Foods
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2025
·Vol. 14
·期 24
·4267
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IF 5.1
Jing Xu,Wen-Zhao Wen,Jun-Hui Zhao,Jun-Rong Guo,Zhuo-Ya Zhang,Ping Xiong
Citri grandis exocarpium ( Citri grandis ) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE −/− C57BL/6J mice. ApoE −/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE −/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE −/− mice were upregulated ( p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed ( p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE −/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis.
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高影响因子
BIOCHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 3.8
Chuanfu Huo,Yuanyuan Zhao,Meng Song,Yuzhe Guo,Shihao Li,Wensong Tan,Yan Zhou
Exosomes are nanoscale vesicles containing a variety of bioactive factors, showing significant potential as cell-free therapeutic agents. However, the large clinical doses required for exosome administration highlight the need for a scalable serum-free production system to increase exosome yield. In this study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs) were cultured in three-dimensional (3D) environments using polyethylene terephthalate (PET) fiber membranes. Two key pathways promoting exosome secretion and biogenesis through 3D culture were identified. Specifically, 3D culture reduced the expression of Integrin β1, leading to the decondensation of cortical actin, and increased the expression of RAC1, which promoted actin aggregation on the membranes of multivesicular bodies (MVBs). Building on this mechanistic understanding, we simulated the depolymerization/aggregation of the cytoskeleton in 3D culture and designed a serum-free medium optimized for exosome production. For large-scale exosome production, hUCMSCs were cultured in a fixed-bed bioreactor using PET fiber rolls as the fixed-bed layer with the developed serum-free medium. This setup increased exosome production per cell by 16-fold compared to 2D culture, yielding 2.6 × 10^14 exosome particles. The exosome products demonstrated enhanced in vitro angiogenesis, immunomodulation, and in vivo wound healing capabilities. This study provides valuable insights and strategic guidance for the serum-free, large-scale production of exosomes using bioreactors, with significant implications for therapeutic applications.
研究领域:
细胞生物学
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再生医学
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生物工程
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高影响因子
Frontiers in Endocrinology
·
2023
·
IF 5.2
Zhao Qingsong,Xu Jinmei,Han Xu,Zhang Zheqi,Qu Jiahui,Cheng Zhifeng
Background: Diabetic foot ulcer (DFU) represents a highly-prevalent complication of diabetes mellitus (DM). Herein, the current study sought to identify the role of growth differentiation factor 10 (GDF-10) in wound healing in DFU via regulation of the transforming growth factor-beta 1 (TGF-β1)/Smad3 pathway.Methods: DM- and DFU-related microarray datasets GSE29221 and GSE134431 were firstly retrieved, and weighted gene co-expression network analysis (WGCNA) was carried out to construct a co-expression network affecting wound healing in DFU, followed by differential analysis. A protein-protein interaction (PPI) network of the DFU-related genes was subsequently constructed, and the core genes and signaling pathways in DFU were screened with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses. A DFU rat model was constructed for mechanism verification of the effect of GDF-10 on wound healing in DFU.Results: WGCNA screened five co-expression modules, and the brown module was most closely-related to DM. Clustering analysis screened 4417 candidate genes, of which 175 differential genes were associated with wound healing, further involved in TGF-β1/Smad3 signaling pathway regulation of wound healing in DFU. The PPI network analysis predicted that GDF-10 might regulate the TGF-β1/Smad3 signaling pathway to participate in DFU development. Results of animal experimentation showed that the wound healing rates of NFU, DFU, DFU + GDF and GDF + SIS3 groups on the 22nd day were (87.66 ± 6.80)%, (56.31 ± 7.29)%, (71.64 ± 9.43)% and (55.09 ± 7.13)%, respectively. Besides, the expression of TGF-β1 in NFU, DFU, DFU + GDF and GDF + SIS3 groups was 0.988 ± 0.086, 0.297 ± 0.036, 0.447 ± 0.044, and 0.240 ± 0.050, respectively, and that of Smad3 was 1.009 ± 0.137, 0.145 ± 0.017, 0.368 ± 0.048, and 0.200 ± 0.028, respectively. Specifically, GDF-10 exerted a significant diminishing effect on fasting blood glucose level, and promoted wound healing in DFU rats, in addition to up-regulation of VEGF, FGF, Ang-1, TGF-β1, Smad3 and enhancement of IL-1b, IL-6, TNF-a and MMP-9, thereby promoting fibroblast proliferation, collagen deposition and angiogenesis.Conclusions: Our findings highlight that GDF-10 may promote angiogenesis by activating TGF-β1/Smad3 signaling, thereby promoting wound healing in DFU rats.
研究领域:
糖尿病
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分子生物学
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药理学
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Yuling Tong,Ruilin Wang,Xia Liu,Miao Tian,Yanling Wang,Yanfei Cui,Wenjun Zou,Yanling Zhao
Ethnopharmacological relevance Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases . Aim of this study The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG . Materials and methods The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot . Results The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1. Conclusion ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
研究领域:
药理学
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民族药理学
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胃肠病学
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分子生物学
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细胞生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 13
·10839
·
IF 5.6
Mingkang Zhang,Ruirui Cui,Yan Zhou,Yanrong Ma,Yongwen Jin,Lina Wang,Wen Kou,Xin’an Wu
Renal fibrosis is relentlessly progressive and irreversible, and a life-threatening risk. With the continuous intake of a high-purine diet, hyperuricemia has become a health risk factor in addition to hyperglycemia, hypertension, and hyperlipidemia. Hyperuricemia is also an independent risk factor for renal interstitial fibrosis. Numerous studies have reported that increased mast cells (MCs) are closely associated with kidney injury induced by different triggering factors. This study investigated the effect of MCs on renal injury in rats caused by hyperuricemia and the relationship between MCs and renal fibrosis. Our results reveal that hyperuricemia contributes to renal injury, with a significant increase in renal MCs, leading to renal fibrosis, mitochondrial structural disorders, and oxidative stress damage. The administration of the MCs membrane stabilizer, sodium cromoglycate (SCG), decreased the expression of SCF/c-kit, reduced the expression of α-SMA, MMP2, and inhibited the TGF-β1/Smad2/3 pathway, thereby alleviating renal fibrosis. Additionally, SCG reduced renal oxidative stress and mitigated mitochondrial structural damage by inhibiting Ang II production and increasing renal GSH, GSH-Px, and GR levels. Collectively, the recruitment of MCs, activation of the TGF-β1/Smad2/3 pathway, and Ang II production drive renal oxidative stress, ultimately promoting the progression of renal fibrosis in hyperuricemic rats.Keywords:hyperuricemia;renal fibrosis;mast cells;TGF-β1/Smad2/3 pathway;oxidative stress
研究领域:
肾病学
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病理生理学
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药理学
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高影响因子
MOLECULAR CARCINOGENESIS
·
2025
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IF 3.2
Fei Chen,Caitang Liu,Rongrong Jiang,Hao Wang
Colon cancer treatment remains a clinical challenge. Chaperonin containing TCP1 subunit 6 A (CCT6A) acts as an oncogene in multiple tumors. In this study, we investigated its roles in colon cancer cells. We analyzed CCT6A expression using single-cell datasets and the Gene Expression Profiling Interactive Analysis based on The Cancer Genome Atlas database. Immunohistochemistry, quantitative reverse transcription polymerase chain reaction, and western blot analysis were used to assess CCT6A expression levels in colon cancer tissues and cell lines. Additionally, specific roles of CCT6A in colon cancer was analyzed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining, flow cytometry, wound healing, transwell, boron dipyrromethene staining, western blot analysis, and nude model mice. We found that CCT6A expression levels were significantly elevated in colon cancer tissues compared to those in normal tissues and predicted a worse prognosis. CCT6A induced proliferation, migration, invasion, epithelial-mesenchymal transition, and fatty acid synthesis and suppressed apoptosis in colon cancer cells. Mechanistically, CCT6A promoted colon cancer progression by increasing the cleavage of latency-associated peptide (LAP)-transforming growth factor-β1 (TGF-β1) to mature form of TGF-β and inducing Smad2/3 phosphorylation in colon cancer cells. Overall, CCT6A promoted colon cancer progression by modulating fatty acid metabolism and activating the TGF-β1/Smad signaling, serving as a potential therapeutic target for colon cancer.
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CELL PROLIFERATION
·
2023
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IF 8.5
Guanhui Cai,Yahui Lu,Weijie Zhong,Ting Wang,Yingyi Li,Xiaolei Ruan,Hongyu Chen,Lian Sun,Zhaolan Guan,Gen Li,Hengwei Zhang,Wen Sun,Minglong Chen,Wei-Bing Zhang,Hua Wang
Macrophages are multifunctional immune system cells that are essential for the mechanical stimulation-induced control of metabolism. Piezo1 is a non-selective calcium channel expressed in multifarious tissues to convey mechanical signals. Here, a cellular model of tension was used to study the effect of mechanical stretch on the phenotypic transformation of macrophages and its mechanism. An indirect co-culture system was used to explore the effect of macrophage activation on bone marrow mesenchymal stem cells (BMSCs), and a treadmill running model was used to validate the mechanism in vivo for in vitro studies. p53 was acetylated and deacetylated by macrophages as a result of mechanical strain being detected by Piezo1. This process is able to polarize macrophages towards M2 and secretes transforming growth factor-beta (TGF-β1), which subsequently stimulates BMSCs migration, proliferation and osteogenic differentiation. Knockdown of Piezo1 inhibits the conversion of macrophages to the reparative phenotype, thereby affecting bone remodelling. Blockade of TGF-β I, II receptors and Piezo1 significantly reduced exercise-increased bone mass in mice. In conclusion, we showed that mechanical tension causes calcium influx, p53 deacetylation, macrophage polarization towards M2 and TGF-β1 release through Piezo1. These events support BMSC osteogenesis.
研究领域:
免疫学
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细胞生物学
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力学生物学
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骨生物学
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高影响因子
BIOORGANIC CHEMISTRY
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2022
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IF 5.307
Tingting Ma,Huanli Cheng,Tongxi Li,Yifan Chen,Tianying Cai,Junjie Bai,Ziming Wu,Xianming Xia,Tiancheng Liang,Yichao Du,Wenguang Fu
Background Although liver fibrosis is a key pathologic process in many liver diseases, therapeutic approaches for inhibiting liver fibrosis are still very limited. N-Acetyl- l -tryptophan ( l -NAT) has a hepatoprotective effect via inhibiting the destruction of liver cells, enhancing cell viability and reducing the inflammation. However, the effect of l -NAT on liver fibrosis is not determined. Purpose The present study investigated the effect of l -NAT on liver fibrosis and explored it potential molecular mechanism. Methods To address this concern, this study was carried out via fibrotic mice model induced by CCl 4 and many approaches such as various histological staining methods, western blot assay, etc. Result l -NAT decreased the levels of alanine aminotransferase (ALT) and aspartate transaminase (AST) in fibrotic mice model induced by carbon tetrachloride (CCl 4 ). Histological staining showed that l -NAT ameliorated liver injury and fibrosis, and reduced the expression of α-smooth muscle actin (α-SMA) and Collagen I protein. l -NAT also attenuated apoptosis by down-regulating the level of pro-apoptotic protein Bax and up-regulating that of anti-apoptotic protein Bcl-2. Moreover, l -NAT inhibited the expressions of TGF-β1/SMAD and matrix metalloproteinase 9 (MMP9) proteins, and reversed the expression of YAP1 protein in CCl 4 -induced liver fibrosis. Conclusion These results clearly demonstrated that l -NAT attenuated CCl 4 -induced liver fibrosis in mice, and this protective mechanism might relate to TGF-β1/SMAD and Hippo/YAP1 signaling pathway. Thus, this study provided data basis for the prevention and treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF CARDIOLOGY
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2024
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IF 3.2
Zihan Wei,Ying Lu,Cheng Qian,Jing Li
Background Atrial fibrosis is associated with the pathogenesis of atrial fibrillation (AF). This study aims to discuss the function of circ_0079480 in atrial fibrosis and its underlying mechanism. Methods In vitro and in vivo models of atrial fibrosis were established by using angiotensin II (Ang II) to treat human atrial fibroblasts (HAFs) and C57/B6J mice. qRT-PCR and western blot were used to examine the mRNA and protein expression levels. CCK-8, EdU, cell strach, and transwell assays were performed to determine the proliferation and migration of HAFs. Dual-luciferase reporter and RIP/RNA pull-down assays were explored to identify the interaction of miR-338-3p and circ_0079480/THBS1. HE and Masson's trichrome staining experiments were performed to analyze the histopathological change in mice atrial tissues. Results Circ_0079480 expression was increased in AF patients' atrial tissues and Ang II-treated HAFs. Silencing circ_0079480 inhibited cell proliferation and migration and reduced fibrosis-associated gene expression in Ang II-treated HAFs. Circ_0079480 could target miR-338-3p to repress its expression. MiR-338-3p inhibitor blocked the inhibitory effects of circ_0079480 knockdown on HAFs proliferation, migration, and fibrosis. Thrombospondin-1 (THBS1) was confirmed as a downstream target of miR-338-3p, and circ_0079480 could sponge miR-338-3p to upregulate THBS1 expression. Moreover, silencing THBS1 suppressed Ang II-induced proliferation, migration, and fibrosis in HAFs. More importantly, depletion of circ_0079480 inactivated the THBS1/TGF-β1/Smad3 signaling by upregulating miR-338-3p. Mice experiments also confirmed the suppression of circ_0079480 knockdown on atrial fibrosis. Conclusion Circ_0079480 acts as a sponge of miR-338-3p to upregulate THBS1 expression and activate the TGF-β1/Smad3 signaling, finally promoting Ang II-induced atrial fibrosis.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
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IF 11.3
Run Ling,Xin Yin,Liyao Ma,Yan Zhang,Yidan Ma,Rufei Gao,Yanqing Geng,Xinyi Mu,Xuemei Chen,Fangfang Li,Junlin He
Decabromodiphenyl ethane (DBDPE) is a brominated flame retardant widely used for its high flame retardancy and low bioavailability. However, DBDPE exhibits bioaccumulative potential. The placental vasculature, critical for the exchange between maternal and fetal circulation, is susceptible to environmental factors. We aimed to understand the potential toxicity of DBDPE to the placental vasculature. Gestational CD-1 mice and human umbilical vein endothelial cells (HUVECs) were exposed to 0, 0.5, 5, 50 mg/kg·bw·day or 0, 6.25, 12.5, 25, 50 μmol/L DBDPE, respectively. DBDPE exposure impaired placental angiogenesis and inhibited the proliferation and invasion of HUVECs by activating the endothelial-to-mesenchymal transition (EndMT) through the TGF-β1/Smad pathway, in vivo and in vitro . DBDPE upregulated the transcription factor TWIST2 and mRNA acetyltransferase NAT10. Knockdown or overexpression of TWIST2 reversed the vascular dysfunction and EndMT mechanism. DBDPE facilitated the recruitment of NAT10 by TWIST2, promoting N4-acetylcytidine (ac4C) RNA modifications and stabilizing the TGF-β1 mRNA. NAT10 inhibition rescued the effects caused by DBDPE. These findings uncover molecular mechanisms linking DBDPE exposure to adverse pregnancy outcomes, highlighting potential risks to pregnant women.
研究领域:
毒理学
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生殖生物学
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分子生物学
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环境健康
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细胞生物学
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RNA修饰
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发育生物学
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
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IF 3.361
Chunyan Li,Xiao Sun,Ang Li,Min Mo,Zhongxi Zhao
Pulmonary fibrosis (PF) is a disease characterized by diffusing alveolar inflammation and alveolar structural disorders that ultimately lead to pulmonary interstitial fibrosis. S-allylmercaptocysteine (SAMC) as a water-soluble organosulfur garlic derivative exhibits efficient anti-inflammatory and anti-oxidative activities. In this study, we attempted to explore the function of SAMC in inhibiting bleomycin (BLM)-induced pulmonary fibrosis in mice. 0.035 U/g of BLM was intraperitoneally injected into mice twice per week for 4 weeks to induce fibrosis. SAMC (25 and 50 mg/kg) and N-acetylcysteine (NAC, 600 mg/kg) were given to mice for 28 days. The results indicate that SAMC could significantly ameliorate the pathological structure, and decrease inflammatory cell infiltration and pro-inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in BLM-induced pulmonary fibrosis mice. SAMC showed an anti-fibrosis effect by increasing anti-oxidants like HO-1, GSH and SOD as well as decreasing hydroxyproline (HYP) in BLM-induced mice. Mechanistic studies suggested that SAMC alleviated oxidative stress probably by impacting the Nox4/Nrf2 pathways, and played an anti-fibrosis role with decreasing the expression of α-SMA, collagen III, collagen I by suppressing the TGF-β1/Smad pathway. These findings indicate that SAMC may be partially responsible for the therapeutic effect on PF patients.
研究领域:
药理学
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肺科学
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免疫学
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病理学
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PubMed
高影响因子
FEBS Open Bio
·
2023
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IF 2.6
Yu Zhu,Longmei Wang,Rui Liu,Xiurong Ding,Song Yin,Yuankun Chen,Chuanlong Zhu,Zheng Wang,Wenting Li
Sepsis-induced acute kidney injury (SI-AKI) causes renal dysfunction and has a high mortality rate. Protein arginine methyltransferase-1 (PRMT1) is a key regulator of renal insufficiency. In this study, we explored the potential involvement of PRMT1 in SI-AKI. A murine model of SI-AKI was induced by cecal ligation and perforation (CLP). The expression and localization of PRMT1 and molecules involved in the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were detected in mouse kidney tissues by western blot, immunofluorescence, and immunohistochemistry. The association of PRMT1 with downstream molecules of the TGF-β1/Smad3 and IL-6/STAT3 signaling pathways were further verified in vitro in mouse renal tubular epithelial cells (mRTECs). CLP caused epithelial-mesenchymal transition (EMT), apoptosis, and inflammation in renal tissues, and this was alleviated by inhibition of PRMT1. Inhibition of PRMT1 in SI-AKI mice decreased the expression of TGF-β1 and phosphorylation of Smad3 in the renal cortex, and downregulated the expression of sIL-6R and phosphorylation of STAT3 in the medulla. Knockdown of PRMT1 in mRTECs restricted the expression of Cox-2, E-cad, Pro-caspase3 and p-Smad3 (involved in the TGF-β1-mediated signaling pathway), and blocked IL-6/sIL-6R, inducing the expression of Cox-2 and p-STAT3. In conclusion, our findings suggest inhibition of PRMT1 mitigates SI-AKI by inactivating the TGF-β1/Smad3 pathway in the cortex and IL-6/STAT3 pathway in the medulla. Our findings may aid in the identification of potential therapeutic target molecules for SI-AKI.
研究领域:
肾病学
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免疫学
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分子生物学
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病理生理学
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高影响因子
危险品化学品经营许可证（带存储）