FISH & SHELLFISH IMMUNOLOGY
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2025
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IF 3.9
Hai-Chuan Yu,Meng-Yao Chen,Shuang-Ling Zhang,Fang-Chao Tong,Fan-Ping Wang,Lin Wang,Jia-Long Zhang,Jiao-Jie Guo,Bing-Yang Zhang,Jia-Qi Tian,Jiao Wu
Maintaining the hematopoietic balance between erythroid and myeloid lineages is crucial for immune function and oxygen transport. However, the mechanisms underlying the disruption of this balance during acute inflammation remain unclear. In this study, we investigated the effects of Lipopolysaccharide (LPS)-induced acute inflammation on erythroid-myeloid hematopoiesis in zebrafish (Danio rerio) and elucidated the key signaling pathways involved. LPS treatment significantly suppressed erythropoiesis, as evidenced by reduced expression of gata1a and hbae3 and decreased red blood cell production in the caudal hematopoietic tissue (CHT). Conversely, myelopoiesis was enhanced, with increased neutrophil and macrophage accumulation at inflammatory sites. Bioinformatics analysis revealed that LPS modulates hematopoietic differentiation via the Jak2/Stat3-Hif1a signaling axis. Experimental validation demonstrated that LPS activates Jak2/Stat3 signaling, leading to increased expression of hif1a in zebrafish and HIF1α in human hematopoietic cell lines (K562 and THP-1). Inhibition of Jak2 with Ruxolitinib or knockdown of hif1a reversed the LPS-induced suppression of erythropoiesis and expansion of myelopoiesis. Strikingly, acute hypoxia similarly disrupted the hematopoietic balance via the Jak2/Stat3-Hif1a pathway, suggesting a conserved, stress-responsive mechanism. Our findings highlight the critical role of Jak2/Stat3-Hif1a signaling in acute inflammation-induced hematopoietic lineage bias and propose potential therapeutic strategies for hematological disorders associated with acute infection or hypoxia.
研究领域:
发育生物学
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免疫学
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血液学
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信号转导
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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 ETHNOPHARMACOLOGY
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2025
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IF 5.4
Wēi Wang,Jian Zhang,Song-Lin Jiang,Zhi-Min Rao,Hui Liu,Lei Wang,Chun-Li Cai,Xin-Chang Xu,Chen-Huan Yu,Wéi Wang
Ethnopharmacological relevance Psoriasis is an immune-mediated genetic skin disease, which is characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes. Recently, there are not any cures for psoriasis because of the limited availability of safe and effective medications. Dictamni Cortex is the root bark of Dictamnus dasycarpus Turcz. And exhibits anti-inflammatory, antibacterial, hepatoprotective and anticancer activities. It is widely used for preventing various bone and skin diseases, including rheumatoid arthritis, psoriasis, eczema and impetigo. However, the active compounds responsible for treating psoriasis in the herb remain unknown. Aim of the study To investigate the inhibitory effects of active compounds in the herb against the hyperproliferation of human HaCaT keratinocytes in vitro and imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Materials and methods The effects of each active compound in the herb against the proliferation, apoptosis, migration, and invasion of HaCaT cells were analyzed by MTT, flow cytometry, and Transwell assays, respectively. The profiles of differentially expressed mRNAs between model group and dictamnine (DIC)-treated group were compared by transcriptome sequencing. The levels of inflammatory cytokines and chemokines in the mediums and skin tissues were measured by ELISA assay. IMQ-induced psoriasis-like dermatitis in mice were evaluated by HE stain and immunohistochemical analysis. The expressions of HIF1A and its downstream were measured by western blotting analysis. Results Compared with the methanol extract and other active compounds, DIC displayed the strongest inhibition on the hyperproliferation of KGF-stimulated HaCaT cells. DIC remarkably inhibited the proliferation, migration and invasion of HaCaT cells in a concentration-dependent manner. It also reduced the production of IL-6, IL-23 and VEGF, the activities of GSH and SOD, and the expressions of K17 , CCL20 and CXCL2 mRNAs, but elevated the levels of ROS, Fe 2+ and MDA in KGF-exposed HaCaT cells. Moreover, DIC significantly mitigated imiquimod-induced psoriasis-like dermatitis in mice. Mechanically, DIC promoted the ferroptosis of HaCaT cells via targeting HIF1A, thereby suppressing the nuclear translocation of HIF1A and its dowmstream GPX4 and SLC7A11. These benefits of DIC treatment could be reversed by ferroptotic inhibitor Ferrostatin-1 and HIF1A stabilizer DMOG. Conclusions DIC ameliorated psoriasis in part by triggering HIF1A-dependent ferroptosis in keratinocytes. It suggested that DIC was the main active compound in D. Cortex and has therapeutic potential for the treatment of psoriasis.
研究领域:
药理学
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皮肤科
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分子生物学
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民族药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Tong Chen,Lijun Ai,Ruonan Shuang,Jichen Diao,Xinyi Yuan,Weiwei Tao,Ling He,Chang Chen
Background Cognitive impairment is the common complication of diabetes, while its etiology remains not fully understood. Gardenia jasminoides is used in traditional Chinese medicine for clearing heat and detoxification. Its effective components Geniposide and Genipin have been found to show protective effect on diabetic cognitive impairment in our previous study. Whereas the effect and mechanism of Shanzhiside methyl ester (SME), another major component of Gardenia jasminoides , on cognitive impairment has been scarcely reported. Purpose The present study was conducted to evaluate the effect of SME on cognitive impairment symptom in diabetic mice. Methods Diabetes was induced by HFD/STZ. HG/PA induced BV2 cells were used as the in vitro model. Results Network pharmacology and bioinformatic analyses showed that HSP90AA1 might be the target of SME. As a result, SME attenuated cognitive impairment-related behavior in Morris water maze and passive avoidance tests. The treatment with SME inhibited inflammation, glycolysis via HSP90AA1/HIF1A/STAT1 signaling both in vivo and in vitro. SME regulated the transcriptions of inflammation, glycolysis, oxidative phosphorylation, oxidative stress, lipid metabolism, and mitochondrial stress related genes. The transfection with HSP90AA1 SiRNA or overexpression plasmid, the treatment with HIF1A inhibitor PX478, STAT1 inhibitor Fludarabine suggested that HSP90AA1/HIF1A/STAT1 signaling was required for the anti-inflammatory and anti-glycolytic effects of SME. The treatment with glycolysis agonist oligomycin, hexokinase inhibitor 2-DG, PKM2 activator TEPP46, PKM2 inhibitor Shikonin displayed that glycolysis was critical for the anti-inflammatory effect of SME. It was found that SME might combine with HSP90AA1. Conclusion SME attenuated cognitive impairment symptom of diabetic mice possibly via HSP90AA1/HIF1A/STAT1 mediated anti-inflammatory and anti-glycolytic effects.
研究领域:
药理学
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神经科学
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分子生物学
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生物信息学
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内分泌学
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中医药学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Qianrang Lu,Meiching Ong,Xuewen Yi,Muqiong Xing,Xinyao Tian,Ke Zhang,Ling Lu,Hao Wang,Xiaohan Lin,Jun Fang,Aibo Mu,Jiaying Cao,Jingyu Jiang,Feng Gao,Hongjun Li,Baohong Wang,Qi Ling
Macrophages are central mediators of hepatic inflammation and fibrosis in metabolic-associated steatohepatitis (MASH), yet the mechanisms driving their activation remain unclear. Integration of four human single-nucleus transcriptomic datasets identified Coagulation Factor XIII-A (F13A1)-positive macrophages as the predominant subset in MASH livers, a finding validated in patient samples and murine models. Lipid-stressed hepatocytes induce F13A1 expression through a sphingosine-1-phosphate (S1P)-dependent mechanism. Silencing F13A1 suppressed the pro-inflammatory phenotype and alleviated hepatic injury in vivo. Mechanistically, F13A1 directly interacted with pyruvate kinase M2 (PKM2), promoting its dimerization, a process enhanced by intracellular calcium levels. Dimerized PKM2 translocated into the nucleus and upregulates interleukin-1 beta (IL1B) expression via the PKM2/HIF1A (Hypoxia-inducible factor 1-alpha) axis. In addition, F13A1 enhanced the Warburg effect in macrophages through PKM2-mediated metabolic reprogramming. Pharmacologic activation of PKM2 with DASA-58 abrogated F13A1-driven inflammation, and PEG-PLA micelle-mediated delivery of DASA-58 ameliorated hepatic inflammation in vivo. These findings establish F13A1 as a critical driver of macrophage-mediated inflammation in MASH and highlight the F13A1/PKM2/HIF1A pathway as a promising therapeutic target.
✓ 已验证
DOI
高影响因子
iScience
·
2023
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IF 5.8
Zhijie Zhang,Jiangzhou Shi,Qifang Wu,Zijian Zhang,Xiaoyan Liu,Anqi Ren,Guanlin Zhao,Ge Dong,Han Wu,Jiaxuan Zhao,Yuan Zhao,Jia Hu,Hui Li,Tongcun Zhang,Fuling Zhou,Haichuan Zhu
Dexamethasone (Dex) plays a critical role in T-ALL treatment, but the mechanisms of Dex resistance are poorly understood. Here, we demonstrated that the expression of JUN was regulated in Dex-resistant T-ALL cell lines and patient samples. JUN knockdown increased the sensitivity to Dex. Moreover, the survival data showed that high expression of JUN related to poor prognosis of T-ALL patients. Then, we generated dexamethasone-resistant clones and conducted RNA-seq and ATAC-seq. We demonstrated that the upregulation of JUN was most significant and regulated by JNK pathway in Dex-resistant cells. High-throughput screening showed that HIF1α inhibitors synergized with Dex could enhance Dex resistance cells death in vitro and in vivo. Additionally, JUN combined and stabilized HIF1α in Dex resistance cells. These results reveal a new mechanism of Dex resistance in T-ALL and provide experimental evidence for the potential therapeutic benefit of targeting the JNK-JUN-HIF1α axis for T-ALL treatment.
研究领域:
肿瘤学
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免疫学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Huanchen Yao,Dayang Wang,Jiashuo Ye,Hailin Cong,Bing Yu
Ethnopharmacological relevance Lung cancer is a common respiratory cancer worldwide, which seriously threatens people's lives. The current treatment of lung cancer is not satisfactory. Traditional Chinese medicine records that Hedyotis diffusa Willd (HDW) has effects that include clearing heat and detoxifying, promoting diuresis and dehumidification, relieving pain and resolving masses, and exhibiting anti-cancer properties. It has shown extraordinary therapeutic value in the clinical practice of traditional Chinese medicine. It is commonly used to treat various tumors, inflammation, and other diseases. Aim of the study The purpose of this experiment is to isolate the components with anti-lung cancer effects from HDW and to explore its anti-lung cancer effect and mechanism through network pharmacology and in vitro cell experiments in order to find more effective and less side effects—anticancer drugs. Materials and methods We used ethanol to extract HDW preliminarily and then used ethyl acetate, n-butanol, petroleum ether, and water to extract it, obtaining the ethyl acetate fraction with the highest inhibition rate on lung cancer H1299 cells. The silica gel column purification, TOF, and nuclear magnetic resonance analysis yielded the Fisetin, which has an inhibitory effect on H1299 cells. The mechanism and application of Fisetin in inhibiting lung cancer were explored by network pharmacology and in vitro cell experiments. Results Using network pharmacology to explore the mechanism of Fisetin inhibiting lung cancer, 115 Fisetin targets, and 26,857 lung cancer targets were obtained, and 90 GO functions and 19 KEGG pathways were obtained (P < 0.01). Molecular docking results demonstrated that target protein-drug binding was stable. Afterward, the toxicity of Fisetin to H1299 cells was verified by in vitro cell experiments. MTT, live-dead staining, and confocal microscopy all showed that Fisetin had a good inhibitory effect on H1299 cells and had good cell compatibility. Through Western blot analysis, Fisetin can reduce the protein content of PI3K, MTOR, HIF1A and VEGFA. And it can reduce the mRNA expression levels of HIF1A and VEGFA. Moreover, Fisetin can also increase the expression of tumor suppressor molecule PTEN protein and mRNA in H1299 cells. Conclusions Fisetin and HDW can successfully stop lung cancer H1299 cells from growing. The mechanism of Fisetin may be related to the inhibition of PI3K/MTOR/HIF1A/VEGFA signaling pathway.
研究领域:
药理学
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肿瘤学
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生物信息学
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细胞生物学
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药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2026
·
IF 6.6
Yuehui Zhao,Ya Zhao,Junshuai Lv,Hailin Gong,Hui Yang
Nitrite (NO₂⁻) is a common nitrogenous contaminant in aquatic environments and drinking water, but its mechanisms of action on male reproduction are still not fully understood. In this study, male rare minnow ( Gobiocypris rarus ) were used as a model to investigate the effects of chronic NO₂⁻ exposure on testicular structure, energy metabolism, and sperm quality, and to elucidate the roles of hypoxia-inducible factor-1 ( hif1a ) and its associated metabolic genes. Fish were exposed for 21 days to control water or two environmentally relevant NO₂⁻ concentrations (0.5 and 2 mg/L NO₂⁻-N, respectively). Exposure to NO₂⁻ did not significantly affect body length or body weight, but low-dose NO₂⁻ increased testis weight and gonadosomatic index (GSI). At both doses, testicular histology was disrupted, ATP content decreased, and sperm concentration and motility were reduced, suggesting that the elevated GSI more likely reflects pathological changes in the testes rather than enhanced reproductive function. The rare minnow hif1a encoded a protein containing the typical structural domains of Hif1a, was highly conserved with other vertebrates, and was constitutively expressed in the testis. Early during NO₂⁻ exposure (1 week), testicular hif1a mRNA and protein levels were significantly upregulated, before gradually declining with prolonged exposure and falling below control levels by week 3. Immunofluorescence revealed that NO₂⁻ exposure caused disordered Hif1a distribution and patchy accumulation within the seminiferous epithelium of the testis. A series of genes involved in glucose uptake, glycolysis, lactate transport, and mitochondrial function showed time- and dose-dependent expression changes in the testis, and most of them were positively correlated with hif1a expression. These findings indicate that the “early activation followed by suppression” pattern of Hif1a dynamics is closely associated with testicular energy imbalance under NO₂⁻ exposure. In summary, chronic NO₂⁻ exposure impaired spermatogenesis and sperm motility without significantly affecting somatic growth and was associated with altered testicular hif1a/Hif1a dynamics and transcriptional changes in energy metabolism-related genes. These findings provide new evidence for understanding the reproductive toxicity of environmental nitrite in vertebrates.
✓ 已验证
DOI
PubMed
高影响因子
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