Journal of Natural Medicines
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2026
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IF 2.6
Chen Peiyao,Wan Baolian,Yu Fei,Zhang Yanqiu,He Mengmeng,Wu Enyi,He Yanjun,Zhong Hui,Zhang Hao
Liver aging is a critical contributor to metabolic dysregulation and the development of various liver diseases. Currently, there is no approved therapy specifically targeting liver aging. The potential of medicinal and edible herbs in preventing and treating liver aging has attracted increasing attention. Accordingly, we constructed a self-built compound library containing 87 bioactive constituents isolated from these herbs. This study aimed to identify the potential compound capable of alleviating hepatic senescence from the constructed library and to elucidate the underlying mechanism. Isomucronulatol (Iso), a bioactive isoflavone isolated from Astragalus membranaceus , exhibited potential anti-hepatic senescence activity in a p21 promoter-driven luciferase reporter assay. Iso exhibited significant anti-hepatic senescence activity in H₂O₂-stimulated and doxorubicin (DOX)-stimulated HepG2 cells, as well as in mitomycin C (MC)-exposed AML12 cells, as evidenced by reduced SA-β-Gal positivity, downregulated p21 and p16 expression, and decreased secretion of SASP factors (IL-6, IL-1β, CCL2). In a D-galactose (D-gal)-induced mouse aging model, Iso treatment attenuated liver histological damage, lowered serum ALT and AST levels, and suppressed senescence markers in liver tissues. Transcriptomic and network pharmacology analyses revealed that Iso could activate Wnt/β-catenin signaling pathway to delay hepatic senescence. Mechanistically, Iso could facilitate nuclear accumulation of β-catenin by inhibiting GSK-3β acetylation, thereby restoring Wnt signaling. Collectively, these findings highlight Iso as a potential therapeutic agent against hepatic senescence. Graphical abstract
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2026
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IF 5.9
Liping Zhang,Yanyan Wang,Wenxin Qiu,Shuangling Liu,Shengxuan Xu,Hongwei Wang,Lin Yuan
Neural differentiation of embryonic stem cells (ESCs) holds significant therapeutic potential for the treatment of neurodegenerative diseases. A cell conversion strategy was developed to induce neural differentiation of ESCs by utilizing exosomes (Exo) derived from mesenchymal stem cells (MSCs) as efficient delivery vehicles for retinoic acid (RA) and fibroblast growth factor 2 (FGF2). The abundant surface proteins and phospholipid bilayer of Exo provided protective effects for FGF2 and RA, 88 % of RA remained within the Exo, and the residual amount of exosome-bound FGF2 was nearly 5-fold higher than that of free FGF2, after storage at 4 °C for 5 days. Exo co-loaded with RA and FGF2 exhibited excellent biocompatibility and promoted cell proliferation, resulting in a 3.3-fold higher proliferation over the free RA+FGF2 within 3 days. Neural differentiation was enhanced through dual signaling pathways mediated by RA and FGF2, leading to a nearly 3-fold increase in the relative expression of neuronal marker genes and 8.3-fold increase in the number of differentiated neural cells, compared to the RA+FGF2 group by day 7. This approach significantly enhanced both the efficiency and yield of neural differentiation, presenting a promising nanomedicine strategy by applying engineered Exo to guide the neural lineage commitment of ESCs.
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Cell and Bioscience
·
2026
·
IF 6.2
Jiajun Li,Changjiang Xu,Bingbo Shi,Yawen Lyu,Zejie Lin,Wei Shi,Jiachen Xu,Xinle Zou,Xiaomin Wang,Hanqing Zhao,Chengchen Zhao,Duanqing Pei
Background: One promising strategy to generate humanized organs is through embryo complementation by injecting human pluripotent stem cells (PSCs) into gene-edited porcine embryos. This strategy is predicated on how human cells adapt to a porcine environment, which has a body temperature of 38.5 °C, much higher than that of the human body. Results: Here, we present an in vitro model to address this problem by coculturing human and porcine induced PSCs at 38.5 °C and inducing them to generate cardiomyocytes. We show that co-cultured human cells can differentiate into myocardial features with the help of porcine cells at an enhanced differentiation rate. Mechanistically, we show that co-cultured human cells respond to elevated temperature by activating a stress response with the PI3K-Akt-mTOR signaling pathway activated. Moreover, a model mimicking embryo complementation by knocking out MYH6 in pig PSCs reveals the potential risk of porcine cells leaking into human-derived tissues. Conclusions: Together, our studies present a novel model system to evaluate human and porcine cell co-differentiation that may guide the planning of in vivo experiments.
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Frontiers in Pharmacology
·
2023
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IF 5.6
Xiu Yanghui,Su Yu,Gao Lihua,Yuan Hui,Xu Sennan,Liu Ying,Qiu Yan,Liu Zhen,Li Yuhang
Introduction: Chronic non-healing wound is a considerable clinical challenge and research into the discovery of novel pro-healing agents is underway as existing therapeutic approaches cannot sufficiently meet current needs.Method: We studied the effects of corylin in cell line fibroblasts and macrophages by Western blots, PCR, Flow cytometry assay, Immunofluorescence.Results: We showed that corylin, a main flavonoid extracted from Psoralea corylifolia L, reduced inflammatory responses, promoted collagen deposition, and accelerated the healing of full-thickness skin wounds in mice. Exploration of the underlying mechanisms showed that corylin activated the PI3K/AKT signaling, leading to fibroblasts’ migration, proliferation, and scratch healing. Corylin also activated sirtuin 1 (SIRT1) signaling, enhanced the deacetylation and cytoplasmic translocation of NF-κB p65, and therefore reduced lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Furthermore, inhibition of PI3K/AKT and sirtuin 1 pathway with LY294002 and EX527 prevent the therapeutic potency of corylin against chronic wounds.Conclusion: In summary, our results suggested that corylin may be a candidate for the development of novel pro-healing agents.
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Materials Express
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2023
·Vol. 13
·期 1
·81-84
·
IF 0.7
Wang Wen-Wen,Yang Li-Jie,Guo Jun-Feng
Pancreatic cancer is a common tumor of the digestive system with a high degree of malignancy and poor prognosis. Its incidence has significantly increased worldwide in recent years. Currently, approximately 90% of patients cannot be treated surgically. Thus, drug therapy plays an important
role in pancreatic cancer treatment. In this study, hydrogels loaded with mitomycin were prepared from hyaluronic acid and carboxymethyl chitosan, which have excellent biocompatibility. SEM results showed that the hydrogels had a three-dimensional interoperable porous structure, and CCK-8
results showed that hydrogels loaded with mitomycin significantly reduced cancer-cell proliferation. The hydrogels also reduced the migration of cancer cells in a dose-dependent manner, indicating their potential use as a drug-carrier material for pancreatic cancer treatment.
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CARBOHYDRATE POLYMERS
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2023
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IF 11.2
Die Dong,Rimei Chen,Jihong Jia,Chao Zhao,Zhiping Chen,Qin Lu,Yupei Sun,Weiyi Huang,Chunfang Wang,Yao Li,Hui He
The rapid loss of drugs and the weak curative effects due to cyclical urination are the main reasons why wound heal with difficulty after bladder tumour resection. Here, a bioinspired cellulose nanofibre (CNF)-based magnetic 3D nanonetwork wound dressing with excellent tissue adhesion and biocompatibility is designed by the assembly of pH- and near infrared-responsive CNF nanoskeletons, magnetic switching Fe 3 O 4 nanoparticles , and temperature switching Pluronic®F-127. The dressing with high loading capacity for mitomycin and indocyanine green can form a sticky 3D nanonetwork at the wound site and remain for a long time to release drugs through an external magnetic field. Interestingly, the dressing possessed excellent antibacterial activity , bacterial biofilm elimination, T24 tumour cell killing, and wound healing promotion through photothermal, photodynamic , and chemotherapy. Therefore, it has promising application for bladder postoperative infected wound healing to avoid rapid loss of drugs due to cyclical urination.
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PHARMACOLOGICAL RESEARCH
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2022
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IF 10.334
Xiaohua Xie,Xiaofeng Wu,Dongsheng Zhao,Ying Liu,Qiyue Du,Yitian Li,Yaping Xu,Yuhang Li,Yan Qiu,Yungang Yang
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with high mortality and limited effective therapy. Herein, we reported that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), used in depression and anxiety treatment, also exhibited therapeutic activities in IPF. Fluvoxamine inhibited cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), restrained the activation of their downstream targets, including PERK/ eIF2α/ c-Myc/ miR-9–5p/ TBPL1 and TBK1/ YAP/ JNK1/2/ Bnip3/ CaMKII/ cofilin signaling, thus attenuated the activation and migration of fibroblasts upon TGF-β1 challenge. Fluvoxamine dose-dependently improved pulmonary function, decreased the expression of inflammatory factors, reduced excessive production of extracellular matrix, and thus alleviated bleomycin (BLM)-induced lung fibrosis in mice. Moreover, fluvoxamine at a dose of 10 mg/ kg showed similar efficacy as pirfenidone (PFD) at a dose of 30 mg/kg in a mice model of lung fibrosis. In summary, our results suggest that fluvoxamine is an effective anti-fibrotic agent for IPF.
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ANALYTICAL CHEMISTRY
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2023
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IF 7.4
Qunfei Tai,Hailong Yu,Mingxia Gao,Xiangmin Zhang
From metabolic waste to biological mediators, exosomes have emerged as the key player in a variety of pathological processes, particularly in oncogenesis. The exosome-mediated communication network involves nearly every step of cancer progression, promoting the proliferation and immune escape of cancer cells. Therefore, the removal of cancer-derived exosomes has profound clinical significance. Current methods for exosome separation and enrichment are either for large-scale samples or require complex pretreatment processes, lacking effective methods for trace-volume exosome capture in situ. Herein, we have developed an in situ exosome capturing and counting device based on the antibody-functionalized capillary. Specific antibodies targeting exosome biomarkers were immobilized to the inner wall of the capillary via biotin-streptavidin interaction for direct cancer exosome capturing. Subsequent exosome staining enabled imaging and enumeration. Acceptable linearity and reproducibility were achieved with our device, with the capturing and detective range between 3.3 × 104 and 3.3 × 108 particles, surpassing the nanoparticle tracking analysis by 2 orders of magnitude while requiring merely 30 μL sample. We demonstrated that MCF-7-derived exosomes induced epithelial–mesenchymal transition of epithelial cells MCF-10A, and our method was able to completely or partially reverse the transition by complete depletion or specific depletion of cancer exosomes without any preprocessing. Moreover, both whole exosomes and cancer-specific exosomes alone from mimic blood samples were successfully captured and counted, without obvious non-specific adsorption. In all, our approach realized the in situ depletion and number-counting of cancer-derived exosomes directly from the complex humoral environment, having the potential to provide a comprehensive tumor therapeutic and prognosis evaluation tool by targeted hemodialysis and counting of tumor-derived exosomes.
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ONCOGENE
·
2023
·Vol. 42
·期 29
·2278-2293
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IF 8
Chen Yihuan,Dai Xiaoshuo,Chen Wei,Qiao Yan,Bai Ruihua,Duan Xiaoxuan,Zhang Kai,Chen Xinhuan,Li Xin,Mo Saijun,Cao Wenbo,Li Xiang,Liu Kangdong,Dong Ziming,Lu Jing
Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.
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BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Xuchen Feng,Jun Ge,Hui Fu,Lin Miao,Feng Zhao,Jingyu Wang,Yujiao Sun,Yingpeng Li,Yunfei Li
Small molecules directly downregulating β-catenin could potentially offer a more effective therapeutic approach for combating against cancer stem cells, as compared to targeting the downstream components of the Wnt/β-catenin pathway. The challenge, however, lies in the fact that very few β-catenin suppressors have proven clinically effective, leaving a significant gap in medical solutions. Given that E-cadherin has a natural affinity for β-catenin, it stands to reason that agents designed to increase E-cadherin expression might provide an alternative method of regulating β-catenin levels. In this study, we report our discovery of DSS-C12 and DSS-B8, specific ester-based drugs derived from Dan-Shen-Su (DSS) extracted from the herb Salvia miltiorrhiza . Remarkably, these compounds display a potent ability to downregulate β-catenin, while also improving overall survival in post-surgery mice. Additionally, when these drugs are used in combination with PD-L1 checkpoint blockade, they stimulate enhanced systemic immune responses leading to significant suppression of primary tumor growth. In-depth mechanistic studies revealed that DSS-B8 functions as a vitamin D receptor agonist without inducing hypercalcemic effects. Collectively, our findings indicate that DSS-derived small molecules have considerable potential as clinically viable therapeutic strategies for β-catenin deactivation.
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FOOD AND CHEMICAL TOXICOLOGY
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2013
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IF 3.01
Jianyong Li,Xiaojun Kong,Xiwang Li,Yajun Yang,Jiyu Zhang
Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects and it is important to characterize its genotoxicity. In this study, the genotoxicity of AEE was assessed with two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and the mouse bone marrow micronucleus assay. In the Ames test , Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation with a S9 fraction from Acroclor-induced rat liver. The doses of AEE were 5 mg/plate, 2.5 mg/plate, 1.25 mg/plate, 0.625 mg/plate and 0.3125 mg/plate, respectively. In the above tested strains, mutagenicity with or without the S-9 mixture was not detected. In the mammalian erythrocyte micronucleus assay, fifty mice were divided into five groups evenly and the AEE dose at 5000 mg/kg, 2500 mg/kg and 1250 mg/kg and the cyclophosphamide dose at 40 mg/kg as a positive control, the 0.5% of CMC-Na as negative control were administered. The results showed that AEE did not induce any significant increase in micronucleated erythrocytes after 24 h ( p < 0.01). Our results suggested that AEE was non-genotoxic in vivo or in vitro .
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2015
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IF 4.152
Jixiang Zhu,Fanwen Yang,Fupo He,Xiumei Tian,Shuo Tang,Xiaoming Chen
A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65 kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies.
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