Journal of Functional Foods
·
2018
·
IF 3.47
Cuicui Duan,Yujuan Zhao,Cheng Huang,Zijian Zhao,Lei Gao,Chunhua Niu,Chao Wang,Xiaoxiao Liu,Chuan Zhang,Shengyu Li
Acute liver failure (ALF) is a life-threatening clinical condition resulting from massive apoptosis of hepatocytes. This study aims to examine the protective effects of Lactobacillus plantarum C88 on LPS/D-GalN-induced ALF and elucidate its underlying molecular mechanisms in mice. The results showed that L. plantarum C88 pretreatment significantly reduced the levels of plasma ALT and AST in mice with LPS/D-GalN–induced liver injury. L. plantarum C88 pretreatment decreased the secretion of inflammatory cytokines. In addition, L. plantarum C88 remarkably increased the expression levels and nuclear translocations of Nrf2 mRNA in liver tissues, but inhibited NF-κB nuclear translocations and P65, P38 phosphorylation levels. Moreover, L. plantarum C88 enhanced the intestinal mucosal barrier by upregulating the expressions of tight junction proteins as well as HIF-1α. These results suggest that L. plantarum C88 protects against ALF associated with Nrf2 and the MAPK/NF-κB signaling pathways.
研究领域:
药理学
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免疫学
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分子生物学
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胃肠病学
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DOI
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-18
·
IF 7.5
Li Xing,Zhang Wansong,Fang Yitong,Sun Tianhu,Chen Jian,Tian Ruilin
Background Glioblastoma (GBM) patients frequently develop resistance to temozolomide (TMZ), the standard chemotherapy. While targeting cancer metabolism shows promise, the relationship between metabolic perturbation and drug resistance remains poorly understood.Methods We performed high-throughput CRISPR interference screens in GBM cells to identify genes modulating TMZ sensitivity. Findings were validated using multiple GBM cell lines, patient-derived glioma stem cells, and clinical data. Molecular mechanisms were investigated through transcriptome analysis, metabolic profiling, and functional assays.Results We identified phosphoglycerate kinase 1 (PGK1) as a key determinant of TMZ sensitivity. Paradoxically, while PGK1 inhibition suppressed tumor growth, it enhanced TMZ resistance by inducing metabolic stress. This activated AMPK and HIF-1α pathways, leading to enhanced DNA damage repair through 53BP1. PGK1 expression levels correlated with TMZ sensitivity across multiple GBM models and patient samples.Conclusion sOur study reveals an unexpected link between metabolic stress and chemoresistance, demonstrating how metabolic adaptation can promote therapeutic resistance. These findings caution against single-agent metabolic targeting and suggest PGK1 as a potential biomarker for TMZ response in GBM.
研究领域:
癌症生物学
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分子生物学
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基因组学
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转化医学
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DOI
PubMed
高影响因子
Journal of Agriculture and Food Research
·
2026
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IF 7.2
Yizhu Chen,Yi Liu,Yurong Fang,Huixue Huang,Zhihong Long,Bomi Ryu,Haisheng Xie,Zhong-Ji Qian
Age related macular degeneration (AMD) is one of the main causes of blindness in. elderly patients, and its treatment methods include intraocular injection and oral. administration, requiring long-term treatment and suboptimal efficacy. Tilapia skin-derived oligopeptides, characterized by high safety and bioactivity, emerge as a promising source of functional food ingredients. Here, we investigated the protective mechanism of TBP-1 (Ser-Val-Val-Ala-Ile), a pentapeptide isolated from tilapia skin, against hypoxia-induced damage in retinal pigment epithelial (ARPE-19) cells and angiogenesis in human umbilical vein endothelial cells (HUVECs). In the functional evaluation, TBP-1 notably attenuated ROS overproduction in CoCl 2 -induced ARPE-19 cells, simultaneously suppressing the stabilization of hypoxia-inducible factor-1α (HIF-1α), which was associated with reduced vascular endothelial growth factor (VEGF) transcription, diminished inflammatory factor levels, and restoration of normal autophagic flux. To validate the ROS-dependent nature of this regulatory pathway, we performed a rescue experiment using N-acetylcysteine (NAC), a well-characterized ROS scavenger. In HUVECs activated by VEGF, TBP-1 decreased the phosphorylation of VEGFR-2 and dampened the activation of the MAPK signaling pathway, resulting in dose-dependent inhibition of cell migration, invasion, and the formation of capillary-like tubular structures. Molecular docking and quantum chemical analyses suggested that the bioactivity of TBP-1 may rely on the electron-donating property of the Ser residue and hydrophobic interactions mediated by Ile, both of which are critical for its ROS scavenging ability and predicted interaction with HIF-1α. Collectively, these findings suggest that TBP-1 is a multi-target functional food supplement for preventing AMD by targeting the ROS/HIF-1α/VEGF axis, providing a theoretical basis for the high-value utilization of tilapia skin.
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高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yifan Li,Qiangwei Liang,Liyue Zhou,Yongjing Cao,Jiayu Yang,Juan Li,Jinxia Liu,Jiawei Bi,Yanhua Liu
The signaling cascade between nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1α (HIF-1α) can be activated by proinflammatory M1 macrophages in rheumatoid arthritis (RA), which produces reactive oxygen species (ROS) and enhances M1 macrophage polarization, thus aggravating the development of RA. Therefore, an ROS-responsive artesunate prodrug micellar nanosystem for co-delivery of dexamethasone (DEX/HA-TK-ART micelles , abbreviated as DEX/HTA) was developed for synergistic inhibition of the HIF-1α/NF-κB cascade to regulate ROS scavenging and macrophage repolarization in RA combination therapy. DEX/HTA micelles displayed prolonged circulation in blood and efficiently co-delivered ART&DEX in the inflamed joints of adjuvant-induced arthritis (AIA) rats; moreover, they were specifically recognized and internalized into M1 macrophages through CD44 receptor-mediated endocytosis . ROS-responsive co-released ART&DEX then exerted a synergistic action to efficiently perform ROS scavenging and repolarization of M1 to M2 macrophages by inhibition of the HIF-1α/NF-κB cascade. The intravenous administration of DEX/HTA micelles into AIA rat models significantly alleviated inflammatory cell infiltration and repaired cartilage injury in the joint. Collectively, our study highlights the therapeutic potential of DEX/HTA micelles for treating RA through synergistic inhibition of the HIF-1α/NF-κB signaling cascade to regulate ROS scavenging and macrophage repolarization. Statement of significance An ROS-responsive artesunate (ART) prodrug micellar nanosystem for co-delivering dexamethasone (DEX), abbreviated as DEX/HA-TK-ART micelle, was developed for synergistic cascade regulation of the HIF-1α/NF-κB pathway on ROS scavenging and macrophage repolarization in combination therapy for rheumatoid arthritis. The well-designed nanosystem showed prolonged circulation in blood and superior ART&DEX accumulation in the inflamed joints of AIA rats; moreover, the micelles were specifically internalized into M1 macrophages and co-released ART&DEX, subsequently leading to inhibition of the HIF-1α/NF-κB pathway for ROS scavenging and macrophage repolarization, thus generating synergistic anti-inflammatory effects in RAW 264.7 cells and AIA rats. The HIF-1α/NF-κB cascade regulation on ROS scavenging and macrophage repolarization based on ART&DEX combination with smart nanotechnology could serve as a promising approach for rheumatoid arthritis therapy.
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2025
·
IF 7.5
Yinlan Xu,Hejun Liu,Haonan Guo,Jinmei Zheng,Ling Tao,Weidong Wu
Non-small cell lung cancer (NSCLC) is the major type of malignant tumor in the lungs. Emerging epidemiological evidence implicates environmental copper exposure as a potential risk modulator for NSCLC progression. This study investigated the effects of low-dose Copper (Cu) exposure on A549 cells and evaluated the therapeutic potential of two natural compounds, osthole and matrine. The results demonstrated that Cu exposure (5 μg/mL, 12 h) significantly promoted the migration, invasion and colony formation of A549 cells ( P < 0.05), accompanied by a reduction in cell apoptosis, a decrease in ROS levels and an increase in mitochondrial membrane potential. Meanwhile, osthole and matrine treatment could reverse these phenotypes and arrest the cell cycle of A549 in the G1 phase. Transmission electron microscopy results revealed that Cu exposure induced slightly swollen mitochondria and as well as the increase in the number of mitochondria, while osthole and matrine treatments resulted in severe degenerative changes in mitochondria. Both qPCR and Western blot examinations indicated that Cu exposure promoted the expression of PGC-1α but inhibited the expressions of STAT1, TNF-α and IL-2. Osthole treatment could down-regulate the expression of PGC-1α and up-regulate the expressions of STAT1, TNF-α and IL-2, while matrine treatments could up-regulate the expressions of STAT1 and TNF-α and down-regulate the expressions of PGC-1α and IL-2. Taken together, these findings indicate that low-dose Cu exposure can promote the proliferation, migration, invasion and mitochondrial damage of A549 cells, while osthole and matrine treatments inhibit Cu effects by regulating the STAT1, BGC-1 α, TNF-α and IL-2.
研究领域:
肿瘤学
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环境毒理学
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药理学
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细胞生物学
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分子生物学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Jingtao Du,Daniel Rybak,Qi Su,Qiusheng Wang,Qifan Yuan,Jinlong Gao,Yuhang Wang,Paweł Nakielski,Xianfeng Wang,Filippo Pierini,Jianyong Yu,Xiaoran Li,Bin Ding
The treatment of infected irregular wounds remains one of the most significant challenges in clinical practice. Sprayable hydrogels have attracted considerable attention due to their favorable fitting with irregular wounds. However, the development of hydrogels with programmable anti-bacterial, anti-inflammatory, and regenerative properties to match the healing process still faces severe challenges. Herein, a versatile strategy is demonstrated to develop sprayable and photothermal fiber-embedded hydrogel dressings by incorporating the gold nanorods (AuNRs) and anti-inflammatory drug diclofenac sodium (DS)-loaded poly(lactic- co -glycolic acid) (PLGA) electrospun fibers into the stromal-cell-derived factor 1α (SDF-1α)-immobilized gelatin methacrylate hydrogel. Benefiting from the photothermal conversion property of AuNRs and the suitable glass transition temperature of PLGA short fibers, the hydrogels can not only realize a photothermal anti-bacterial effect, but also photo-triggered on-demand release of DS for anti-inflammatory activity. Furthermore, the sustained release of SDF-1α facilitates endogenous stem cell recruitment. The in vivo experiments demonstrate accelerated healing of infected wounds. The RNA-sequencing analysis reveals that the hydrogel is capable of suppressing the inflammatory response-related pathway. The photo-responsive fiber-embedded hydrogels offer a promising strategy for constructing a photo-triggered programmable therapeutic platform for regenerative medicine.
研究领域:
生物材料
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纳米医学
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再生医学
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创面愈合
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药物递送
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生物工程
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产品关联
DOI
高影响因子
Arabian Journal of Chemistry
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2022
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IF 6.212
Zizhen Zhao,Chen Fu,Yuping Zhang,Yingying Zhang,Xiaoxi Yang,Ailing Fu
The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo . The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.
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
高影响因子
MICROBIOLOGY AND IMMUNOLOGY
·
2017
·Vol. 62
·期 3
·187-194
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IF 1.706
Cenrong Zhang,Wei Xu,Jian Chen,Ran Guan,Shicheng Bi,Haibo Jin,Xuemei Cui,Fushan Shi,Songhua Hu
In the present study, the adjuvant effect of soybean oil containing ginseng root saponins (SO-GS-R) on the immune response to foot-and-mouth disease vaccine (FMDV) in mice was investigated. When immunized with FMDV antigen emulsified in an SO-GS-R formulation, mice generated remarkably higher serum antibody and cytokine responses than mice immunized with FMDV antigen alone. To elucidate the mechanisms underlying the adjuvant effect of SO-GS-R, we measured cytokines in serum and muscle tissue after intramuscular injection of SO-GS-R. The results showed that injection of SO-GS-R significantly increased the levels of IL-1β, IL-5, IL-6, G-CSF, KC, MCP-1, MIP-1α, and MIP-1β in both serum and muscle. These results suggested that SO-GS-R recruits neutrophils, eosinophils, T cells and macrophages, causing immune cell recruitment at the injection site, driving antigen-presenting cells to actively participate in the onset of immunity, and amplifying the immune responses. Considering its adjuvant activity and plant-derived properties, SO-GS-R should be further studied for its adjuvant effect on vaccines used in food animals.
研究领域:
免疫学
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兽医学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
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IF 8.3
Ming-Xuan Liu,Yu-Ting Cai,Ruo-Jia Wang,Peng-Fei Zhu,Yan-Chao Liu,Hao Sun,Yong Ling,Wei-Zhong Zhu,Jing Chen,Xiao-Ling Zhang
Hypoxia can lead to liver fibrosis and severely limits the efficacy of photodynamic therapy (PDT). Herein, carbon nitride (CN)-based hybrid nanoparticles (NPs) VPSGCNs@TSI for light-driven water splitting were utilized to solve this problem. CNs were doped with selenide glucose (Se-glu) to enhance their red/NIR region absorption. Then, vitamin A-poly(ethylene glycol) (VA-PEG) fragments and aggregation-induced emission (AIE) photosensitizers TSI were introduced into Se-glu-doped CN NPs (VPSGCNs) to construct VPSGCNs@TSI NPs. The introduction of VA-PEG fragments enhanced the targeting of the NPs to activated hepatic stellate cells (HSCs) and reduced their toxicity to ordinary liver cells. VPSGCN units could trigger water splitting to generate O2 under 660 nm laser irradiation, improve the hypoxic environment of the fibrosis site, downregulate HIF-1α expression, and activate HSC ferroptosis via the HIF-1α/SLC7A11 pathway. In addition, generated O2 could also increase the reactive oxygen species (ROS) production of TSI units in a hypoxic environment, thereby completely reversing hypoxia-triggered PDT resistance to enhance the PDT effect. The combination of water-splitting materials and photodynamic materials showed a 1 + 1 > 2 effect in increasing oxygen levels in liver fibrosis, promoting ferroptosis of activated HSCs and reversing PDT resistance caused by hypoxia.
研究领域:
材料科学
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生物医学工程
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治疗学
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纳米技术
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Regenerative Biomaterials
·
2024
·
IF 5.6
Ji Minrui,Yuan Zaixin,Ma Hongdong,Feng Xian,Ye Cong,Shi Lei,Chen Xiaodong,Han Fei,Zhao Caichou
The management of full-thickness skin injuries continues to pose significant challenges. Currently, there is a dearth of comprehensive dressings capable of integrating all stages of wound healing to spatiotemporally regulate biological processes following full-thickness skin injuries. In this study, we report the synthesis of a dandelion-shaped mesoporous strontium-gallium microparticle (GE@SrTPP) achieved through dopamine-mediated strontium ion biomineralization and self-assembly, followed by functionalization with gallium metal polyphenol networks (MPNs). As CroCfunctional wound dressing, GE@SrTPP can release bioactive ions in a spatiotemporal manner akin to dandelion seeds. During the early stages of wound healing, GE@SrTPP demonstrates rapid and effective hemostatic performance while also exhibiting antibacterial properties. In the inflammatory phase, GE@SrTPP promotes M2 polarization of macrophages, suppresses the expression of pro-inflammatory factors, and decreases oxidative stress in wounds. Subsequently, during the stages of proliferation and tissue remodeling, GE@SrTPP facilitates angiogenesis through the activation of the HIF-1α/VEGF pathway. Analogous to the dispersion and rooting of dandelion seeds, the root-like new blood vessels supply essential nutrients for wound healing. Ultimately, in a rat chronic wound model, GE@SrTPP achieved successful full-thickness wounds repair. In summary, these dandelion-shaped GE@SrTPP microparticles demonstrate comprehensive regulatory effects in managing full-thickness wounds, making them highly promising materials for clinical applications.
研究领域:
材料科学
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生物医学工程
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伤口愈合
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生物材料
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xudong Xie,Weixian Hu,Yue An,Yuheng Liao,Shengming Zhang,Yanzhi Zhao,Kangkang Zha,Wenqian Zhang,Zhenhe Zhang,Fan Xia,Bobin Mi,Benjie Zhou,Hankun Hu,Mengfei Liu,Guohui Liu
Diabetic wounds are characterized by an imbalance between impaired angiogenesis and persistent pro-inflammatory immune responses, leading to chronic non-healing. Under hyperglycemic and oxidative stress conditions, the glycolytic function of endothelial cells is significantly compromised. However, solely enhancing angiogenesis does not effectively promote diabetic wound healing due to concomitant dysregulation of the local immune microenvironment, which further suppresses vascularization. Notably, Th1 cells dominate the diabetic wound immune milieu and exacerbate inflammatory responses, thereby aggravating immune imbalance. Thus, an optimal therapeutic strategy should simultaneously target both inflammatory dysregulation and vascular dysfunction. To address the phenomenon of cell-specific metabolic reprogramming within diabetic wounds, where glycolytic activity is impaired in endothelial cells yet enhanced in Th1 cells, this study developed a glucose-responsive NG@B87@HA hydrogel system designed to reprogram the local metabolic network and modulate Th1 cell metabolism while restoring endothelial function. The hydrogel incorporates nanoparticles functionalized with CXCR3 antibody to specifically target Th1 cells and deliver the glycolysis inhibitor Bay87-2243 (B87), thereby suppressing their glycolytic flux and inflammatory activity via inhibition of the HIF-1α–GLUT1 signaling axis. Simultaneously, naringin (NG), which acts as a crosslinker, forms dynamic boronic ester bonds with HA-PBA and PVA, enabling glucose-dependent responsiveness. This mechanism not only mitigates local oxidative stress but also enhances the tube-forming capacity of endothelial cells, ultimately promoting angiogenesis. The results demonstrated that the NG@B87@HA hydrogel effectively restores the dysregulated metabolic network in diabetic wounds. By concurrently rectifying immune microenvironment imbalance and endothelial dysfunction, this system provides a novel therapeutic strategy for accelerating diabetic wound healing.
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高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Tianci Zhang,Ruofei Zhang,Wei Liu,Yucheng Qi,Hongyi Wang,Hu Zhang,Zhixiong Xiao,Stephen J. Pandol,Yuan-Ping Han,Xiaofeng Zheng
Transcription factor EB (TFEB), a master lysosomal biogenesis and autophagy regulator, is crucial for cellular homeostasis, and its abnormality is related to diverse inflammatory diseases. Genetic variations in autophagic genes are associated with susceptibility to inflammatory bowel disease (IBD); however, little is known about the role and mechanism of TFEB in disease pathogenesis. In this study, we found that the genetic deletion of TFEB in mouse intestinal epithelial cells (IEC) caused intestinal barrier dysfunction, leading to increased susceptibility to experimental colitis. Mechanistically, TFEB functionally protected IEC in part through peroxisome proliferator-activated receptor gamma coactivator 1alpha (TFEB-PGC1α axis) induction, which consequently suppressed reactive oxygen species. TFEB can directly regulate PGC-1α transcription to control antioxidation level. Notably, TFEB expression is impaired and downregulated in the colon tissues of IBD patients. Collectively, our results indicate that intestinal TFEB participates in oxidative stress regulation and attenuates IBD progression.
研究领域:
免疫学
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胃肠病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）