CLINICAL SCIENCE
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2025
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IF 7.7
Renzi Zhang,Yuhua Zhong,Qiudie Liu,Mengqi Zhang,Daoxin Wang,Sheng Li,Di Qi
Acute respiratory distress syndrome (ARDS) is an acute and severe disease with a high mortality rate. The outbreak of immune inflammation in the lung is an important pathogenic mechanism of ARDS. Notably, an imbalance in macrophage polarization is an important link in the occurrence and development of this inflammatory response. Recently, neuropeptides have been shown to regulate inflammation, but the role of neuropeptides in ARDS remains unclear. The aim of this study was to investigate the regulatory effect of calcitonin gene-related peptide (CGRP) on the inflammatory response in ARDS. We found that CGRP expression was increased in the serum of ARDS patients and in both in vitro and in vivo models of ARDS. CGRP can regulate the polarization of macrophages by targeting its receptor (receptor activity-modifying protein 1); reduce the proportion of M1 macrophages; increase the proportion of M2 macrophages; and reduce pathological injury, inflammation, oxidative stress, and apoptosis in lung tissue in LPS-induced ARDS both in vitro and in vivo . Additionally, we performed transcriptome sequencing and found that hypoxia-inducible factor-1α (HIF-1α) is involved in the above process and that CGRP can alleviate ARDS-related pathological damage, inflammation, and oxidative stress by inhibiting the HIF-1α pathway to regulate macrophage polarization balance. These results indicate that CGRP has good potential for clinical translation in the treatment of pulmonary infection in ARDS. Furthermore, this study provides new ideas for the treatment of inflammatory bursts in ARDS.
研究领域:
免疫学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 1
·e70054
·
IF 3.3
Lichao Ji,Yingjie Chai,Chenhao Tong,Yanxin Hu,Jiandong Li,Baochun Lu,Jianhua Yu
Gallbladder cancer is the most prevalent malignancy of the biliary tract and has a dismal overall survival even in the present day. The development of new drugs holds promise for improving the prognosis of this lethal disease. The possible anti-neoplastic role of morusin was investigated both in vitro and in vivo. Through cell viability and colony formation assays, we observed that morusin inhibited the proliferation of gallbladder cancer cells in vitro. Wound healing and transwell assays revealed that morusin impeded the migration and invasion of gallbladder cancer cells. Given the observed morphological changes, we examined epithelial-mesenchymal transition (EMT) markers. Subsequent investigations demonstrated that morusin treatment, both in vitro and in vivo, downregulated the expression of phospho-STAT3 (Signal transducer and activator of transcription 3) and HIF-1α (Hypoxia-inducible factor 1α) in gallbladder cancer cells. Furthermore, morusin effectively reversed EMT induced by phospho-STAT3 or HIF-1α. Morusin has a reversing effect on the EMT of gallbladder cancer cells by modulating STAT3/HIF-1α 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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DOI
PubMed
高影响因子
Scientific Reports
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2025
·Vol. 15
·期 1
·1-14
·
IF 3.9
Tang Di,Lin Qiang,Li Pei-Wen,Wang Song,Xu Kai,Huang Yue-Sheng,Lu Qi-Ping
Chronic refractory wounds are a common, costly and recurrent complication of diabetes. Platelet-rich plasma (PRP), a new therapy for chronic wounds, is limited by a long treatment period and unstable effects. FG-4592(Roxadustat) is a new prolyl-4-hydroxylation domain(PHD) inhibitor, which can stabilize hypoxia-inducible factor-1α(HIF-1α) effectively. It is a promising drug for wound repair and needs to be demonstrated via various appropriate application scenarios. This study investigated the effects of combining FG-4592 and PRP to promote diabetic wound healing. Diabetic rats were randomly assigned to five groups: nondiabetic control, diabetic untreated, diabetic + PRP, diabetic + FG-4592, and diabetic + PRP + FG-4592. Diabetes was induced with streptozotocin (STZ). A full-thickness skin defect was created, and FG-4592 (peritoneal injection) and PRP (periwound injection) were administered alone or together. Wound healing was assessed by histological analysis (Hematoxylin-Eosin (HE) and Masson staining) and protein expression of HIF-1α, VEGF(vascular endothelial growth factor), α-SMA(α-smooth muscle actin), CoL1α1(collagen type 1 alpha 1), and SDF-1(Stromal Cell-derived Factor 1) via Western blotting and qRT-PCR(Quantitative real time polymerase chain reaction). Immunohistochemistry(IHC) and immunofluorescence(IF) were also used to evaluate CD34 (Cluster of Differentiation 34), CD31(Cluster of Differentiation 31), VEGF(vascular endothelial growth factor), SDF-1(Stromal Cell-derived Factor 1), PCNA(Proliferating Cell Nuclear Antigen), and Integrin-β1 expression. The untreated diabetic group exhibited impaired wound healing, histological damage, and reduced expression of key proteins compared to the nondiabetic control group. Both PRP and FG-4592 alone improved wound healing, reduced damage, and upregulated protein expression. However, the combination of FG-4592 and PRP showed the most significant improvement. This study suggests that FG-4592 combined with PRP accelerates diabetic wound healing by enhancing endothelial progenitor cell recruitment, neovascularization, and cell proliferation and migration via upregulation of HIF-1α and its target genes. This combination therapy may provide a novel approach for treating chronic diabetic wounds.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
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IF 2.5
Jiajia Pan,Lijun Meng,Rujun Li,Zicheng Wang,Wenjie Yuan,Yucheng Li,Lin Chen,Qinhao Shen,Weili Liu,Li Zhu
Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2024
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IF 7.6
Jinmei Cheng,Yushun Dou,Jiaxin Li,Tingting You,Yihai Wang,Mengchuan Wang,Shengjun Shi,Chun-hui Cui,Xiaopin Duan,Jisheng Xiao
Critical limb ischemia (CLI) remains a significant clinical challenge with high morbidity and mortality. Considering the critical role of hypoxia-inducible factor 1α (HIF-1α) in hypoxic site to induce angiogenesis by regulating the expression of growth factors, we prepared a cooperative composite (P-F-HKUST-1) by mixing thermo-responsive hydrogel (PPCN) with folic acid modified copper-based MOFs (F-HKUST-1) for the hindlimb ischemia therapy. The gelation of P-F-HKUST-1 in hindlimb muscle generated a more serious ischemia environment and subsequently induced the expression of HIF-1α, while the slowly released Cu 2+ from P-F-HKUST-1 increased HIF-1α stability by inactivating the factor-inhibiting hypoxia-inducible factor 1 (FIH-1), which synergistically induced the productions of downstream growth factors and finally restored the blood perfusion rapidly. In addition, P-F-HKUST-1 hydrogel exhibited a long in vivo retention time, which endowed the sustaining action on HIF-1α to reduce the frequency of administration. The rapid blood flow recovery, together with the good biocompatibility suggested that P-F-HKUST-1 could be a potential novel combined therapy (HIF-1α stimulation and stabilization) for critical limb ischemia.
研究领域:
生物医学工程
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药学
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组织工程
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分子生物学
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DOI
高影响因子
DIGESTIVE DISEASES AND SCIENCES
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2025
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IF 2.5
Gao Tao,Zhang Huaisheng,Xu Yuan,He Guosong,Ma Huicong,Zheng Chuanming,Li Lei,Cheng Feng,Dou Hehe,Zhang Fulong,Zhao Heng,Qiu Zhaolei
Background Severe Acute Pancreatitis (SAP) is associated with significant intestinal injury and inflammation. Hypoxia-Inducible Factor-1α (HIF-1α) and NLRP3 inflammasome have been implicated in this process, but their specific roles remain unclear. Objective This study aims to elucidate the roles of HIF-1α and NLRP3 in the pathogenesis of SAP and their effects on intestinal injury, barrier function, and inflammatory responses. Methods A SAP rat model was established, and histological changes were assessed via HE staining. Western blot was used to analyze HIF-1α and NLRP3 expression in intestinal mucosa. The effects of HIF-1α modulation were examined using the activator DMOG and inhibitor BAY87-2243. Immunohistochemistry, ELISA, and TUNEL staining were used to evaluate intestinal barrier function, permeability markers, and apoptosis. Results HIF-1α and NLRP3 expression significantly increased in SAP rats, peaking at 72 h. HIF-1α activation aggravated intestinal injury and barrier dysfunction, decreasing tight junction protein levels and increasing epithelial apoptosis. Enhanced intestinal permeability and elevated pro-inflammatory cytokines were also observed. Furthermore, HIF-1α activation promoted NLRP3 inflammasome assembly, resulting in increased caspase-1 and IL-1β expression. Conclusion HIF-1α exacerbates intestinal injury and inflammation in SAP, likely through NLRP3 inflammasome activation. Targeting HIF-1α may offer a potential therapeutic approach for SAP-induced damage and inflammation.
研究领域:
医学
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分子生物学
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DOI
PubMed
高影响因子
FITOTERAPIA
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2024
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IF 2.5
Ye-Fang Lu,Chuang Liu,Juan Ma,Hu-Ri Piao,Changhao Zhang,Xuejun Jin,Cheng-Hua Jin
Hypoxia-inducing factor-1α (HIF-1α) is overexpressed in variety of tumor patients and plays an important role in the regulation of hypoxia response in tumor cells. Therefore, its inhibitors have become one of the targets for the treatment of a variety of cancers. Two series of panaxadiol (PD) ester derivatives containing pyrazole ( 18a–j ) and pyrrole ( 19a–n ) moiety were synthesized and their HIF-1α inhibitory activities were evaluated. Among all the target compouds, compounds 18c , 19d , and 19n (IC 50 = 8.70 – 10.44 μM) showed better HIF-1α inhibitory activity than PD (IC 50 = 13.35 μM). None of these compounds showed cytotoxicity above 100 μM and inhibited HIF-1α transcription in a dose-dependent manner. These compounds showed good antitumor activity and provide lead compounds for further design and activity study of PD ester derivatives.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
PubMed
高影响因子
INFLAMMATION
·
2018
·Vol. 41
·期 6
·2068-2078
·
IF 2.884
Zhou Qin,Gong Xia,Kuang Ge,Jiang Rong,Xie Tianjun,Tie HongTao,Chen XiaHong,Li Ke,Wan JingYuan,Wang Bin
Ferulic acid (FA), derived from fruits and vegetables, is well-known as a potent antioxidant of scavenging free radicals. However, the role and underlying mechanism of FA on kidney ischemia reperfusion (I/R) injury are limited. Here, we explored the effects of FA on kidney I/R injury. The kidney I/R injury models were carried out by clamping bilateral pedicles for 35 min followed by reperfusion for 24 h. Mice were orally pretreated with different doses of FA for three times 24 h before I/R. The renal function was assessed by serum creatine (Scr) and blood urea nitrogen (BUN). Kidney histology was examined by hematoxylin and eosin (HE) staining and terminal deoxynucleotidly transferased UTP nick-end labeling (TUNEL) assay. Proinflammatory cytokines, caspase-3 activity, adenosine generation, adenosine signaling molecules, and hypoxia inducible factor-1 alpha (HIF-1α) were also detected, respectively. The siHIF-1α adenovirus vectors were in vivo used to inhibit the expression of HIF-1α. The results showed that FA significantly attenuated kidney damage in renal I/R-operated mice as indicated by reducing levels of Scr and BUN, ameliorating renal pathological structural changes, and tubular cells apoptosis. Moreover, FA pretreatment inhibited I/R-induced renal proinflammatory cytokines and neutrophils recruitment. Interestingly, the levels of HIF-α, CD39, and CD73 mRNA and protein as well as adenosine production were all significantly increased after FA pretreatment in the kidney of I/R-performed mice, and inhibiting HIF-α expression using siRNA abolished this protection of FA on I/R-induced acute kidney injury as evidenced by more severe renal damage and reduced adenosine production. Our findings indicated that FA protected against kidney I/R injury by reducing apoptosis, alleviating inflammation, increasing adenosine generation, and upregulating CD39 and CD73 expression, which might be mediated by HIF-1α.
研究领域:
药理学
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分子生物学
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肾脏病学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2023
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IF 4.3
Xin Xie,Yan Zhu,Huimin Cheng,Haili Li,Yadi Zhang,Rong Wang,Wenyong Li,Fengrui Wu
Long-term exposure to bisphenol A (BPA) in humans may promote ovarian cancer development. In present study, the mechanisms by which BPA mediates the aggression metastatic behavior of ovarian cancer were investigated in vitro/in vivo . The results showed that BPA (10 μM) significantly promoted the proliferation, migration and invasion of human ovarian cancer cells (ES-2 and OVCAR-3 cells); moreover, it promoted ES-2 and OVCAR-3 cell glucose uptake, lactic acid release and intracellular ATP synthesis. After administration of 5 μg/kg/day BPA, tumor volume was increased compared with that in control group. KEGG and GO enrichment analyses showed that the genes from ES-2 cell in 10 μM BPA-treated group were enriched mainly in central carbon metabolism and PI3K-AKT signaling pathway. Then, qRT‒PCR and western blotting results showed that BPA (10 μM) increased the mRNA and protein expression levels of glycolysis-related genes and mTOR, p-AKT HIF-1α and ERα in vitro/vivo ; whereas this effect was reduced after treatment with the ERα inhibitor methyl-piperidino-pyrazole. Furthermore, coimmunoprecipitation and mass spectrometry showed that BPA promoted the direct interaction of ERα with lactate dehydrogenase A. These results show that BPA directly promoted the proliferation, migration and invasion of ovarian cancer cells through the ERα/AKT/mTOR/HIF-1α signaling axis to enhance glycolysis.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Nature Communications
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2025
·Vol. 16
·期 1
·1-19
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IF 15.7
Li Wenchao,Chen SaiSai,Lu Jian,Mao Weipu,Zheng Shiya,Zhang Minhao,Wu Tiange,Chen Yurui,Lu Kai,Chu Chunyan,Shu Chuanjun,Hou Yue,Yang Xue,Shi Naipeng,Chen Zhijun,Zhang Lihua,Zhang Lei,Na Rong,Chen Ming,Ju Shenghong,Zhang Dingxiao,Ma Yi,Xu Bin
Immune checkpoint therapy for prostate cancer (PCa), a classic ‘immune-cold’ tumor characterized by an immunosuppressive tumor microenvironment, failed previously in clinical trials, but the underlying causes remain elusive. Here we find that YY1 + , immunosuppressive macrophages aggregate in the hypoxic areas of PCa. Mechanistically, hypoxia promotes the phase separation of YY1 in the nucleus, where YY1 binds to NUSAP1 and promotes the SUMOylation, phase separation and stabilization of HIF-1α. Either myeloid-specific conditional knockout of YY1 or a treatment with tenapanor for decreasing the YY1–NUSAP1–HIF-1α interaction impairs subcutaneous PCa tumor formation in mouse prostate tumor models. Lastly, a first-generation tetrahedral DNA nanostructure based on the proteolysis targeting chimera technique, termed YY1-DcTAC, allows targeting and degrading YY1 in tumor-associated macrophages for inducing antitumor effects and CD8 + T cell tumor infiltration in mouse tumor models. In summary, our findings underscore the pivotal role of YY1 in the hypoxia/HIF-1α pathway in tumor-associated macrophages and support the targeting of YY1 for treating PCa.
研究领域:
肿瘤生物学
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免疫学
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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
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jia Liu,Mengyu Li,Guobao Chen,Junhui Yang,Ying Jiang,Fang Li,Haibing Hua
Ethnopharmacological relevance Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. Purpose To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. Methods In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. Results Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin , paeoniflorin , lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability , migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 μg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of Western blot , immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. Conclusion JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.
研究领域:
药理学
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中医中药
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分子生物学
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病理学
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DOI
PubMed
高影响因子
Cell Death Discovery
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2024
·Vol. 10
·期 1
·1-13
·
IF 6.1
Ruan Yuxia,Qiao Jianghua,Wang Jiabin,Liu Zhenzhen
Breast cancer (BC) poses a great threat to women’s health. Neuronal regeneration related protein (NREP) is a multifunctional protein that is involved in embryonic development, regeneration, and human disease. However, the biological function of NREP in tumors is rarely reported and its role in BC remains unknown. Bioinformatics analysis showed that NREP is highly expressed and closely correlated with poor survival in BC patients. Under hypoxic conditions, NREP was upregulated in BC cells, and this promotion was reversed by hypoxia-inducible factor HIF-1α suppression. Luciferase reporter system and chromatin immunoprecipitation assays confirmed that HIF-1α directly binds to the promoter of NREP to increase the transcriptional activity of NREP. NREP suppression inhibited cell proliferation, arrested the cell cycle at the G1/S phase, and promoted apoptosis and caspase-3 activity in BC cells. Suppression of NREP decreased the tube formation ability of HUVECs. In addition, NREP downregulation showed an inhibition effect on cell migration, invasion, and EMT of BC cells. In NREP overexpressed cells, all these changes were reversed. In vivo, animal experiments also confirmed that NREP promotes BC tumor growth and metastasis. In addition, NREP promoted cellular glycolysis and enhanced the levels of glucose consumption, ATP, lactate production, and glucose transporters expression in NREP-overexpressed BC cells. In summary, our results demonstrated that NREP could be transcriptional activated by HIF-1α, which may aggravate BC tumor growth and metastasis by promoting cellular glycolysis. This result suggested that NREP may play an essential part in BC progression.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
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