ADVANCED FUNCTIONAL MATERIALS
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2026
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IF 19.9
Fengfeng Xiao,Shengni Hua,Fei Liu,Ziliang Yan,Zhengsheng Yi,Yanxia Xu,Haichuan Peng,Jing Xiao,Yongjun Peng,Liewei Wen,Yunlu Dai
Radiotherapy triggers an adaptive upregulation of transforming growth factor-β (TGF-β), which paradoxically promotes radioresistance by reinforcing the stromal barrier, suppressing immunity and accelerating DNA repair. To overcome these limitations, we engineered a multifunctional nanocoordinator (ASO TGF /MPN-aPD-L1) by leveraging the multimodal molecular interaction of bismuth-phenolic networks, creating an “all-in-one” platform that densely encapsulates TGF-β antisense oligonucleotides (ASO TGF ) via metal coordination and π–π stacking while adsorbing aPD-L1 on the surface for sensitizing radio-immunotherapy. Mechanistically, the bismuth component acts as a high-Z radiosensitizer to amplify initial DNA damage, while ASO TGF concurrently blocks TGF-β signaling by inhibiting its translation. This dual action not only abrogates DNA repair pathways but also suppresses cancer-associated fibroblasts (CAFs) activation and remodels the extracellular matrix (ECM) to facilitate cytotoxic T cell infiltration. Furthermore, surface-adsorbed aPD-L1 prevents T cell exhaustion, sustaining long-term antitumor immunity. Our results confirm that this strategy significantly alleviates tumor fibrosis, enhances CD8 + T cell infiltration, and potentiates radiotherapy efficacy in hepatocellular carcinoma models (HCC). Collectively, except for radiosensitization, by simultaneously targeting TGF-β signaling and PD-L1-mediated immune evasion, our nanocoordinator represents a promising strategy to potentiate radioimmunotherapy for HCC.
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DOI
高影响因子
Frontiers in Oncology
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2020
·
IF 4.848
Chen Shuo,Shen Jiaqi,Zhao Jing,Wang Jiazhong,Shan Tao,Li Junhui,Xu Meng,Chen Xi,Liu Yang,Cao Gang
Magnolol, a hydroxylated biphenyl extracted from Magnolia officinalis, has recently drawn attention due to its anticancer potential. The present study was aimed to explore the effects of Magnolol on restraining the proliferation, migration and invasion of pancreatic cancer in vivo and in vitro. Magnolol showed significant anti-growth effect in an orthotopic xenograft nude mouse model, and immunohistochemical staining of the xenografts revealed that Magnolol suppressed vimentin expression and facilitated E-cadherin expression. The cytoactive detection using CCK-8 assay showed Magnolol inhibited PANC-1 and AsPC-1 concentration-dependently. Scratch healing assay and the Transwell invasion assay proved the inhibiting effects of Magnolol on cellular migration and invasion at a non-cytotoxic concentration. Western blot and rt-PCR showed that Magnolol suppressed epithelial-mesenchymal-transition by increasing the expression level of E-cadherin and decreasing those of N-cadherin and vimentin. Magnolol suppressed the TGF-β/Smad pathway by negatively regulating phosphorylation of Smad2/3. Moreover, TGF-β1 impaired the antitumor effects of Magnolol in vivo. These results demonstrated that Magnolol can inhibit proliferation, migration and invasion in vivo and in vitro by suppressing the TGF-β signal pathway and EMT. Magnolol could be a hopeful therapeutic drug for pancreatic malignancy.
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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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2018
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IF 4.432
Hongjie Huang,Xiaoqing Hu,Xin Zhang,Xiaoning Duan,Jiying Zhang,Xin Fu,Linghui Dai,Lan Yuan,Chunyan Zhou,Yingfang Ao
Synovium-derived mesenchymal stem cells (SMSCs) are attractive tissue-specific cells for cartilage regeneration because of their easy availability, higher chondrogenic potential, and joint specificity. In the present study, we established a hybrid scaffold to codeliver SMSCs and transforming growth factor beta (TGF-β), which can integrate the scaffolds, the growth factor, and the autogenous cells within rabbit cartilage defects. A chitosan hydrogel and a decellularized bone matrix were used to fabricate the gel–solid duplex phase biomaterials, which were proven to retain more cells, promote tissue integration, and provide mechanical support. In vitro experiments demonstrated that this hybrid scaffold could release TGF-β in a controlled biphasic pattern, which can promote cell proliferation and chondrogenic differentiation of loaded rabbit SMSCs. For in vivo experiments, we filled cartilage defects with the hybrid materials, delivering autogenous SMSCs and TGF-β simultaneously via chitosan’s sol–gel transition. Histological analysis, magnetic resonance imaging, and nanoindentation assessment indicated superior cartilage regeneration using this codelivery system compared with that from routine microfracture or control delivery scaffolds. Beyond cartilage regeneration, the easy preparation, favorable biophysical properties, and controlled release ability make this codelivery system applicable to transport other tissue-specific cells or biofactors for tissue engineering.
研究领域:
生物医学工程
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再生医学
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组织工程
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DOI
PubMed
高影响因子
Scientific Reports
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2025
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IF 3.9
Xu Qiuling,Liu Zhuoxi,Wang Liyuan,Liu Guoyang,Zhao Long,Yue Hui,Liu Yong
Diabetic cardiomyopathy (DCM) requires a systematic approach for effective management. Focusing on key signaling pathways in myocardial fibrosis could offer novel therapeutic approaches for DCM. The objective of this research is to investigate new biomarker and the underlying mechanisms by which baicalin intervenes in the progression of DCM. Swiss Target Prediction databases and weighted correlation network analysis (WGCNA) were employed to collect and analyze targets of baicalin and DCM. Intersection targets were obtained through venn online website, network visualization was conducted through STRING database and Cytoscape 3.7.2 software. Molecular docking validation was completed via AutoDock Vina software. Western blotting, RT-qPCR and histology were carried out to validate the direct targets of baicalin and explore the molecular mechanism during DCM progression. In mice induced to DCM, we observed that disruptor of telomeric silencing 1-like (DOT1L) was upregulated. Baicalin (BC) reduced myocardial fibrosis in mice as indicated by the reduced expression levels of fibrosis markers COL-1 and TGF-β. The inhibitory effect of BC was reversed by overexpressed DOT1L and further enhanced by silenced DOT1L. Our results indicate that cardiomyocyte DOT1L exerts a pathogenic role in DCM and BC specifically targets DOT1L/COL-1 signaling to reduce myocardial fibrosis in DCM.
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PubMed
高影响因子
Biomolecules
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2020
·Vol. 10
·期 3
·398
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IF 4.082
Shan Shan Qi,Hong Xing Zheng,Hai Jiang,Li Ping Yuan,Le Chen Dong
Diabetic nephropathy (DN) is one of the most important complications of diabetes, and the leading cause of end-stage renal disease (ESRD). While Chromium picolinate (CrPic) supplementation has been found to be effective in treating diabetes, its effects on diabetic-induced nephropathy have not been studied. Therefore, in this study, CrPic (1 mg kg−1d−1) was administered to a DN rat model by oral gavage for eight weeks to investigate its effects. The results show that CrPic supplementation caused a decrease in levels of blood glucose, serum insulin, blood urea nitrogen (BUN), serum creatinine, and urinary albumin in DN rats. It also reversed renal pathological changes, including renal glomerular sclerosis and interstitial fibrosis. In addition, the oxidative defense system in the kidneys of DN rats was found to be improved; the biological activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) increased; and the content of malondialdehyde (MDA) lowered. Immunohistochemical results reveal that the expression levels of renal transforming growth factor-β1 (TGF-β1), Smad 2, and Smad 3 decreased significantly in the kidneys of rats in the CrPic-treated group. CrPic administration was thus found to ameliorate diabetic nephropathy in SD rats via an antioxidative stress mechanism, as well the ability to inhibit TGF-β1/Smad2/3 expression. This study suggests that CrPic could be a potential renal-protective nutrient against diabetic nephropathy.Keywords:diabetic nephropathy;chromium picolinate;renal fibrosis;antioxidative stress
研究领域:
内分泌学
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肾病学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·
IF 12.6
Shijin Xu,Naidi Yang,Fangning Du,Ziying Zhang,Yin Zhang,Yixuan Zhang,Jiawei Liang,Yihan Zhao,Jiajun Zhang,Ziwei Zhang,Xiaoxuan Han,Zena Chen,Zhiqiang Zhou,Shu Zhang,Lin Li,Ying Lv
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, marked by extensive stromal fibrosis and a profoundly immunosuppressive, immune-excluded tumor microenvironment (TME) that hampers the efficacy of immune checkpoint blockade. Although photodynamic therapy (PDT) can induce immunogenic cell death (ICD) and stimulate anti-tumor immunity, its effectiveness against PDAC is limited by insufficient immune activation and persistent stromal-mediated immunosuppression. To address these challenges, we develop a liposomal nanodrug that co-encapsulates a mitochondrial-targeted photosensitizer (MP) and a TGF-β receptor inhibitor (LY2109761) to synergize PDT with PD-1 checkpoint blockade. MP selectively accumulates in mitochondria and, upon light activation, amplifies mitochondrial reactive oxygen species production, inducing mitochondrial damage. This damage triggers the release of mitochondrial DNA and damage-associated molecular patterns, activating the STING pathway and eliciting potent ICD and anti-tumor immune responses. Simultaneously, liposome-mediated delivery of LY2109761 mitigates stromal desmoplasia and reverses TGF-β-driven immune suppression, enhancing effector T cell infiltration and activity. In murine PDAC models, this dual-action strategy transforms the immune-cold TME into an immune-inflamed phenotype, sensitizing tumors to PD-1 therapy and leading to pronounced tumor regression and prolonged survival. Our findings present a promising nanodrug-based approach to remodel the fibrotic and immunosuppressive TME of PDAC and enhance immunotherapeutic outcomes.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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光动力治疗
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肿瘤微环境
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分子生物学
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DOI
PubMed
高影响因子
Virulence
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2026
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IF 5.4
Kun Yan,Xiuling Wang,Zongyi Bo,Chengcheng Zhang,Mengjiao Guo,Xiaorong Zhang,Yantao Wu
Avian infectious bronchitis virus (IBV) belongs to the genus Gammacoronavirus (family Coronaviridae), causes severe multi-system disease in chickens, inflicting major global economic losses. The molecular interplay between IBV and host metabolic networks remains poorly understood. Through integrated transcriptomic, metabolomic, and lipidomic profiling of oviduct tissues from specific-pathogen-free (SPF) chickens infected with the IBV QXL strain, we demonstrate tripartite metabolic reprogramming: 1) redirected glucose flux through the pentose phosphate pathway (PPP) to fuel nucleotide synthesis, 2) rewired lipid metabolism to prioritize de novo membrane biogenesis over fatty acid β-oxidation, and 3) orchestrated glycerophospholipid remodeling. This integrated analysis revealed a coordinated upregulation of fatty-acid biosynthesis genes and accumulation of specific glycerophospholipids and eicosanoids. Mechanistically, IBV co-opts the Warburg effect and PPP activation while uniquely suppressing fatty acid β-oxidation to channel fatty acids toward lipid droplets (LDs) biogenesis. Phosphatidylserine (PS) overproduction (e.g. 2.55-fold increase in PS(22:0/22:6)) and phospholipase A2 (PLA2)-mediated lysophospholipids (Lyso-PLs) and eicosanoids generation (e.g. 7.09-fold increase in prostaglandin E2 (PGE2)) emerged as critical regulators of membrane dynamics and inflammatory signaling. This process was centrally coordinated by the significant activation of peroxisome proliferator-activated receptor (PPAR) (e.g. 1.74-fold increase in ACSL1) and transforming growth factor-beta (TGF-β) (e.g. significant increase in p-SMAD2) signaling pathways, directly linking lipid remodeling to immunomodulation. Functionally, targeting acetyl-CoA carboxylase (ACC) or glucose-6-phosphate dehydrogenase (G6PD), alongside TGF-β pathway modulation, synergistically curtailed viral replication in vitro. Our findings delineate a critical PPAR-TGF-β cross-talk that governs lipid remodeling during infection and identify host metabolic nodes that are potentially targetable for antiviral intervention.
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DOI
PubMed
高影响因子
Journal of Inflammation Research
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2026
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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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DOI
PubMed
高影响因子
BIOTECHNIC & HISTOCHEMISTRY
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2026
·
IF 1.4
Ying Xun,Xiaoli Wang,Lili Chen,Yu Fu,Xiang Wu,Wenqing Zeng
Glucose-lowering treatment and antidiabetic drugs show great potential for preventing and intervening in diabetes mellitus (DM)-associated cognitive dysfunction or advanced dementia. This study delves into the role and mechanism of low-carbohydrate diet (LCD) combined with Xiaokeping (XKP) on these conditions. Type 2 diabetes (T2D) rat models were constructed via high-fat diet and streptozotocin (STZ) injection, and treated with LCD and XKP alone or in combination for 8 weeks. Body weight and indicators of blood glucose and lipids were determined. Additionally, memory and spatial learning abilities were assessed. Tissue staining of the hippocampus was used to observe pathological changes. Oxidative stress, levels of inflammatory factors, and phosphatidylinositol 3-kinase (PI3K)/Akt serine/threonine kinase (Akt) were analyzed. The results demonstrated that LCD and/or XKP treatment recovered body weight, blood glucose, and lipid balance, while enhancing spatial memory and attenuating lesion in the hippocampus of diabetic rats. LCD and/or XKP treatment increased superoxide dismutase, decreased malondialdehyde, interleukin-1β/6, and tumor necrosis factor alpha level in the hippocampus of diabetic rats, which suggests a reduction in oxidative stress and neuroinflammation. Moreover, LCD and/or XKP treatment activated the PI3K/Akt pathway. LCD combined with XKP displayed superior efficacy compared to monotherapy. Collectively, LCD combined with XKP mixture improves cognitive decline of T2D rats by suppressing oxidative stress and neuroinflammation in the hippocampus, through a mechanism involving the activation of the PI3K/Akt pathway.
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2021
·
IF 5.279
Miao Song,Yilong Cui,Qi Wang,Xuliang Zhang,Jian Zhang,Menglin Liu,Yanfei Li
Aluminum (Al)-induced bone formation and metabolism disorder through inhibition of the TGF-β1/Smad signaling pathway is one of the important mechanisms of bone impairment. Ginsenoside Rg3 (Rg3), a specific biological effector molecule, can provide protection to bones. Previously, we demonstrated that Rg3 can reverse aluminum chloride (AlCl3)-induced oxidative stress and metabolic disorder of bones; however, whether the TGF-β1/Smad signaling pathway is involved in it remains unclear. First, we found that Rg3 attenuated Al-induced bone impairment in vivo and in vitro by relieving structural damage to the femur, increasing MC3T3-E1 cell activity, differentiation, mineralization, inhibition of cell apoptosis, and upregulating the extracellular matrix (ECM) synthesis and the expression of TGF-β1/Smad signaling pathway key factors. Subsequently, in the signal pathway intervention experiment, the protective effect of Rg3 on bone impairment induced by Al was weakened; these results indicate that activating the TGF-β1/Smad signaling pathway is one of the mechanisms of Rg3-attenuated Al-induced bone impairment.
研究领域:
药理学
·
毒理学
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骨生物学
·
信号转导
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DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2025
·
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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DOI
PubMed
高影响因子
MOLECULAR DIVERSITY
·
2024
·
IF 3.9
Ding Shu-Yan,Yang Yu-Xuan,Liu Chuang,Quan Xu-Yin,Zhao Zi-Han,Jin Cheng-Hua
Four series of sulfonamide derivatives ( 13a – b , 14a – d , 15a – b , and 16a – d ) were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) inhibitory activities. Of these, compounds 13b (IC 50 = 0.130 μM) and 15a (IC 50 = 0.130 μM) showed the highest inhibitory activities against ALK5 kinase, with activities similar to the positive control LY - 2157299 . Notably, we discovered that introduction of sulfonamide group at the 2-position of the central imidazole ring significantly increased ALK5 inhibitory activity. Compounds 13b and 15a did not show toxicity in A549 cells up to the maximum concentration of 50 μM, and effectively inhibited TGF-β1-induced Smad-signaling and cell motility in A549 cells. The results indicate that compounds 13b and 15a are worth of further development as anticancer agents.
研究领域:
药物化学
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分子生物学
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肿瘤学
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DOI
PubMed
高影响因子
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