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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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
·
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
·
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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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
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
·
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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Nanoscience and Nanotechnology Letters
·
2020
·Vol. 12
·期 6
·774-781
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IF 1.128
Su Fanfan,Guo Ming,Wang Jinhua
Using nanomaterials is a potential way to improve the accuracy and safety of chemotherapeutic drugs and avoid the toxic side effects caused by the non-selectivity of traditionally used chemotherapeutic agents. Vincristine is a commercial clinical chemotherapeutic drug with good anti-tumor
effects. However, the effects of vincristine decorated hybrid nanoparticles (VCR-HNPs) on human retinoblastoma cells have not been previously reported. In this study, we explored the impact of VCR-HNPs exposure on retinoblastoma cells and identified the corresponding mechanism involved in
their activity. Retinoblastoma WERI-Rb1 and Y-79 cell lines were treated with different concentrations of VCR-HNPs and effects on cell proliferation were analyzed using the CCK8 assay, while apoptosis was measured and analyzed by flow cytometry. To further analyze the outcome of apoptosis,
Western blot assay was used to evaluate the expression levels of proteins correlating with apoptosis. Proteins involved in the PI3K/Akt pathway were also analyzed by western blotting to identify whether this pathway was involved in the molecular response to VCR-HNPs exposure. Compared with
the control group, VCR-HNPs markedly inhibited cell proliferation and induced apoptosis, at concentrations greater than 20 mg/L. In addition, western blotting experiments confirmed that VCR-HNPs could downregulate the phosphorylation of proteins involved in the PI3K/Akt signaling pathway leading
to the inactivation of the signaling pathway. VCR-HNPs exerted tumor suppressor effects on human retinoblastoma via inhibition of the PI3K/Akt signaling pathway.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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DOI
高影响因子
CARBOHYDRATE POLYMERS
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2026
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IF 13.2
Jia-Mei Geng,Pei-Feng Zhu,Lu-Shuang Xu,Ji-Lai Liu,Zheng-Qing Yang,Zhu-Ya Yang,Qiong Jin,Lu Liu
The medicinal moss Rhodobryum giganteum is rich in polysaccharides, whose structural and biofunctional properties remain largely unexplored. In this study, a novel glucose-rich polysaccharide fraction (named RGP, 29.8 kDa) was isolated and characterized from R. giganteum . Structural analysis revealed a unique α -1,6-linked glucan backbone with C-2 acetylation, along with side chains composed of →4)- α - d -glucopyranosyl-(1 → and terminal α - d -glucopyranose units. RGP significantly promoted proliferation, phagocytosis, and cytokine (TNF- α , IL-6) secretion via the TLR4/PI3K-Akt/IκB α pathway in RAW264.7 cells. In immunosuppressed mice, RGP restored immune function, as shown by improved organ indices, elevated serum immunoglobulins (IgA, IgG, IgM), and alleviated splenic damage. Molecular docking revealed that RGP binds the hydrophobic pocket of the TLR4/PI3K-Akt/IκB α complex via its glucose chain, and dynamics simulations confirmed the stability of this interaction. These findings reveal the bioactivity of bryophyte polysaccharides and suggest RGP as a potential immunomodulatory agent.
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Photodiagnosis and Photodynamic Therapy
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2018
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IF 2.895
Kunpeng Wang,Zijian Zhang,Kai Liu,Xin Yang,Heng Zou,Jiangjiao Zhou,Xiongying Miao,Wei Chen,Li Xiong,Yu Wen
Background Inflammatory bowel disease (IBD) is a group of inflammatory conditions characterized by chronic inflammation of the gastrointestinal (GI) tract. Recent preclinical and clinical studies have shown the therapeutic value of photodynamic therapy with low doses of photosensitizer and/or light in colitis treatment, but the detailed mechanism is unclear. Methods We examined 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy (PDT) in dextran sulfate sodium (DSS)-induced colitis in mice. Endoscopic and macroscopic observations as well as the Disease Activity Index score (DAI) was used to monitor the disease. Cytokine expression was measured by quantitative RT-PCR analysis to evaluate the efficacy of PDT. We applied the Clariom™ D bioinformatics analysis to investigate the differentially expressed genes after PDT. Finally, we used quantitative RT-PCR analysis and Western blotting to validate the targets of differentially expressed genes. Results 5-ALA-PDT improved the DAI score and decreased the expression of various inflammatory cytokines. The Clariom™ D bioinformatics analysis identified 2043 diff ;erentially expressed genes (702 up-regulated and 1341 down-regulated). We confirmed the down-regulation of lncRNA-Neat1, lncRNA-Snhg5 and lncRNA-Gm9926 and the up-regulation of miRNA-204-5p, miRNA-218-5p, miRNA-200a-3p and miRNA-466h-5p. Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed. Conclusions This study provides in vivo comprehensive lncRNA and miRNA microarray analysis after 5-ALA-PDT treatment in DSS-induced colitis, and it may help to develop novel lncRNA-miRNA-related therapeutic approaches, such as the Neat1-miRNA204-5p-PI3K-AKT axis, to further increase the efficiency of PDT in IBD.
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FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Eun-Ji Han,Eun-Young Choi,Su-Ji Jeon,Sang-Woo Lee,Jun-Mo Moon,Soo-Hyun Jung,Bumseok Kim,Sung-Dae Cho,Jeong-Seok Nam,Changsun Choi,Jeong-Hwan Che,Ji-Youn Jung
Natural products are continuously being researched to develop safe and effective treatment options for cervical cancer , the fourth most common cancer in women. Piperlongumine (PL), an amide alkaloid mainly present in long pepper , exhibits neuroprotective and anti-cancer properties. However, the specific effect of PL in cervical cancer and the relationship between the anti-cancer pathway and autophagy remain unclear. Therefore, we aimed to investigate PL-induced apoptosis in KB human cervical cancer cells and the relationship between apoptosis and autophagy therein. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and wound-healing assays showed that PL treatment suppressed KB cell viability and proliferation. Apoptosis was identified through 4′,6-diamidino-2-phenylindole and annexin V-propidium iodide staining, increased cleaved-poly (ADP-ribose) polymerase and Bcl-2 associated X levels, and decreased B cell lymphoma 2 levels. Acridine orange staining and increased microtubule-associated protein 1A/1B-light chain 3-II and Beclin-1 levels confirmed autophagy. We determined that KB cell-related autophagy exerted cytoprotective effects using the autophagy inhibitors 3-methyladenine and hydroxychloroquine . PL treatment promoted apoptosis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in KB cells; inhibiting the pathway using PI3K inhibitors increased autophagy. We suggest that PL is a potential natural anticancer agent for cervical cancer treatment.
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高影响因子
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