International Journal of Oral Science
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2023
·Vol. 15
·期 1
·1-13
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IF 14.9
Lan Tingting,Bi Fei,Xu Yuchan,Yin Xiaoli,Chen Jie,Han Xue,Guo Weihua
Xenogenic organ transplantation has been considered the most promising strategy in providing possible substitutes with the physiological function of the failing organs as well as solving the problem of insufficient donor sources. However, the xenograft, suffered from immune rejection and ischemia-reperfusion injury (IRI), causes massive reactive oxygen species (ROS) expression and the subsequent cell apoptosis, leading to the xenograft failure. Our previous study found a positive role of PPAR-γ in anti-inflammation through its immunomodulation effects, which inspires us to apply PPAR-γ agonist rosiglitazone (RSG) to address survival issue of xenograft with the potential to eliminate the excessive ROS. In this study, xenogenic bioroot was constructed by wrapping the dental follicle cells (DFC) with porcine extracellular matrix (pECM). The hydrogen peroxide (H 2 O 2 )-induced DFC was pretreated with RSG to observe its protection on the damaged biological function. Immunoflourescence staining and transmission electron microscope were used to detect the intracellular ROS level. SD rat orthotopic transplantation model and superoxide dismutase 1 (SOD1) knockout mice subcutaneous transplantation model were applied to explore the regenerative outcome of the xenograft. It showed that RSG pretreatment significantly reduced the adverse effects of H 2 O 2 on DFC with decreased intracellular ROS expression and alleviated mitochondrial damage. In vivo results confirmed RSG administration substantially enhanced the host’s antioxidant capacity with reduced osteoclasts formation and increased periodontal ligament-like tissue regeneration efficiency, maximumly maintaining the xenograft function. We considered that RSG preconditioning could preserve the biological properties of the transplanted stem cells under oxidative stress (OS) microenvironment and promote organ regeneration by attenuating the inflammatory reaction and OS injury.
研究领域:
移植学
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再生医学
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药理学
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细胞生物学
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牙科学
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PubMed
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Food Bioscience
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2025
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IF 5.9
Cuiting Yang,Yingying Zhang,Mingyue Jia,Qingsong Qu,Zhixun Li,Qing Zhou,Minfang Feng,Yuting Tian,Weishuo Ren,Xinyuan Shi
Monascus fermented Ginseng exhibits superior lipid-regulation activity compared to the raw materials, which undoubtedly related to fermentation-induced changes. This study aims to elucidate the interactions between Monascus purpureus (M. purpureus) and ginseng during fermentation and identify an effective ginseng fraction optimal for co-fermentation. Initially, the effective fractions extracted from ginseng—total polysaccharides, amino acids, and ginsenosides, were separately added to the basic medium to assess their impact on M. purpureus growth and metabolism. Meanwhile, ginsenoside transformation during fermentation was also investigated. The fermentation product derived from the selected ginseng fraction and M. purpureus was assessed for its lipid-lowering efficacy. The results indicated that total amino acids and total ginsenosides, except for total polysaccharides, facilitated the growth of M. purpureus and enhanced Monacolin K production. The expression levels of genes associated with M. purpureus metabolism exhibited significant alterations. The changes in various ginsenoside monomers revealed potential ginsenoside transformation pathways during the fermentation process. Additionally, Monascus purpureus fermented Ginsenosides exhibited lipid-lowering efficacy comparable to Monascus fermented Ginseng, potentially regulating the lipid metabolism via the Peroxisome proliferator-activated receptor and Sterol regulatory element-binding protein (PPAR/SREBP) signaling pathway. These insights not only elucidate the interaction mechanisms between M. purpureus and ginseng fractions during fermentation but also demonstrate the lipid-lowering potential of Monascus purpureus fermented Ginsenosides at both cellular and molecular levels, highlighting certain significance for the rational utilization of ginseng resources, revealing the key role of microorganisms in the fermentation process.
研究领域:
微生物学
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药理学
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代谢生物学
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MOLECULAR GENETICS AND GENOMICS
·
2025
·Vol. 300
·期 1
·1-16
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IF 2.1
Tian Xinyuan,Bai Xiaoping,Han Yunqi,Ye Yu,Peng Meiling,Cui Hongwei,Li Kai
PPAR γ, as a widely present receptor in tissues, plays a key role in lipid metabolism, energy balance, inflammatory response, and cell differentiation. It plays an important role in the occurrence and development of various tumors, including prostate cancer, gastric cancer, lung cancer, etc., by regulating lipid metabolism. However, the specific mechanism by which it affects lung cancer growth is not yet clear. To investigate how PPAR γ affects lung cancer cell growth by altering ALDH1A3 levels through its impact on lipid metabolism. Bioinformatics analysis was used to predict the correlation between PPAR γ, ALDH1A3 and lung cancer. Based on the results of bioinformatics analysis, PPAR γ activator (Pioglitazone, Pio) and ALDH1A3 inhibitor (diethylaminobenzaldehyde, DEAB) were used to act on lung cancer cells and observe their growth. After measuring the IC50 value of the drug in vitro experiments, lipid metabolomics analysis was conducted to identify the significant changes in differential metabolites and metabolic pathways under the combined influence of Pio and DEAB. Through bioinformatics analysis, it was found that there were significant differences in the levels of PPAR γ and ALDH1A3 between lung cancer and normal lung tissues, and ALDH1A3 was positively correlated with PPAR γ. AUC analysis found that PPAR γ and ALDH1A3 have good predictive value in the diagnosis and prognosis of lung cancer. GSEA enrichment analysis showed that PPAR γ and ALDH1A3 were significantly correlated with lipid oxidation. Combining relevant literature to demonstrate the inhibitory effect of PPAR γ receptors on lung cancer cells and the ability of PPAR γ activation to inhibit ALDH1A3 levels. Further in vitro CCK-8 and IC50 measurements of lung cancer cells A549 and H1299 were conducted, followed by non targeted lipidomics analysis. It was found that the metabolic pathways upregulated by activation of PPAR γ and inhibition of ALDH1A3 included glycerophospholipid metabolism, cholesterol metabolism, arachidonic acid metabolism, and fat digestion and absorption, with glycerophospholipid metabolism pathway accounting for the highest percentage. Conclusion: PPAR γ activation can inhibit the production of ALDH1A3, alter the glycerophospholipid metabolism pathway, and thus inhibit the proliferation of lung cancer cells. This study confirms that PPAR γ affects lung cancer proliferation by influencing the glycerophospholipid metabolism pathway.
研究领域:
肿瘤学
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分子生物学
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代谢学
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药理学
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PubMed
高影响因子
Journal of Functional Foods
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2016
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IF 3.973
Limin Xiang,Yihai Wang,Xiaomin Yi,Xinluan Wang,Xiangjiu He
Chinese hickory ( Carya cathayensis Sarg.) is a common and nutritious nut. Twenty-nine phenolic compounds, together with three quinones and three triterpenoids , were isolated from Chinese hickory husks. Their structures were determined by comprehensive spectroscopic methods. The total methanolic extract, chloroform and ethyl acetate fractions and all the isolated compounds were evaluated for antioxidant activity and neuroprotective effects on SH-SY5Y cells, as well as the effects on the expression of PPAR-γ in 3T3-L1 cells. Quercetin ( 10 ) and protocatechuic acid methyl ester ( 24 ) showed pronounced antioxidant activities in all of the different antioxidant assays and neuroprotective effect against H 2 O 2 -induced oxidative stress . Some of the flavonoids could significantly decrease the mRNA expression level of PPAR-γ by approximately 70%. The present study provided supplement information for the evaluation of antioxidant activity and health benefit of Chinese hickory.
研究领域:
植物化学
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药理学
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营养学
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高影响因子
RENAL FAILURE
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2025
·
IF 3
Neng Bao,Ming-Jia Gu,Qiu-Ya Huang,Hai-Jian Sun,Xue-Xue Zhu,Xin Gu,Jin Wang,Xiang Yu,Qing-Bo Lu,Ya-Fen Yu
Purpose This study aims to investigate the protective effect of baicalin on sepsis-associated acute kidney injury (SA-AKI) and its molecular mechanism.Materials and methods An SA-AKI mouse model was established via lipopolysaccharide (LPS) injection. Baicalin’s effects on renal function, oxidative stress, and apoptosis were evaluated using histopathology, dihydroethidium, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Bioinformatics, molecular docking, ribonucleic acid (RNA) sequencing, and Western blotting were employed to investigate the role of baicalin in regulating the peroxisome proliferator‑activated receptor‑γ (PPAR-γ)/uncoupling protein 1 (UCP1) pathway. Human kidney-2 cells were used for in vitro validation.Results In this study, baicalin significantly ameliorated LPS-induced acute kidney injury by modulating the PPAR-γ/UCP1 signaling pathway. Both in vivo and in vitro experiments revealed that baicalin attenuates inflammation, oxidative stress, and apoptosis while restoring mitochondrial function. RNA sequencing analysis revealed significant upregulation of PPAR-γ/UCP1 in the baicalin-treated group. Further molecular docking and molecular dynamics simulations confirmed a stable interaction between baicalin and UCP1. Validation via small interfering RNA-mediated knockdown of PPAR-γ and UCP1 revealed that inhibition of the PPAR-γ/UCP1 pathway abrogated baicalin’s protective effects, highlighting the critical role of this pathway in mediating baicalin’s renoprotection.Conclusion Baicalin protects against SA-AKI by activating the PPAR-γ/UCP1 signaling pathway. This study provides new insights into the mechanisms through which baicalin mitigates kidney injury in sepsis, suggesting its potential as a therapeutic agent for SA-AKI.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 5.9
Sule Bai,Yi Zou,Yanping Li,Wenjun Yang,Futao Liu,Jiawen Wang,Zhenzhen Qie,Zhen Liu,Peng Yu,Cen Xiang,Yuou Teng
Peroxisome proliferator-activated receptor γ (PPARγ) full agonists are limited in clinical applications due to adverse effects—including adipogenesis and fluid retention—resulting from excessive activation. Using a functional group-oriented strategy, this study integrated structural features of GFT505-3d and ZLY06 to develop two novel compounds: the pan-PPAR agonist 1d and the PPARγ agonist 2d. Both compounds significantly enhanced glucose uptake in adipocytes while exhibiting minimal adipogenic activity. In HFD/STZ-induced type 2 diabetes mellitus (T2DM) models, 1d and 2d improved insulin resistance and hepatic lipid metabolism by suppressing PPARγ Ser273 phosphorylation in white adipose tissue and upregulating insulin-sensitizing genes such as adiponectin, without causing weight gain or fluid retention typically associated with conventional PPARγ agonists. Transcriptome analysis further confirmed their selective modulation of PPAR signaling pathways without activation of adipogenic gene programs. These findings highlight the unique dual regulatory advantages of 1d and 2d as next-generation PPAR modulators in glucose and lipid metabolism, offering novel insights for the design of PPAR-targeted anti-diabetic drugs.
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Molecular Medicine Reports
·
2019
·Vol. 19
·期 6
·5417-5423
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IF 1.851
Zhimin Wang,Fang Li,Yuan Quan,Junye Shen
Hepatocellular carcinoma (HCC) has become a global public health problem. Therefore, the development of novel and effective therapeutic agents for the treatment of HCC is considered an emergency. Avicularin, a bio‑active flavonoid from plants, has been reported to exhibit diverse pharmacological properties. The aim of the present study was to investigate the role of avicularin in HCC and the underlying mechanism of action. Huh7 cells were treated with avicularin in a concentration‑dependent manner, and the cell proliferation was examined using a 3‑(4, 5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide assay kit. The cell migration and invasion abilities were detected using wounding‑healing assays and Transwell assays. Flow cytometric analysis was performed to investigate the cell cycle distribution and cell apoptosis. The activity of nuclear factor (NF)‑κB (p65), cyclooxygenase‑2 (COX‑2) and peroxisome proliferator‑activated receptor γ (PPAR‑γ) were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that avicularin treatment markedly decreased cell proliferation concentration‑dependently in HCC, and inhibited cell migration and invasion in Huh7 cells. It was also found that the treatment of avicularin markedly inhibited the G0/G1‑phase cells and decreased the accumulation of S‑phase cells in the cell cycle and induced cell apoptosis. In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF‑κB (p65), COX‑2 and PPAR‑γ activities. In conclusion, the findings suggested that avicularin serves an antineoplastic role in HCC and may provide a potential therapeutic strategy for the treatment of HCC.
研究领域:
肿瘤学
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药理学
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分子生物学
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PubMed
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JOURNAL OF MEDICINAL CHEMISTRY
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2025
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IF 6.8
Xinlin Zhu,Yi Dong,Ya Zhang,Chenghai Gao,Lijian Ding,Yonghong Liu,Zhiran Ju
Gouty arthritis, driven by monosodium urate (MSU) crystal deposition and dysregulated inflammation, remains a therapeutic challenge due to the limitations of current treatments. Here, we investigate Herdmanine D (HDD), a marine-derived alkaloid from the ascidian Herdmania momus. It was optimized via structure–activity relationship (SAR) studies and computational modeling to enhance its binding to peroxisome proliferator-activated receptor γ (PPAR-γ), which regulates the PPAR-γ/NF-κB signaling pathway in gout pathogenesis. The optimized HDD derivative 9a demonstrated potent PPAR-γ binding affinity and pharmacokinetic properties, effectively suppressing NF-κB-driven pro-inflammatory cytokines in vitro. In murine MSU-induced gouty arthritis models, 9a alleviated synovial inflammation and tissue damage. Mechanistically, 9a activated PPAR-γ to inhibit NF-κB and attenuate NLRP3 inflammasome assembly. This work highlights HDD as a unique marine scaffold for next-generation antigout therapeutics, merging marine natural product safety with rational design to address unmet clinical needs.
研究领域:
药理学
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海洋天然产物
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炎症性疾病
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药物设计与开发
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风湿病学
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PubMed
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Biomaterials Science
·
2026
·
IF 5.7
Shan Yu,Ling Wang,Zhenbo Peng,Yanjun Chen,Peifang Xu
Chronic diabetic wounds remain difficult to heal due to persistent inflammation and impaired macrophage polarization. Herein, we developed an immunoregulatory dressing using a hybrid hydrogel (C-B-S) synthesized from natural polysaccharides through the photo-polymerization of carboxymethyl chitosan methacrylate (CMCMA), Bletilla striata polysaccharide methacrylate (BSPMA), and thiolated hyaluronic acid (HA-SH). The hydrogel demonstrated dual functionality by promoting hemostasis and inducing macrophage polarization toward the M2 phenotype. RNA sequencing analysis revealed that the immunomodulatory effect of Bletilla striata polysaccharide is mediated via the PPAR signaling pathway. In vivo studies demonstrated the C-B-S hydrogel enhanced angiogenesis, re-epithelialization, and collagen deposition, leading to the fastest wound closure among all groups. This study offers a transformative therapeutic strategy to restore immune balance and accelerate diabetic tissue repair, highlighting its potential for clinical translation in treating chronic diabetic wounds.
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Molecular Catalysis
·
2026
·
IF 4.3
Bingchuan Yang,Fengshan Zhang,Jingpeng Zhou,Qianwen Chen,Lihui Zhan,Yinuo Li,Hengyu Chen,Jianing Xu,Dong Yuan
Cu transition lacunary polyoxometalates Cu-LPOMs@PPAR (20%) based 3D printing have been synthetized, which exhibit outstanding qualities. • The catalyst can reuse for eight cycles. • This synthesis strategy can be easily scaled up to a gram scale. • Various thiols can be used to obtain disulfides in good yields. • The efficient environmental friendliness electrochemical reaction strategy with oxidant-free and low-cost graphite electrodes. Polyoxometalates (POMs) are promising molecular electrocatalysts owing to their rapid and reversible multi-electron transfer properties. However, their practical application is often hindered by poor recyclability and dissolution in polar media. Herein, a 3D-printed photopolyacrylate resin-supported copper-substituted lacunary phosphotungstate (PW 11 Cu) catalyst (Cu-LPOMs@PPAR) was successfully fabricated through a facile additive manufacturing strategy. The resulting macroporous catalyst efficiently promotes the oxidative coupling of thiols to disulfides under external oxidant-free electrochemical conditions. Under optimized conditions, a variety of thiols were converted into the corresponding disulfides in yields of up to 95%, and simultaneous hydrogen evolution. The catalyst exhibited excellent recyclability over eight consecutive cycles without significant loss of activity. Remarkably, in the kilogram-scale experiment, a single batch production yielded 9.77 g of the disulfide product, with a yield as high as 90%. This work demonstrates a practical strategy for integrating POM electrocatalysts into 3D-printed architectures and provides a promising platform for sustainable heterogeneous electrosynthesis. Download: Download high-res image (166KB) Download: Download full-size image
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Microbial Biotechnology
·
2025
·Vol. 18
·期 11
·e70227
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IF 5.2
Yecheng Gao,Anqi Zhu,Jingjin Li,Hualin Liu,Xiaomin Li,Heping Zhang
LPPerfectus001 (LPP; GDMCC 62334) is a strain isolated from traditional pickled vegetables and identified as Lactiplantibacillus plantarum by 16s rRNA sequencing and biochemical analysis. Whole-genome sequencing and functional prediction revealed that it is rich in carbohydrate metabolism and lipid metabolism genes, as well as short-chain fatty acid synthesis genes. Preliminary experiments on high-sugar and high-fat zebrafish showed that LPP has the potential to improve glucose and lipid metabolism. Subsequently, in a high-fat/high-fructose obese rat experiment, a 7-week intervention with LPP was conducted. Without altering energy intake, the high-dose LPP (LPPH) significantly reduced body weight and fat mass ( p < 0.05), improved insulin sensitivity (reduced HOMA-IR and fasting blood glucose, p < 0.01) and normalised lipid profiles, thereby enhancing glucose homeostasis. This intervention reversed gut microbial dysbiosis by enriching beneficial bacteria ( Akkermansia and Lactobacillus ) and suppressing pathogens ( Klebsiella pneumoniae and Ruminococcus ), while also increasing short-chain fatty acids (butyrate/acetate) associated with improved metabolism. Transcriptome analysis revealed that LPPH remodelled adipose tissue through the PPAR signalling pathway (downregulating Pparg and upregulating Cpt1a ) and activated the hepatic PI3K-Akt signalling pathway to enhance insulin sensitivity. These results suggest that LPPH alleviates metabolic disorders by synergistically regulating the gut microbiota-fat-liver axis (independent of appetite suppression), making it a promising probiotic therapy for the treatment of obesity-related metabolic disorders. Graphical Lactobacillus plantarum LPPerfectus001 (LPPH) reduced weight and fat, improved insulin sensitivity and normalised lipids in high-fat/fructose-fed rats without altering energy intake. It restored gut microbiota (↑Akkermansia, ↓pathogens), elevated SCFAs and modulated adipose, liver and muscle metabolism via PPAR, PI3K-Akt and AMPK pathways, demonstrating therapeutic potential for metabolic disorders.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
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IF 5.7
Lan Luo,Wei Liu,Shenglan Qi,Jiamei Chen,Hua Zhang,Yongping Mu,Gaofeng Chen,Wei'an Yuan,Ping Liu,Linzhang Zhang
DDC-induced cholestatic liver injury in mice was significantly ameliorated by IAS II through the suppression of ductular reaction, hepatic fibrosis, and inflammatory responses. • Gut microbiota integrity is essential for IAS II efficacy, as its protective effects are lost upon antibiotic depletion. • IAS II activates PPAR-α and FXR signaling in a receptor-dependent manner to restore BA homeostasis, a mechanism validated by in vitro inhibitor studies. Cholestatic liver disease (CLD) is a severe hepatobiliary disorder with limited treatment options. Although the natural compound Isoastragaloside II (IAS II) has been suggested to possess general hepatoprotective properties, its therapeutic efficacy against CLD has not been reported. In this study, the therapeutic potential and underlying mechanisms of IAS II for CLD were investigated using a murine model established by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding. It was demonstrated that DDC-induced cholestatic liver injury was significantly alleviated by IAS II treatment, as indicated by the normalization of key serum biochemical parameters. An integrated analysis of histopathological, protein, and gene expression data demonstrated that IAS II treatment effectively suppressed the ductular reaction, inhibited hepatic fibrosis, and attenuated inflammation. Analysis of 16S rRNA sequencing data revealed that IAS II treatment was accompanied by alterations in gut microbiota composition, including an enrichment of Bacteroides and a reduction in Lachnospiraceae_NK4A136_group . Antibiotic depletion experiments demonstrated that the hepatoprotective effects of IAS II were abrogated by gut microbiota depletion, confirming the essential role of the gut microbiota in its pharmacological action. At the molecular level, IAS II activated both the PPAR-α pathway (as indicated by transcriptomic analysis) and the FXR pathway (as confirmed by subsequent validation), which collectively resulted in a significant reduction in the hepatic accumulation of toxic bile acids (BAs). In vitro studies in LCA-induced HepG2 cells further revealed that the restoration of PPAR-α, ACOX2, FXR, and BSEP protein expression by IAS II required receptor activation, as these effects were blocked by specific inhibitors. In summary, to our knowledge, this study provides the first demonstration that a protective effect against DDC-induced cholestatic liver injury is conferred by IAS II through coordinated regulation of PPAR-α and FXR signaling, restoration of BA homeostasis, and in a gut microbiota-dependent manner, with these effects requiring the activation of both PPAR-α and FXR pathways, thereby identifying IAS II as a novel and promising therapeutic candidate for CLD. Download: Download high-res image (191KB) Download: Download full-size image
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高影响因子
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