CELLULAR SIGNALLING
·
2024
·
IF 4.4
Xin Chen,Liming Yu,Shan Meng,Jikai Zhao,Xinyi Huang,Zhishang Wang,Zijun Zhou,Yuting Huang,Tao Hong,Jinfeng Duan,Tong Su,Zijun Cao,Yanbang Chi,Tao Huang,Huishan Wang
Inflammation and infiltration of immune cells are intricately linked to the pathogenesis of atrial fibrillation (AF). Triggering receptor expressed on myeloid cells-1 (TREM-1), an enhancer of inflammation, is implicated in various cardiovascular disorders. However, the precise role and potential mechanisms of TREM-1 in the development of AF remain ambiguous. Atrial samples from patients with AF were used to assess the expression levels of TREM-1. An angiotensin II (Ang II)-induced AF mouse model was established to assess the functionality of TREM-1. Cardiac function and AF inducibility were assessed through echocardiography, programmed transvenous cardiac pacing, and atrial electrophysiological mapping. Peripheral blood and atrial inflammatory cells were assessed using flow cytometry. Using histology, bulk RNA sequencing, biochemical analyses, and cell cultures, the mechanistic role of TREM-1 in AF was elucidated. TREM-1 expression was upregulated and co-localized with macrophages in the atria of patients with AF. Pharmacological inhibition of TREM-1 decreased Ang II-induced atrial enlargement and electrical remodeling. TREM-1 inhibition also ameliorated Ang II-induced NLRP3 inflammasome activation, inflammatory factor release, atrial fibrosis, and macrophage infiltration. Transcriptomic analysis revealed that TREM-1 modulates Ang II-induced inflammation through the PI3K/AKT/FoxO3a signaling pathway. In vitro studies further supported these findings, demonstrating that TREM-1 activation exacerbates Ang II-induced inflammation, while overexpression of FoxO3a counteracts this effect. This study discovered the critical role of TREM-1 in the pathogenesis of AF and its underlying molecular mechanisms. Inhibition of TREM-1 provides a new therapeutic strategy for the treatment of AF.
研究领域:
心脏病学
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免疫学
·
分子生物学
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药理学
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DOI
PubMed
高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Anran Li,Cong Chen,Tongjia Zhang,Yuxin Tian,Yifan Cao,Xiaoming Zhao,Liping Wang
Human umbilical cord mesenchymal stem cell extracellular vesicles (hucMSC-EVs) exhibit remarkable potential for alleviating type 2 diabetes mellitus (T2DM). However, the role of hucMSC-EVs in T2DM, particularly concerning oxidative damage to pancreatic β cells, remains underexplored. This study utilized a high-fat diet and streptozotocin (STZ)-induced T2DM mouse model and an STZ-induced INS-1 cell damage model to investigate the effects and mechanisms of hucMSC-EVs. In the T2DM mouse model, hucMSC-EVs effectively lowered blood glucose levels, improved lipid metabolism disorders, and preserved liver function. Moreover, hucMSC-EVs enhanced insulin sensitivity and mitigated oxidative damage. Histological analysis confirmed that hucMSC-EVs marked alleviated liver, kidney, and pancreatic tissue damage. In vitro studies demonstrate that hucMSC-EVs enhance glucose absorption and glycogen synthesis in an insulin-resistant HepG2 model and stimulated insulin secretion in INS-1 cells under high-glucose conditions. In the STZ-induced INS-1 oxidative damage model, hucMSC-EVs protect against oxidative damage by increasing antioxidant enzyme activities, reducing reactive oxygen species production, and decreasing cell apoptosis. The effects were partially mediated by the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT and signal transducer and activator of transcription (STAT) signaling pathways, as well as the up-regulation of key antioxidant proteins such as Nrf2, SOD1, and Bcl2. Further research revealed that miR-191-5p, which is enriched in hucMSC-EVs, targets DAPK1 to activate the PI3K/AKT pathway, thereby contributing to the protective effects against oxidative damage. These findings highlight the critical role and underlying mechanisms of hucMSC-EVs in ameliorating metabolic dysfunction in T2DM, particularly the protective effects against oxidative damage, thus providing a novel strategy for the treatment of T2DM.
研究领域:
生物学
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医学
·
细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Mingxiu Long,Hui Wang,Fang Zhang,Yaoqi Ran,Yongfu Li,Jingwen Luo,Zhaojun Chen,Zhuxi Tian,Shuming Tan,Xiong Liu
Rosa roxburghii Tratt fruit polyphenols (RP) possess antioxidant, anti-inflammatory, and immunomodulatory properties, showing potential for ulcerative colitis (UC) treatment. However, their efficacy is limited by bioavailability and targeting efficiency. To address this, RP were encapsulated into acylated chitosan-crosslinked carboxymethyl konjac glucomannan (ACs-CKGM) nanogel (RPNG). Experimental results demonstrated that RPNG significantly enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1, Occludin and Claudin-3) and mucus secretion (MUC2). It effectively mitigated oxidative stress by restoring antioxidant enzymes (SOD, GSH-Px and CAT) while reducing MPO, COX-2 and iNOS activation. Through integrated ELISA, western blot, and transcriptomic analyses, we emonstrated that RPNG specifically inhibited PI3K/Akt/mTOR and NF-κB signaling pathways, decreasing inflammatory cytokines (e.g., TNF-α, IL-6) while increasing anti-inflammatory mediators (e.g., IL-10). Gut microbiome analysis showed RPNG reversed DSS-induced dysbiosis by enriching beneficial bacteria (e.g., Muribaculum sp.) and suppressing pathogens (e.g., Escherichia coli ). These findings highlight RPNG as a novel targeted strategy for UC management, supported by multi-omics mechanistic insights.
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Shaojun Pan,Yuhui Zhang,Mark Huang,Zhoufeng Deng,Amin Zhang,Lijia Pei,Lirui Wang,Weiyong Zhao,Lijun Ma,Qian Zhang,Daxiang Cui
s Multi-functional nanovectors based on exosomes from cancer cell culture supernatants in vitro has been successfully utilized for tumor-specific targeting and immune escape. However, the labor-intensive purification procedures for rich-dose and high-purity homogeneous exosomes without using targeting ligands are still a challenging task. Herein, we developed a nanovector Exo-PMA/ [email protected] through cloaked by urinary exosome membrane as a chemo/chemodynamic theranostic nano-platform for targeted homologous prostate cancer therapy which pertain to the abrogation of Epidermal Growth Factor Receptor (EGFR) and its downstream AKT/NF-kB/IkB signaling instead of ERK signaling cascades. Urinary exosomes-based nanovectors own the same urological cancer cell membrane antigen inclusive of E-cadherin, CD 47 and are free from intracellular substance such as Histone 3 and COX Ⅳ. The targeting properties of the homologous cancer cell are well preserved in Exo-PMA/ [email protected] nanovectors in high purity. Meanwhile, the nanovectors based on urinary exosomes from prostate patients deeply penetrated into prostate cancer DU145 3D MCTS , and successfully achieve superior synergistic low-dose chemo/chemodynamic performance in vivo . In addition, the blockage of bypassing EGFR/AKT/NF-kB/IkB signaling pathway is greatly enhanced via elevated intracellular PMA/ [email protected] nanoparticles (NPs). It is expected that the rich source and high purity of urinary exosomes offer a reliable solution for mass production of such nanovectors in the future. The targeted homologous cancer therapy based on the urinary exosomes from cancer patients exemplifies a novel targeted anticancer scheme with efficient and facile method.
研究领域:
癌症生物学
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纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2017
·
IF 2.916
Mingtong Ye,Sufan Wang,Ting Wan,Rui Jiang,Yun Qiu,Lei Pei,Nengzhi Pang,Yuanling Huang,Yufeng Huang,Zhenfeng Zhang,Lili Yang
Efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, to treat human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR is not persistent due to drug resistance. Reprogramming in energy (especially glucose) metabolism plays an important role in development and progression of acquired resistance in cancer cells. We hypothesize that glucose metabolism in EGFR-TKI sensitive HCC827 cells and erlotinib-resistant sub-line of HCC827 (which we name it as erlotinib-resistant 6, ER6 cells in this study) is different and targeting glucose metabolism might be a treatment strategy for erlotinib-resistant NSCLCs. In this study, we found increased glucose uptakes, significant increase in glycolysis rate and overexpression of glucose transporter 1 in ER6 cells compared to its parental cells HCC827. We also found AKT and autophagy of ER6 cells were more activated than HCC827 cells after glucose starvation. Combining glucose deprivation and AKT or autophagy inhibitor could synergize and overcome the acquired resistance against EGFR-targeted therapy for NSCLCs. Our data suggest that the combinations of inhibitors of AKT or autophagy together with glucose deprivation could be novel treatment strategies for NSCLC with acquired resistance to targeted therapy.
研究领域:
肿瘤学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
·
2022
·
IF 1.61
Wei-Wei Ye,Xiang-Ying Meng,Qian Zhao,Jian-Yang Chen,Cong Liu,Feng Chen,Yong Zhou,Yi Wang
Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.
研究领域:
药理学
·
糖尿病研究
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Zhenming Tian,Han-Jian Hu,Chun Cheung Chan,Tian Hu,Chaoyang Cai,Hong Li,Limin Rong,Gang-Biao Jiang,Bin Liu
In the realm of neural regeneration post-spinal cord injury, hydrogel scaffolds carrying induced neural stem cells (iNSCs) have demonstrated significant potential. However, challenges such as graft rejection and dysfunction caused by mitochondrial damage persist after transplantation, presenting formidable barriers. Tacrolimus, known for its dual role as an immunosuppressant and promoter of neural regeneration, holds the potential for enhancing iNSC transplantation. However, systemic administration of tacrolimus often comes with severe side effects. This study pioneers the development of a self-healing hydrogel with sustained-release tacrolimus (COCu-Tac), tailored specifically for iNSC transplantation after spinal cord injury. This research reveals that the sustained release of tacrolimus enhances axonal growth and improves mitochondrial quality control in iNSCs and neurons. Further analysis shows that tacrolimus targets FKBP52 rather than FKBP51, enhancing mitophagy via the FKBP52/AKT pathway. This advanced system demonstrates significant efficacy in promoting neural regeneration and restoring motor function following spinal cord injury.
研究领域:
神经科学
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再生医学
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药理学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-10
·
IF 5.228
Peng Mei,Huang Yanjun,Tao Ting,Peng Cai-Yun,Su Qiongli,Xu Wanjun,Darko Kwame Oteng,Tao Xiaojun,Yang Xiaoping
EGFR is a potential therapeutic target for treating bladder cancer, but has not been approved for clinical use yet. Metformin is a widely used antidiabetic drug and has demonstrated interesting anticancer effects on various cancer models, alone or in combination with chemotherapeutic drugs. The efficacy of gefitinib, a well-known EGFR tyrosine kinase inhibitor, combined with metformin was assessed on bladder cancer and underlying mechanisms were explored. This drug combination induced a strong anti-proliferative and anti-colony forming effect and apoptosis in bladder cancer cell lines. Gefitinib suppressed EGFR signaling and inhibited phosphorylation of ERK and Akt. Metformin amplified this inhibitory effect and enhanced gefitinib-induced activation of AMPK signaling pathway. In vivo intravesical treatment of metformin and gefitinib on syngeneic orthotopic mice confirmed the significant inhibitory effect on bladder tumor growth. These two drugs may be an excellent combination for the treatment of bladder cancer through intravesical instillation.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
AGING CLINICAL AND EXPERIMENTAL RESEARCH
·
2017
·Vol. 30
·期 7
·737-743
·
IF 1.394
Yan Bing Chun,Jiang Dan,Wang Jie,Zhang Yuanyuan,Zhu Xiaolu,Xu Pei,Yu Xing,Won Moo-Ho,Su Pei Qing
Background Aging is an inevitable process which results in many changes. These changes are closely related to the hippocampus which is in charge of long-term learning and episodic memory. Aim This study was to investigate age-related changes of the cell proliferation, neuroblast differentiation and Akt/mTOR signaling in the hippocampal alveus of aged mice. Methods In the present study, we compared the differences of neurogenesis in the hippocampal alveus between adult (postnatal month 6) and aged (postnatal month 24) mice using immunohistochemistry and western blot analysis. Results The cell proliferation, neuroblast differentiation, and the increased astrocyte activation in the hippocampal alveus of mice were decreased in an age-dependent manner. In addition, during normal aging, the protein level of AKT, mTOR and the phosphorylation of mTOR were all decreased. However, the protein level of AKT was increased. Discussion These results indicate the neurogenesis in the immature neurons in the hippocampal alveus of aged mice was closely related to the normal aging process. In addition, during normal aging, the increased AKT phosphorylation and decreased mTOR phosphorylation in the hippocampus may play a role in aging development. Conclusion The result indicates that increased activation of astrocyte, increased phosphorylation of AKT and decreased phosphorylation of mTOR may be involved in the decreased cell proliferation and neuroblast differentiation in the alveus of hippocampus of aged mice.
研究领域:
神经科学
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衰老研究
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 15
·e70744
·
IF 4.2
Xuan Li,Shiyu Meng,Jiayi Liu,Meixian Sun,Mao Zhou,Fengtao Ji,Yu Hong
In this study, we investigated the therapeutic potential of Berberine (BBR), an anti‐inflammatory agent capable of penetrating the blood–brain barrier, for mitigating postoperative cognitive dysfunction (POCD) in aged mice. BBR was administered at a dose of 10 mg/kg daily for 2 weeks and significantly improved cognitive impairments induced by surgical and anaesthesia‐related factors. Specifically, BBR markedly suppressed glial cell activation and reduced levels of pro‐inflammatory cytokines such as tumour necrosis factor alpha (TNF‐α) and interleukin‐1 beta (IL‐1β). Additionally, it alleviated oxidative stress markers and lipid accumulation. Using network pharmacology analysis, we demonstrated that BBR modulates neuroinflammation, oxidative processes and lipid metabolism by inhibiting the phosphorylation of the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway. Furthermore, extended research revealed that BBR upregulated the expression of PPAR‐ γ mRNA, suggesting a neuroprotective mechanism via regulation of the PI3K‐Akt pathway. These findings support the potential application of BBR as a therapeutic agent for managing POCD in elderly populations.
研究领域:
药理学
·
神经科学
·
老年医学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 10
·5767-5780
·
IF 5.882
Lin Zhu,Zhenchao Liu,Yuqian Ren,Xiaolin Wu,Yingjuan Liu,Tingting Wang,Yizhao Li,Yusheng Cong,Yunliang Guo
Studies have found that salidroside, isolated from Rhodiola rosea L , has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced β-galactosidase (β-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment.
研究领域:
神经科学
·
药理学
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衰老研究
·
分子生物学
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 7
·1110
·
IF 5.1
Yuxin Zhang,Zeyuan Deng,Hongyan Li,Zeyin Jiang
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent episodes and an inability to achieve a complete cure. The spermidine derivative (di- p -coumaroyl-caffeoyl spermidine, SPDD), as a key alkaloid, exhibits unique health benefits. However, it has not yet been reported whether SPDD can improve dextran sulfate sodium (DSS)-induced colitis in mice. Herein, we investigated the effects and mechanisms of SPDD on DSS-induced colitis in mice. SPDD was successfully purified from rose bee pollen and was found to have a protective effect on colitis, evidenced by reduced disease activity index (DAI) scores and colonic inflammation, increased colonic length and upregulated the expression of tight junction proteins (TJs) in the model ( p < 0.05). Importantly, the IL-17 signaling pathway showed significant enrichment by RNA sequencing (RNA-seq) technology with SPDD treatment, which resulted in the downregulation of MAPK4 expression ( p < 0.05). Furthermore, SPDD weakened the interaction between MAPK4 and AKT, resulting in a decrease in the phosphorylation level of AKT, thereby reducing the expression of IL-6, IL-1β, iNOS, and COX-2, and alleviating colitis ( p < 0.05). In addition, SPDD treatment also ameliorated TNF-α-induced inflammation in Caco-2 cells. Overall, our study demonstrated that SPDD reversed colonic inflammation in colitis mice through the MAPK4/AKT pathway and might be a promising candidate for UC intervention.
研究领域:
药理学
·
免疫学
·
胃肠病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
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