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Prostate cancer (PCa) has garnered significant attention due to its rising incidence, variable therapeutic outcomes, and the absence of reliable prognostic markers. The significance of different cell death patterns in tumor development underscores their potential as predictors of PCa prognosis. This study utilized The Cancer Genome Atlas (TCGA) datasets to evaluate the prognostic capabilities of 15 cell death patterns and established a Cell Death Index (CDI) signature based on necrosis and cuproptosis-related genes. The predictive efficacy of the CDI signature was validated in our PCa cohort and in two public datasets: Deutsches Krebsforschungszentrum (DKFZ) and Memorial Sloan-Kettering Cancer Center (MSKCC) PCa cohorts. Our comprehensive analysis examined the relationship between CDI signature and clinical characteristics, published prognostic signatures, gene mutations, immune cell infiltration, enrichment pathways, and drug sensitivity in PCa. In vitro and in vivo studies assessed the impact of EDA2R and LOXL2 on PCa progression. The CDI signature exhibited robust predictive performance across three independent validation sets, with 1-, 2-, 3-, 4-, and 5-year area under the curve (AUC) values in the TCGA cohort of 0.866, 0.77, 0.836, 0.776, and 0.787, respectively. Higher CDI scores were correlated with advanced T and N stages, elevated Gleason scores, increased immune cell infiltration, gene mutations, and drug sensitivity. EDA2R inhibited PCa cell proliferation and migration, related to tumor necrosis, while LOXL2 promoted these processes and was associated with cuproptosis. In summary, our study identified a novel CDI signature as an effective indicator for diagnosis, personalized treatment, and prognostic assessment in PCa.
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Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/mortalidad , Masculino , Pronóstico , Animales , Línea Celular Tumoral , Muerte Celular , Biomarcadores de Tumor/genética , Aminoácido Oxidorreductasas/genética , Regulación Neoplásica de la Expresión Génica , Ratones , AncianoRESUMEN
Protein Disulfide-Isomerase A2 (PDIA2) is a gene that encodes proteins, responsible for protein folding and modification within cells. The development and course of many disorders are intimately linked to the aberrant expression of PDIA2. Nevertheless, more research is necessary to fully understand PDIA2's biological significance in pan-cancer, notably in prostate cancer (PCa). PDIA2 expression is elevated in various tumors and closely related to patient prognosis. Patients with prostate cancer who express PDIA2 high in particular have a bad prognosis in terms of progression-free survival. In addition, the upregulation of PDIA2 expression in prostate cancer patients is accompanied by higher Gleason scores, advanced tumor staging, lymph node metastasis, and elevated PSA levels. Detailed experiments further demonstrate that PDIA2 is a carcinogenic gene affecting prostate cancer cells' response to dasatinib therapy. For patients with prostate cancer, there is a clear positive connection between the expression level of PDIA2 and a bad prognosis. The prostate cancer treatment efficacy of dasatinib is hampered by PDIA2, which is intimately linked to the growth, invasion, and metastasis of PCa cells. In summary, our research highlights the potential of PDIA2 as a biomarker for the diagnosis and management of PCa.
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Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Próstata , Proteína Disulfuro Isomerasas , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Proteína Disulfuro Isomerasas/genética , Pronóstico , Línea Celular Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Regulación hacia AbajoRESUMEN
The natural healing process of extraction socket and traditional socket plug material could not prevent buccal bone wall resorption and down growth of epithelium from the socket orifice. A multiphase bioactive socket plug (BP) is designed to overcome the natural healing process by maintaining the three-dimensional (3D) volume of extraction sockets, particularly in sockets with wall defects, and later provide sufficient alveolar bone volume for implant placement. The study aimed to fabricate and evaluate the physical, chemical, and biological performance of BPin vitro. The BP was fabricated through freeze-drying and layer-by-layer assembly, comprised of a base serving as a scaffold, a central portion for promoting bone regeneration, an upper buccal portion for maintaining alveolar socket dimension with a covering collagen membrane (Memb) on the top and upper buccal surface to prevent soft tissue infiltration. The BP as the experimental group and a pure collagen plug (CP) as the control group were investigated and compared. Radiograph, scanning electron microscopy, and energy-dispersive spectroscopy mapping confirmed that the four-part BP was successfully assembled and fabricated. Swelling rate analysis indicated that BP, CP, and Memb reached swelling equilibrium within 1 hour. BP exhibited a high remaining weight percentage in collagenase solution (68.81 ± 2.21% on day 90) and sustained calcium ion release, reaching the maximum 0.13 ± 0.04 mmol l-1on day 14. In biological assays, BP exhibited excellent cell proliferation (The OD value increased from 0.02 on day 1 to 0.23 on day 21.). The BP group exhibited higher alkaline phosphatase activity and osteocalcin content than the CP group within 21 days. Memb and BP exhibited outstanding barrier function, as evidenced by Hematoxylin and eosin staining. In summary, the multiphase bioactive socket plug represents a promising scaffold for alveolar ridge preservation application.
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Colágeno , Andamios del Tejido , Alveolo Dental , Alveolo Dental/cirugía , Animales , Colágeno/química , Andamios del Tejido/química , Materiales Biocompatibles/química , Regeneración Ósea/efectos de los fármacos , Proceso Alveolar , Proliferación Celular , Microscopía Electrónica de Rastreo , Humanos , Ensayo de Materiales , Aumento de la Cresta Alveolar/métodos , Extracción Dental , Osteoblastos/citología , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Cicatrización de Heridas , Calcio/metabolismo , Calcio/química , Osteocalcina/metabolismoRESUMEN
One strategy to correct alveolar bone defects is use of bioactive bone substitutes to maintain the structure of defect site and facilitate cells and vessels' ingrowth. This study aimed to fabricate and characterize the freeze-dried bone regeneration scaffolds composed of polymeric Type I collagen, nano Beta-tricalcium phosphate (ß-TCP), and gelatin. The stable structures of scaffolds were obtained by thermal crosslinking and EDC/NHS ((1-ethyl-3-(3-dimethylaminopropyl) carbodiimide)/(N-hydroxysuccinimide)) chemical crosslinking processes. Subsequently, the physicochemical and biological properties of the scaffolds were characterized and assessed. The results indicated the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP exhibited suitable porosity (84.45 ± 25.43 nm, and 94.51 ± 14.69 nm respectively), a rapid swelling property (reaching the maximum swelling rate at 1 h), excellent degradation resistance (residual mass percentage of scaffolds higher than 80% on day 90 in PBS and Type I collagenase solution respectively), and sustained calcium release capabilities. Moreover, they displayed outstanding biological properties, including superior cell viability, cell adhesion, and cell proliferation. Additionally, the scaffolds containing 10% and 20% (w/v) nano ß-TCP could promote the osteogenic differentiation of MC3T3-E1. Therefore, the bioactive composite scaffolds containing 10% and 20% (w/v) nano ß-TCP could be further studied for being used to treat alveolar bone defects in vivo.
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Gelatina , Osteogénesis , Gelatina/farmacología , Andamios del Tejido/química , Regeneración Ósea , Colágeno/química , Fosfatos de Calcio/farmacología , Fosfatos de Calcio/química , Polímeros , Ingeniería de Tejidos/métodosRESUMEN
Bone tissue is a highly vascularized tissue. When constructing tissue-engineered bone models, both the osteogenic and angiogenic capabilities of the construct should be carefully considered. However, fabricating a vascularized tissue-engineered bone to promote vascular formation and bone generation, while simultaneously establishing nutrition channels to facilitate nutrient exchange within the constructs, remains a significant challenge. Triaxial bioprinting, which not only allows the independent encapsulation of different cell types while simultaneously forming nutrient channels, could potentially emerge as a strategy for fabricating vascularized tissue-engineered bone. Moreover, bioinks should also be applied in combination to promote both osteogenesis and angiogenesis. In this study, employing triaxial bioprinting, we used a blend bioink of gelatin methacryloyl (GelMA), sodium alginate (Alg), and different concentrations of nano beta-tricalcium phosphate (nano ß-TCP) encapsulated MC3T3-E1 preosteoblasts as the outer layer, a mixed bioink of GelMA and Alg loaded with human umbilical vein endothelial cells (HUVEC) as the middle layer, and gelatin as a sacrificial material to form nutrient channels in the inner layer to fabricate vascularized bone constructs simulating the microenvironment for bone and vascular tissues. The results showed that the addition of nano ß-TCP could adjust the mechanical, swelling, and degradation properties of the constructs. Biological assessments revealed the cell viability of constructs containing different concentrations of nano ß-TCP was higher than 90% on day 7, The cell-laden constructs containing 3% (w/v) nano ß-TCP exhibited better osteogenic (higher Alkaline phosphatase activity and larger Osteocalcin positive area) and angiogenic (the gradual increased CD31 positive area) potential. Therefore, using triaxial bioprinting technology and employing GelMA, Alg, and nano ß-TCP as bioink components could fabricate vascularized bone tissue constructs, offering a novel strategy for vascularized bone tissue engineering.
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Alginatos , Bioimpresión , Huesos , Fosfatos de Calcio , Gelatina , Células Endoteliales de la Vena Umbilical Humana , Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Bioimpresión/métodos , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones , Animales , Gelatina/química , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Alginatos/química , Huesos/irrigación sanguínea , Osteogénesis/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Andamios del Tejido/química , Metacrilatos/química , Osteoblastos/citología , Osteoblastos/metabolismo , Impresión TridimensionalRESUMEN
BACKGROUND: The Prostate Imaging Reporting and Data System (PI-RADS) is an established reporting scheme for multiparametric magnetic resonance imaging (mpMRI) to distinguish clinically significant prostate cancer (csPCa). Deep learning (DL) holds great potential for automating csPCa classification on mpMRI. METHOD: To compare the performance between a DL algorithm and PI-RADS categorization in PCa detection and csPCa classification, we included 1,729 consecutive patients who underwent radical prostatectomy or biopsy in Tongji hospital. We developed DL models by integrating individual mpMRI sequences and employing an ensemble approach for distinguishing between csPCa and CiSPCa (specifically defined as PCa with a Gleason group 1 or benign prostate disease, training cohort: 1,285 patients vs. external testing cohort: 315 patients). RESULTS: DL-based models exhibited higher csPCa detection rates than PI-RADS categorization (area under the curve [AUC]: 0.902; sensitivity: 0.728; specificity: 0.906 vs. AUC: 0.759; sensitivity: 0.761; specificity: 0.756) (P < 0.001) Notably, DL networks exhibited significant strength in the prostate-specific antigen (PSA) arm < 10 ng/ml compared with PI-RADS assessment (AUC: 0.788; sensitivity: 0.588; specificity: 0.883 vs. AUC: 0.618; sensitivity: 0.379; specificity: 0.763) (Pâ¯=â¯0.041). CONCLUSIONS: We developed DL-based mpMRI ensemble models for csPCa classification with improved sensitivity, specificity, and accuracy compared with clinical PI-RADS assessment. In the PSA-stratified condition, the DL ensemble model performed better than PI-RADS in the detection of csPCa in both the high PSA group and the low PSA group.
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Aprendizaje Profundo , Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodosRESUMEN
Biological soil crusts (biocrusts) are considered "desert ecosystem engineers" because they play a vital role in the restoration and stability maintenance of deserts, including those cold sandy land ecosystems at high latitudes, which are especially understudied. Microorganisms participate in the formation and succession of biocrusts, contributing to soil properties' improvement and the stability of soil aggregates, and thus vegetation development. Accordingly, understanding the composition and successional characteristics of microorganisms is a prerequisite for analyzing the ecological functions of biocrusts and related applications. Here, the Hulun Buir Sandy Land region in northeastern China-lying at the highest latitude of any sandy land in the country-was selected for study. Through a field investigation and next-generation sequencing (Illumina MiSeq PE300 Platform), our goal was to assess the shifts in diversity and community composition of soil bacteria and fungi across different stages during the succession of biocrusts in this region, and to uncover the main factors involved in shaping their soil microbial community. The results revealed that the nutrient enrichment capacity of biocrusts for available nitrogen, total nitrogen, total phosphorus, total content of water-soluble salt, available potassium, soil organic matter, and available phosphorus was progressively enhanced by the succession of cyanobacterial crusts to lichen crusts and then to moss crusts. In tandem, soil bacterial diversity increased as biocrust succession proceeded but fungal diversity decreased. A total of 32 bacterial phyla and 11 fungal phyla were identified, these also known to occur in other desert ecosystems. Among those taxa, the relative abundance of Proteobacteria and Cyanobacteria significantly increased and decreased, respectively, along the cyanobacterial crust-lichen-moss crust successional gradient. However, for Actinobacteria, Chloroflexi, and Acidobacteria their changed relative abundance was significantly hump-shaped, increasing in the shift from cyanobacterial crust to lichen crust, and then decreasing as lichen crust shifted to moss crust. In this process, the improved soil properties effectively enhanced soil bacterial and fungal community composition. Altogether, these findings broaden our understanding about how soil microbial properties can change during the succession of biocrusts in high-latitude, cold sandy land ecosystems.
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Cianobacterias , Líquenes , Microbiota , Ecosistema , Suelo , Arena , Microbiología del Suelo , Nitrógeno , Fósforo , ChinaRESUMEN
BACKGROUND: Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. METHODS: We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. RESULTS: GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. CONCLUSIONS: GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.
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BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with early recurrence and a poor prognosis in clear cell renal cell carcinoma (ccRCC). Studies have shown that EMT-related genes play an important regulatory role in tumor invasion, metastasis, and drug resistance, but the biological functions of EMT-related genes in ccRCC have not been specifically described. METHODS: The mRNA and clinicopathological data of 532 ccRCC and 72 normal samples were downloaded from The Cancer Genome Atlas as a training set. The gene expression matrix and survival data of 91 and 101 ccRCC samples were obtained from the International Cancer Genome Consortium and the ArrayExpress databases as validation sets, respectively. Univariate Cox analysis was used to identify and cluster prognostic genes, and multivariate Cox was performed to construct a prognostic signature. Moreover, CIBERSORT and CellMiner were used to assess immune cell infiltration and prognostic gene-drug sensitivity of the signature, respectively. Most importantly, we performed detailed experiments to verify the oncogenic function of a significant gene, OLFML2B, in vitro and in vivo. RESULTS: We constructed a prognostic signature including seven genes and divided patients into high-risk and low-risk groups. The prognosis of the high-risk group was significantly worse than that of the low-risk group through Kaplan-Meier survival analysis. Interestingly, significant differences were observed in clinical characteristics and immune cell infiltration between the two groups. In addition, a significant correlation was found between the expression of prognostic genes and the sensitivity of tumor cells to chemotherapeutics. Most importantly, OLFML2B was proved to contribute to the proliferation and metastasis of ccRCC through detailed functional experiments in vitro and in vivo, and its prognostic efficacy for ccRCC patients was affirmed. CONCLUSION: We identified the prognostic signature of seven genes based on EMT-related genes as prognostic biomarkers for ccRCC. Besides, OLFML2B was validated as a potential diagnostic and therapeutic target for ccRCC by our detailed experiments.
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The Warburg effect-related metabolic dysfunction of the tricarboxylic acid (TCA) cycle has emerged as a hallmark of various solid tumors, particularly renal cell carcinoma (RCC). RCC is characterized by high immune infiltration and thus recommended for immunotherapeutic interventions at an advanced stage in clinical guidelines. Nevertheless, limited benefits of immunotherapy have prompted investigations into underlying mechanisms, leading to the proposal of metabolic dysregulation-induced immunoevasion as a crucial contributor. In this study, a significant decrease is found in the abundance of alpha-ketoglutarate (αKG), a crucial intermediate metabolite in the TCA cycle, which is correlated with higher grades and a worse prognosis in clinical RCC samples. Elevated levels of αKG promote major histocompatibility complex-I (MHC-I) antigen processing and presentation, as well as the expression of ß2-microglobulin (B2M). While αKG modulates broad-spectrum demethylation activities of histone, the transcriptional upregulation of B2M is dependent on the demethylation of H3K4me1 in its promoter region. Furthermore, the combination of αKG supplementation and PD-1 blockade leads to improved therapeutic efficacy and prolongs survival in murine models when compared to monotherapy. Overall, the findings elucidate the mechanisms of immune evasion in anti-tumor immunotherapies and suggest a potential combinatorial treatment strategy in RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Animales , Ratones , Carcinoma de Células Renales/terapia , Carcinoma de Células Renales/patología , Receptor de Muerte Celular Programada 1 , Ácidos Cetoglutáricos , Neoplasias Renales/terapia , InmunoterapiaRESUMEN
Bioprinting has demonstrated great advantages in tissue and organ regeneration. However, constructing large-scale tissue and organsin vitrois still a huge challenge due to the lack of some strategies for loading multiple types of cells precisely while maintaining nutrient channels. Here, a new 3D bioprinting strategy was proposed to construct large-scale vascularized tissue. A mixture of gelatin methacrylate (GelMA) and sodium alginate (Alg) was used as a bioink, serving as the outer and middle layers of a single filament in the triaxial printing process, and loaded with human bone marrow mesenchymal stem cells and human umbilical vein endothelial cells, respectively, while a calcium chloride (CaCl2) solution was used as the inner layer. The CaCl2solution crosslinked with the middle layer bioink during the printing process to form and maintain hollow nutrient channels, then a stable large-scale construct was obtained through photopolymerization and ion crosslinking after printing. The feasibility of this strategy was verified by investigating the properties of the bioink and construct, and the biological performance of the vascularized construct. The results showed that a mixture of 5% (w/v) GelMA and 1% (w/v) Alg bioink could be printed at room temperature with good printability and perfusion capacity. Then, the construct with and without channels was fabricated and characterized, and the results revealed that the construct with channels had a similar degradation profile to that without channels, but lower compressive modulus and higher swelling rate. Biological investigation showed that the construct with channels was more favorable for cell survival, proliferation, diffusion, migration, and vascular network formation. In summary, it was demonstrated that constructing large-scale vascularized tissue by triaxial printing that can precisely encapsulate multiple types of cells and form nutrient channels simultaneously was feasible, and this technology could be used to prepare large-scale vascularized constructs.
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Bioimpresión , Humanos , Nutrientes , Alginatos , Cloruro de Calcio , Gelatina , Células Endoteliales de la Vena Umbilical Humana , MetacrilatosRESUMEN
Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin (UCN) was chosen for further study; some necessary vitro experiments proved that the UCN could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. UCN played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Pronóstico , Neoplasias Renales/genética , Estrés Oxidativo/genéticaRESUMEN
While charitable donations help to raise funds and contribute to pandemic prevention and control, there are many unanswered questions about how people make such donation decisions, especially in countries like China where charitable donations have played an increasing role in recent years. This study contributes to the literature by assessing the potential impacts of Chinese netizens' experience with the 2002 severe acute respiratory syndrome (SARS) epidemic on their willingness to donate for COVID-19 pandemic prevention and control. Specifically, this study applies a difference-in-differences (DID) model to a dataset collected from a nationwide survey to examine how individuals' exposure to the SARS epidemic affects their willingness to donate to alleviate the COVID-19 pandemic. The results suggest that individuals' SARS epidemic experiences in their early lives, especially during the "childhood-adolescence" period, had a lasting and far-reaching impact on their willingness to donate toward COVID-19 pandemic prevention and control. Also, the impacts were likely heterogeneous by such sociodemographic factors as educational background, health status, and income level. The empirical findings highlight the importance of considering early-life experiences in developing and implementing epidemic prevention and control policies. While the SARS experience likely affected Chinese netizens' willingness to donate toward COVID-19 pandemic prevention and control, lessons learned from both the SARS epidemic and COVID-19 pandemic could be used to develop more effective public health education and prevention programs as well as to increase public donations for future pandemic prevention and control.
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Hydroxysafflower yellow A (HSYA) protects against acute kidney injury through TLR4/NF-κB pathway. However, the effect and potential mechanism of HSYA in ulcerative colitis (UC) have been rarely reported, which is thus investigated in this research. An in vivo UC model was established by oral administration of 5% dextran sulfate sodium (DSS) in Sprague-Dawley rats. After HSYA treatment, the daily body weight and colon length of rats were measured. Then rat colon tissues, myeloperoxidase (MPO) activity, and the levels of inflammatory cytokines were examined by histopathological examination (HE) staining, immunohistochemistry, ultraviolet spectrophotometry, and enzyme-linked immune sorbent assay (ELISA) respectively. The activated TLR4/NF-κB pathway was detected by Western blot. RAW 264.7 cell viability was detected by MTT assay after lipopolysaccharide (LPS) treatment, and ELISA and Western blot were performed again to investigate the effects of HSYA on LPS-treated cells. DSS administration increased body weight and colon length of rats and induced colon tissue injury. DSS or LPS treatment up-regulated the levels of TNF-α, IL-1ß, and IL-6 and activated TLR4/NF-κB pathway of colon tissues and cells, respectively. HSYA partially reversed the above effect of DSS and LPS treatment, and the effects of the drug were improved with the dosage. Taken together, HSYA alleviates UC by suppressing TLR4/NF-κB signaling pathway, which may provide a new insight for the treatment of UC.
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Chalcona , Colitis Ulcerosa , FN-kappa B , Quinonas , Receptor Toll-Like 4 , Animales , Peso Corporal/efectos de los fármacos , Chalcona/análogos & derivados , Chalcona/farmacología , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Lipopolisacáridos/farmacología , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Quinonas/farmacología , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismoRESUMEN
In the coastal zones, numerous ecological shelterbelt projects were conducted to protect against natural hazards. However, it is still not fully understood whether phytoremediation with native legume Albizzia julibrissin plantation can improve saline soil structural development or microbial community structure. In this study, a field experiment was conducted to investigate the responses of rhizosphere soil salinity, nutrients, bacterial community, and aggregate structure to A. julibrissin plantation in a recently reclaimed area along Zhejiang coast, China. After ~3-year plantation, rhizosphere soil pH and EC reduced to 8.25 and 0.14 dS·m-1, respectively, belonging to non-saline soil. Meanwhile, total organic carbon (TOC), permanganate-oxidizable carbon (POXC), total nitrogen (TN), alkali-hydrolyzable nitrogen (AN), and ammonium nitrogen (NH4+-N) were significantly increased in rhizosphere soil compared with bare land (P < 0.05). Consequently, rhizosphere soil had favorable habitat condition for copiotrophic bacterial taxa (e.g., Chloroflexi, Acidobacteria, and Bacteroidates), as well as high diversity, complex co-occurrence network, and catabolism related with nutrient cycling. The soil particle size of bare land was < 0.053 mm, while microaggregate (0.053-0.25 mm) and macroaggregate (0.25-2 mm) were formed in the rhizosphere and coupled with C accumulation and Fe removal. Soil aggregates were of great importance to soil fertility with more efficient bacterial network and biogeochemical cycles of nutrients. N-fixing Rhizobiales preferred to inhabit large soil particle and might primarily contribute to N accumulation. Generally, A. julibrissin was a suitable pioneer tree for mudflat reclamation projects, which effectively improved saline soil rhizosphere environment by reducing salinity, accumulating C and N, and promoting microbial community succession, as well as aggregate structure formation.
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Albizzia , Fabaceae , Microbiota , Nitrógeno/análisis , Nutrientes , Rizosfera , Suelo , Microbiología del SueloRESUMEN
The platform consists of three modules, which are pre-configured bioinformatic pipelines, cloud toolsets, and online omics' courses. The pre-configured bioinformatic pipelines not only combine analytic tools for metagenomics, genomes, transcriptome, proteomics and metabolomics, but also provide users with powerful and convenient interactive analysis reports, which allow them to analyze and mine data independently. As a useful supplement to the bioinformatics pipelines, a wide range of cloud toolsets can further meet the needs of users for daily biological data processing, statistics, and visualization. The rich online courses of multi-omics also provide a state-of-art platform to researchers in interactive communication and knowledge sharing.
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BACKGROUND AND AIMS: LncRNA plasmacytoma variant translocation 1 (PVT1) plays a regulatory role in some cardiovascular diseases, but its role in atherosclerosis (AS) remains barely explored. The study aimed to investigate the effects of PVT1 on high fat diet-induced AS and its potential mechanisms. METHODS AND RESULTS: ApoE -/- mice were fed with high fat diet for 8 weeks to establish an AS model. Lentiviral vectors containing PVT1 short hairpin RNA (PVT1-shRNA) or NC-shRNA were administered by tail vein injection. Cell viability, apoptosis, inflammatory factor secretion, and cellular oxidative stress were measured to evaluate oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cell (HUVEC) injury. Dual-luciferase reporter gene and RNA immunoprecipitation assays were used to confirm the interaction between miR-153-3p and PVT1 or growth factor receptor binding protein 2 (GRB2). Atherosclerotic lesions, lipid deposition, and cell apoptosis in aorta were analyzed by H&E, Oil Red O, and TUNEL straining. PVT1 knockdown alleviated ox-LDL-induced inflammation, apoptosis and oxidative stress in HUVECs. PVT1 acted as a sponge of miR-153-3p, and GRB2 was confirmed as a target of miR-153-3p. MiR-153-3p overexpression attenuated the enhanced effects of PVT1 on ox-LDL-induced cell damage. GRB2 overexpression reversed the mitigating effects of miR-153-3p on ox-LDL-caused injury. Inhibiting PVT1 restrained the activation of ERK1/2 and p38 pathway via miR-153-3p/GRB2 axis. Additionally, silencing PVT1 in vivo reduced atherosclerotic plaques, lipid deposition, inflammation, oxidative stress, and apoptosis in AS mice. CONCLUSION: PVT1 knockdown alleviated ox-LDL-induced vascular endothelial cell injury and atherosclerosis through miR-153-3p/GRB2 axis via ERK1/2 and p38 pathway.
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Aterosclerosis , MicroARNs , ARN Largo no Codificante , Animales , Apoptosis , Aterosclerosis/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación , Lipoproteínas LDL/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Interferente PequeñoRESUMEN
This study aimed to quantify greenhouse gas emissions derived from the production-consumption of rice in Hubei-a major rice-producing province in central China. This research employed primary and secondary data collection methods. Primary data sources included interviews and experimental observations from seven counties in Hubei collected from June 2016 to December 2016. Secondary data sources-including national datasets, inter-governmental reports, and peer-reviewed articles-were used to extract relevant data, such as emission factors, and national and provincial rice output. Life Cycle Assessment was employed to build a comprehensive inventory and map of the rice carbon footprint, including the following five stages: production inputs, farm management, growth period, processing and sale, and consumption. Uncertainty analysis was performed to validate the reliability of carbon footprint estimations. Results showed that the carbon footprint for every 1 ton of polished rice in Hubei ranged between 4.19-6.81 t CO2e/t and was 5.39 t CO2e/t on average. Greenhouse gas emissions were primarily produced from rice fields during the growth stage (over 60% of greenhouse gas emissions of the whole life cycle of rice), followed by the consumption stage, and the production and transportation of agricultural inputs. Uncertainty analysis estimations indicated acceptable levels of reliability. This study's results indicate that the production and consumption of rice is a significant contributor to agricultural carbon emissions in Hubei-consistent with national estimates that place China as the largest carbon dioxide emitter globally. This research provides further insight into future policies and targeted initiatives for the efficient use of low-carbon agricultural inputs for rice production and consumption stages in China.
Asunto(s)
Agricultura , Huella de Carbono , Oryza , China , Efecto Invernadero , Oryza/crecimiento & desarrollo , Reproducibilidad de los Resultados , IncertidumbreRESUMEN
The effects of agricultural green production technologies (AGPTs) on agricultural productivity and the environment have received increasing attention. With the panel data of agricultural production of mainland China from 2000 to 2017, this study investigates the role of AGPTs adoption rates in improving low-carbon efficiency by adopting a random-effects panel Tobit model. Results indicate that average adoption rates of AGPTs are less than 20% and unbalanced adoptions vary between the main and non-main grain-producing areas, as well as the northern and southern main grain-producing areas. Furthermore, AGPTs adoption reduces low-carbon efficiency at nationwide and main grain-producing areas. In the northern main grain-producing areas, water-saving irrigation and no-tillage seeding reduce low-carbon efficiency, while mechanized returning straw crushing promotes it. In the southern main grain-producing areas, deep tillage with fertilizer application and no-tillage seeding decrease low-carbon efficiency, while mechanized deep ploughing and scarification increases it. We also find that AGPTs can promote low-carbon efficiency through comprehensive mechanization level and mechanical input density. To improve low-carbon efficiency, we suggest that the improvement and diffusion of applicable AGPTs should be adapted to the local production conditions, and the agricultural machinery service, research and development system should be improved as well.