WT mice. Serum from IAP-KO mice induced a significantly higher inflammatory target cell response. CONCLUSIONS: Through its multiple functions, IAP seems to play a crucial role in connecting the gut to the bone. IAP deficiency leads to chronic changes in bone formation, most likely through dysbiosis and systemic dissemination of proinflammatory mediators.
Assuntos
Fosfatase Alcalina/deficiência , Remodelação Óssea/fisiologia , Duodeno/metabolismo , Fêmur/patologia , Mucosa Intestinal/metabolismo , Fosfatase Alcalina/sangue , Fosfatase Alcalina/genética , Animais , Células Cultivadas , Disbiose/metabolismo , Feminino , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Microbioma Gastrointestinal/fisiologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Cultura Primária de Células , RNA Mensageiro/isolamento & purificação , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Organismos Livres de Patógenos Específicos , Microtomografia por Raio-XRESUMO
Three-dimensional cell culture techniques can better reflect the in vivo characteristics of tumor cells compared with traditional monolayer cultures. Compared with their 2D counterparts, 3D-cultured tumor cells showed enhanced resistance to the cytotoxic T cell-mediated immune response. However, it remains unclear whether 3D-cultured tumor cells have an enhanced resistance to NK cell cytotoxicity. In this study, a total of 363 differentially expressed proteins were identified between the 2D- and 3D-cultured U251 cells by comparative proteomics, and an immune-associated protein-protein interaction (PPI) network based on these differential proteins was constructed by bioinformatics. Within the network, HLA-E, as a molecule for inhibiting NK cell activation, was significantly up-regulated in the 3D-cultured tumor cells. Then, we found that the 3D-cultured U251 cells exhibited potent resistance to NK cell cytotoxicity in vitro and were prone to tumor formation in vivo. The resistance of the 3D-cultured tumor cells to NK cell lysis was mediated by the HLA-E/NKG2A interaction because the administration of antibodies that block either HLA-E or NKG2A completely eliminated this resistance and significantly decreased tumor formation. Taken together, our findings indicate that HLA-E up-regulation in 3D-cultured cells may result in enhanced tumor resistance to NK cell-mediated immune response.
Assuntos
Técnicas de Cultura de Células/métodos , Citotoxicidade Imunológica/imunologia , Glioma/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Células Matadoras Naturais/imunologia , Modelos Biológicos , Proteômica/métodos , Animais , Anticorpos Bloqueadores/imunologia , Anticorpos Bloqueadores/farmacologia , Western Blotting , Linhagem Celular Tumoral , Cromatografia Líquida , Citotoxicidade Imunológica/efeitos dos fármacos , Expressão Gênica/imunologia , Glioma/metabolismo , Glioma/patologia , Antígenos de Histocompatibilidade Classe I/genética , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Células Matadoras Naturais/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/imunologia , Mapas de Interação de Proteínas/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas em Tandem , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Antígenos HLA-ERESUMO
Colorectal cancer (CRC) displays a predilection for metastasis to liver. Although stromal cell-derived factor-1 (SDF-1)/CXCR4 plays an important role in the liver metastasis, the molecular mechanism still remains obscure. We previously reported that integrin αvß6 was implicated in the progression of CRC. However, no data are currently available on the cross talk between CXCR4 and αvß6. In the present study, we first demonstrated the cross talk between CXCR4 and αvß6 and their role in liver metastasis of CRC. We analyzed 159 human CRC samples and found that expression of CXCR4 and αvß6 was significantly associated with liver metastasis, and interestingly expression of αvß6 significantly correlated with expression of CXCR4. Both CXCR4 and αvß6 were highly expressed in metastatic CRC cell lines HT-29 and WiDr, whereas both of them were exiguous in non-metastatic cell line Caco-2. Furthermore, inhibition of αvß6 significantly decreased SDF-1α-induced cell migration in vitro. SDF-1/CXCR4 could upregulate αvß6 expression through phosphorylation of ERK and activation of Ets-1 transcription factor. In conclusion, we demonstrate that SDF-1/CXCR4 induces directional migration and liver metastasis of CRC cells by upregulating αvß6 through ERK/Ets-1 pathway. These data support combined inhibition of CXCR4 and αvß6 to prevent development of liver metastasis of CRC.
Assuntos
Antígenos de Neoplasias/metabolismo , Movimento Celular , Quimiocina CXCL12/metabolismo , Neoplasias Colorretais/patologia , Integrinas/metabolismo , Neoplasias Hepáticas/secundário , Proteína Proto-Oncogênica c-ets-1/metabolismo , Receptores CXCR4/metabolismo , Antígenos de Neoplasias/genética , Apoptose , Western Blotting , Células CACO-2 , Proliferação de Células , Quimiocina CXCL12/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Citometria de Fluxo , Imunofluorescência , Células HT29 , Humanos , Técnicas Imunoenzimáticas , Integrinas/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores CXCR4/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Although many scholars have utilized high-throughput microarrays to delineate gene expression patterns after spinal cord injury (SCI), no study has evaluated gene changes in raphe magnus (RM) and somatomotor cortex (SMTC), two areas in brain primarily affected by SCI. In present study, we aimed to analyze the differentially expressed genes (DEGs) of RM and SMTC between SCI model and sham injured control at 4, 24 h, 7, 14, 28 days, and 3 months using microarray dataset GSE2270 downloaded from gene expression omnibus and unpaired significance analysis of microarray method. Protein-protein interaction (PPI) network was constructed for DEGs at crucial time points and significant biological functions were enriched using DAVID. The results indicated that more DEGs were identified at 14 days in RM and at 4 h/3 months in SMTC after SCI. In the PPI network for DEGs at 14 days in RM, interleukin 6, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), FBJ murine osteosarcoma viral oncogene homolog (FOS), tumor necrosis factor, and nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) were the top 5 hub genes; In the PPI network for DEGs at 3 months in SMTC, the top 5 hub genes were ubiquitin B, Ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1), FOS, Janus kinase 2 and vascular endothelial growth factor A. Hedgehog and Wnt signaling pathways were the top 2 significant pathways in RM. These hub DEGs and pathways may be underlying therapeutic targets for SCI.
RESUMO
The brain microenvironment is tightly regulated, and the blood-brain barrier (BBB) plays a pivotal role in maintaining the homeostasis of the central nervous system. It effectively safeguards brain tissue from harmful substances in peripheral blood. However, both acute pathological factors and age-related biodegradation have the potential to compromise the integrity of the BBB and are associated with chronic neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), as well as Epilepsy (EP). This association arises due to infiltration of peripheral foreign bodies including microorganisms, immune-inflammatory mediators, and plasma proteins into the central nervous system when the BBB is compromised. Nevertheless, these partial and generalized understandings do not prompt a shift from passive to active treatment approaches. Therefore, it is imperative to acquire a comprehensive and in-depth understanding of the intricate molecular mechanisms underlying vascular disease alterations associated with the onset and progression of chronic neurodegenerative disorders, as well as the subsequent homeostatic changes triggered by BBB impairment. The present article aims to systematically summarize and review recent scientific work with a specific focus on elucidating the fundamental mechanisms underlying BBB damage in AD, PD, and EP as well as their consequential impact on disease progression. These findings not only offer guidance for optimizing the physiological function of the BBB, but also provide valuable insights for developing intervention strategies aimed at early restoration of BBB structural integrity, thereby laying a solid foundation for designing drug delivery strategies centered around the BBB.
RESUMO
Fermentation of pulses as a clean processing technique has been reported to have a favorable impact on the functional and nutritional quality of the starting materials. Compared to commonly fermented pulses such as peas and chickpeas, limited information is available on the effect of fermentation on lentils, especially when using a high protein isolate (>80% protein) as compared to seeds or flours. Therefore, in the present work, lentil protein isolate was used as a feedstock for submerged fermentation with Aspergillus niger, Aspergillus oryzae, or Lactobacillus plantarum. After 48 h, the samples showed increased protein content with enhanced solubility and oil-holding capacity. Controlled fermentation, as opposed to spontaneous fermentation, maintained the high foaming capacity; however, all fermented samples had lower foam and emulsion stabilizing properties and reduced water-holding capacity compared to the control. The fermented proteins were also less digestible, possibly due to an increase in phenolics and saponins. New volatile compounds were identified in fermented samples that show promise for improved sensory attributes. Significant differences were observed in specific quality attributes depending on the microbial strain used. Further research is required to better understand the fermentative metabolism of microbial communities when provided high-protein lentil ingredients as growth substrates. PRACTICAL APPLICATION: Fermented lentil protein isolate has promising flavor profiles that may improve its sensory properties for food application.
Assuntos
Aspergillus niger , Fermentação , Lactobacillus plantarum , Lens (Planta) , Valor Nutritivo , Compostos Orgânicos Voláteis , Lens (Planta)/microbiologia , Lens (Planta)/química , Lactobacillus plantarum/metabolismo , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Aspergillus niger/metabolismo , Proteínas de Plantas/metabolismo , Aspergillus oryzae/metabolismo , Sementes/química , Sementes/microbiologia , Paladar , Manipulação de Alimentos/métodosRESUMO
BACKGROUND: Malignant gliomas are the leading cause of morbidity and mortality in brain and central nervous system tumors. Recently, casticin has drawn wide attention to its critical role in tumor progression. However, the effect of casticin on glioma remains undefined. METHODS: Following treatment with casticin, cell viability, apoptosis, and cell cycle arrest were examined in U251 glioma cells. Additionally, the involved molecular mechanism was assessed by western blotting and flow cytometry. RESULTS: Casticin triggered an obvious dose-dependent decrease in U251, U87 and U373 glioma cell viability, and the growth inhibitory effect of casticin was correlated with cell cycle arrest and cell apoptosis. Further mechanistic analysis indicated that casticin induced G2/M phase arrest by attenuating the polymerization of tubulin. Furthermore, striking apoptosis was also confirmed, accompanied by the up-regulation of caspase-3, p53 and proapoptotic protein Bax. These effects were absent when the caspase inhibitor z-VAD-fmk or p53 inhibitor PFTα were applied, suggesting that casticin could trigger cell apoptosis in a caspase-3 and p53-dependent manner. CONCLUSION: These findings provide a prominent insight into how casticin abrogates the pathogenesis of glioma, and support its potential clinical prospect for further development of anti-brain cancer therapy.
Assuntos
Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Flavonoides/farmacologia , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Clorometilcetonas de Aminoácidos/farmacologia , Benzotiazóis/farmacologia , Caspase 3/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , Glioma/metabolismo , Glioma/patologia , Humanos , Tolueno/análogos & derivados , Tolueno/farmacologia , Tubulina (Proteína)/metabolismo , Proteína Supressora de Tumor p53/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND/AIMS: To investigate Omi/HtrA2 expression and its clinical significance in hepatocellular carcinoma. METHODOLOGY: We analyzed Omi/HtrA2 expression in hepatocellular carcinoma, paracancerous tissues and normal hepatic tissues by immunohistochemistry, RT-PCR and Western blot. Hypoxia-inducible factor-1α (HIF-1α) expression was also detected in hepatocellular carcinoma samples by immunohistochemistry. Meanwhile, we retrospectively analyzed the relationship between Omi/HtrA2 expression and the survival times of the patients. RESULTS: We found that Omi/HtrA2 overexpressed in hepatocellular carcinoma and was correlated with hepatocellular carcinoma differentiation, tumor size, portal vein invasion, clinical stage and lymph node metastasis. We also observed a significant inverse correlation between the expression of Omi,/HtrA2 and HIF-1α in hepatocellular carcinoma. The Kaplan-Meier estimates showed that patients who were Omi/HtrA2 positive had much longer survival times than those who were Omi/HtrA2 negative. Both univariate and multivariate analysis using the Cox regression model indicated that Omi/HtrA2 expression was a significant factor for prognosis. CONCLUSIONS: Hepatocellular carcinoma cells may need Omi/HtrA2 expression for apoptosis and Omi/HtrA2 might be an important prognostic marker for primary hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/química , Neoplasias Hepáticas/química , Proteínas Mitocondriais/análise , Serina Endopeptidases/análise , Adolescente , Adulto , Idoso , Apoptose , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Pessoa de Meia-Idade , Proteínas Mitocondriais/fisiologia , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Serina Endopeptidases/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.
Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Serotonina/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Hipocampo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Modelos Animais de Doenças , Comportamento AnimalRESUMO
Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an important role in regulating hepatoma cell apoptosis. However, conclusions of different studies about the effects of HIF-1alpha expression on hepatoma cell apoptosis remain controversial. Omi/HtrA2 promotes cell apoptosis in some human cancer cells. Our previous experiments have demonstrated that primary hepatocellular carcinoma may need Omi/HtrA2 expression for cell apoptosis. Thus, we investigated the effect of HIF-1alpha on hepatocellular carcinoma cell apoptosis and Omi/ HtrA2 expression. In our study we found that HIF-1alpha gene could suppress hepatoma cell apoptosis, and Omi/HtrA2 mRNA and protein expression decreased with HIF-1alpha expression increase while Bcl-2 mRNA and protein expression increased with HIF-1alpha expression increase in HepG2 cells under normoxia condition. Meanwhile, Omi/HtrA2 protein expression increased with HIF-1alpha expression decrease in HepG2 cells under hypoxia culture. Taken together, these results demonstrated that HIF-1alpha suppressed hepatocellular carcinoma cell apoptosis through inhibiting Omi/HtrA2 expression and upregulating Bcl-2 expression to impede Omi/ HtrA2 releasing from the mitochondrion. The present finding further enriched and supported the role of HIF-1alpha expression on cell apoptosis of hepatoma cells.
Assuntos
Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Mitocondriais/metabolismo , Serina Endopeptidases/metabolismo , Apoptose , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Hipóxia Celular , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Serina Endopeptidases/genéticaRESUMO
OBJECTIVES: To investigate the prognostic significance of Omi/HtrA2 expression, and the correlation between Omi/HtrA2 and Hypoxia-inducible factor (HIF)-1α in primary hepatocellular carcinoma cells. METHODS: The expression of HIF-1α and Omi/HtrA2 in 43 cases of hepatic carcinoma tissues were detected immunohistochemically. Follow-up data were obtained to perform the Kaplan-Meier survival analysis. The change of Omi/HtrA2 expression in HepG2 cell was measured after HIF-1α expression of HepG2 in vitro was regulated by Tet-on expression system. RESULTS: Omi/HtrA2 expression was correlated with lymph node metastasis and recurring within liver during 2 years. Statistical analysis estimation showed the cumulative survival rate of post-hepatectomy for the patients with the positive expression of Omi/HtrA2 was higher than that for other patients with the negative expression of Omi/HtrA2 (χ(2) = 6.13, P = 0.013). In the common paraffin-embedded specimen of hepatocellular carcinoma, most of the samples showing negative or weak positive HIF-1α immunopositivity showed moderate positive or strong positive Omi/HtrA2 immunopositivity, while most of the samples showing moderate positive or strong positive HIF-1α immunopositivity showed negative or weak positive Omi/HtrA2 immunopositivity. The mRNA expression intensity of Omi/HtrA2 was decreasing with the HIF-1α expression increasing, and the difference was statistically significant(F = 106.766, P < 0.01). CONCLUSIONS: Omi/HtrA2 may be an important prognostic marker for primary hepatocellular carcinoma. Omi/HtrA2 expression is reversely correlated with HIF-1α expression in hepatocellular carcinoma. During the apoptotic process Omi/HtrA2 participating in hepatocellular carcinoma cells, HIF-1α is involved in the controlling and regulating of Omi/HtrA2 expression.
Assuntos
Carcinoma Hepatocelular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Mitocondriais/metabolismo , Serina Endopeptidases/metabolismo , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Seguimentos , Células Hep G2 , Serina Peptidase 2 de Requerimento de Alta Temperatura A , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Transfecção , Células Tumorais Cultivadas , Adulto JovemRESUMO
Bioretention has been considered as an effective management practice for urban stormwater in the removal of pollutants including polycyclic aromatic hydrocarbons (PAHs). However, the accumulation of high-molecular-weight (HMW) PAHs in bioretention systems and their potential impact on the pollutants removal performance and microbial ecology are still not fully understood. In this study, comparisons of treatment effectiveness, enzyme activity and microbial community in bioretention systems with different types of media amendments were carried out at different spiking levels of pyrene (PYR). The results showed that the removal efficiencies of chemical oxygen demand (COD) and total nitrogen in the bioretention systems were negatively impacted by the PYR levels. The relative activities of soil dehydrogenase and urease were increasingly inhibited by the elevated PYR level, indicating the declining microbial activity regarding organic matter decomposition. The spiking of PYR negatively affected microbial diversity, and distinct time- and influent-dependent changes in microbial communities were observed. The relative abundance of PAH-degrading microorganisms increased in PYR-spiked systems, while the abundance of nitrifiers decreased. The addition of media amendments was beneficial for the enrichment of microorganisms that are more resistant to PYR-related stress, therefore elevating the COD concentration removal rate by â¼50%. This study gives new insight into the multifaceted impacts of HMW PAH accumulation on microbial fingerprinting and enzyme activities, which may provide guidance on better stormwater management practices via bioretention in terms of improved system longevity and performance.