MICROBIOLOGICAL RESEARCH
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2025
·
IF 6.9
Zheng Jia,Lingdi Niu,Junjie Guo,Jiaqing Wang,Hai Li,Runhang Liu,Ning Liu,Shuhe Zhang,Fang Wang,Junwei Ge
Regulation of the innate immune response may be an effective strategy to enhance Staphylococcus aureus vaccines. Based on our previous findings that the Listeria peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-β following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant S. aureus challenge and also provides protection against S. aureus CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1α and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to β-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.
研究领域:
免疫学
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微生物学
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疫苗研发
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产品关联
DOI
PubMed
高影响因子
Journal of Oncology
·
2022
·
IF 4.501
Hongliang You,Dao Wang,Linlin Wei,Jiao Chen,Huanhuan Li,Yufeng Liu
Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer, with a feature of easy to induce multidrug resistance and relapse. Abundant studies have proved that iron overload strengthens the growth and metastasis of tumor cells. Herein, we found that deferoxamine (DFO) effectively decreased the concentration of intracellular iron in ALL cells. DFO inhibited proliferation, induced apoptosis, and obstructed cell cycle of ALL cells, whereas DFO and dextriferron (Dex) used in combination significantly decreased the sensitivity of ALL cells to DFO. Reactive oxygen species (ROS) level was reduced in ALL cells treated with DFO, and the combination of DFO and Dex reversed the effects of DFO. In vivo, DFO inhibited mouse tumor growth. Besides, cyclinD1, β-catenin, c-Myc, hypoxia inducible factor 1 (HIF-1), p-p38MAPK, and p-ERK1/2 protein levels were significantly downregulated, and the levels of prolyl hydroxylase-2 (PHD-2) were upregulated after treated with DFO, whereas Dex treatment reversed those in vivo and in vitro. In conclusion, DFO inhibited the proliferation and ALL xenograft tumor growth, obstructed the cell cycle, and induced apoptosis of ALL cells, probably via inactivating the ROS/HIF-1α, Wnt/β-catenin, and p38MAPK/ERK signaling.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Jingyu Li,Zhuoting Lu,Liwang Xu,Jing Wang,Shaojie Qian,Qinglian Hu,Yunfen Ge
Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-β-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1α-mediated gene therapy might be a practical strategy for the treatment of limb ischemia.
研究领域:
生物医学工程
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分子生物学
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基因治疗
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药学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Pingchuan Wang,Tianming Li,Changping Niu,Siyu Sun,Dongyan Liu
Reactive oxygen species (ROS) damage to the intestinal barrier is a side effect of prolonged hyperoxia therapy in neonates, which impairs growth and development of the intestine and promotes intestinal diseases. However, the research on clinical prevention and treatment is lacking. Therefore, we investigated the molecular mechanisms of the neonate intestinal response against hyperoxia-derived ROS to find targets for intestinal barrier damage prevention. Human intestinal epithelial cells were incubated under hyperoxia (85% oxygen) to build an in vitro model. ROS and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway were inhibited to detect the MAPK/ERK pathway, nuclear factor erythroid factor 2-related factor 2 (Nrf2), hypoxia-inducible factor-1α (Hif-1α), and interleukin-17D (IL-17D) expression. Nrf2 was inhibited to detect Hif-1α and IL-17D expression. Hif-1α was inhibited to detect Nrf2, IL-17D, and tight junction proteins expression and apoptosis. Cells were treated with human recombinant IL-17D to detect TNF-α, IL-1β, IL-10, and tight junction proteins expression. ROS, Nrf2, Hif-1α, and IL-17D were upregulated and the MAPK/ERK pathway was activated under hyperoxia. But ROS inhibition downregulated the MAPK/ERK pathway, Nrf2, Hif-1α, and IL-17D. MAPK/ERK pathway inhibition downregulated Nrf2, Hif-1α, and IL-17D. Nrf2 inhibition downregulated Hif-1α and IL-17D. Hif-1α inhibition downregulated Nrf2, IL-17D, tight junction proteins, and exacerbated apoptosis. The recombinant IL-17D downregulated TNF-α, IL-1β, but upregulated IL-10 and tight junction proteins. We concluded that Hyperoxia-generated ROS activated the MAPK/ERK pathway to regulate Nrf2, Hif-1α, and IL-17D expression. Nrf2 and Hif-1α were interdependent and promoted IL-17D. Importantly, Hif-1α and IL-17D expression protected the intestinal epithelial barrier.
研究领域:
分子生物学
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细胞生物学
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儿科
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肠道生理学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wenjia CHEN,Chu ZHANG,Mingzhu XU,Tao LI,Xin LI,Peihao LI,Xun GONG,Yang QU,Chunling ZHOU,Xia MAO,Na LIN,Wei LIU,Quan JIANG,Haiyu XU,Yanqiong ZHANG
Background : Specific treatment for rheumatoid arthritis (RA) is still an unmet need. Yu-Xue-Bi (YXB) capsule effectively treats RA with blood stasis syndrome (BS). However, its mechanism remains unclear. Purpose : Exploring and elucidating the therapeutic effect and pharmacological mechanism of YXB capsule in treating RA. Methods : This study identified differentially expressed genes (DEGs) in patients with RA and BS compared to healthy controls using clinical transcriptomics data. Clinical symptoms of RA and BS, and the related genes were collected from the SoFDA and HPO databases. Candidate bioactive constituents in YXB were identified via UPLC-QTOF/MS and evaluated using ADMET rules. Putative targets were predicted, and a network linking disease-related DEGs and drug targets was constructed. Key targets were screened utilizing random walk-with-restart (RWR) algorithms and verified through experiments using rat models of collagen-induced arthritis with BS (CIA-BS model) in vivo . Results : We found 1220 DEGs along with 976 clinical symptom-related genes, as RA with BS-related genes. Chemical profiling identified 193 YXB constituents, with 98 meeting optimal ADMET criteria. We predicted 459 putative targets for these constituents. Network calculations screened 209 key targets, 129 RA with BS-related genes and 92 YXB targets involved in immune inflammation, blood stagnation, and hyperalgesia imbalance. Notably, the SUCNR1/HIF-1α/TRPV1 axis was enriched by YXB targets against RA with BS. Experimentally, YXB inhibited inflamed joint deterioration, including synovial inflammation, cartilage damage and bone erosion, relieving mechanical and cold allodynia hyperglasia. It reversed hemorrheology and vascular function in CIA-BS rats, restoring SDHB and eNOS expression, preventing SDHA, SUCNR1 and HIF-1α activation, reducing SUCN, TNF-1α and IL-1β production, and TRPV1 and TRPA1 expression. Conclusion : Our data support YXB's therapeutic effects on aggressive RA-BS by modulating the SUCNR1/HIF-1α/TRPV1 axis.
研究领域:
药理学
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分子生物学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2019
·
IF 4.825
Peng-Chao Zhang,Xiao Liu,Man-Mei Li,Yan-Yan Ma,Hong-Tao Sun,Xu-Yan Tian,Yan Wang,Min Liu,Liang-Shun Fu,Yi-Fei Wang,Hong-Yuan Chen,Zhong Liu
The inhibition of angiogenesis is suggested to be an attractive strategy for cancer therapeutics. Heat shock protein 90 (Hsp90) is closely related to tumorigenesis as it regulates the stabilization and activated states of many client proteins that are essential for cell survival and tumor growth. Here, we investigated the mechanism whereby AT-533, a novel Hsp90 inhibitor, inhibits breast cancer growth and tumor angiogenesis. Based on our results, AT-533 suppressed the tube formation, cell migration, and invasion of human umbilical vein endothelial cells (HUVECs), and was more effective than the Hsp90 inhibitor, 17-AAG. Furthermore, AT-533 inhibited angiogenesis in the aortic ring, Matrigel plug, and chorioallantoic membrane (CAM) models. Mechanically, AT-533 inhibited the activation of VEGFR-2 and the downstream pathways, including Akt/mTOR/p70S6K, Erk1/2 and FAK, in HUVECs, and the viability of breast cancer cells and the HIF-1α/VEGF signaling pathway under hypoxia. In vivo, AT-533 also inhibited tumor growth and angiogenesis by inducing apoptosis and the HIF-1α/VEGF signaling pathway in breast cancer cells. Taken together, our findings indicate that the Hsp90 inhibitor, AT-533, suppresses breast cancer growth and angiogenesis by blocking the HIF-1α/VEGF/VEGFR-2 signaling pathway. AT-533 may thus be a potentially useful drug candidate for breast cancer therapy.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Yinghan Guo,Lulu Jin,Zhipeng Shen,Linfeng Fan,Xian Yu,Yirui Kuang,Lingxin Cai,Jiayin Zhou,Zihang Chen,Feng Yan,Jianmin Zhang,Minfeng Tong,Jianlie Yuan,Zhengwei Mao,Gao Chen
The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA-like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood-brain barrier (BBB) and non-specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP-M-M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP-M-M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF-1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma-associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re-educate immunosuppressive TME, and inhibit the progression of GBM.
研究领域:
肿瘤学
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神经科学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Chao Ma,Chunran Zhu,Yajun Zhang,Mei Yu,Yizhi Song,Yulong Chong,Yan Yang,Chan Zhu,Yucui Jiang,Changming Wang,Shuo Cheng,Keke Jia,Guang Yu,Jia Li,Zongxiang Tang
Background Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. Purpose Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. Methods/results After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca 2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca 2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. Conclusion This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.
研究领域:
神经科学
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药理学
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代谢
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2017
·Vol. 14
·期 5
·4307-4311
·
IF 1.261
Tao Zhou,Shanliang Guo,Shaolin Wang,Qiong Li,Mingsheng Zhang
This study was designed to investigate possible protective effects of sevoflurane on myocardial ischemia-reperfusion injury (MIRI) and its impact on expression of HIF-1α and caspase-3 in rats, so as to provide new insights for the treatment of MIRI. Forty SD rats were randomly divided into four groups (n=10) including Sham operation (Sham), ischemia-reperfusion (IR), sevoflurane preconditioning group (Sevo-Pre) and sevoflurane post-conditioning (Sevo-Post) groups. Perfusion was performed using ex vivo heart perfusion. The baseline values of cardiac function were recorded in each group at the end of balanced perfusion and after 60 min of reperfusion. Myocardial infarct size (MIS) was calculated at the end of perfusion using TTC staining. Levels of HIF-1α and caspase-3 protein and HIF-1α (western blotting) and Bcl-2 mRNA (RT-qPCR) were detected at the end of reperfusion. Our results showed no significant differences in cardiac function between the groups at the end of the balanced perfusion. After reperfusion for 60 min, however, the cardiac functions of the Sevo-Pre and Sevo-Post groups were significantly better than those in the IR group, and the MIS at the end of reperfusion was significantly decreased. Western blotting and RT-qPCR showed that expression of HIF-1α protein was significantly increased, expression of caspase-3 protein was significantly decreased and expression of HIF-1α and Bcl-2 mRNA were significantly increased in Sevo-Pre and Sevo‑Post groups compared with the levels in the IR group at the end of reperfusion. There were no significant differences in experimental results between Sevo-Pre and Sevo-Post groups. Our data support the idea that sevoflurane can improve MIRI in rats by improving cardiac function and reducing MIS. This protective effect seems to be achieved by activation of HIF-1α and inhibition of caspase-3.
研究领域:
药理学
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心脏病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2023
·
IF 5.1
Huijuan Ma,Qi Shu,Peiyao Wang,Ruilin Qin,Sijia Li,Huan Xu
Exposure to formaldehyde (FA) has been indicated to be positively correlated with increased incidence of allergic asthma in many epidemiological and experimental studies. However, few studies have ever addressed the molecular basis of the correlation. In the present study, it was found that inhaling 2.0 mg/m 3 FA for 2 weeks could exacerbate the pulmonary inflammation and mucus over-accumulation in OVA-induced murine asthmatic model. The pro-inflammatory cytokines, such as IL-1β, TNF-α, IL-6 and IL-8, were increased in lung and serum of FA-exposed asthmatic mice. The contribution of HIF-1α signaling in FA-exacerbated allergic asthma was confirmed by bioinformatic analysis. HIF-1α and its downstream proteins, which are known as mediators of glycolysis, were found to be upregulated by 50 μM FA, and the FA-enhanced of glycolysis was reversed by inhibition of HIF-1α with PX-478 in vitro and YC-1 in vivo . Furthermore, it was confirmed that inhibition of HIF-1α signaling could restrain the macrophagic inflammatory responses and asthma exacerbation induced by FA. Collectively, these results revealed that FA could exacerbate asthma through the potentiation of HIF-1α-mediated inflammatory responses in macrophages, which also indicated the universal roles of FA-triggered macrophage metabolic and functional alterations in inflammatory or allergic diseases.
研究领域:
免疫学
·
呼吸病学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Hongmei Chang,Siqi Zhao,Yuzhu Lei,Yunhua Hu,Yizhong Yan,Guanling Song
Titanium dioxide nanoparticles (nano-TiO 2 ) can cause a reduction in sperm counts, and lactate production in Sertoli cells plays a key role in spermatogenesis. The aim of this study was to evaluate the effect of nano-TiO 2 on lactate production in mouse Sertoli cell line (TM4 cells) and to investigate whether the effect is mediated through the PI3K/AKT/HIF-1α pathway. After TM4 cells were treated with different concentrations of nano-TiO 2 for 48 h, cell viability, contents of glucose and lactate, and the expression levels of GLUT3 and key enzymes (HK1, HK2, PFKM, ENO1, LDH) during lactate production were detected. PI3K/AKT/HIF-1α pathway proteins were measured. In addition, PI3K agonist (IGF-1) was added to explore whether nano-TiO 2 regulates HIF-1α through PI3K/AKT pathway, thereby affecting the production of lactate in TM4 cells. The results showed that nano-TiO 2 significantly inhibited TM4 cell viability, increased glucose content, decreased lactate content, and downregulated the expression levels of GLUT3 and key enzymes during lactate production. Meanwhile, nano-TiO 2 decreased the expression of PI3K/AKT pathway phosphorylated proteins and HIF-1α, and IGF attenuated this effect of nano-TiO 2 . Collectively, nano-TiO 2 downregulated the expression level of proteins and enzymes related to lactate production in TM4 cells by inhibiting PI3K/AKT/HIF-1α pathway, resulting in the decrease of lactate production in TM4 cells.
研究领域:
生殖生物学
·
细胞生物学
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纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Applied Materials Today
·
2020
·
IF 8.352
Yanxin Chen,Mengqi Ye,Liwan Song,Junwen Zhang,Yao Yang,Sha Luo,Minjie Lin,Qianwen Zhang,Shengyu Li,Yajiao Zhou,Anqi Chen,Ying An,Wen Huang,Tengxiao Xuan,Yugui Gu,Huacheng He,Jiang Wu,Xiaokun Li
Skin wounds, especially chronic wounds such as pressure and diabetic ulcers, are posing a huge threat to healthcare systems worldwide. Thus, novel strategies to realize effective wound therapy are nowadays extremely needed. Herein, we are the first to report a combination therapy of electric stimulation and heat for wound healing just using a facile piezoelectric and photothermal dual functional film. The film, name as [email protected] , is simply fabricated by coating polydopamine on a chitosan film. [email protected] generates electric voltages under mechanical pressure and shows photothermal effect with irradiation of near-infra red (NIR) light. In vivo experiment with rat full-thickness wound model validates that [email protected] with NIR can effectively promote wound regeneration due to the generation of electric stimulation and heat on wounds. The healing mechanism of [email protected] is further investigated, and the result demonstrates that [email protected] enhances wound healing through a pathway in which heat shock protein 90 (Hsp90) and hypoxia-inducible factor 1α (HIF-1α) participate. These results indicate that [email protected] is a promising wound dressing candidate for clinical application in the future.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）