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
Drug Design Development and Therapy
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2022
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IF 4.319
Yu Li,Ximei Wang
Purpose High glucose environment in diabetes mellitus induces the dysfunction of bone marrow-derived mesenchymal stromal cells (BMSCs) and impairs bone regeneration. Chrysin is a natural polyphenol with outstanding anti-inflammation and anti-oxidation ability. However, whether and how chrysin affects BMSCs in high glucose conditions remain poorly understood. The present study aimed to explore the effects and underlying mechanisms of chrysin on the BMSCs exposed to high glucose environment.Materials and Methods Cell viability was detected by cell counting kit 8 assay and 5-ethynyl-2’-deoxyuridine staining, while cell apoptosis was determined through flow cytometry using Annexin V-FITC/PI kit. The oxidative stress in BMSCs was evaluated by detecting the reactive oxygen species production, malondialdehyde content, and superoxide dismutase activity. Alkaline phosphatase staining, Alizarin Red staining, and quantitative real-time PCR were performed to determine the osteogenic differentiation. Western blot was used to examine the expression of the PI3K/ATK/Nrf2 signaling pathway. Furthermore, chrysin was injected into calvarial defects of type 1 diabetic SD rats to assess its in vivo bone formation capability.Results Chrysin reduced oxidative stress, increased cell viability, and promoted osteogenic differentiation in BMSCs exposed to high glucose. Blocking PI3K/ATK/Nrf2 signaling pathway weakened the beneficial effects of chrysin, indicating that chrysin at least partly worked through the PI3K/ATK/Nrf2 pathway.Conclusion Chrysin can protect BMSCs from high glucose-induced oxidative stress via the activation of the PI3K/AKT/Nrf2 pathway, and promote bone regeneration in type 1 diabetic rats.
研究领域:
细胞生物学
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分子生物学
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糖尿病研究
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PubMed
高影响因子
DISEASE MARKERS
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2022
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IF 3.464
Zhiwen Wang,Changfeng Wang,Jieping Fu,Ruen Liu,Xinhui Zhou
Purpose. Cinnamaldehyde (CA) is the main ingredient in cinnamon, and it has been proven to have an inhibitory effect on many different tumor types. However, it lacks effect on glioma. This paper explores the effect CA has on glioma cells U87 and U251 at the cellular and molecular levels. Methods. The relationship between Hif-1α and Sept9 was found by CGGA. Cell Viability Assay (CCK8) was made to detect the proliferation ability. The scratch experiment and the transwell experiment were applied to the migration and invasion ability. Annexin V-FITC/PI were used to detect the cell apoptosis. Western blotting was used to determine the specified protein level. Results. Cell proliferation assay results revealed CA to inhibit the proliferation of glioma cells in a dose-dependent manner. It promoted apoptosis for upregulating the expression of Bax and downregulating the expression of Bcl-2. Wound Healing Assay and transwell test found CA to have anti-invasion ability and that it upregulated the expression of E-cadherin and downregulated the expressions of MMP-2 and MMP-9. The molecular mechanism was studied from a tumor microenvironment (TME) perspective. Pi3k inhibitor (LY294002) was used for interfering with cells, and the results found CA to demonstrate a similar effect. Hif-1α and Sept9 expressions were inhibited, and Akt and p-Akt were also inhibited. By using CoCl2 to make hypoxia, CA was discovered to inhibit the high expression of Hif-1α and Sept9, demonstrating a correlation with the Pi3k/Akt pathway. It is suggested that the mechanism of Sept9 under hypoxia regulation can be realized through the Pi3k/Akt pathway. Conclusions. This study proves for the first time that CA is an effective drug for inhibiting the proliferation of glioma through Sept9 and reveals Sept9 to be related to the Pi3k/Akt pathway in terms of tumor microenvironment, providing a molecular basis for the further study of CA in glioma treatment.
研究领域:
肿瘤学
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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
EXPERIMENTAL CELL RESEARCH
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2021
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IF 3.905
Decai Chi,Dong Wang,Minghui Zhang,Hui Ma,Fuhui Chen,Yajiao Sun
Lung cancer is the leading cause of cancer mortality worldwide. CLEC12B , a C-type lectin-like receptor, is low-expressed in lung cancer tissues. However, the function of CLEC12B in lung cancer and its underlying mechanism remain unclear. Here, an obvious down-regulation of CLEC12B was observed in lung cancer cells compared with the normal lung epithelial cells. CLEC12B over-expression suppressed cell viability and cell cycle entry in lung cancer, along with the reduction of PCNA and cyclin D1 expressions, while silencing CLEC12B possessed the opposite effects. Over-expression of CLEC12B promoted lung cancer cell apoptosis, accompanied by decreased Bcl-2 and increased Bax, cleaved caspase-3 and cleaved caspase-9. Moreover, CLEC12B decreased phosphorylation of PI3K-p85 and AKT proteins. By contrast, CLEC12B knockdown activated the PI3K/AKT pathway. In vivo , CLEC12B inhibited tumor growth in lung cancer, which can be reversed by CLEC12B inhibition. Co-IP and immunofluorescence assays confirmed the interaction between CLEC12B and SHP-1, and CLEC12B over-expression increased SHP-1 level. Furthermore, knocking down SHP-1 abrogated the above biological phenotypes caused by CLEC12B elevation. Taken together, our findings demonstrate that CLEC12B serves as a tumor-suppressing gene in lung cancer through positively regulating SHP-1 expression, which may be mediated by the PI3K/AKT signaling pathway .
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
PLATELETS
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2026
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IF 3.1
Shaochuan Wang,Debin Guo,Shidan Li,Ruohui Tang,Hao Jiang,Xiaoming Li,Youbin Li,Jing Yang,Lei Li,Jun Fei
Bone maintains a dynamic and stable state through the orchestration of osteoclasts and osteoblasts. Osteoblasts are derived mainly from mesenchymal stem cell (MSC) and are responsible for bone formation. The inhibition of osteoblast proliferation and differentiation is involved in many diseases, including osteoporosis, osteoarthritis, infected bone defects, and inflammatory aseptic loosening of implants. Given the currently limited treatment options, exploring new methods to promote bone formation is an important focus significant for orthopedists. Platelet-rich plasma (PRP), an autologous substance that is rich in various growth factors, is widely used in regenerative medicine. However, the effect of PRP on inflammatory bone destruction remains unclear. We investigated the effects of PRP on the viability of MSC, and the impact of different concentrations of PRP (1% and 3%, respectively) on cell death, proliferation, and differentiation. Furthermore, we tested the therapeutic effect of different concentrations of PRP (1% and 3%) on LPS-induced inflammatory bone destruction in vivo. PRP enhanced the cellular activity of MSC and promoted osteogenesis. A higher concentration of PRP (3%) primarily reduced the death and increased the proliferation of in LPS-treated MSC via the PI3K/AKT pathway, while a lower concentration of PRP (1%) promoted MSC differentiation into osteoblasts through the MAPK pathway. Consistent with in vitro experiments, we validated the protective effect of PRP against LPS-induced bone loss by increasing bone formation in vivo. These results suggest that different concentrations of PRP can ameliorate LPS-induced inflammatory bone loss through distinct mechanisms.
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高影响因子
PHYTOMEDICINE
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2026
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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
FITOTERAPIA
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2026
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IF 2.9
Zihan Zhou,Fanxing Zhou,Xudong Xing,Zuguo Zheng,Guangji Wang,Hua Yang
QGJZF reduces aortic plaque in AS mice with PCSK9 overexpression induced by HFD. • 16 blood-absorbed components and 23 metabolites identified from QGJZF in vivo . • Network pharmacology and omics reveal QGJZF modulates lipid metabolism via PI3K-AKT. • QGJZF suppresses macrophage foam cell formation. • QGJZF activates PI3K-AKT pathway and upregulates ABCA1 for cholesterol export. Objective Qigui Jiangzhi Formula (QGJZF) is a traditional Chinese medicine formulation developed based on the principles of regulating Qi, warming Yang, and resolving dampness. All of its herbs have historically been used to treat obesity, hypertension, and hyperlipidemia. However, its therapeutic mechanism in atherosclerosis (AS)-related cardiovascular disease remains unclear. This study aimed to investigate the anti-atherosclerotic activity and explain the mechanism of QGJZF. Methods PCSK9 overexpressing mice induced by high-fat diet were used to establish an in vivo model. Aortic pathology and inflammation were assessed via histology, immunofluorescence, and Enzyme-linked immunosorbent assay. Chemical characterisation was performed by LC-MS. Network pharmacology and multi-omics were combined to elucidate the mechanism of QGJZF, validated by molecular docking and surface plasmon resonance (SPR). An in vitro foam cell model using ox-LDL-induced RAW264.7 macrophages was analysed by qPCR and Western blot. Results QGJZF effectively reduced aortic lipid plaque deposition, ameliorated plaque pathology, and suppressed macrophage infiltration in AS mice. LC-MS identified 93 non-volatile components, including 16 blood-entering constituents and 23 metabolites. Network pharmacology and multi-omics analyses indicated QGJZF regulates lipid metabolism via the PI3K-AKT pathway. Molecular docking and SPR confirmed strong binding of five major blood-entering components to PI3K/AKT proteins. In vitro , QGJZF activates the PI3K-AKT pathway, upregulated ABCA1 expression, inhibited macrophage foam cell formation, and improved lipid metabolism. Conclusion QGJZF inhibits the formation of foam macrophages through the PI3K-AKT-ABCA1 signalling pathway, thereby improving AS. This provides a scientific foundation for the clinical application of QGJZF in AS-related cardiovascular disease. Download: Download high-res image (195KB) Download: Download full-size image
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ALLERGOLOGY INTERNATIONAL
·
2025
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IF 6.7
Maoxin Huang,Liping Dong,Yue He,Xinying Cai,Yun Lu,Jinlei Xu,Fengli Xiao
Background YTHDF1, a critical regulator of cellular processes, has attracted attention for its involvement in some inflammatory diseases. However, its specific association with atopic dermatitis (AD) remains unclear. The objective is to investigate the functional roles and underlying mechanisms of YTHDF1 in AD. Methods The expression of YTHDF1 was investigated by bioinformatics analysis and skin lesions of AD patients. The functional role and upstream and downstream regulatory mechanisms of YTHDF1 were examined through a series of in vitro and in vivo experiments. Adeno-associated virus (AAV)-mediated delivery of YTHDF1 in the AD mouse model was evaluated for its therapeutic potential. Results Bioinformatics analysis revealed that the YTHDF1 mRNA level in the skin lesions of AD was significantly higher than that in healthy people. YTHDF1 expression was significantly elevated in AD skin lesions, the DNCB-induced AD mouse model, and primary human keratinocytes and HaCaT cells stimulated with interleukin (IL)-4/IL-13, compared to controls. Both in vitro and in vivo experiments revealed that upregulation of YTHDF1 in AD exacerbated cell proliferation and inhibited keratinization by activating the PI3K/AKT pathway, which was modulated via the IL-4/IL-13/STAT3 axis. Moreover, topical application of AAV-YTHDF1 significantly improved AD-like lesions in the mouse model. Conclusions This study identifies YTHDF1 as a contributor to AD pathogenesis by influencing keratinocyte proliferation and differentiation. It also suggests that YTHDF1 could be a potential therapeutic target for AD treatment.
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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
LIVER INTERNATIONAL
·
2026
·Vol. 46
·期 6
·e70696
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IF 6.2
Ling Liu,Jintao Zheng,Ye Wang,Chenao Yang,Yuqiang Shan,Changku Jia
Background & Aims Hepatic fibrosis (HF) is a key pathological process in the development of chronic liver disease, and the activation of hepatic stellate cells (HSCs) is its core driving factor. Although curcumin, as a natural polyphenolic compound, has therapeutic potential, its specific mechanism in HF is still unclear. Methods This study used the CCl4-induced mouse HF model and explored its mechanism through single-cell RNA sequencing (scRNA-seq) combined with in vitro and in vivo experimental systems. Results The results showed that curcumin attenuated liver injury and fibrosis levels in mice with HF in a dose-dependent way, alleviated liver pathological damage, improved liver function indicators, and inhibited the release of inflammatory factors. ScRNA-seq analysis revealed a significant reduction in the number of activated HSCs after curcumin treatment, and the key gene Crispld2 was identified through perturbation model prediction and pseudo-temporal analysis. Curcumin significantly downregulated the expression of Crispld2 and inhibited the activation of the PI3K/AKT signalling pathway. In the TGF—β—induced LX-2 cell activation model, curcumin inhibited HSC proliferation, promoted apoptosis, reduced fibrosis-related protein expression, and decreased inflammatory cytokine secretion by regulating Crispld2. Overexpression of Crispld2 reversed the anti-fibrotic effect of curcumin, while the PI3K/AKT pathway inhibitor LY294002 restored its therapeutic effect. Animal experiments further confirmed that curcumin improved HF by regulating the Crispld2/PI3K/AKT axis. Conclusions This study elucidates the molecular mechanism by which curcumin exerts anti-HF effects by inhibiting the activation of the PI3K/AKT pathway mediated by Crispld2, providing a new strategy for targeted therapy of Crispld2. Lay Summary This study investigated the ameliorative effects of curcumin, a natural compound, on hepatic injury and fibrosis in mouse models of liver fibrosis. The underlying mechanism involves the suppression of the key gene Crispld2, which subsequently blocks the aberrant activation of the PI3K/AKT signalling pathway, thereby inhibiting the activation of hepatic stellate cells and exerting hepatoprotective functions. These findings furnish novel scientific evidence supporting the therapeutic application of curcumin in patients with liver fibrosis and shed new light on the development of Crispld2-targeted pharmaceutical agents. Curcumin can alleviate liver injury and fibrosis in mice with hepatic fibrosis. The underlying mechanism is that curcumin blocks the PI3K/AKT signalling pathway by targeting and inhibiting Crispld2, thereby suppressing the activation of HSCs and ameliorating hepatic fibrosis.
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高影响因子
Biology-Basel
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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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高影响因子
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