Schisandrin inhibits VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway.

Abnormal proliferation, migration, and foam cell formation of Vascular smooth muscle cells (VSMCs) each play a role in the development of atherosclerosis (AS). Schisandrin (Sch) is the active lignan ingredient with broad-spectrum pharmacological effects. However, the role of Sch in the AS process is not clear. Therefore, this study was proposed to explore the therapeutic effect and potential mechanism of Sch on VSMCs. Ox-LDL was selected to create an atherosclerosis injury environment for VSMCs and macrophages. The MTT assay, Oil red O staining, wound healing, transwell experiments and ELISA were used to investigate the phenotype effects of Sch. Network pharmacology, molecular docking, flow cytometry, and western blot were used to investigate the underlying mechanisms of Sch on AS progression. Our findings implied that Sch treatment inhibited the proliferation and migration of VSMCs, and suppressed the ROS production and inflammatory cytokines up-regulation of VSMCs and macrophages. Moreover, Sch reduced lipid uptake and foam cell formation through downregulating LOX-1. Mechanistically, we found that Sch can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2, and arrest cell cycle in GO/G1 phase. In summary, Sch can inhibit VSMCs proliferation and migration by arresting cell cycle and targeting JAK2 to regulating the JAK2/STAT3 pathway. Sch may serve as a potential drug for patients with AS.

An integrated magnetic separation enzyme-linked colorimetric sensing platform for field detection of Escherichia coli O157: H7 in food.

An intelligent colorimetric sensing platform integrated with in situ immunomagnetic separation function was developed for ultrasensitive detection of Escherichia coli O157: H7 (E. coli O157: H7) in food. Captured antibody modified magnetic nanoparticles (cMNPs) and detection antibody/horseradish peroxidase (HRP) co-functionalized AuNPs (dHAuNPs) were firstly synthesized for targeted enrichment and colorimetric assay of E. coli O157: H7, in which remarkable signal amplification was realized by loading large amounts of HRP on the surface of AuNPs. Coupling with the optical collimation attachments and embedded magnetic separation module, a highly integrated optical device was constructed, by which in situ magnetic separation and high-quality imaging of 96-well microplates containing E. coli O157: H7 was achieved with a smartphone. The concentration of E. coli O157: H7 could be achieved in one-step by performing digital image colorimetric analysis of the obtained image with a custom-designed app. This biosensor possesses high sensitivity (1.63 CFU/mL), short detecting time (3 h), and good anti-interference performance even in real-sample testing. Overall, the developed method is expected to be a novel field detection platform for foodborne pathogens in water and food as well as for the diagnosis of infections due to its portability, ease of operation, and high feasibility.

(-)-Epicatechin gallate prevented atherosclerosis by reducing abnormal proliferation of VSMCs and oxidative stress of AML 12 cells.

(-)-Epicatechin gallate (ECG) is beneficial to the treatment of cardiovascular diseases (CVDs), especially atherosclerosis (AS) through antioxidant stress, but there is a lack of detailed mechanism research. In this study, the therapeutic target of ECG was determined by crossing the drug target and disease target of CVDs and AS. The combination ability of ECG with important targets was verified by Discovery Studio software. The abnormal proliferation of vascular smooth muscle cells (VSMCs) induced by Ang-II and the oxidative damage of AML 12 induced by H2O2 were established to verify the reliability of ECG intervention on the target protein. A total of 120 ECG targets for the treatment of CVDs-AS were predicted by network pharmacology. The results of molecular docking showed that ECG has strong binding force with VEGFA, MMP-9, CASP3 and MMP-2 domains. In vitro experiments confirmed that ECG significantly reduced the expression of VEGFA, MMP-9, CASP3 and MMP-2 in Ang-II-induced VSMCs, and also blocked the abnormal proliferation, oxidative stress and inflammatory reaction of VSMCs by inhibiting the phosphorylation of PI3K signaling pathway. At the same time, ECG also interfered with H2O2-induced oxidative damage of AML 12 cells, decreased the expression of ROS and MDA and cell foaming, and increased the activities of antioxidant enzymes such as SOD, thus playing a protective role.

ß-Cyclodextrin and Hyaluronic Acid-Modified Targeted Nanodelivery System for Atherosclerosis Prevention.

Natural products have been widely recognized in clinical treatment because of their low toxicity and high activity. It is worth paying attention to modifying the biopolymer into nanostructures to give natural active ingredients additional targeting effects. In this study, based on the multifunctional modification of ß-cyclodextrin (ß-CD), a nanoplatform encapsulating the unstable drug (-)-epicatechin gallate (ECG) was designed to deliver to atherosclerotic plaques. Acetalization cyclodextrin (PH-CD), which responds to low-pH environments, and hyaluronic acid cyclodextrin, which targets the CD44 receptor on macrophage membranes, were synthesized from ß-CD and hyaluronic acid using acetalization and transesterification, respectively. The resulting dual-carrier nanoparticles (Double-NPs) loaded with ECG were prepared using a solvent evaporation method. The Double-NPs effectively scavenged reactive oxygen species, promoted macrophage migration, inhibited macrophage apoptosis, and suppressed abnormal proliferation and migration of vascular smooth muscle cells. Furthermore, the Double-NPs actively accumulated in atherosclerotic plaques in ApoE-/- mice fed with a high-fat diet, leading to a reduced plaque area, inflammatory infiltration, and plaque instability. Our findings demonstrate that the newly developed ECG nanopreparation represents an effective and safe nanotherapy for diseases such as atherosclerosis.

Anti-inflammatory effect of proanthocyanidins from blueberry through NF-κß/NLRP3 signaling pathway in vivo and in vitro.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC. METHODS: Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis. RESULTS: Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway. CONCLUSION: PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway.

The inhibitory impact of Schisandrin on inflammation and oxidative stress alleviates LPS-induced acute kidney injury.

Inflammation and oxidative stress (OS) are the major pathogenic characteristics of acute kidney injury (AKI). Studies have shown that Schisandrin (Sch) could regulate inflammatory disease. However, the function and mechanism of Sch in AKI progression are still unknown. Here, we investigated Sch's potential effects and mechanism on mice's renal damage and macrophages induced by lipopolysaccharide (LPS). Sch decreased LPS-induced inflammatory factor production while increasing the activity of related antioxidant enzymes in macrophages and mouse kidney tissues. Hematoxylin and eosin staining revealed that Sch may have the ability to profoundly inhibit inflammatory cell invasion and tissue damage caused by LPS in renal tissue. Furthermore, Western blot and immunohistochemical studies showed that Sch exerted its effects mainly through up-regulation of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 and inhibition of Toll-like receptor 4‒mitogen-activated protein kinases/nuclear factor-kappa B pathways. Collectively, this study illustrates that Sch suppresses LPS-stimulated AKI by descending inflammation and OS, illuminating prospective AKI treatment options.

Taxonomic and functional ß-diversity patterns reveal stochastic assembly rules in microbial communities of seagrass beds.

Microorganisms are important members of seagrass bed ecosystems and play a crucial role in maintaining the health of seagrasses and the ecological functions of the ecosystem. In this study, we systematically quantified the assembly processes of microbial communities in fragmented seagrass beds and examined their correlation with environmental factors. Concurrently, we explored the relative contributions of species replacement and richness differences to the taxonomic and functional ß-diversity of microbial communities, investigated the potential interrelation between these components, and assessed the explanatory power of environmental factors. The results suggest that stochastic processes dominate community assembly. Taxonomic ß-diversity differences are governed by species replacement, while for functional ß-diversity, the contribution of richness differences slightly outweighs that of replacement processes. A weak but significant correlation (p < 0.05) exists between the two components of ß-diversity in taxonomy and functionality, with almost no observed significant correlation with environmental factors. This implies significant differences in taxonomy, but functional convergence and redundancy within microbial communities. Environmental factors are insufficient to explain the ß-diversity differences. In conclusion, the assembly of microbial communities in fragmented seagrass beds is governed by stochastic processes. The patterns of taxonomic and functional ß-diversity provide new insights and evidence for a better understanding of these stochastic assembly rules. This has important implications for the conservation and management of fragmented seagrass beds.

Multiparametric MRI-based radiomics combined with pathomics features for prediction of the efficacy of neoadjuvant chemotherapy in breast cancer.

Purpose: The aim of this study is to investigate a new method that combines radiological and pathological breast cancer information to predict discrepancies in pathological responses for individualized treatment planning. We used baseline multiparametric magnetic resonance imaging and hematoxylin and eosin-stained biopsy slides to extract quantitative feature information and predict the pathological response to neoadjuvant chemotherapy in breast cancer patients. Methods: We retrospectively collected data from breast cancer patients who received neoadjuvant chemotherapy in our hospital from August 2016 to January 2018; multiparametric magnetic resonance imaging (contrast-enhanced T1-weighted imaging and diffusion-weighted imaging) and whole slide image of hematoxylin and eosin-stained biopsy sections were collected. Quantitative imaging features were extracted from the multiparametric magnetic resonance imaging and the whole slide image were used to construct a radiopathomics signature model powered by machine learning methods. Models based on multiparametric magnetic resonance imaging or whole slide image alone were also constructed for comparison and referred to as the radiomics signature and pathomics signature models, respectively. Four modeling methods were used to establish prediction models. Model performances were evaluated using receiver operating characteristic curve analysis and the area under the curve, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. Results: The radiopathomics signature model had favourable performance for the prediction of pathological complete response in the training set (the best value: area under the curve 0.83, accuracy 0.84, and sensitivity 0.87), and in the test set (the best value: area under the curve 0.91, accuracy 0.90, and sensitivity 0.88). In the test set, the radiopathomics signature model also significantly outperformed the radiomics signature (the best value: area under the curve 0.83, accuracy 0.64, and sensitivity 0.62), pathomics signature (the best value: area under the curve 0.60, accuracy 0.74, and sensitivity 0.62) (p > 0.05). Decision curve analysis and calibration curves confirmed the excellent performance of these prediction models in discrimination, calibration, and clinical usefulness. Conclusions: The results of this study suggest that radiopathomics, the combination of both radiological information regarding the whole tumor and pathological information at the cellular level, could potentially predict discrepancies in pathological response and provide evidence for rational treatment plans.

Harmine ameliorates CCl4-induced acute liver injury through suppression of autophagy and inflammation.

CCl4-induced acute liver injury (ALI) is characterized by heightened autophagy, inflammation, and oxidative damage. Accumulating evidence suggests that harmine exerts beneficial effects in countering CCl4-induced ALI by mitigating inflammation and oxidative stress. However, the impact of autophagy on CCl4-induced ALI and the protective role of harmine remain unclear. This study aimed to investigate the potential protective effects of harmine against CCl4-induced ALI in mice by suppressing autophagy and inflammation. Male Kunming mice were orally administered harmine or bifendate for seven days. Subsequently, one hour after the final administration, the model group and treatment groups were intraperitoneally injected with CCl4 to induce ALI. The findings revealed that harmine significantly reduced the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum, and ameliorated the liver histopathological changes induced by CCl4. Furthermore, harmine diminished the levels of TNF-α and IL-6, restored the levels of glutathione (GSH) and superoxide dismutase (SOD), and suppressed the production of nitric oxide (NO) and malondialdehyde (MDA) in the liver. Mechanistically, harmine down-regulated LC3B II/I, p38 MAPK, TLR4, and NF-κB levels, while upregulating p62, Bcl-2, Beclin1, ULK1, and p-mTOR expression. In conclusion, harmine mitigated CCl4-induced ALI by inhibiting autophagy and inflammation through the p38 MAPK/mTOR autophagy pathway, the Bcl-2/Beclin1 pathway, and the TLR4/NF-κB pathway.

Bletilla striata polysaccharide attenuated the progression of pulmonary fibrosis by inhibiting TGF-ß1/Smad signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata, a traditional medicinal plant, has been utilized as a folk medicine for many years because of its superior biological activity in China. However, Bletilla striata polysaccharide (BSP) has received less attention, and its specific mechanism for ameliorating pulmonary fibrosis is completely unclear. AIMS OF THE STUDY: In this study, we aim to assess BSP on the treatment of PF and explore potential mechanisms. MATERIALS AND METHODS: BSP was successfully extracted and purified from Bletilla striata. The mechanisms were assessed in bleomycin-induced pulmonary fibrosis model and lung fibroblasts activated by transforming growth factor-ß1 (TGF-ß1). Histological analysis, immunofluorescence, Western blot and flow cytometry were used to explore the alterations after BSP intervention. RESULTS: The results in vivo showed an anti-PF effect of BSP treatment, which reduced pathogenic damages. Furthermore, TGF-ß1-induced abnormal migration and upregulated expression of collagen I (COL1A1), vimentin and α-smooth muscle actin (α-SMA) were suppressed by BSP in L929 cells. Moreover, the abnormal proliferation was retarded by inhibiting the cell cycle of G1 to S phase. Immunofluorescence assay showed that BSP activated autophagy and played an antifibrotic role by inhibiting the expression of p62 and phospho-mammalian target of rapamycin (p-mTOR). Last but not least, the suppression of TGF-ß1/Smad signaling pathway was critical for BSP to perform therapeutic effects in vitro and in vivo. CONCLUSION: The possible mechanisms were involved in improving ECM deposition, regulating cell migration and proliferation, and promoting cellular autophagy. Briefly, all of the above revealed that BSP might be a novel therapy for treating pulmonary fibrosis.

Rapid analysis of the chemical constituents in Qiangli Dingxuan tablets using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Qiangli Dingxuan (QLDX) tablet is a widely recognized traditional Chinese medicine formula that has been extensively used in China for decades to treat vertigo, tinnitus, and dizziness owing to its outstanding therapeutic outcomes. However, the complexity of the chemical components in this tablet makes it challenging to separate and identify these components. This study presented an effective and sensitive strategy for the rapid separation and simultaneous structural identification of QLDX tablet components using ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry and the UNIFI platform. Based on retention times, accurate masses, fragment ions, related literature, and authentic standards, 119 compounds were identified or tentatively characterized; these included 9 iridoids, 12 lignans, 21 phenylpropanoids, 27 flavonoids, 7 phthalides, and 43 others. Among them, 36 were confirmed using reference standards. The representative compounds with various chemical structures were studied by analyzing their fragmentation patterns and characteristic ions. In conclusion, this study established a rapid approach for characterizing the chemical constituents in QLDX tablet. The proposed approach provides a basis for qualitative analysis and quality control in the manufacturing process and is beneficial for advancing investigations into the efficacy and mechanism of action of this tablet.

Tectoridin alleviates caerulein-induced severe acute pancreatitis by targeting ERK2 to promote macrophage M2 polarization.

Severe acute pancreatitis (SAP) is an inflammatory disease of the pancreas with a high mortality rate. Macrophages play a crucial role in the pathogenesis of pancreatitis. Tectoridin (Tec) is a highly active isoflavone with anti-inflammatory pharmacological activity. However, the role of Tec in the SAP process is not known. The purpose of this study was to investigate the therapeutic effect and potential mechanism of Tec on SAP. To establish SAP mice by intraperitoneal injection of caerulein and Lipopolysaccharide (LPS), the role of Tec in the course of SAP was investigated based on histopathology, biochemical indicators of amylase and lipase and inflammatory factors. The relationship between Tec and macrophage polarization was verified by immunofluorescence, real-time quantitative PCR and Western blot analysis. We then further predicted the possible targets and signal pathways of action of Tec by network pharmacology and molecular docking, and validated them by in vivo and in vitro. In this study, we demonstrated that Tec significantly reduced pancreatic injury in SAP mice, and decreased serum levels of amylase and lipase. The immunofluorescence and Western blot analysis showed that Tec promoted macrophage M2 polarization. Network pharmacology and molecular docking predicted that Tec may target ERK2 for the treatment of SAP, and in vivo and in vitro experiments proved that Tec inhibited the ERK MAPK signal pathway. In summary, Tec can target ERK2, promote macrophage M2 polarization and attenuate pancreatic injury, Tec may be a potential drug for the treatment of SAP.

The combination of multiple environmental stressors strongly alters microbial community assembly in aquatic ecosystems.

Microorganisms play a critical role in maintaining the delicate balance of ecosystem services. However, the assembly processes that shape microbial communities are vulnerable to a range of environmental stressors, such as climate change, eutrophication, and the use of herbicides. Despite the importance of these stressors, little is known about their cumulative impacts on microbial community assembly in aquatic ecosystems. To address this knowledge gap, we established 48 mesocosm experiments that simulated shallow lake ecosystems and subjected them to warming (including continuous warming (W) and heat waves (H)), glyphosate-based herbicides (G), and nutrient loading (E). Our study revealed that in the control group, both deterministic and stochastic processes codominated the assembly of microbial communities in water, whereas in sediment, the processes were primarily stochastic. Interestingly, the effects of multiple stress factors on assembly in these two habitats were completely opposite. Specifically, stressors promoted the dominance of stochastic processes in water but increased the importance of deterministic processes in sediment. Furthermore, warming amplified the effects of herbicides but exerted an opposite and stronger influence on assembly compared to nutrients, emphasizing the complexity of these mechanisms and the significance of considering multiple stressors. The interaction of some factors significantly affected assembly (p < 0.05), with the effects of WEG being most pronounced in water. Both water and sediment exhibited homogeneous assembly of microbial communities (mean NTI >0), but the phylogenetic clustering of microbial communities in water was more closely related (NTI >2). Our research revealed the response model of microbial community assembly in aquatic ecosystems to multiple environmental stresses, such as agricultural pollution, climate change, and eutrophication, and indicated that microbial community changes in sediment may be an important predictor of lake ecosystem development. This provides scientific evidence that better environmental management can reduce impacts on aquatic ecosystems under the threat of future warming.

Automatically transferring supervised targets method for segmenting lung lesion regions with CT imaging.

BACKGROUND: To present an approach that autonomously identifies and selects a self-selective optimal target for the purpose of enhancing learning efficiency to segment infected regions of the lung from chest computed tomography images. We designed a semi-supervised dual-branch framework for training, where the training set consisted of limited expert-annotated data and a large amount of coarsely annotated data that was automatically segmented based on Hu values, which were used to train both strong and weak branches. In addition, we employed the Lovasz scoring method to automatically switch the supervision target in the weak branch and select the optimal target as the supervision object for training. This method can use noisy labels for rapid localization during the early stages of training, and gradually use more accurate targets for supervised training as the training progresses. This approach can utilize a large number of samples that do not require manual annotation, and with the iterations of training, the supervised targets containing noise become closer and closer to the fine-annotated data, which significantly improves the accuracy of the final model. RESULTS: The proposed dual-branch deep learning network based on semi-supervision together with cost-effective samples achieved 83.56 ± 12.10 and 82.67 ± 8.04 on our internal and external test benchmarks measured by the mean Dice similarity coefficient (DSC). Through experimental comparison, the DSC value of the proposed algorithm was improved by 13.54% and 2.02% on the internal benchmark and 13.37% and 2.13% on the external benchmark compared with U-Net without extra sample assistance and the mean-teacher frontier algorithm, respectively. CONCLUSION: The cost-effective pseudolabeled samples assisted the training of DL models and achieved much better results compared with traditional DL models with manually labeled samples only. Furthermore, our method also achieved the best performance compared with other up-to-date dual branch structures.

One-Step Electrocatalytic Approach Applied to the Synthesis of ß-Propiolactones from CO2 and Dienes.

ß-Lactones are common substructures in a variety of natural products and drugs, and they serve as versatile synthetic intermediates in the production of valuable chemical derivatives. Traditional ß-lactone synthesis relies on laborious multi-step synthetic methods that use toxic compounds, sophisticated catalysts, expensive, and/or reactive chemicals. Based on the in situ electrochemical formation of metal-based nanoclusters, this paper describes the development of a one-step, room temperature electrocatalytic method for the formation of stable ß-lactone from CO2 and dienes. This one-step "electrosynthesis" method results in the formation of a new class of ß-lactone with high selectivity (up to 100%) and activity (up to 80% yields with respect to the reacted diene) by regulating the applied potential and current density. This work paves the way for more sustainable and environmentally friendly reaction pathways based on the in situ formation of nanoclusters as organic electrosynthesis catalysts.

Comprehensive evaluations of a prototype full field-of-view photon counting CT system through phantom studies.

Objective. Photon counting CT (PCCT) has been a research focus in the last two decades. Recent studies and advancements have demonstrated that systems using semiconductor-based photon counting detectors (PCDs) have the potential to provide better contrast, noise and spatial resolution performance compared to conventional scintillator-based systems. With multi-energy threshold detection, PCD can simultaneously provide the photon energy measurement and enable material decomposition for spectral imaging. In this work, we report a performance evaluation of our first CdZnTe-based prototype full-size PCCT system through various phantom imaging studies.Approach.This prototype system supports a 500 mm scan field-of-view and 10 mmz-coverage at isocenter. Phantom scans were acquired using 120 kVp from 50 to 400 mAs to assess the imaging performance on: CT number accuracy, uniformity, noise, spatial resolution, material differentiation and quantification.Main results.Both qualitative and quantitative evaluations show that PCCT, under the tested conditions, has superior imaging performance with lower noise and improved spatial resolution compared to conventional energy integrating detector (EID)-CT. Using projection domain material decomposition approach with multiple energy bin measurements, PCCT virtual monoenergetic images have lower noise, and good accuracy in quantifying iodine and calcium concentrations. These results lead to increased contrast-to-noise ratio (CNR) for both high and low contrast study objects compared to EID-CT at matched dose and spatial resolution. PCCT can also generate super-high resolution images using much smaller detector pixel size than EID-CT and greatly improve image spatial resolution.Significance.Improved spatial resolution and quantification accuracy with reduced image noise of the PCCT images can potentially lead to better diagnosis at reduced radiation dose compared to conventional EID-CT. Increased CNR achieved by PCCT suggests potential reduction in iodine contrast media load, resulting in better patient safety and reduced cost.

Surgical management of acute combined injuries of the ipsilateral wrist and elbow joints.

Background: Combined injuries of ipsilateral wrist and elbow joints are rare in clinical practice, characterized by multiple joint dislocations or/and fractures and varying manifestations. As there are still no clinical guidelines and no consensus on the standard treatment, this study aimed to explore the surgical intervention and complications of this kind of combined injuries. Methods: This retrospective study was conducted in a single center. A total of 13 patients with acute combined injuries of the ipsilateral wrist and elbow joints receiving surgical treatment from August 2013 to May 2016 were retrospectively analyzed. The fracture and joint instability and structural damages were repaired and reconstructed. Results: All 13 patients were followed up for a mean duration of 17 months (range: 14 to 22 months). The X-ray films showed good fracture reduction and joint alignment, no fixation failure, re-displacement, bone nonunion, or ischemic necrosis in all cases. According to the Mayo Elbow Performance Score (MEPS), the excellent and good rate of joint function was 84.6%. According to the Mayo Modified Wrist Score (MMWS), the excellent and good rate of joint function was 76.9%. There were no significant restrictions on elbow and wrist movements. The disabilities of the arm, shoulder, and hand (DASH) score was excellent, with an average of 18.5 points. Conclusions: The key to intervention of combined injuries of the wrist and elbow is to identify the types of injuries and conduct an overall assessment to determine the appropriate surgical methods. Early surgical intervention and rehabilitation exercise are the main principles for the treatment.

(-)-Epicatechin gallate blocked cellular foam formation in atherosclerosis by modulating CD36 expression in vitro and in vivo.

Green tea is popular worldwide, so its main active ingredients have attracted people's attention. (-)-Epicatechin gallate (ECG) is the main active component of green tea polyphenols, which has good antioxidant activity, but its cardiovascular intervention is unknown. This study established in vitro and in vivo models of ox-LDL-induced macrophages and HFD-induced ApoE-/- mice to study the effects of ECG on atherosclerotic lesions. Firstly, the study confirmed that ECG has a therapeutic effect in different stages of atherosclerotic plaques. Subsequently, the results showed that the ox-LDL-induced release of pro-inflammatory mediators and the expression of the related protein CD86 in macrophages were inhibited by ECG. ECG blocked the formation of cellular foam by downregulating the expression of CD36 and LOX-1 proteins, thereby increasing SOD activity and reducing MDA production in cells. ECG also prevented ox-LDL-induced apoptosis, promoted macrophage migration, and increased plaque stability. The results confirmed that ECG attenuated ox-LDL-induced green fluorescence of ROS in macrophages by inhibiting the expression of related proteins in the NF-κB signaling pathway and activating the HO-1/Nrf2 signaling pathway. These results indicated that ECG has anti-oxidative stress and anti-inflammatory potential, and its molecular mechanism may be related to the inhibition of intracellular NF-κB signaling pathway proteins and activation of the HO-1/Nrf2 signaling pathway.

Panlongqi tablet suppresses adjuvant-induced rheumatoid arthritis by inhibiting the inflammatory reponse in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Panlongqi Tablet is prepared with the ancestral secret recipe provided by Mr. Wang Jiacheng, a famous specialist in orthopedics and traumatology of China. The efficacy and safety of PLQT have been supported by years of clinical practice in the treatment of joint-related conditions. Has remarkable effect for treating rheumatoid arthritis (RA) clinically. However, its mechanism is not entirely clear. AIM OF THE STUDY: We aim to evaluate the anti-inflammatory activity of PLQT and explore its mechanism in adjuvant-induced arthritis (AA) mice and LPS-induced Human fibroblast-like synovial (HFLS) cells. MATERIALS AND METHODS: To this end, we analyzed the active ingredients in PLQT by HPLC-MS/MS. Furthermore, the anti-RA effect of PLQT was studied through proliferation, apoptosis, foot swelling, cytokine levels, immune organ index, histopathology and related signal pathways in LPS-induced HFLS cells and AA-treated mice. RESULTS: HPLC-MS/MS results showed that PLQT contained a variety of active compounds, such as epicatechin, imperatorin, hydroxysafflor yellow A and so on. PLQT significantly inhibited the abnormal proliferation of HFLS cells induced by LPS, promoted cell apoptosis. In AA-treated mice, PLQT alleviated RA symptoms by alleviating paw swelling, synovial hyperplasia, pannus formation, inflammatory cell infiltration, and inhibiting abnormal immune responses. The results showed that PLQT significantly decreased the expression of inflammatory mediators (IL-1ß, IL-6, IL-17) in vivo and in vitro, which may be related to the regulation of PI3K/Akt, MAPK and JAK/STAT signaling pathways. CONCLUSION: Based on serum pharmacology and in vivo pharmacology studies, PLQT may regulate RA symptoms by regulating inflammatory and immune response-related pathways, which is an effective method for the treatment of RA.

TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs.

The pregnane X receptor (PXR) is an important regulator of hepatocellular carcinoma cellular resistance to antitumor drugs. Activation of PXR was modulated by the co-regulators. The target protein for the Xenopus plus end-directed kinesin-like protein (Xklp2) known as TPX2 that was previously considered as a tubulin regulator, also functions as the regulator of some transcription factors and pro-oncogenes in human malignances. However, the actions of TPX2 on PXR and HCC cells are still unclear. In the present study, our results demonstrate that the high expression of endogenous mRNA level of TPX2 not only correlated with the poor prognosis of advanced HCC patients who received sorafenib treatment but also with expression of PXR's downstream genes, cyp3a4 and/or mdr-1. Results from luciferase and real-time polymerase chain reaction (qPCR) showed that TPX2 leads to enhancement of the transcription factor activation of PXR. Protein-protein interactions between PXR and TPX2 were identified using co-immunoprecipitation. Mechanically, overexpression of TPX2 led to enhancement of PXR recruitment to its downstream gene cyp3a4's promoter region (the PXRE region) or enhancer region (the XREM region). Treatment of HCC cells with paclitaxel, a microtubule promoter, led to enhancement of the effects of TPX2, whereas vincristine, a microtubule depolymerizing agent caused a decrease in TPX2-associated effects. TPX2 was found to cause acceleration of the metabolism or clearance of sorafenib, a typical tyrosine kinase inhibitor (TKI) in HCC cells and in turn led to the resistance to sorafenib by HCC cells. By establishing novel actions of TXP2 on PXR in HCC cells, the results indicate that TPX2 could be considered a promising therapeutic target to enhance HCC cells sensitivity to antitumor drugs.