Journal of Functional Foods
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2020
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IF 3.701
ShiFa Ruan,ShiJian Xiang,WenFeng Wu,SiWei Cao,QunQun Du,ZhuXian Wang,TingTing Chen,Qun Shen,Li Liu,HuoJi Chen,LiDong Weng,HongXia Zhu,Qiang Liu
We applied a label-free proteomic method to explore the mechanisms of Licorice flavonoid anti-acne effects in rat. Acne model was established in the back of rats as model group (MDL), then treated with licorice flavonoid (LCF), while none treated rats as control groups (CTR). In MDL, 314 differentially expressed proteins (DEPs) and 27 significantly differentially expressed proteins (SDEPs) were identified compared to what was identified in CTR. While in LCF, 359 DEPs and 15 SDEPs were identified in comparison to MDL. Bioinformatics analysis showed that pathways related to metabolism, tight junction, PI3K-Akt signaling, focal adhesion, regulation of actin cytoskeleton, and leukocyte transendothelial migration were activated. The results of proteomics data were validated by qRT-PCR and western blot. Transdermal administration of LCF may exert anti-acne effects by inhibiting PI3K-Akt signaling pathway and mitochondrial activity. Hence, our results elucidated the underlying mechanisms of LCF anti-acne effect.
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高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
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2017
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IF 4.521
Jing Zhang,Li Li,Yueting Peng,Yu Chen,Xiaoying Lv,Shun Li,Xiang Qin,Hong Yang,Chunhui Wu,Yiyao Liu
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH 3 , NH 2 , OH), it was found that hydrophobic surfaces modified with CH 3 and NH 2 suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH 3 and NH 2 triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH 3 - and NH 2 -modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH 3 - and NH 2 -modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
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PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
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2025
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IF 4.3
Li Ting,Zhou Sheng-Yang,Quan Wei,Zhou Yu,Wu Jian,Zhao Li-Ping,Qiao Chen-Meng,Zhao Wei-Jiang,Cui Chun,Shen Yan-Qin
More than 80% of patients with Parkinson’s disease (PD) exhibit severe gastrointestinal symptoms, which seriously affect life quality of life. Several large-scale epidemiological studies have confirmed that exercise can improve motor symptoms of PD patients, but the influence on gastrointestinal symptoms has not been reported. To clarify whether exercise can enhance intestinal barrier and ameliorate intestinal inflammation in PD mice, we examined whether moderate-intensity treadmill exercise for 6 weeks could alleviate gastrointestinal symptoms in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute PD mice. Our results demonstrated that 6 weeks moderate-intensity treadmill exercise enhanced the expression of Muc-2 and tight junction proteins, while reducing the expression of cytokines and chemokines, in the distal colon. Moreover, 6 weeks of treadmill exercise reduced the concentrations of short-chain fatty acids (SCFAs) and the expression of G protein-coupled receptor 43 (GPR43) to maintain the intestinal barrier and alleviate intestinal inflammation. Further data showed that 6 weeks of moderate-intensity treadmill exercise enhanced insulin-like growth factor 1 (IGF-1) expression and activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Taken as a whole, these results revealed that 6 weeks of moderate-intensity treadmill exercise enhanced intestinal barrier function, reduced intestinal inflammation and corrected abnormal concentrations of SCFAs by activating IGF-1/PI3K/Akt pathway in MPTP-induced subacute PD mice.
研究领域:
神经生物学
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运动医学
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胃肠病学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Wei Wei,Siting Pu,Chengxin Yan,Hongzao Yang,Hongwei Chen
The rapid growth of lithium (Li)-related industrial activities and the application of Li-containing products have become an emerging human health concern. Li has been employed to treat human mental disorders; however, excessive Li salt accumulation can lead to brain damage. The mechanism of toxicity of long-term exposure to Li in the brain warrants further investigation. This research study established a network toxicology strategy to evaluate the molecular mechanisms and putative toxicity of lithium chloride (LiCl). The analysis of online databases identified 80 intersection targets for LiCl-induced neurotoxicity. Further refinements via STRING and Cytoscape software highlight 10 core targets. Furthermore, phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), apoptosis pathways, and mitogen-activated protein kinase (MAPK) were enriched. Molecular docking validated the robust interaction of core targets with Li + . In vivo analyses of mice brains revealed substantial pathological alterations, neuronal degeneration, and nerve cell apoptosis. LiCl elevated the mRNA level of core genes. Further, the phosphorylation status of core proteins was primarily modulated by LiCl. Our investigation employs novel strategies for assessing the environmental pollutant toxicity and gives theoretical basis for elaborating the LiCl-induced neurotoxicity-related molecular mechanism. This may be employed to guide risk assessment of environmental Li exposure.
研究领域:
毒理学
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神经科学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
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IF 4.7
Qiqi Yang,Yuan Yao,Junping Wang,Mengdi Pang,Jinyan Wu,Fusheng Yin,Jun He,Yanyan Wang,Weidong Chen
Non-small cell lung cancer (NSCLC) is characterized by a complex pathogenesis and high mortality. Targeted drug therapy represents a precise method of treatment. However, Improving sensitivity to targeted agents is currently a major challenge in clinical tumor therapy. Neogambogic acid (NGA), a bioactive compound isolated from the Traditional Chinese Medicine (TCM) Gamboge, has shown potential in NSCLC treatment. Nonetheless, the mechanism by which NGA enhances the sensitivity of NSCLC to the targeted drug Almonertinib remains unclear. This study aimed to elucidate the mechanisms underlying the ability of NGA to enhance the sensitivity of NSCLC to Almonertinib, revealing the synergistic effect exerted by the combination therapy. We established a subcutaneous grafted tumor model of mouse lung cancer by injecting Lewis cells, and evaluated the therapeutic efficacy in vivo . The study demonstrated that NGA combined with Almonertinib effectively suppressed NSCLC tumor growth by promoting cancer cell apoptosis and reducing serum tumor marker levels. In vitro experiments revealed that this combination synergistically inhibited lung cancer cell proliferation and induced apoptosis. Mechanistically, NGA demonstrated the ability to bind to Pregnane X receptor (PXR), regulating the expression of drug-metabolizing enzymes and transporters. We further validated this effect using PXR agonists and inhibitors in A549 cells. Additionally, the combination of NGA with Almonertinib significantly inhibited aberrant EGFR activation and downstream PI3K/AKT signaling, leading to enhanced apoptosis. This study demonstrated that the combination of NGA and Almonertinib inhibited the expression of CYP3A4, P-gp, and BCRP via PXR modulation. Meanwhile, it inhibited the EGFR/PI3K/AKT pathway and enhanced the sensitivity of NSCLC to Almonertinib, exerting synergistic anti-tumor effects. Our findings suggest a promising strategy for integrating active TCM components with targeted therapy in NSCLC management.
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
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
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IF 6.3
Li Li,Wenqian Cai,Hao Zhang,Jiuren Tang,Yongjie Yang,Yang Huang,Qing Xi,Rongxin Zhang
Renal fibrosis is the most common pathway for the development of end-stage renal disease (ESRD) in various kidney diseases. Currently, the treatment options for renal fibrosis are limited. Ferroptosis is iron-mediated lipid peroxidation, triggered mainly by iron deposition and ROS generation. Notably, the kidney is the most sensitive of all tissues to iron-dependent ferroptosis, and the inhibition of ferroptosis is an effective therapeutic strategy for the treatment of kidney fibrosis. Nonetheless, the pathways involved in ferroptosis in renal fibrosis are still unclear. Bergapten, a natural coumarin derivative, is mainly found in bergapten essential oil, grapefruit juice, and other commonly used plants, and it has various pharmacological effects. However, the role that ferroptosis plays in renal fibrosis and the potential therapeutic benefits of bergapten remain unclear. In this study, we investigated the therapeutic effects of bergapten on renal fibrosis and its mechanisms. We investigated the anti-fibrotic effects of bergapten in in vivo and in vitro models of renal fibrosis. Initially, network pharmacological analysis was employed to predict the potential therapeutic impact of bergapten on renal fibrosis. We then explored the potential therapeutic role of bergapten in obstructive nephropathy, which is due to unilateral ureteral obstruction (UUO). Furthermore, RNA-Seq was conducted to investigate the possible mechanism of bergapten against renal fibrosis. Additionally, Bergapten demonstrated a significant improvement in TGF-β1-induced fibrosis and RSL3-induced renal tubular epithelial cell ferroptosis; these findings are consistent with those of the in vivo studies. Our findings indicate that bergapten is a potential treatment for renal fibrosis. Treatment with bergapten significantly reduced the expression of fibronectin and α-SMA in the damaged kidneys of UUO mice, thereby improving fibrosis. Meanwhile, bergapten protected against fibrosis caused by TGF-β1 and ferroptosis induced by glutathione peroxidase 4 (GPX4) inhibitor RSL3. Significantly, bergapten therapy alleviated renal fibrosis by modulating ferroptosis. We found that bergapten inhibited PI3K phosphorylation and indirectly restored GPX4 expression. In conclusion, we have revealed the nephroprotective effect of bergapten, whose mechanism of action is related to the inhibition of ferroptosis, and it is expected that it will be developed as a therapeutic agent for the treatment of renal fibrosis. This study aims to explore the effect of bergapten on renal fibrosis ferroptosis. Collectively, these results demonstrate that bergapten is an inhibitor of ferroptosis and provides a new treatment strategy for diseases associated with ferroptosis.
研究领域:
肾病学
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药理学
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分子生物学
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PubMed
高影响因子
CELLULAR SIGNALLING
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2025
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IF 3.7
JingjingLi,Juan Gu,SijiaPan,Nuo Deng,Muhammad Khan,Lingyan Li,Xiao Wu,Yongming Li
Despite continuous therapeutic interventions, the prognosis of hepatocellular carcinoma (HCC) remains very poor. Thus, quest for novel treatment strategies to improve therapeutic window of HCC therapy is paramount. Arsenic trioxide (ATO) is commonly used as the first-line treatment for acute promyelocytic leukemia (APL). Isoliquiritigenin (ISL) is a potential plant-based bioactive molecule with versatile biological and pharmacological effects including anticancer effect. The present study aimed to investigate the potential synergistic effects of combination of ISL and ATO in HCC cells. The data revealed that the combination of ISL and ATO synergistically inhibited HCC cell proliferation. The collective data demonstrate that synergistic anticancer effect of combined treatment of ISL + ATO was achieved via cooperative induction of mitochondrial apoptosis through ROS generation and inhibition of PI3K/Akt/mTOR pathway. In addition, ROS generation and suppression of PI3K/Akt/mTOR pathway were found to be two independent events in induction of apoptosis. Finally, we observed that combination treatment effectively suppressed tumor growth in nude mice xenograft model through induction of intrinsic apoptosis and inhibition of PI3K/Akt/mTOR pathway. In conclusion, the findings of this study suggest that both drugs work synergistically to exert anti-tumor effect in HCC, both in-vitro and in-vivo and could offer novel strategy for liver cancer treatment.
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
高影响因子
CELLULAR SIGNALLING
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2025
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IF 3.7
Tingjuan Huang,Ziyi Shang,Lina Nie,Haichao Diao,Qizhi Shuai,Junjie Ren,Jun Xu,Jun Xie
Hepatic stellate cells (HSCs) are the central link of the occurrence and development of hepatic fibrosis, and autophagy promotes HSCs activation. N6-methyladenosine (m6A) RNA modification can also control autophagy by targeting selected autophagy-associated genes. but up to now, little research has been done on the m6A modification autophagy-related genes (ATGs) in hepatic fibrosis. Here, we identify ATG9A as a previously unrecognized m6A modified ATG using m6A-sequencing (m6A-seq). Importantly, ATG9A is upregulated in liver fibrosis mice and primary biliary cirrhosis (PBC) patient liver tissue. Mechanistically, based on the presence of m6A binding sites on ATG9A, ATG9A promotes HSCs autophagy in an m6A dependent manner, thereby enhancing HSCs activation. Noteworthy, FTO is identified as the upstream of ATG9A, and knockdown of ATG9A can prevent FTO-induced HSCs autophagy and activation. In bile duct ligation (BDL) or CCL4-induced liver fibrosis mouse models, lowering ATG9A alleviated liver fibrosis through PI3K/AKT/mTOR pathway and TGFβ1/smad3 pathway. Taken together, our results provided that ATG9A is a potential prognostic biomarker and therapeutic target for patients with liver fibrosis.
研究领域:
分子生物学
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遗传学
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肝病学
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PubMed
高影响因子
Microorganisms
·
2024
·Vol. 12
·期 6
·1132
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IF 4.1
Peng Jin,Lin-Sheng Zhao,Tong-Qiang Zhang,Han Di,Wei Guo
Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed toMycoplasma pneumoniae(MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15–20 min) and intratracheal administration (6–50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 108CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.
研究领域:
医学研究
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病理学
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免疫学
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PubMed
高影响因子
Biology-Basel
·
2025
·Vol. 14
·期 11
·1573
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IF 3.5
Shize Zhang,Tian Cheng,Yuang Chen,Mengqin Wang,Guangji Wang,Jiye Aa
Based on emerging evidence linking vitamin homeostasis to inflammatory bowel disease, this study investigated the causal role and therapeutic potential of folate in ulcerative colitis. By employing Mendelian randomization and experimental models, we demonstrated that folate supplementation markedly attenuated colitis severity, suppressed inflammatory responses, and restored the structure and function of the epithelial barrier. Mechanistically, folate acts through inhibition of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis, leading to improved barrier integrity and reduced mucosal inflammation. These findings establish folate not only as a protective nutrient but also as a potential therapeutic agent, supporting its use in clinical nutritional strategies for ulcerative colitis management. Vitamin homeostasis plays a critical role in inflammatory bowel disease management, yet the protective mechanisms and clinical utility of specific vitamins remain incompletely characterized. Within this context, a two-sample Mendelian randomization analysis leveraging genetic instruments for measuring circulating vitamin levels identified folate as a protective factor against ulcerative colitis (UC). To validate these findings, a DSS-induced colitis model was established with serial serum folate measurements. Therapeutic folate supplements were subsequently administered, followed by a comprehensive evaluation of epithelial barrier modulation through in vivo and recombinant TNF-α/IFN-γ-induced in vitro models. This included assessment of junctional proteins, ultrastructural analysis by transmission electron microscopy, and functional quantification of barrier integrity using transepithelial electrical resistance with paracellular permeability assays in epithelial monolayers. Molecular mechanisms were investigated through RNA sequencing complemented by immunoblot validation of key pathway components. The results demonstrated decreased serum folate levels in DSS-induced colitis mice, whereas folate supplementation ameliorated disease severity and attenuated intestinal inflammation and histopathological damage. Crucially, folate restored epithelial barrier structural integrity and function both in vivo and in vitro. Mechanistically, folate mediated barrier restoration through suppression of the PI3K/AKT/NF-κB/MLCK/MLC2 signaling axis. Collectively, the results of this study provide mechanistic insights that support the use of folate as an active therapeutic molecule in patients with UC.
研究领域:
免疫学
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胃肠病学
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营养科学
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分子生物学
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药理学
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PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Qiaomei Zheng,Xia Zhang,Shaozhan Chen,Shaoyu Wang,Lihong Chen,Jinhua Wang
Purpose This study investigated indirubin's effects on ovarian cancer cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), both in vitro and in vivo, while exploring its underlying mechanisms. Methods The anti-tumor activity of indirubin was evaluated using ovarian cancer cell lines (A2780, SKOV-3, OVCAR-3) through MTT, colony formation, wound healing, and Transwell assays. Patient-derived organoids and a nude mouse xenograft model were employed for further validation. Mechanistic studies integrated bioinformatics analysis (SymMap database and transcriptome sequencing) with experimental assessment of EMT markers and PI3K/AKT pathway activity, including the use of specific inhibitors (MK2206, SB 216763). Results Indirubin significantly suppressed ovarian cancer cell proliferation, colony formation, migration, and invasion, as well as inhibited patient-derived organoid growth. In a xenograft model, indirubin effectively attenuated tumor growth without inducing pathological changes in major organs. Through SymMap database and transcriptomic analyses, indirubin was shown to modulate multiple signaling pathways, particularly impairing cell adhesion. Mechanistically, indirubin downregulated AKT and GSK-3β phosphorylation in the PI3K/AKT pathway, and upregulated E-cadherin while suppressing Vimentin and N-cadherin, thereby inhibiting EMT. Notably, indirubin, the PI3K/AKT inhibitor MK2206, and the GSK-3β inhibitor SB216763 all exhibited strong antitumor efficacy in vivo. Conclusion Indirubin exerts broad anti-ovarian cancer effects by inhibiting proliferation, migration, invasion as well as EMT, with demonstrated efficacy in xenograft models and no observed organ toxicity. Its mechanistic overlap with PI3K/AKT inhibitors underscores its potential as a multitargeted therapeutic agent.
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高影响因子
JOURNAL OF HUMAN GENETICS
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2025
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IF 2.5
Yin Bin,Li Mu-Jia,Sun Jia-Lin,You Yue,Zhang Si-Di,Wan Qian-Xue,Yao Mei-Lin,Yang Cheng-Wei,Sun Hua-Qin,Lin Zi-Yuan,Shi Bing,Jia Zhong-Lin
The biological interactions between genetic and environmental modifiers play critical roles in the etiology of non-syndromic orofacial cleft (NSOC), but it is rarely studied. This study selected 47 environmental related genes from the metabolic pathways of smoking, drinking, hypoxia, and vitamins (including vitamin A, vitamin B9 (folic acid), vitamin C (ascorbic acid), vitamin D, and vitamin E), and test their associations with NSOC and its subtypes. We found that a novel gene SLC23A2 , the vitamin C transporter gene is significantly associated with non-syndromic cleft palate only (NSCPO) ( p = 3.25E-07, OR = 8.45, 95%CI:3.73–19.17). SLC23A2 is expressed in the craniofacial region of zebrafish (24hpf to 120hpf), obvious craniofacial abnormalities appeared in zebrafish (48hpf) when knock down the slc23a2 ( slc23a2 -MO). Knock down SLC23A2 in human embryonic palatal mesenchymal cell line (HEPM) induced decreased intracellular ascorbic acid (AA), increased reactive oxygen species (ROS), inhibited cell proliferation and triggered apoptosis, activated the PI3K-AKT-mTOR signaling pathway and inhibited autophagy; ROS levels and apoptosis ratio significantly decreased when we supplemented AA to HEPM cells with high ROS levels induced by Sin-1 (an exogenous ROS mimic). Knocked down SLC23A2 in HEPM cells or zebrafish, they became more sensitive to Sin-1, and AA supplementation was ineffective. In conclusion, we identified a novel susceptibility gene SLC23A2 for NSCPO, it may function by decreasing AA level, increasing the ROS levels, inducing apoptosis, and inhibiting autophagy through the activation of the PI3K-AKT-mTOR pathway in etiology of cleft palate.
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高影响因子
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