Journal of Translational Medicine
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2024
·Vol. 22
·期 1
·1-19
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IF 6.1
Qin Qian,Shan Zhiyan,Xing Lei,Jiang Yutong,Li Mengyue,Fan Linlin,Zeng Xin,Ma Xinrui,Zheng Danyang,Wang Han,Wang Hui,Liu Hao,Liang Shengjun,Wu Lijie,Liang Shuang
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.
研究领域:
神经科学
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干细胞生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
Journal of Advanced Research
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2024
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IF 11.4
Xue Bai,Zhiguang Duan,Jianjun Deng,Zhuo Zhang,Rongzhan Fu,Chenhui Zhu,Daidi Fan
Introduction Dysbiosis of the gut microbiota is emerging as a pivotal factor in the pathogenesis of colorectal cancer (CRC). Ginsenoside Rh4 (Rh4) is an active compound isolated from ginseng with beneficial effects in modulating intestinal inflammation and gut microbiota dysbiosis, but how Rh4 regulates the gut microbiota to alleviate CRC remains underexplored. Objectives We investigated the impact of Rh4 on CRC and the mechanism of its action in inhibiting CRC via modulation of gut microbiota. Methods We used the AOM/DSS model and employed transcriptomics, genomics and metabolomics techniques to explore the inhibitory impact of Rh4 on CRC. Furthermore, we employed experiments involving antibiotic treatment and fecal microbiota transplantation (FMT) to investigate the role of the gut microbiota. Finally, we elucidated the pivotal role of key functional bacteria and metabolites regulated by Rh4 in CRC. Results Our research findings indicated that Rh4 repaired intestinal barrier damage caused by CRC, alleviated intestinal inflammation, and inhibited the development of CRC. Additionally, Rh4 inhibited CRC in a gut microbiota-dependent manner. Rh4 increased the diversity of gut microbiota, enriched the probiotic Akkermansia muciniphila ( A. muciniphila ), and alleviated gut microbiota dysbiosis caused by CRC. Subsequently, Rh4 regulated A. muciniphila -mediated bile acid metabolism. A. muciniphila promoted the production of UDCA by enhancing the activity of 7α-hydroxysteroid dehydrogenase (7α-HSDH). UDCA further activated FXR, modulated the TLR4-NF-κB signaling pathway, thus inhibiting the development of CRC. Conclusion Our results confirm that Rh4 inhibits CRC in a gut microbiota-dependent manner by modulating gut microbiota-mediated bile acid metabolism and promoting the production of UDCA, which further activates the FXR receptor and regulates the TLR4-NF-κB signaling pathway. Our results confirm that Rh4 has the potential to be used as a modulator of gut microbiota for preventing and treatment of CRC.
研究领域:
癌症生物学
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微生物学
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药理学
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分子生物学
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胃肠病学
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产品关联
DOI
PubMed
高影响因子
TECHNOLOGY AND HEALTH CARE
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2024
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IF 1.4
Jiang Yanan,Zhang Chengyi,Zhang Xinyue,Lan Na,Zhao Zihan,Xv Yawei,Wang Qi,Wang Siwei,Chen Baifeng,Chen Xi,Wang Yilin
BACKGROUND: In recent years, hyperuricemia and acute gouty arthritis have become increasingly common, posing a serious threat to public health. Current treatments primarily involve Western medicines with associated toxic side effects. OBJECTIVE: This study aims to investigate the therapeutic effects of total flavones from Prunus tomentosa (PTTF) on a rat model of gout and explore the mechanism of PTTF’s anti-gout action through the TLR4/NF- κ B signaling pathway. METHODS: We measured serum uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), tumor necrosis factor-alpha (TNF- α ), interleukin-1 beta (IL-1 β ), and interleukin-6 (IL-6) levels using an enzyme-linked immunosorbent assay (ELISA). Histopathological changes were observed using HE staining, and the expression levels of relevant proteins were detected through Western blotting. RESULTS: After PTTF treatment, all indicators improved significantly. PTTF reduced blood levels of UA, Cr, BUN, IL-1 β , IL-6, and TNF- α , and decreased ankle swelling. CONCLUSIONS: PTTF may have a therapeutic effect on animal models of hyperuricemia and acute gouty arthritis by reducing serum UA levels, improving ankle swelling, and inhibiting inflammation. The primary mechanism involves the regulation of the TLR4/NF- κ B signaling pathway to alleviate inflammation. Further research is needed to explore deeper mechanisms.
研究领域:
药理学
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免疫学
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风湿病学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Jixu Wu,Huarong Shao,Jinhua Zhang,Yong Ying,Yanling Cheng,Dan Zhao,Xixi Dou,Huimin Lv,Shuaiguang Li,Fei Liu,Peixue Ling
We isolated and characterized a Mussel polysaccharide, α -D-glucan (MP-A), from Mytilus coruscus earlier. In this work, the pharmacological activity and mechanisms of MP-A as an oral supplement for non-alcoholic fatty liver disease (NAFLD) were explored. High fat diet (HFD) was utilized to induce NAFLD in Sprague Dawley male rats and MP-A (0.6 g/kg) was supplemented for 4 weeks. The results showed that MP-A supplementation reduced blood lipid levels, intrahepatic lipid accumulation and NAFLD activity score in HFD-fed rats. Additionally, the analysis of 16S rDNA sequencing on gut microbiota samples revealed that HFD could induce microbial dysbiosis. However, MP-A supplementation could remodel gut microbiota structure, inhibit LPS-TLR4-NF- κ B pathway activation, and restrain subsequent inflammation factors secretion. Furthermore, MP-A regulated the lipid metabolism by promoting the production of short chain fatty acids and suppressing PPAR γ and SREBP-1c expression. Our results support that MP-A can prevent against NAFLD and act as an oral supplementation for hepatoprotection via modulating gut microbiota and related gut-liver axis signaling pathways.
研究领域:
药理学
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胃肠病学
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微生物学
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代谢学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Zhuojun Yu,Yi Li,Liping Bai,Yanbo Zheng,Xiujun Liu,Yongsu Zhen
Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.
研究领域:
免疫学
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药理学
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炎症
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呼吸医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Xiaoyu Wu,Chuanbo Ding,Xinglong Liu,Qiteng Ding,Shuai Zhang,Yue Wang,Chenran Xin,Hewei Wei,Rui Mao,Guiping Zhang,Ting Zhao,Wencong Liu
Wound healing in diabetic patients is often complicated by issues like inflammation, infection, bleeding, and fluid retention. To tackle these challenges, it is essential to create hydrogel dressings with anti-inflammatory, antibacterial, and antioxidative properties. This study aimed to synthesize Phlorizin-Liposomes (PL) through the thin-film dispersion method and integrate them into an oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMCS) hydrogel scaffold, resulting in an OSA/CMCS/PL (PLOCS) composite hydrogel via a Schiff base reaction. Characterization of the composite was performed using FTIR, TEM, and SEM techniques. The research assessed the swelling behavior, antibacterial effectiveness, and biocompatibility of the PLOCS composite hydrogel, while also investigating how PLOCS facilitates diabetic wound healing. The results demonstrated that PLOCS effectively controls drug release, possesses favorable swelling and degradation characteristics, and shows significant antioxidative properties along with in vitro biocompatibility. Histological analysis confirmed that PLOCS supports the proliferation of healthy epithelial tissue and collagen production. Western blotting indicated that PLOCS diminishes inflammation by inhibiting the TLR4/NF-κB/MyD88 pathway and activates Nrf2 to boost wound healing, increasing the levels of antioxidative enzymes such as HO-1, NQO1, and GCLC. In summary, PLOCS presents a promising new option for advanced wound dressings aimed at treating diabetic ulcers.
研究领域:
材料科学
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生物医学工程
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药剂学
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伤口愈合
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糖尿病
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产品关联
DOI
PubMed
高影响因子
Small
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2024
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IF 13
Yu He,Ejun Peng,Xiaozhuo Ba,Jian Wu,Wen Deng,Qiu Huang,Yonghua Tong,Haojie Shang,Zichen Zhong,Xiao Liu,Yanlong Zhang,Tao Ye,Xiaoqi Yang,Kangyang Wang,Yabin Xie,Kehua Jiang,Ding Xia,Zhiqiang Chen,Kun Tang
Emerging studies have demonstrated that M1 macrophage polarization and oxidative stress play important roles in calcium oxalate (CaOx) induced kidney injury, which leads to increased crystals deposition. ROS scavenging nanozymes and kidney-targeted nanoparticles for antioxidant drugs delivery have emerged as an arisen methodology for kidney injury therapy. However, cell membrane biomimetic-modified nanozymes as anti-inflammatory drug delivery systems for the treatment of kidney injury is rarely reported. Herein, the ROS responsive red blood cell-membrane-coated resatorvid-loaded cerium oxide nanoparticles (RBCM@CeO 2 /TAK-242) are constructed to suppress CaOx induced kidney injury and crystals deposition. In vitro, RBCM@CeO 2 /TAK-242 shows effective internalization by renal tubular epithelial cells, along with demonstrated antioxidative, anti-inflammatory, and macrophage reprogramming effects. Glyoxalate(Gly)-induced renal CaOx crystals mouse model is established, RBCM@CeO 2 /TAK-242 shows excellent injured kidney targeting and biosafety, and could effectively suppress CaOx induced kidney injury and crystals deposition. RBCM@CeO 2 /TAK-242 has a dual protective effect by both inhibiting oxidative stress and modulating macrophage polarization in vivo. In addition, RNA seq analysis reveals that RBCM@CeO 2 /TAK-242 protects against CaOx induced kidney injury via suppressing the TLR4/NF-κB pathway. This study provides an innovative strategy for RBCM@CeO 2 /TAK-242 as injured kidney targeting and dual protective effects for the treatment of CaOx induced kidney injury and crystals deposition.
研究领域:
纳米技术
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药理学
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肾脏生理学
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炎症
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氧化应激
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2024
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IF 12.8
Jiani Huang,Fei Wu,Wenzhao Cao,Yuhan Chen,Qiong Yao,Peili Cen,Jing Wang,Lu Hong,Xiaohui Zhang,Rui Zhou,Chentao Jin,Mei Tian,Hong Zhang,Yan Zhong
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder globally, with no effective treatment available yet. A crucial pathological hallmark of AD is the accumulation of hyperphosphorylated tau protein, which is deteriorated by reactive oxygen species (ROS) and neuroinflammation in AD progression. Thus, alleviation of ROS and inflammation has become a potential therapeutic strategy in many studies. Herein, we reported ultrasmall coordination polymer nanoparticles formed by ferric ions and gallic acid (Fe-GA CPNs), which owned antioxidant and anti-inflammation properties for AD therapeutics. The facilely prepared Fe-GA CPNs exhibited remarkable superoxide dismutase, peroxidase enzyme activity, and ROS eliminating ability with great water solubility, compared with gallic acid. We demonstrated that Fe-GA CPNs effectively relieved oxidative stress, ameliorated inflammation by downregulating TLR4/NF-κB and modulating microglial polarization towards anti-inflammation phenotype, and reduced hyperphosphorylated tau protein levels. Furthermore, Fe-GA CPNs treatment significantly improved cognitive function in tauopathy-induced AD rats, and achieved a neuroprotective effect against AD pathology. This study highlights the potential of coordination polymer nanoparticles as promising therapeutic candidates for AD and other tau-related neurodegenerative diseases.
研究领域:
神经退行性疾病
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纳米技术
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药理学
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神经科学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Yuan Xu,Xin An,Lei Liu,Xinran Cao,Zhanfeng Wu,Wang Jia,Jiacheng Sun,Haoyu Wang,Jiawei Huo,Zihao Sun,Mingming Zhen,Chunru Wang,Chunli Bai
Endotoxemia is a life-threatening multiple organ failure disease caused by bacterial endotoxin infection. Unfortunately, current single-target therapy strategies have failed to prevent the progression of endotoxemia. Here, we reported that alanine fullerene redox modulator (AFRM) remodeled the intestinal microenvironment for multiple targets endotoxemia mitigation by suppressing inflammatory macrophages, inhibiting macrophage pyroptosis, and repairing epithelial cell barrier integrity. Specifically, AFRM exhibited broad-spectrum and self-cascade redox regulation properties with superoxide dismutase (SOD)-like enzyme, peroxidase (POD)-like enzyme activity, and hydroxyl radical (•OH) scavenging ability. Guided by proteomics, we demonstrated that AFRM regulated macrophage redox homeostasis and down-regulated LPS/TLR4/NF-κB and MAPK/ERK signaling pathways to suppress inflammatory hyperactivation. Of note, AFRM could attenuate inflammation-induced macrophage pyroptosis via inhibiting the activation of gasdermin D (GSDMD). In addition, our results revealed that AFRM could restore extracellular matrix and cell-tight junction proteins and protect the epithelial cell barrier integrity by regulating extracellular redox homeostasis. Consequently, AFRM inhibited systemic inflammation and potentiated intestinal epithelial barrier damage repair during endotoxemia in mice. Together, our work suggested that fullerene based self-cascade redox modulator has the potential in the management of endotoxemia through synergistically remodeling the inflammation and epithelial barriers in the intestinal microenvironment.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Kunmei Xie,Feibiao Wang,Yue Yang,Shoujie Pan,Junyao Wang,Nan Xiao,Xinyan Wang,Zhihao Ma,Xiaolong Xu,Zibo Dong
Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.
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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细胞生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
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2024
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IF 3.8
Qiaoling Zhao,Fei Yang,Qiuyan Pu,Rui Zhao,Su Jiang,Yunping Tang
The protective effects of docosahexaenoic acid-enriched phosphatidylserine (DHA-PS, 50 or 100 mg/kg) on bisphenol A (BPA)-induced intestinal damage were assessed. The biochemical indices, pathological examination, non-targeted metabolomics integrated with gut microbiota analysis, and immunofluorescence analysis were used to investigate the protective effects of DHA-PS and its underlying regulatory mechanism. The DHA-PS treatment improved the pathology of intestinal tract and increased the expression levels of Claudin-1, Occludin, and ZO-1. In addition, the DHA-PS treatment also notably decreased the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, and increased the antioxidant enzymes activities. Moreover, DHA-PS treatment increased the relative abundances of Akkermansia, Alistipes, Butyricicoccus, Coriobacteriaceae_ UCG-002 , Enterorhabdus , and Lachnospiraceae_ UCG-006. DHA-PS treatment alleviated BPA-induced intestinal damage by regulating the kynurenine pathway of tryptophan, lipid, and arachidonic acid metabolisms. Overall, this study suggested that DHA-PS could alleviate BPA-induced intestinal damage by enhancing the intestinal barrier integrity, improving gut microbial composition and metabolites, and inhibiting the TLR4/NF-κB pathways.
研究领域:
营养学
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药理学
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微生物学
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代谢组学
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毒理学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）