Tectorigenin Alleviates Inflammation, Apoptosis, and Ossification in Rat Tendon-Derived Stem Cells via Modulating NF-Kappa B and MAPK Pathways

Moqbel, Safwat Adel Abdo; Xu, Kai; Chen, Zhonggai; Xu, Langhai; He, Yuezhe; Wu, Zhipeng; Ma, Chiyuan; Ran, Jisheng; Wu, Lidong; Xiong, Yan

doi:10.3389/fcell.2020.568894

Cited by 27 publications

(19 citation statements)

References 38 publications

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“…Consistently, autophagy inhibitors could counteract the inhibitory effect of TEC on lipid droplet formation and enhance the expression of pyroptosis protein and release of LDH. Combined with TEC improving liver failure by regulating autophagy pathway, and TEC regulated TLR4, NF-κB and MAPK pathway to inhibit the occurrence of inflammatory response, which all proved our view that TEC may improve NASH by regulating hepatocyte autophagy and pyroptosis [ 23 , 44 ].…”

Section: Discussionmentioning

confidence: 73%

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

et al. 2022

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Background Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and has no safe and effective drug for treatment. We have previously reported the function of blueberry, but the effective monomer and related molecular mechanism remain unclear. Methods The monomer of blueberry was examined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The NASH cell model was constructed by exposing HepG2 cells to free fatty acids. The NASH mouse model was induced by a high-fat diet for 12 weeks. NASH cell and mouse models were treated with different concentrations of blueberry monomers. The molecular mechanism was studied by Oil Red O staining, ELISA, enzyme activity, haematoxylin–eosin (H&E) staining, immunohistochemistry, immunofluorescence, western blot, RNA sequencing, and qRT-PCR. Results We identified one of the main monomer of blueberry as tectorigenin (TEC). Cyanidin-3-O glucoside (C3G) and TEC could significantly inhibit the formation of lipid droplets in steatosis hepatocytes, and the effect of TEC on the formation of lipid droplets was significantly higher than that of C3G. TEC can promote cell proliferation and inhibit the release of inflammatory mediators in NASH cell model. Additionally, TEC administration provided a protective role against high-fat diets induced lipid damage, and suppressed lipid accumulation. In NASH mouse model, TEC can activate autophagy, inhibit pyroptosis and the release of inflammatory mediators. In NASH cell model, TEC inhibited pyroptosis by stimulating autophagy. Then, small RNA sequencing revealed that TEC up-regulated the expression of tRF-47-58ZZJQJYSWRYVMMV5BO (tRF-47). The knockdown of tRF-47 blunted the beneficial effects of TEC on NASH in vitro, including inhibition of autophagy, activation of pyroptosis and release of inflammatory factors. Similarly, suppression of tRF-47 promoted the lipid injury and lipid deposition in vivo. Conclusions These results demonstrated that tRF-47-mediated autophagy and pyroptosis plays a vital role in the function of TEC to treat NASH, suggesting that TEC may be a promising drug for the treatment of NASH.

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Section: Discussionmentioning

confidence: 73%

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

et al. 2022

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“…And there are also studies suggesting that the activation of NF-κB can induce the activation of the MAPK pathway [62]. Another study showed that TNF-α can induce TDSC in ammation and apoptosis, and promote the development of tendinopathy by up-regulating the activation of MAPK and NF-κB pathways [63]. Our analysis of the difference in immune cell in ltration of the whole gene of the samples showed that the in ltration of M1 macrophages, activated mast cells, activated NK cells, and regulatory T cells (Tregs) in tendinopathy samples increased, while the in ltration of plasma cells and memory B cells decreased.…”

Section: Discussionmentioning

confidence: 99%

Screening of key biomarkers of tendinopathy based on bioinformatics and machine learning algorithms

Zhu

Huang

Zhou³

et al. 2021

Preprint

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Tendinopathy is a complex, multifaceted tendon disease that is often associated with overuse and causes significant health care costs with its high prevalence. At present, the pathogenesis and effective treatment of tendinopathy cannot be fully elucidated. This study aims to deeply explore and analyze the key genes, functional pathways, and immune infiltration characteristics of the occurrence and development of tendinopathy.MethodsThe gene expression profiles of GSE106292, GSE26051 and GSE167226 were downloaded from GEO database. The WGCNA analysis was performed on GSE106292 data set by the R package in R software, and differential gene analysis was performed on GSE26051 and GSE167226 data sets by combining and screening. The gene enrichment analysis of GO and KEGG and immune cell infiltration analysis were performed. Lasso logistic regression, support vector machine (SVM-REF) and Gaussian mixture model (GMMS) algorithm were used to screen and identify early diagnostic genes.ResultsWe have obtained a total of 171 DEGs through WGCNA analysis and screening of different expressed genes. By GO and KEGG enrichment analysis, it was found that these malregulated genes were related to mTOR, HIF-1, MAPK, NF-κB and VEGF signaling pathways. Immunoinfiltration analysis showed that M1 macrophages, activated mast cells and activated NK cells had infiltration significance. MacroD1 may be an early diagnosis gene, and it was found based on Lasso, SVM-REF and GMMS algorithm.ConclusionsBased on comprehensive bioinformatics analysis, we identified the potential early diagnosis genes MACROD1, key regulatory pathways and immune infiltration characteristics of tendinopathy. These key genes and pathways may be used as biomarkers and molecular therapeutic targets for early tendon injury to guide drugs and basic research.

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“…during joint degeneration, especially that of the cartilage, the levels of some inflammatory cytokines, (including TNF-α and IL-1β) are increased, and subsequently cause a progressive, cell-mediated cascade of molecular and structural deterioration (36,37). TNF-α and IL-1β exert their detrimental functions via multiple important intracellular cascades, such as the NF-κB and MAPK pathways (38,39), In general, TNF-α and IL-1β transmit inflammatory signals via their receptors and activate the phosphorylation of the IKK complex (40), which then phosphorylates IκBα (41). Subsequently, IκBα is unbound and phosphorylates NF-κB, which translocates into the nucleus to initiate the transcription of inflammatory products, catabolic enzymes and apoptotic mediators (42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice

et al. 2021

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At present, an increasing number of individuals are affected by osteoarthritis (OA), resulting in a heavy socioeconomic burden. OA in knee joints is caused by the release of inflammatory cytokines and subsequent biomechanical and structural deterioration. To determine its anti-inflammatory function, the current study investigated the use of the plant-derived medicine, curcumenol, in OA treatment. curcumenol was not cytotoxic to ATdc5 chondrocytes and primary chondrocytes, as determined using a cell viability test. When these cells were treated with TNF-α and IL-1β to induce inflammation, curcumenol treatment inhibited the progression of inflammation by inactivating the NF-κB and MAPK signaling pathways, as well as decreasing the expression levels of MMP3 (as indicated by reverse transcription-quantitative PcR and western blotting). Moreover, to analyze metabolic and catabolic status in high-density and pellet culture, catalytic changes and the degradation of the extracellular matrix induced by TNF-α and IL-1β, were evaluated by alcian blue staining. These catalytic deteriorations were ameliorated by curcumenol. Using curcumenol in disease management, the mechanical and metabolic disruption of cartilage caused in the destabilization of medial meniscus (dMM) model was prevented in vivo. Thus, curcumenol mitigated inflammation in ATdc5 chondrocytes and primary mice chondrocytes, and also ameliorated OA in a dMM-induced mouse model.

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Tectorigenin Alleviates Inflammation, Apoptosis, and Ossification in Rat Tendon-Derived Stem Cells via Modulating NF-Kappa B and MAPK Pathways

Cited by 27 publications

References 38 publications

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

Screening of key biomarkers of tendinopathy based on bioinformatics and machine learning algorithms

Curcumenol mitigates chondrocyte inflammation by inhibiting the NF‑κB and MAPK pathways, and ameliorates DMM‑induced OA in mice

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