In this study, we aimed to investigate whether resveratrol has anti-inflammatory effects on LPS-induced ALI via TTP enhancement.
Acute lung injury (ALI) is a syndrome of diffuse infammatory lung ...injury with increased pulmonary edema and the rapid onset of hypoxemic respiratory failure. Resveratrol is a stilbenoid, a form of natural phenol, and a phytoalexin produced by a variety of plants in reaction to injury or when they are attacked by pathogens like bacteria or fungi. Resveratrol exhibits a potent antiinflammatory effect in LPS-induced ALI, while the underlying mechanisms remain elusive.
Tristetraprolin (TTP) is a RNA binding protein that is an important endogenous inhibitor of inflammation. The objective of the present study is to investigate whether resveratrol has anti- inflammatory effects on LPS-induced ALI via TTP enhancement.
Forty male C57BL/6 mice were randomly assigned to four groups and intratracheally instilled with 5 mg/kg lipopolysaccharide (LPS) to induce ALI.
LPS-induced lung pathological damage, lung edema, and neutrophil infiltration were reduced by resveratrol pretreatment. Furthermore, resveratrol inhibited the LPS-induced rise in TNF- α, IL-1β and IL-6 levels in BAL fluids. In the LPS-challenged mouse's lung tissue, resveratrol clearly boosted sirtuin1 (SIRT1) and TTP protein expression, while also increasing TTP expression while reducing proinflammatory cytokines. EX527, on the other hand, reversed resveratrol's effects.
According to our findings, resveratrol attenuated pulmonary inflammation and lung injury in mice with LPS‑induced ALI, at least partly correlated with promoting the activation of SIRT1/TTP signaling pathway, highlighting these pathways as potential targets for intervention in LPS -induced lung injury.
Mesenchymal stem cells (MSCs) have the potential to reduce healing time and treat nonunion in fracture patients. In this study, bone marrow MSCs-derived extracellular vesicles (B-EVs) were firstly ...extracted and identified. CD9
and normal mice were enrolled for the establishment of fracture models and then injected with B-EVs. Osteoblast differentiation and fracture recovery were estimated. The levels of osteoblast-related genes were detected, and differentially expressed microRNAs (miRs) in B-EVs-treated normal fracture mice were screened and verified. The downstream mechanisms of miR were predicted and assessed. The loss-of functions of miR-335 in B-EV and gain-of-functions of VapB were performed in animal and cell experiments to evaluate their roles in bone fracture. Collectively, B-EVs promoted bone fracture recovery and osteoblast differentiation by releasing miR-335. miR-335 downregulation in B-EVs impaired B-EV functions in fracture recovery and osteoblast differentiation. miR-335 could target VapB, and VapB overexpression reversed the effects of B-EVs on osteoblast differentiation. B-EV treatment activated the Wnt/β-catenin pathway in fracture mice and osteoblasts-like cells. Taken together, the study suggested that B-EVs carry miR-335 to promote bone fracture recovery via VapB and the Wnt/β-catenin pathway. This study may offer insights into bone fracture treatment.
To investigate the risk factors for recurrence in patients with early-stage hepatocellular carcinoma (HCC) after minimally invasive treatment with curative intent, then to construct a prediction ...model based on Lasso-Cox regression and visualize the model built.
Clinical data were collected from 547 patients that received minimally invasive treatment in our hospital from January 1, 2012, to December 31, 2016. Lasso regression was used to screen risk factors for recurrence. Then we established Cox proportional hazard regression model and random survival forest model including several parameters screened by Lasso regression. An optimal model was selected by comparing the values of C-index, then the model was visualized and the nomogram was finally plotted.
The variables screened by Lasso regression including age, gender, cirrhosis, tumor number, tumor size, platelet-albumin-bilirubin index (PALBI), and viral load were incorporated in the Cox model and random survival forest model (P<0.05). The C-index of these two models in the training sets was 0.729 and 0.708, and was 0.726 and 0.700 in the validation sets, respectively. So we finally chose Lasso-Cox regression model, and the calibration curve in the validation set performed well, indicating that the model built has a better predictive ability. And then a nomogram was plotted based on the model chosen to visualize the results.
The present study established a nomogram for predicting recurrence in patients with early-stage HCC based on the Lasso-Cox regression model. This nomogram was of some guiding significance for screening populations at high risk of recurrence after treatment, by which doctors can formulate individualized follow-up strategies or treatment protocols according to the predicted risk of relapse for patients to improve the long-term prognosis.
Traditional Chinese medicine (TCM) has been garnering ever-increasing worldwide attention as the herbal extracts and formulas prove to have potency against disease. Fuzhengjiedu San (FZJDS), has been ...extensively used to treat viral diseases in pigs, but its bioactive components and therapeutic mechanisms remain unclear.
In this study, we conducted an integrative approach of network pharmacology and experimental study to elucidate the mechanisms underlying FZJDS's action in treating porcine reproductive and respiratory syndrome virus (PRRSV). We constructed PPI network and screened the core targets according to their degree of value. GO and KEGG enrichment analyses were also carried out to identify relevant pathways. Lastly, qRT-PCR, flow cytometry and western blotting were used to determine the effects of FZJDS on core gene expression in PRRSV-infected monkey kidney (MARC-145) cells to further expand the results of network pharmacological analysis.
Network pharmacology data revealed that quercetin, kaempferol, and luteolin were the main active compounds of FZJDS. The phosphatidylinositol-3-kinase (PI3K)/Akt pathway was deemed the cellular target as it has been shown to participate most in PRRSV replication and other PRRSV-related functions. Analysis by qRT-PCR and western blotting demonstrated that FZJDS significantly reduced the expression of P65, JNK, TLR4, N protein, Bax and IĸBa in MARC-145 cells, and increased the expression of Bcl-2, consistent with network pharmacology results. This study provides that FZJDS has significant antiviral activity through its effects on the PI3K/AKT signaling pathway.
We conclude that FZJDS is a promising candidate herbal formulation for treating PRRSV and deserves further investigation.
Staphylococcus aureus is one of the most important pathogens causing mastitis in dairy cows. The objective of this study was to establish a rat model of mastitis induced by S. aureus infection and to ...explore changes in the proteomes of mammary tissue in different udder states, providing a better understanding of the host immune response to S. aureus mastitis. On day 3 post-partum, 6 rats were randomly divided into two groups (n = 3), with either 100 μL of PBS (blank group) or a S. aureus suspension containing 2×107 CFU·mL-1 (challenge group) infused into the mammary gland duct. After 24 h of infection, the rats were sacrificed, and mammary gland tissue was collected. Tandem mass tag (TMT)-based technology was applied to compare the proteomes of healthy and mastitic mammary tissues. Compared with the control group, the challenge group had 555 proteins with significant differences in expression, of which 428 were significantly upregulated (FC>1.2 and p<0.05) and 127 were downregulated (FC>0.83 and p<0.05 or p<0.01). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that upregulated differentially significant expressed proteins (DSEPs) were associated with mainly immune responses, including integrin alpha M, inter-α-trypsin inhibitor heavy chain 4, and alpha-2-macroglobulin. This study is the first in which a rat model of S. aureus-induced mastitis was used to explore the proteins related to mastitis in dairy cows by TMT technology, providing a model for replication of dairy cow S. aureus-induced mastitis experiments.
•This paper introduces a time series change detection method for land cover.•This method integrates both intensity differences and polarization correlation.•This method improves the efficiency and ...accuracy of change detection.•A general change descriptor severs for both multi-data and bi-data analysis.
To detect historical cumulative changes in land cover, this study introduces a novel time series PolSAR change detection method. The objective is to address the inefficiency of traditional detection methods that use multiple pairwise comparisons, as well as to alleviate false positives and false negatives caused by the insufficient utilization of polarization and spatial context information in previous methods. The proposed method initially constructs a temporal difference matrix for time series PolSAR images and computes the difference image (DI) using the maximum eigenvalue of this matrix to depict the cumulative changes over time. Subsequently, the DI is segmented using an MRF-based image segmentation method with a limited amount of supervised information, yielding the cumulative change binary map. The efficacy of the proposed method is validated using three time series datasets covering different scenes acquired by different sensors, namely GaoFen3, Radarsat2 and Sentinel-1. The experimental results demonstrate that the method effectively characterizes cumulative changes in the time series while simultaneously considering disparities in radar backscatter intensity and polarization correlation. As a result, it significantly reduces erroneous and missed change detections and surpasses the existing methods by achieving the highest Recall, F1-score, IOU, Kappa, and overall accuracy. Furthermore, the DI calculation method serves as a versatile change descriptor applicable not only for capturing cumulative changes in time series but also for describing changes between dual temporal images.
Chronic hepatitis B virus (HBV) infection is a worldwide public health threat that results in huge morbidity and mortality. Late diagnosis and delayed treatment of HBV infections can cause ...irreversible liver damages and occurrence of cirrhosis and hepatocellular carcinoma (HCC). Detection of the presence and activity of HBV are the cornerstones of diagnosis and management in HBV related disease. Moreover, comprehensive knowledge of the mechanisms regulating HBV immunobiology is pivotal for managing diseases related with HBV. Here we tried to categorize and illustrate the classical and novel approaches used for diagnosis of HBV. Also, we reviewed our current knowledge on the immunobiology of HBV related HCC.
The first classical heterocyclic ionic liquid (IL) promoted C–H bond oxidant cross-coupling reaction for the intramolecular annulation of 5-(aryloxy)-1H-pyrazole-4-carbaldehydes to ...chromeno2,3-cpyrazol-4(1H)-ones has been disclosed. The promoter 1,3-dibutyl-1H-benzod1,2,3triazol-3-ium bromide can be easily recycled and reused with the same efficacies for at least five cycles in aqueous medium. The strategy works smoothly and provides an applicable protocol to construct a wide range of products.