Evidence-based Complementary and Alternative Medicine
·
2023
·
IF 2.65
Xingcai Zhang,Wei Zhang,Xianhai Chen,Yuli Cai
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Bilobalide (BB) is a sesquiterpene isolated from Ginkgo biloba, and its role in IPF is poorly understood. Mice were intratracheally instilled with 2.5 mg/kg bleomycin (BLM) to induce IPF and then treated with 2.5, 5, and 10 mg/kg BB daily for 21 days. Treatment with BB ameliorated pathological injury and fibrosis of lung tissues in BLM-induced mice. BB suppressed BLM-induced inflammatory response in mice as demonstrated by reduced inflammatory cells counts (leukocytes, neutrophils, macrophages, and lymphocytes) and pro-inflammatory factors (CCL2 and TNF-α), as well as increased CXCL10 levels in BALF. The expression of BLM-induced hydroxyproline, LDH, and pro-fibrotic mediators including fibronectin, collagen I, α-smooth muscle actin (α-SMA), transforming growth factor (TGF)-β1, matrix metalloproteinase (MMP)-2, and MMP-9 in lung tissue was inhibited by BB treatment, and the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression was increased. BB blocked the phosphorylation of JNK and NF-κB, and the nuclear translocation of NF-κB in the lung tissue of mice induced by BLM. Additionally, it abated the activation of NLRP3 inflammasome in lung tissue induced by BLM, which led to the downregulation of IL-18 and IL-1β in BALF. Our present study suggested that BB might ameliorate BLM-induced pulmonary fibrosis by inhibiting the early inflammatory response, which is probably via the inhibition of the JNK/NF-κB/NLRP3 signal pathway. Thus, BB might serve as a therapeutic potential agent for pulmonary inflammation and fibrosis.
研究领域:
药理学
·
肺病学
·
免疫学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Science
·
2024
·
IF 5.8
Mengwen Li,Yue Tian,Xiaoming Wen,Jingke Fu,Jianyong Gao,Yingchun Zhu
The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable meso-organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The meso-organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.
研究领域:
肿瘤学
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Redox Biology
·
2024
·
IF 10.7
Wei Li,Qingwen Zeng,Bing Wang,Chao Lv,Haoan He,Xi Yang,Bin Cheng,Xiaoan Tao
Although oxidative stress is closely associated with tumor invasion and metastasis, its’ exact role and mechanism in the initial stage of oral cancer remain ambiguous. Glutamine uptake mediated by alanine-serine-cysteine transporter 2 (ASCT2) participates in glutathione synthesis to resolve oxidative stress. Currently, we firstly found that ASCT2 deletion caused oxidative stress in oral mucosa and promoted oral carcinogenesis induced by 4-Nitroquinoline-1-oxide (4-NQO) using transgenic mice of ASCT2 knockout in oral epithelium. Subsequently, we identified an upregulated gene Thbs1 linked to macrophage infiltration by mRNA sequencing and immunohistochemistry. Importantly, multiplex immunohistochemistry showed M1-like tumor-associated macrophages (TAMs) were enriched in cancerous area. Mechanically, targeted ASCT2 effectively curbed glutamine uptake and caused intracellular reactive oxygen species (ROS) accumulation, which upregulated Thbs1 in oral keratinocytes and then activated p38, Akt and SAPK/JNK signaling to polarize M1-like TAMs via exosome-transferred pathway. Moreover, we demonstrated M1-like TAMs promoted malignant progression of oral squamous cell carcinoma (OSCC) both in vitro and in vivo by a DOK transformed cell line induced by 4-NQO. All these results establish that oxidative stress triggered by ASCT2 deletion promotes oral carcinogenesis through Thbs1-mediated M1 polarization, and indicate that restore redox homeostasis is a new approach to prevent malignant progression of oral potentially malignant disorders.
研究领域:
癌症生物学
·
免疫学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2022
·Vol. 17
·期 1
·1-8
·
IF 2.677
Zhang Bin-Fei,Song Wei,Wang Jun,Wen Peng-Fei,Zhang Yu-Min
Objectives The lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model. Methods Seventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses. Results Nine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Conclusion The remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.
研究领域:
病理生理学
·
肺医学
·
创伤外科
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Jialu Zhuang,Hao Zhang,Jin Wu,Danyou Hu,Tao Meng,Jing Xue,Hanyang Xu,Gang Wang,Hua Wang,Guiyang Zhang
The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.
研究领域:
药学
·
材料科学
·
肝病学
·
免疫学
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
Yanyan Zhu,Yameng Jiang,Lei Shi,Linying Du,Xiaodong Xu,Enxia Wang,Yong Sun,Xin Guo,Boyang Zou,Huaxin Wang,Changyuan Wang,Lidan Sun,Yuhong Zhen
7- O -Geranylquercetin (GQ) is a novel O -alkylated derivate of quercetin . In this study, we evaluated its apoptosis induction effects in human gastric cancer cell lines SGC-7901 and MGC-803 and explored the potential molecular mechanisms. The results demonstrated that GQ lowered viability of SGC-7901 and MGC-803 cells in a dose- and time-dependent manner without apparent cytotoxicity to human gastric epithelial cell line GES-1. GQ could induce apoptosis in SGC-7901 and MGC-803cells, and arrest the gastric cancer cells at G2/M phase. Mechanism study showed that GQ triggered generation of reactive oxygen species (ROS), then activated p38 and JNK signaling pathways , subsequently led to mitochondrial impairment by regulating the expression of Bcl-2, Bcl-xl and Bax, and finally promoted the release of cytochrome c and the activation of caspases to induce apoptosis. In addition, Z-VAD-FMK (caspase inhibitor) could reverse GQ-induced apoptosis. SB203580 (p38 inhibitor) and SP600125 (JNK inhibitor) could rescue GQ-induced cell death and attenuate mitochondrial signal pathway activation. Furthermore, NAC (ROS inhibitor) could rescue GQ-induced cell death, reduce ROS generation, decrease the phosphorylation of p38 and JNK, and then attenuate the activation of mitochondrial signal pathway. Taken together, GQ induces caspase-dependent apoptosis in gastric cancer cells through activating ROS-MAPK mediated mitochondrial signal pathway. This study highlights the potential use of GQ as a gastric cancer therapeutic agent.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS Pathogens
·
2024
·Vol. 20
·期 1
·e1011926
·
IF 5.5
Zihao Wang,Ziming Jiang,Yu Zhang,Congwei Wang,Zhaoyang Liu,Zhankui Jia,Sudhanshu Bhushan,Jinjian Yang,Zhengguo Zhang
Uropathogenic Escherichia coli (UPEC) is the primary causative agent of urinary tract infections (UTIs) in humans. Moreover, as one of the most common bacterial pathogens, UPEC imposes a substantial burden on healthcare systems worldwide. Epithelial cells and macrophages are two major components of the innate immune system, which play critical roles in defending the bladder against UPEC invasion. Yet, the routes of communication between these cells during UTI pathogenesis are still not fully understood. In the present study, we investigated the role of membrane-bound nanovesicles (exosomes) in the communication between bladder epithelial cells and macrophages during UPEC infection, using an array of techniques such as flow cytometry, miRNA profiling, RNA sequencing, and western blotting. Moreover, our in vitro findings were validated in a mouse model of UPEC-induced cystitis. We found that UPEC infection induced the bladder epithelial MB49 cell line to secrete large numbers of exosomes (MB49-U-Exo), which were efficiently absorbed by macrophages both in vivo and in vitro. Assimilation of MB49-U-Exo induced macrophages to produce proinflammatory cytokines, including tumor necrosis factor (TNF)α. Exposure of macrophages to MB49-U-Exo reduced their phagocytic activity (by downregulating the expression of phagocytosis-related genes) and increased their rate of apoptosis. Mechanistically, we showed that MB49-U-Exo were enriched in miR-18a-5p, which induced TNFα expression in macrophages by targeting PTEN and activating the MAPK/JNK signaling pathway. Moreover, administration of the exosome secretion inhibitor GW4869 or a TNFα-neutralizing antibody alleviated UPEC-mediated tissue damage in mice with UPEC-induced cystitis by reducing the bacterial burden of the bladder and dampening the associated inflammatory response. Collectively, these findings suggest that MB49-U-Exo regulate macrophage function in a way that exacerbates UPEC-mediated tissue impairment. Thus, targeting exosomal -release or TNFα signaling during UPEC infection may represent promising non-antibiotic strategies for treating UTIs.
Urinary tract infections, which are typically caused by uropathogenic Escherichia coli (UPEC), affect over 150 million people each year, worldwide. Because the incidence of antibiotic resistance among UPEC strains is on the rise, urinary tract infections are becoming increasingly challenging to treat using this standard treatment method. Moreover, although the host immune response against UPEC has been intensively studied, the mechanism of communication between bladder epithelial cells and macrophages during UPEC infection remains largely unexplored. Here, we characterized the exosomes released from bladder epithelial cells following UPEC infection and evaluated their impact on macrophages. We demonstrated that bladder tissue destruction following excessive innate immune cell activation during UPEC infection may be driven by exosomes secreted from bladder epithelial cells. We further showed that pharmacologically inhibiting exosomal release from epithelial cells limited macrophage-associated inflammation, innate immune cell infiltration, and histopathological injuries in a mouse model of UPEC-induced cystitis. Collectively, our findings suggest that modulating exosome release represents a promising non-antibiotic therapy for UTIs.
研究领域:
微生物学
·
免疫学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yuliang Xu,Sihan Wang,Jincheng Xiong,Pimiao Zheng,Huixia Zhang,Shiqi Chen,Qiang Ma,Jianzhong Shen,Tony Velkov,Chongshan Dai,Haiyang Jiang
Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, we propose an enhanced chemodynamic anti-tumor therapy strategy by promoting the Fenton reaction by using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe 3 O 4 as a therapeutic platform. Carboxymethyl cellulose (CMC) was used as a stabilizer of Fe 3 O 4 , which then decorated on the surface of ZIF-8 via the electrostatic interaction and served as an efficient Fenton reaction trigger. Meanwhile, the pH-responsive ZIF-8 scaffold acted as a container to encapsulate the chemotherapeutic drug doxorubicin (DOX). The obtained DOX-ZIF-8@Fe 3 O 4 /CMC nanoparticles concomitantly accelerated DOX release and generated more hydroxyl radicals by targeting the lysosomes in cancer cells. In vitro and in vivo studies verify that the DZFC nanoparticles trigger GPX4-dependent ferroptosis via the activation of the c-Jun N-terminal kinases (JNK) signaling pathway, following to achieve the chemo/ferroptosis synergistic anti-tumor efficacy. No marked toxic effects were detected during DZFC treatment in a tumor-bearing mouse model. This composite nanoparticle remarkably suppressed the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theragnostic nanomedicines. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 16
·8587
·
IF 13.3
Wei-Jia Yu,Wen-Xi Jiang,Shu-Jing Liu,Hui-Hua Li,Qiu-Yue Lin
Rationale: Infiltration of immune cells into the heart plays a crucial role in the transition from adaptive hypertrophy to heart failure (HF) following chronic pressure overload. However, the key factors in myeloid cells that regulate this process are still not well defined. Here, we studied the functional role of S100A8/A9 in myeloid cells during this transition. Methods: Cardiac hypertrophy and HF models were induced by transverse aortic constriction (TAC) for 1 to 4 weeks. The heterogeneity of CD45 + immune cells and the cellular sources of S100A8/A9 were analyzed using published single-cell RNA sequencing datasets. The effects of S100A8/A9 on TAC-induced hypertrophy and HF were verified in S100A9 knockout (KO) and bone marrow (BM)-chimeric mice and in an in vitro coculture system. Results: S100A8/A9 levels were significantly increased in HF patients and in TAC-induced HF model mice. Moreover, the TAC-induced transition from adaptive hypertrophy to HF was significantly attenuated in S100A9-KO mice and WT mice transplanted with S100A9-KO BM cells. Mechanistically, TAC-stimulated upregulation of S100A8/A9 in neutrophils induced an early inflammatory response and adaptive hypertrophy through activation of the p38 MAPK/JNK/AP-1 pathway, leading to increased production of IL-1β and chemokines (CCL2 and CCL6). These chemokines promoted the infiltration of CCR2 + macrophages to the damaged heart. Therefore, they exhibited upregulation of S100A8/A9, which led to exacerbation of inflammation, cardiac hypertrophy and fibrosis via activation of the NF-κB/NLRP3, AKT/Calcineurin A and TGF-β/Smad2 signaling pathways. Additionally, treating WT mice with the S100A9 inhibitor ABR-238901 prevented TAC-induced cardiac hypertrophy-related dysfunction. Conclusion: The present findings establish an S100A8/A9-related axis between myeloid cells and cardiac cells that drives the pressure overload-induced transition from hypertrophy to HF, suggesting that S100A8/A9 is a promising therapeutic target for this disease.
研究领域:
心脏病学
·
免疫学
·
分子生物学
·
基因组学
·
生物医学研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2019
·
IF 3.197
Yanbei Tu,Kai Wang,Jian-Bo Wan,Chengwei He
Glycine tabacina (Labill.) Benth, a renowned Chinese medicinal herb, has been used for treatment of rheumatoid arthritis (RA) and joint infection. This study aimed to investigate inhibitory effect of its ethanol extract (GTE) on RA-associated inflammation. Nine isoflavonoids of twelve ones which were found in G. tabacina roots were identified by UHPLC-DAD-MS/MS. GTE treatment suppressed lipopolysaccharide-stimulated overproduction of nitric oxide, TNF-α and IL-6, and iNOS expression in macrophages. GTE blocked the activation of NF-κB and MAPK pathways, as indicated by reduced levels of phosphorylation of IKKα/β, IκBα, p38, ERK and JNK, and the suppressed nuclear translocation of NF-κB p65. Additionally, GTE administration decreased swelling of arthritic paw and serum TNF-α and IL-1β levels in collagen-induced arthritis (CIA) mice. These results demonstrated that GTE exhibited strong anti-inflammatory and anti-arthritic activities through suppressing NF-κB and MAPK pathways activation in activated macrophages and CIA mice, suggesting the potential applications of this species in RA prevention and treatment as functional food or therapeutic agent.
研究领域:
药理学
·
免疫学
·
炎症研究
·
风湿病学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qingfeng Guo,Shenyu Shen,Xinyang Wang,Lei Shi,Yuwei Ren,Dandan Li,Zhenhua Yin,Juanjuan Zhang,Baocheng Yang,Xuewei Wang,Gang Ding,Lin Chen
The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives ( 1–11 ) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13 – 16 displayed potent phytotoxic effects on Arabidopsis thaliana , while compounds 1 , 2 , 5 , 10 , and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 μM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.
研究领域:
药理学
·
化学工程
·
天然产物化学
·
免疫学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUTRITION RESEARCH
·
2015
·
IF 2.472
Qian Wang,Shuang-ting Wang,Xin Yang,Pan-pan You,Wen Zhang
Myricetin (MyR), a naturally occurring flavonol widely distributed in fruits, vegetables, and medicinal plants , has anticancer, anti-inflammatory, antihyperlipidaemic , and antiobesity activities. In the present study, we hypothesized that the antiobesity property of MyR is mediated via suppression of differentiation of preadipocytes into adipocytes and promotion of lipolysis of mature adipocytes, which effectively decrease the intracellular triglyceride concentration of adipocytes. Accordingly, the aim of this work was to investigate the effects of MyR on adipocyte differentiation and lipolysis in differentiated 3 T3-L1 adipocytes. Our results showed that MyR inhibited differentiation of 3 T3-L1 preadipocytes in a concentration-dependent manner. Myricetin downregulated the mRNA and protein levels of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor γ , both of which are major adipogenic transcription factors. Furthermore, the mRNA levels of other adipogenesis-related transcription factors, namely, CCAAT/enhancer-binding protein β , sterin regulatory element binding protein 1-c, peroxisome proliferator-activated receptor γ coactivator–1, adipocyte protein 2 , lipoprotein lipase and glucose transporter 4 , were also reduced by MyR treatment. Moreover, MyR significantly inhibited the phosphorylation of extracellular signal–regulated kinase, Jun N-terminal kinase, and p38 during the differentiation process. On the other hand, MyR induced a dose-dependent increase in glycerol release in fully differentiated adipocytes, indicating its stimulatory effect on adipocyte lipolysis. Furthermore, MyR downregulated mRNA level of perilipin A and enhanced the phosphorylation level of extracellular signal–regulated kinase, Jun N-terminal kinase, and p38 during lipolysis. Taken together, these findings indicate that MyR exerts antiobesity activity in adipocytes.
研究领域:
药理学
·
细胞生物学
·
分子生物学
·
营养学
✓ 已验证
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）