FASEB JOURNAL
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2026
·Vol. 40
·期 4
·e71580
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IF 4.3
Liujie Zheng,Yinhua Ni,Suyao Xie,Yitian Ji,Jiahong Dong,Lanjun Fu,Zhengwei Fu,Juan Jin,Qiang He
Acute kidney injury (AKI) is a serious complication of cisplatin chemotherapy, requiring new preventive therapies. Germacrone, a sesquiterpenoid derived from Rhizoma Curcuma , has multiple pharmacological effects, including anti-inflammatory, antiapoptotic, and antioxidant effects. The current study aimed to investigate the effect and mechanism of germacrone on AKI. Single high-dose and multiple low-dose cisplatin-induced AKI and AKI-chronic kidney disease (CKD) transition mouse models were used to determine the preventive effect of germacrone, with the mechanism explored in HK-2 and Raw264.7 cells. A breast cancer tumor-bearing model was developed to determine whether the nephron-protective effects of germacrone affect the anticancer properties of cisplatin. Here, we found that germacrone significantly alleviated AKI and fibrosis in cisplatin-treated mice, as demonstrated by decreased serum creatinine and blood urea nitrogen (BUN) levels and improved renal pathology. Germacrone attenuated cisplatin-induced apoptosis and inflammation in vivo and in vitro. RNA sequencing revealed that germacrone restored cisplatin-induced gene dysregulation and regulated inflammation and apoptosis through the PI3K/AKT and Ras/MAPK pathways. Inhibition of these pathways abrogated the renoprotective effect of germacrone in vitro. Moreover, germacrone reduced macrophage activation and induced an M2-dominant shift in macrophage polarization in the kidneys and Raw264.7 cells via similar pathways. Furthermore, germacrone protected the kidneys without affecting the chemotherapeutic effects of cisplatin on a mouse model of breast cancer. Therefore, germacrone is expected to have universal renoprotective effects across different AKI models and a tumor-bearing model through similar signaling pathways, suggesting its potential as a clinical adjuvant therapy for reducing nephrotoxicity in patients receiving cisplatin chemotherapy. Graphical Germacrone alleviates inflammation and apoptosis in cisplatin-injured kidneys by activating PI3K/AKT and suppressing Ras/MAPK signaling, thereby protecting against acute kidney injury (AKI) in mice. This renoprotection is reinforced by its ability to drive an M2-dominant macrophage shift both in vivo and in vitro, ultimately restoring tubular integrity and renal function.
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BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2026
·
IF 2.9
Qing-Mei Wang,Xue-Ying Wang,Fei Lin,Wei-Qun Guan,Wei-Hui Chen
Objective This study aimed to examine the mechanisms by which Interleukin-27 (IL-27) contributes to the pathogenesis of oral squamous cell carcinoma (OSCC) through focal adhesion-induced stemness protein 1 (FSIP1)-mediated activation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway. Methods The effects of IL-27 on cellular proliferation, apoptosis, and migration were examined in human OSCC cell lines [squamous cell carcinoma cell line-27 (CAL-27) and squamous cell carcinoma-4 (SCC-4)] using Cell Counting Kit-8 (CCK-8) assays, flow cytometry, and wound healing assays. Western blot (WB) analysis was performed to determine the expression of epithelial-mesenchymal transition (EMT) markers. High-throughput sequencing was used to identify differentially expressed genes and enriched pathways, while quantitative Polymerase Chain Reaction (qPCR) and WB validated the expression of FSIP1 and PI3K-Akt pathway-related proteins. An oral carcinogenesis mouse model was established using 4-nitroquinoline-1-oxide (4NQO). Following IL-27 treatment, histopathological alterations in tongue tissue were examined with Hematoxylin-Eosin (HE) staining, while IL-27, IL-27 receptor subunit alpha (IL-27RA), FSIP1, and PI3K-Akt pathway proteins were measured through immunohistochemistry and WB. In addition, FSIP1 overexpression vectors and interfering constructs were utilized to examine the regulatory role of FSIP1 in the presence of IL-27. Results Expression levels of IL-27 and IL-27RA were significantly elevated in OSCC. Treatment with IL-27 enhanced proliferation and migration, suppressed apoptosis, upregulated mesenchymal markers [Neural cadherin (N-cadherin), Vimentin], and downregulated the epithelial marker E-cadherin. Sequencing analysis identified FSIP1 as a key differentially expressed gene enriched in the PI3K-Akt pathway. IL-27 upregulated FSIP1 expression and elevated phosphorylation of PI3K and Akt (p-PI3K/PI3K, p-Akt/Akt). In the murine model, oral carcinogenesis was characterized by epithelial dysplasia, squamous epithelial thickening, and inflammatory cell infiltration. IL-27 treatment intensified these histopathological features and further upregulated protein expression. Overexpression of FSIP1 produced effects comparable to IL-27 treatment by enhancing malignant phenotypes and activating related pathways, while FSIP1 interference mitigated IL-27-induced cellular and molecular changes. Conclusion IL-27 promotes OSCC progression by upregulating FSIP1, leading to PI3K-Akt pathway activation, enhanced proliferation and migration, and reduced apoptosis. FSIP1 represents a central mediator of the oncogenic activity of IL-27 and may serve as a potential therapeutic target in OSCC.
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ACS Omega
·
2026
·
IF 4.3
Xianghuai Zheng,Yue Zou,Qinkai Xie,Hao Dong,Jiating Lin,Xianxian Zhuang,Ruoting Xian,Shaobing Li
Oral squamous cell carcinoma (OSCC) presents significant therapeutic challenges due to chemoresistance and limited treatment modalities. Black phosphorus nanosheets (BPNSs), a novel two-dimensional nanomaterial, have shown promising antitumor effects. However, their role in inducing ferroptosis in OSCC and the underlying mechanisms remain to be elucidated. In this study, BPNSs were prepared via liquid-phase exfoliation, and their effects on the OSCC CAL-27 cells were subsequently evaluated. In vitro, BPNSs dose-dependently inhibited CAL-27 cell proliferation, induced G2/M phase arrest, and triggered ferroptosis, indicated by increased intracellular Fe2+, ROS, and lipid peroxidation, along with decreased glutathione (GSH) levels and altered expression of ferroptosis-related proteins (ACSL4, NCOA4, and GPX4). These effects were attenuated by ferroptosis inhibitor ferrostatin-1. In vivo, BPNSs suppressed CAL-27 xenograft growth without systemic toxicity, with elevated tumor malondialdehyde (MDA) and Fe2+ confirming ferroptosis. Mechanistic studies indicated that BPNSs inhibited the PI3K-AKT pathway, leading to the downregulation of SREBP1. Overexpression of SREBP1 attenuated BPNS-induced ferroptosis, confirming its critical role. These findings suggest that BPNSs induce ferroptosis in OSCC via the PI3K-AKT-SREBP1 signaling pathway, providing a novel therapeutic strategy for OSCC treatment.
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Molecular Pain
·
2025
·
IF 2.8
Yu-Na Cheng,Ming-Zhu Zhang,Cui-Qing Xie,Zhi-Qi Li,You-Feng Ge,Zhao-Hui Jin,Zhi-Hua Luo,Chen-Yang Zheng,Liang Chen,dong fang,Chen-Guang Niu,Jin-Jin He
Bone cancer pain (BCP), one of the most intractable symptoms in patients with cancer, remains poorly understood and lacks effective therapeutic interventions. In this study, we employed an established rat model of BCP induced by intratibial injection of MRMT-1 mammary carcinoma cells. Transcriptomic profiling of the L4-L6 dorsal root ganglia (DRGs) revealed an upregulation of the amino acid transporter SLC38A3. This finding was further confirmed by time-dependent increases in both its mRNA and protein levels. Immunofluorescence co-localization indicated that SLC38A3 was expressed in NF200-, CGRP-, and IB4-positive neurons within the L4-L6 DRGs, and its expression was upregulated in the BCP model. Concomitantly, the transient receptor potential vanilloid 1 (TRPV1) expression in BCP rat DRGs was dynamically upregulated at both the mRNA and protein levels, aligning temporally with pain hypersensitivity. Lentivirus-mediated overexpression or knockdown of SLC38A3 in the DRGs led to a corresponding upregulation or downregulation of TRPV1-expression. Activation of the PI3K/AKT signaling pathway corresponds with BCP-related pain behaviors and expression patterns of SLC38A3 and TRPV1. Bexarotene alleviates BCP in rats by suppressing the aberrant overexpression of SLC38A3, thereby blocking the PI3K/AKT signaling pathway-mediated upregulation of TRPV1. These findings indicate that SLC38A3, through its downstream PI3K/AKT-TRPV1 axis, may serve as a potential molecular mechanism for analgesia in BCP.
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JOURNAL OF MOLECULAR HISTOLOGY
·
2026
·Vol. 57
·期 1
·30
·
IF 2.2
Xiang Shouyu,Liu Wei,Tang Cheng,Xie Chuhai,Hu Hailan,Zhou Jianhui,Cao Yanming,Ling Long
Bone marrow mesenchymal stem cells (BMSCs) play a significant role in bone defect repair. Currently, the limited survival and function of transplanted BMSCs pose major obstacles to tissue repair mediated by these cells. Therefore, the exploration of BMSCs transplantation activity has become an urgent clinical problem. In this experiment, we constructed lentiviral vectors with overexpression and silencing of miR-19b-3p and utilized a rat fracture model. The effects of BMSCs proliferation were examined using CCK-8, the Annexin V-FITC apoptosis kit and TUNEL assay, the effects of BMSCs osteogenic differentiation were detected using ALP and Alizarin red staining. Furthermore, Western blotting and qRT-PCR were employed to examine the expression of key proteins in the PTEN/Akt/mTOR signaling pathway and autophagy-related proteins. Moreover, the impact of miR-19b-3p on bone microstructure was assessed using Micro CT, HE, Safranin O/Fast Green, as well as Masson staining, and Immunohistochemistry analysis examined PTEN, p62 and Runx2 expression levels on fracture site. By constructing lentiviral vectors with overexpression and silencing of miR-19b-3p, we found that silencing miR-19b-3p significantly promoted the proliferation as well as the osteogenic differentiation of BMSCs under hypoxia. Western blotting and qRT-PCR results showed that silencing miR-19b-3p significantly increased PTEN, LC3, and Beclin1 expression while decreasing p-Akt, p-mTOR, and p62 expression. Furthermore, by constructing the fracture rats and administering hypoxia-treated BMSCs transfected with miR-19b-3p via tail vein injection, we found that silencing miR-19b-3p obviously increased the formation of trabecular and promoted the healing of the fractures. Immunohistochemistry analysis showed that silencing miR-19b-3p upregulated PTEN and Runx2 expression levels and suppressed p62 expression with statistical significance. In summary, these findings suggest that miR-19b-3p may regulate BMSCs’ autophagy and osteogenic differentiation under hypoxia via the PTEN/Akt/mTOR signaling pathway, thereby promoting fracture healing and providing a potential target for the treatment of fractures.
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BEHAVIOURAL BRAIN RESEARCH
·
2026
·
IF 2.9
Xinyao Zhang,Xu Yang,Dongpei Zhuang,Zhiyi Mu,Chuanxia Ju
Neuronal hyperexcitability is crucial to the pathogenesis of Alzheimer's disease (AD). Activating the Kv7 channel is an effective way to reduce neuronal excitability. The Kv7 channel opener retigabine (RTG) has been demonstrated to alleviate spatial memory deficits in APP/PS1 transgenic mice. However, the mechanism by which RTG reduces cognitive deficits in APP/PS1 mice remains unclear. In this study, we revealed that RTG could ameliorate learning and spatial memory deficits in APP/PS1 mice during novel object recognition and Morris water maze tests. Meanwhile, RTG increased NeuN neuronal fluorescence intensity, increased the expression of the synaptic proteins postsynaptic density protein 95 (PSD95) and synaptophysin (SYN), improved synaptic plasticity, increased insulin-degrading enzyme (IDE) expression, decreased beta-secretase 1 (BACE1) expression, reduced Aβ 1–40 and Aβ 1–42 levels, and increased pAKT (ser473) and pGSK-3β (ser9) expression. These results indicated that RTG alleviates learning and spatial memory deficits in APP/PS1 mice, with potential mechanisms involving a reduction in neuronal loss, attenuation of synaptic damage, a decrease in β-amyloid (Aβ) deposition, and activation of the AKT/GSK-3β pathway.
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Journal of Inflammation Research
·
2026
·
IF 4.6
Jianglong Chen,Yunfei Cui,Rujie Zhou,Yu Zhu,Meijia Chen,Jinhua Su,Jinhui Wang,Guang Li
Objective To explore the therapeutic effect and molecular mechanism of Arundina graminifolia (D.Don) Hochr (BYJ) on renal fibrosis in chronic kidney disease (CKD) mice.Methods Phytochemical profiles of the methanol extract BYJ were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS), while network pharmacology and molecular docking were employed to predict the core active components and therapeutic targets. For experimental validation, a CKD mouse model was established via adenine induction. Mice were randomly assigned to normal control, model, and three BYJ treatment groups (low-dose: 2 g/kg·d, middle-dose: 4 g/kg·d, and high-dose: 8 g/kg·d, crude drug equivalent). Assessments included renal function parameters, histopathological changes, inflammatory markers, and oxidative stress indicators. The associated molecular mechanisms were analyzed using immunohistochemistry staining and Western blot.Results In silico analysis identified five core targets—PIK3R1, AKT1, SRC, MTOR, and EGFR—and suggested esculetin as a key active component with strong binding affinity to these targets. Experimentally, BYJ administration significantly reduced in serum creatinine (SCr), blood urea nitrogen (BUN), and the kidney index, and ameliorated glomerular atrophy and tubular dilation. Furthermore, BYJ treatment downregulated pro-inflammatory factors (eg, IL-1β), elevated superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content. The intervention suppressed the epithelial-mesenchymal transition (EMT) process, as evidenced by the upregulation of E-cadherin and downregulation of α-SMA expression. Mechanistic verification indicated that BYJ treatment was associated with attenuated the overactivated of TGF-β/PI3K-AKT/mTOR pathway in renal tissues.Conclusion The methanolic extract of BYJ effectively attenuates CKD progression in mice, which is associated with by modulated the overactivation of the TGF-β/PI3K-AKT/mTOR pathway, inhibited the EMT process, and ameliorated inflammatory response and oxidative stress. These findings provide a preliminary theoretical basis for the development of BYJ as a potential candidate agent for CKD treatment.
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Communications Biology
·
2026
·
IF 5.8
He Mingli,Yang Cheng,Shi Haiyuan,Xuan Xunrong,Li Juan,Zhang Chunyang,Zhang Han
Cryptochrome 2 (CRY2) has been implicated in blood perfusion recovery. This study aims to explore its effects on the repair of the blood-brain barrier (BBB) during chronic cerebral hypoperfusion (CCH). Human cortical microvessels endothelial cells/D3 (hCMEC/D3) are induced with hypoxia and co-cultured with microvascular pericytes and astrocytes. Mice are induced by bilateral common carotid artery stenosis (BCAS). In hypoxia-induced hCMEC/D3 cells and vascular endothelial cells from BCAS-induced mice, CRY2 is downregulated. CRY2 overexpression ameliorates hCMEC/D3 injury and inhibits BBB disruption and cognitive dysfunction in mice. rs10838524 (A > G) resulted in the CRY2 reduction and correlated with more severe CCH. CRY2 mediates the time-dependent expression of insulin-like growth factor 2 (IGF2). The ameliorative effect of CRY2 on CCH is dependent on the IGF2/Phosphoinositide 3-Kinase (PI3K)/Protein Kinase B (AKT). The findings demonstrate that the rs10838524 (A > G) of CRY2 represses enhancer-mediated transcription of CRY2 , thereby attenuating activation of IGF2 and impairing PI3K/AKT signaling.
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高影响因子
MATERIALS & DESIGN
·
2026
·
IF 8.2
Yue Peng,Cuiman Tang,Mingcong Niu,Tianyi Xu,QingYu Meng,Xinran Li,Rongheng Ma,Huimin Yu
A traditional medicine-inspired strategy provides a logical framework for constructing carrier-free hybrids. • Precise structural modifications successfully circumvent the inherent bioaccessibility limitations of natural products. • The covalent integration of diverse functional modules enables synergistic therapeutic efficacy against arthritis. • The therapeutic action is closely associated with the modulation of protein kinase B and hypoxia-inducible factor signaling. Curcumin (Cur) possesses potent anti-inflammatory activity but faces clinical challenges due to poor aqueous dispersibility, insufficient membrane affinity, and low bioavailability. Borneol (Bor), a classic “envoy” component in Traditional Chinese Medicine (TCM), exhibits prominent membrane-penetrating properties. Inspired by the “monarch-envoy” compatibility theory, we rationally designed carrier-free hybrids by covalently conjugating Cur (“monarch”) with Bor (“envoy”). Systematic characterization confirmed the successful synthesis and controllable optimization of key properties, including enhanced dispersibility, improved cellular uptake, and favorable biocompatibility. Using rheumatoid arthritis (RA) as a disease model, we identified SCBMS as the optimal formulation owing to its superior dispersibility and uptake, which directly translated into the most potent anti-RA efficacy. The hybrids exerted synergistic multifunctional effects—including robust anti-inflammatory and antioxidant activities—effectively reducing the arthritis index and ameliorating synovial hyperplasia and joint destruction in vivo . Mechanistically, our results indicate a close correlation between the therapeutic effects and the downregulation of the AKT/mTOR/HIF-1α signaling pathway, supporting the involvement of this pathway in the observed anti-RA activity. This study provides a generalizable framework for developing functional hybrids guided by TCM principles and validates their translational potential. Download: Download high-res image (152KB) Download: Download full-size image
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Animal Models and Experimental Medicine
·
2026
·
IF 3.3
Yijia Wang,Xing Feng,Shuhui Zhao,Yuchong Fu,Ao Zhang,Xiaofeng Shen,Bowen Yu,Yihao Wang,Jiahui Lin,Bing Zhang,Weiping Ji,Lianpin Wu,Xiaoling Guo
Background Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload–induced myocardial remodeling and to explore the underlying mechanism. Methods Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established. Results The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or Ang II-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol‑3‑kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway. Conclusions Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload–induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.
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Pharmaceutics
·
2026
·Vol. 18
·期 7
·869
·
IF 6.9
Jiangtao Zhou,Yuhui Ge,Ran Li,Zhuoyang Cheng,Jianping Gao,Bin Zheng
Background: Skin photoaging, primarily induced by chronic ultraviolet (UV) radiation exposure, is characterized by dryness, wrinkle formation, pigmentation abnormalities, and reduced skin elasticity, resulting from oxidative stress, inflammation, and degradation of the extracellular matrix. Codonopsis pilosula , a traditional food–medicine homologous plant, is recognized for its anti-aging properties. However, its lipophilic components (designated as CP-L) remain insufficiently explored. Methods: Herein, we developed a thermosensitive nanogel encapsulating CP-L-loaded transferosomes (CP-L nanogel) to enhance topical delivery and evaluated its effects in both a UV-induced photoaging mouse model and UVB-irradiated HaCaT keratinocytes. Results: In UV-induced mice, topical application of the nanogel markedly reduced skin wrinkling and epidermal hyperplasia, with epidermal thickness decreased by 83.2% compared to the model group ( p < 0.01), and restored skin elasticity and collagen deposition, as evidenced by a 35.5% increase in collagen area fraction ( p < 0.01). Correspondingly, in UVB-irradiated HaCaT cells, it significantly increased cell viability from 53.0 ± 9.6% to 89.4 ± 1.0% ( p < 0.01) and suppressed apoptosis from 30.1 ± 0.48% to 12.4 ± 0.66% ( p < 0.01). Furthermore, the CP-L nanogel consistently attenuated oxidative stress, with SOD, CAT, and GSH-Px activities increased by 73.1%, 188.1%, and 18.2%, respectively ( p < 0.01), and MDA levels reduced by 71.0% ( p < 0.01), while inflammatory responses were suppressed, as TNF-α, IL-1α, IL-1β, and IL-6 levels decreased by 28.3%, 22.6%, 12.8% and 31.9%, respectively ( p < 0.01). Mechanistically, transcriptomic and molecular analyses revealed that the nanogel potently inhibited the UV-induced activation of the FGFR/PI3K/AKT/mTOR/p70S6K signaling cascade at both transcriptional and protein levels, with the phosphorylation levels of FGFR, PI3K, AKT, mTOR, and p70S6K significantly reduced by 43.9%, 30.9%, 38.8%, 34.9%, and 57.3%, respectively ( p < 0.01). Molecular docking and dynamics simulations identified isofuranodienone and aromadendrene oxide-(2) as key constituents with high-affinity, stable binding to FGFR1 and AKT1. The cytoprotective effect of the nanogel was completely abolished by co-treatment with the FGFR inhibitor PD173074 , confirming functional reliance on this pathway. Enhanced cellular delivery of the formulation was directly demonstrated by flow cytometry, showing an approximately 1.8-fold increase in cellular uptake compared to the free drug ( p < 0.01). Conclusions: Collectively, these results demonstrated that the CP-L nanogel alleviated skin photoaging through a multi-faceted mechanism involving enhanced cellular delivery, potent antioxidant and anti-inflammatory activities, and specific inhibition of the FGFR/PI3K/AKT/mTOR signaling cascade, highlighting its potential as a multitargeted topical agent derived from an edible plant.
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Cell Death & Disease
·
2026
·Vol. 17
·期 1
·750
·
IF 12.2
Luomeng Qian,Ping Chen,Bo Wang,Qing Zhang,Yuan Guo,Jie Cui,Ran Ding,Hongkai Zhang,Sihe Zhang
Sorafenib is a widely used targeting drug for hepatocellular carcinoma (HCC) patients; however, sorafenib resistance poses a significant clinical challenge. Hypoxia and extracellular vesicles (EVs) induce vasculogenic mimicry (VM) which is linked to sorafenib resistance in HCC. Migrasomes (Migs), the newly discovered large EVs, foster HCC malignant phenotypes by facilitating the intercellular transfer of functional molecules. Despite these advancements, the precise mechanism by which Migs cause sorafenib resistance is still unknown. In this study, we found that hypoxia upregulates the Migs release and CD147 expression on Migs surface, which is related to sorafenib resistance in HCC. Further investigations revealed that hypoxia-induced migrasomes (hypo-Migs) induce VM formation, thereby promoting sorafenib resistance in HCC. Notably, hypo-Migs are internalized into HCC cells through macropinocytosis, which depends on the expression of lysophosphatidic acid receptor 6 (LPAR6). Mechanistically, CD147-positive (CD147 + ) hypo-Migs activate the PI3K/AKT/TWIST1 signaling pathway, subsequently inducing VM formation and promoting sorafenib resistance. Importantly, dual blockade of CD147 + -hypo-Migs macropinocytosis and VM formation enhances the sorafenib-killing efficacy to HCC. Conclusively, our findings uncover a novel sorafenib resistance mechanism induced by CD147 + -hypo-Migs, and highlight dual-targeting of macropinocytosis and VM as a promising strategy to overcome the sorafenib resistance in HCC.
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