Human Cell
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2025
·Vol. 39
·期 1
·20
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IF 3.1
Tian Tian,Luan Xiaona,Wang Lingzhi,Kong Yan,Huang Liying,Wang Yan
Ovarian cancer is one of the most lethal gynecologic malignancies contributing to cancer-related deaths among women. However, the mechanisms underlying its development remain poorly understood. This study aimed to investigate the role of STARD7 in tumorigenesis and its potential molecular mechanisms in ovarian cancer. Cell proliferation was assessed using the Cell Count Kit-8 and colony formation assays. The migration and invasion capabilities of ovarian cancer cells were evaluated through wound healing and Transwell invasion assays. A xenograft tumor model was established in nude mice to examine the role of STARD7 in tumor growth in vivo. The results demonstrated that the knockdown of STARD7 in A2780 and SK-OV-3 cells inhibited cell proliferation, invasion, and migration, while overexpression of STARD7 yielded opposing results. Furthermore, STARD7 was found to enhance the levels of phosphorylated p65 proteins and nuclear protein p65. Treatment with the NF-κB inhibitor PDTC inhibited STARD7 overexpression-induced cell proliferation, invasion, and migration. These results suggest that the activation of the NF-κB pathway is involved in STARD7-mediated ovarian cancer progression. Consistent with the in vitro findings, similar results were observed in in vivo ovarian cancer xenograft models. Additionally, dual luciferase reporter assays indicated that STARD7 was regulated by RUNX1-IT1, which acted as a sponge for miR-377-3p. Collectively, these findings suggest that STARD7 may serve as an independent prognostic indicator, promoting ovarian cancer development by activating the NF-κB pathway. This research expands the current understanding of NF-κB regulatory networks and positions STARD7 as a promising therapeutic target for developing pathway-specific interventions. Graphical abstract
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Cell Communication and Signaling
·
2025
·Vol. 24
·期 1
·6
·
IF 8.9
Yang Xinyi,Ning Tingting,Zhang Wanru,Hou Songyuan,Su Jiayi,Li Wenkun,Wu Jing
Background Gastric microbiota dysbiosis is closely linked to chronic inflammation and carcinogenesis. Fusobacterium nucleatum ( Fn ), an opportunistic gastrointestinal pathogen, is implicated in perturbing the immune system and form an inflammatory microenvironment that fuels the occurrence and progression of gastric cancer (GC). However, the underlying mechanisms remain elusive. We aimd to investigate the impacts of Fn on GC cells and the crosstalk between GC cells and mast cells (MCs). Methods Fn abundance and MC infiltration were assessed in clinical GC tissues. Cell-based functional experiments, including wound healing, transwell, and ELISA, were performed using conditioned medium-based co-culture systems to explore how Fn influenced GC cell migration and the crosstalk with MC. A murine lung metastasis model was employed to evaluate Fn -driven metastasis and the effects of metronidazole and Reparixin. Results We showed that Fn and MCs were enriched and positively correlated in clinical GC tissues compared to paracancerous tissues. Fn and MCs exhibited tumor-promoting properties by facilitating GC cell migration. Besides, Fn and GC cells can recruit MCs and facilitate its activation. This crosstalk between GC cells and MCs was further enhanced by Fn , thereby amplifying this positive feedback loop between them. The production of CXCL8 in response to Fn stimulation was a significant mediator. Suppression of CXCL8 in GC cells weakened Fn ’s promoting effects on GC cell migration, MC recruitment and activation. Similarly, knocking down CXCL8 in MCs reversed the Fn -induced feedback effect of MCs on the highly invasive phenotype of GC cells. Mechanistically, the exoprotein Gbp of Fn activated CypA-NF-κB pathway in both GC cells and MCs, leading to the upregulation of CXCL8 expression. In addition, the in vivo assays substantiated Fn ’s ability to enhance tumor progression by facilitating cell migration, upregulating CXCL8 expression, and inducing MC infiltration and activation. However, these effects were reversed by metronidazole, a highly Fn -susceptible antibiotic, and Reparixin. Conclusions In summary, this study suggests that Fn contributes to GC progression by promoting tumor cell migration, MCs recruitment and activation. Simultaneously, the enhanced CXCL8-mediated crosstalk between GC cells and MCs plays a vital role in the pro-cancer effect of Fn.
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PHYTOMEDICINE
·
2025
·
IF 8.3
Zhongyuan Qu,Huimin Li,Fajing Qiang,Kaili Liu,Shuang Wu,Jianli Li,Xiang Zou
Background Breast cancer-related depression (BCRD) is one of the severest comorbidities, affecting the quality of life and the treatment efficacy in BC patients. Chaihu-Shugan-San (CSS), a traditional Chinese medicine presents a potential therapeutic method in BCRD. Purpose The main purpose of the research was to investigate the effects of CSS on BCRD in a mouse model and to elucidate its mechanisms, particularly its impact on microglial polarization through the IL-17/ NF-κB pathway. Methods A mouse BCRD model was constructed and treated with CSS. Behavioral testing, biochemical parameters, H&E staining, and small animal imaging were used to assess the depressive-like behaviors and tumor growth in mice. RNA sequencing analysis was performed, and the data were authenticated by Western blot as well as quantitative qRT-PCR to explore the mechanisms of CSS treatment in BCRD. The BV2 microglia were stimulated with LPS in vitro and intervened by IL-17 protein, IL-17 antagonist, IMD-0354, and CSS. In addition, western blot was utilized to confirm the expression of IL-17/ NF-κB pathway-related factors. Molecular docking technique and UPLC-Q-TOF/MS were used to find out the key active components of CSS. Results CSS treatment significantly improved depression-like behaviors and retarded tumor growth in mice. Through RNA sequencing analysis, it was indicated that the improvement of BCRD by CSS was highly associated with the regulation of the IL-17/ NF-κB pathway. Western blot and qRT-PCR outcomes suggested that CSS inhibited the IL-17/ NF-κB pathway, facilitating the transformation from pro-inflammatory M1 microglial phenotype to anti-inflammatory M2 phenotype, contributing to the reduction of neuroinflammation. In vitro experiments demonstrated that CSS modulated the immune reaction through the induction of phenotypic transformation of microglia from M1 toward M2 phenotype, hence reducing neuroinflammation. Notably, this therapeutic effect of CSS was highly similar to the effects of IL-17 antagonists, thus suggesting that CSS alleviates the symptoms of BCRD by targeting IL-17. Molecular docking revealed that the major bioactive compounds in CSS were Saikosaponin A, Saikosaponin C, and Saikosaponin D. Conclusion This study systematically demonstrates that CSS ameliorates BCRD by suppressing the IL-17/ NF-κB pathway as well as modulating microglial polarization and elucidates the dual function of IL-17. These results point to a new multi-target intervention strategy for BCRD treatment and fully reflect the holistic effects of CSS by its multi-component as well as multi-target actions.
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Food & Function
·
2019
·Vol. 11
·期 1
·456-471
·
IF 3.241
Manling Hu,Jing Yang,Linlin Qu,Xuqian Deng,Zhiguang Duan,Rongzhan Fu,Lihua Liang,Daidi Fan
Ginsenoside Rk1 is a substance derived from ginseng and exhibits various activities such as anti-diabetic, anti-inflammatory and anti-cancer effects; however, its anti-tumor effect and target signaling mechanism in lung adenocarcinoma are not well understood. Here, we show that Rk1, a natural drug product, can function as an antitumor modulator that induces apoptosis in lung adenocarcinoma cells by inhibiting NF-κB transcription and triggering cell cycle arrest. Mechanistically, Rk1 suppressed the proliferation and clonal formation of two lung adenocarcinoma cell lines (A549 and PC9) in vitro and caused G1 phase cell arrest. In the A549 xenograft model, Rk1 significantly inhibited tumor growth and had few toxic side effects on normal organs. Western blotting results showed that Rk1 increased the protein expression of Bax, cleaved caspase-3, -8, and -9, and PARP, decreased the expression of Bcl-2 and blocked the NF-κB signaling pathway. Furthermore, ginsenoside Rk1 also reduced the high expression of PD-L1 in lung adenocarcinoma cells by inhibiting NF-κB signaling. These data revealed a previously unreported antitumor mechanism of Rk1, providing new ideas and an experimental basis for further study of the mechanism of action of Rk1 in lung adenocarcinoma.
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Evidence-based Complementary and Alternative Medicine
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2022
·
IF 2.65
Ying-Ying Wu,Yi-Lin Huang,Bin Dai,Jian-Wei Liu,Xu Han
Background/Aim. Abnormal proliferation and migration of vascular smooth muscle cells is one of the main causes of atherosclerosis (AS). Therefore, the suppression of abnormal proliferation and migration of smooth muscle cells are the important means for the prevention and inhibition of AS. The clinical effects of Guanxinping (GXP) tablets and preliminary clinical research on the topic have proved that GXP can effectively treat coronary heart disease, but its underlying mechanism remains unclear. This study aimed to confirm the inhibitory effect of GXP on the abnormal proliferation of mouse aortic vascular smooth muscle (MOVAS) cells and to explore the underlying mechanism. Methods. MOVAS cells were divided into two major groups: physiological and pathological groups. In the physiological group, MOVAS cells were directly stimulated with GXP, whereas in the pathological group, the cells were stimulated by endothelin-1 (ET-1) before intervention by GXP. At the same time, atorvastatin calcium, which effectively inhibits the abnormal proliferation of MOVAS cells, was used in the negative control group. CCK8 assay, scratch test, ELISA, Western blotting, and immunofluorescence staining were performed to observe the proliferation and migration of MOVAS cells and the expression levels of related factors after drug intervention in each group. Results. In the physiological group, GXP had no significant effect on the proliferation and migration of MOVAS cells and the related factors. In the pathological group, a high dose of GXP reduced the abnormal proliferation and migration of MOVAS cells. Further, it reduced the expression levels of PI3K; inhibited the phosphorylation of Akt (protein kinase B); upregulated IκB-α levels; prevented nuclear factor kappa B (NF-κB) from entering the nucleus; downregulated the expression of interleukin 6 (IL6), IL-1β, and iNOS; and upregulated the ratio of apoptosis-related factor Bax/Bcl-2. There was no significant difference between the high-dose GXP group and the atorvastatin calcium group (negative control group). Conclusion. Our findings revealed that GXP was able to inhibit the proliferation and migration of MOVAS cells by regulating the PI3K/Akt/NF-κB pathway.
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DALTON TRANSACTIONS
·
2025
·
IF 3.3
Li Zhang,Youwen Li,Yuying Feng,Jiahui Jiang,Ting Zhao,Guancheng Xu
A trimetallic selenide electrocatalyst (Co, Fe, Ni)Se2 supported on nickel foam (NF) has been successfully synthesized for the oxygen evolution reaction (OER) and urea oxidation reaction (UOR). The catalyst was fabricated through a two-step strategy involving the formation of metal-organic frameworks (MOFs) precursors followed by a selenization reaction. The optimized (Co, Fe, Ni)Se2/NF-3:1 exhibited remarkable OER activity with an overpotential as low as 170 mV to achieve 10 mA cm-2, along with excellent stability over 1000 cycles. Its superior UOR performance with even lower overpotential further demonstrates promise for urea-assisted energy-saving hydrogen production. The enhanced electrocatalytic performance originates from the synergistic electronic modulation between Co, Fe, and Ni, the rough surface morphology facilitating mass and charge transport, and the highly conductive NF substrate enabling efficient exposure of active sites. This work provides valuable insights into the design of efficient multimetallic selenide electrocatalysts for sustainable electrochemical energy conversion.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Wen-Jing Xiao,Su Dong,Yue Xuan,Xiao-Jie Huang,Jing-Rui Feng,Hong-Jing You,Yang Chen
Existing studies lack systematic investigation of the polysaccharide components in Citri Reticulatae Pericarpium (CRP), despite established anti-inflammatory and cardioprotective effects of its bioactive constituents. This study isolated and characterized CRP-derived polysaccharides, focusing on CP-0's protective role against Lactobacillus casei cell wall extract (LCWE)-induced endothelial barrier dysfunction. Structural characterization identified CP-0 and CP-1 as novel triple-helical heteropolysaccharides (MW 81,404 and 83,540 Da; glucose, ribose, mannose). Following isolation and physicochemical screening, CP-0 exhibited low cytotoxicity and high anti-inflammatory activity. Mechanistic analyses revealed that CP-0 attenuated LCWE-induced endothelial injury by reducing inflammatory infiltration, IL-1β levels, and adhesion molecules (VCAM-1/ICAM-1) while upregulating tight junction proteins ZO-1/2 in mouse microvascular endothelial cells (MVECs). CP-0 suppressed NLRP3 inflammasome activation via decreased colocalization of NLRP3/Caspase-1/ASC, and competitive binding assays confirmed its interaction with TLR2, which blocked NF-κB nuclear translocation. By targeting TLR2-mediated signaling pathways, CP-0 effectively mitigated LCWE-induced coronary arteritis in vitro, demonstrating potential as a therapeutic candidate for cardiovascular diseases through early-stage anti-inflammatory intervention.
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DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2021
·
IF 3.636
Feng-Ying Gao,Xin Zhou,Mai-Xin Lu,Miao Wang,Zhi-Gang Liu,Jian-Meng Cao,Xiao-Li Ke,Meng-Meng Yi,Deng-Gao Qiu
Toll-like receptors (TLRs) play a critical role in the innate immune response of fish. In this study, we isolated the cDNA sequence of Nile tilapia TLR1 ( On TLR1). The deduced OnTLR1 protein contains a signal peptide , 7 leucine-rich repeats (LRRs), a C-terminal LRR (LRR-CT), a transmembrane region and a highly conserved TIR domain. In healthy Nile tilapia, the On TLR1 transcript was broadly expressed in all examined tissues, with the highest expression levels in the spleen . After infection with Streptococcus agalactiae , the On TLR1 transcripts were upregulated in the gill and kidney. After stimulation with polyinosinic-polycytidylic acid (poly(I:C)), the expression levels of On TLR1 were significantly downregulated in the intestine , whereas On TLR1 transcripts were significantly upregulated in the kidney. After challenge with lipopolysaccharide (LPS), the expression levels of On TLR1 were significantly upregulated in the spleen and kidney. The subcellular localization showed that On TLR1 was expressed in the cytoplasm. TLR1 significantly increased MyD88-dependent NF-κB activity. However, the results of a pull-down assay showed that On TLR1 did not interact with MyD88 or TIRAP. Binding assays revealed the specificity of OnTLR1 for pathogen-associated molecular patterns (PAMPs) and bacteria that included S. agalactiae , Aeromonas hydrophila and poly(I:C) and LPS. Taken together, these findings suggest that OnTLR1, as a pattern recognition receptor (PRR), might play an important role in the immune response to pathogen invasion.
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ACS Applied Materials & Interfaces
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2020
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IF 8.758
Zhenqiang Fan,Zongqiong Lin,Zepeng Wang,Jianfeng Wang,Minhao Xie,Jianfeng Zhao,Kai Zhang,Wei Huang
In this work, we fabricated a dual-wavelength electrochemiluminescence ratiometric biosensor based on electrochemiluminescent resonance energy transfer (ECL-RET). In this biosensor, Au nanoparticle-loaded graphitic phase carbon nitride (Au-g-C3N4) as a donor and Au-modified dimethylthiodiaminoterephthalate (TAT) analogue (Au@TAT) as an acceptor were investigated for the first time. Besides, tetrahedron DNA probe was immobilized onto Au-g-C3N4 to improve the binding efficiency of the transcription factor and ECL ratiometric changes on the basis of the ratio of ECL intensities at 595 and 460 nm, which were obtained through the formation of a sandwich structure of DNA probe–antigen–antibody. Our biosensor achieved the assay of NF-κB p50 with a detection limit of 5.8 pM as well as high stability and specificity.
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Foods
·
2022
·Vol. 11
·期 15
·2381
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IF 5.561
Lilong Wang,Linlin Wang,Chunhong Yan,Chunqing Ai,Chengrong Wen,Xiaoming Guo,Shuang Song
The present study aimed to clarify the potential mechanism of fucoidans found inAscophyllum nodosumon anti-inflammation and to further explore the relationship between their structures and anti-inflammation. Two novel fucoidans named ANP-6 and ANP-7 and found inA. nodosum, were separated and purified and their structures were elucidated by HPGPC, HPLC, GC-MS, FT-IR, NMR, and by the Congo red test. They both possessed a backbone constructed of →2)-α-L-Fucp4S-(1→, →3)-α-L-Fucp2S4S-(1→, →6)-β-D-Galp-(1→, and →3,6)-β-D-Galp4S-(1→ with branches of →2)-α-L-Fucp4S-(1→ and →3)-β-D-Galp-(1→. Moreover, ANP-6 and ANP-7 could prevent the inflammation of the LPS-stimulated macrophages by suppressing the NO production and by regulating the expressions of iNOS, COX-2, TNF-α, IL-1β, IL-6, and IL-10. Their inhibitory effects on the TLR-2 and TLR-4 levels suggest that they inhibit the inflammation process via the blocking of the TLR/NF-κB signal transduction. In addition, ANP-6, with a molecular weight (63.2 kDa), exhibited stronger anti-inflammatory capabilities than ANP-7 (124.5 kDa), thereby indicating that the molecular weight has an influence on the anti-inflammatory effects of fucoidans.Keywords:sulfated polysaccharides;chemical structure;anti-inflammation;molecular weight
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Redox Biology
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2026
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IF 16.2
Fei Yan,Shouwei Tao,Yan Jiao,Ting Kang,Shuangqing Du,Yue Cheng,Zhenbo Huang,Ping Feng,Bowen Ke
A novel hydrogen persulfide donor HPD1 exhibits superior cytoprotective and anti-inflammatory effects over NaHS and Na 2 S 2 . • HPD1 dual-regulates microglial M1/M2 and astrocytic A1/A2 polarizations to alleviate neuroinflammation, thereby preserving neuronal damage. • The anti-inflammatory mechanism of HPD1 relies on blocking the TLR4-MAPK/NF-κB cascade. • Hydrogen persulfide supplementation represents a promising therapeutic strategy for neuroinflammation-related diseases. The biological role of hydrogen persulfide (H 2 S 2 ) has remained elusive due to the scarcity of controllable donors, despite its importance as a reactive sulfur species whose dyshomeostasis drives neuroinflammation. Herein, we employed HPD1, a novel esterase-responsive H 2 S 2 donor, to investigate its anti-inflammatory effects and underlying mechanisms in lipopolysaccharide (LPS)-stimulated glial cells. HPD1 exhibited superior cytoprotective and anti-inflammatory efficacy over inorganic sodium disulfide (Na 2 S 2 ) and sodium hydrosulfide (NaHS) in BV2 microglia, consistent with its superior and sustained intracellular H 2 S 2 release efficiency. Functionally, HPD1 dose-dependently attenuated LPS-induced cytotoxicity and shifted microglia and primary astrocytes from pro-inflammatory, neurotoxic states toward anti-inflammatory, neuroprotective phenotypes, as characterized by M1-to-M2 and A1-to-A2 marker profiles, respectively. Mechanistically, HPD1 downregulated toll-like receptor 4 (TLR4) and attenuated mitogen-activated protein kinase (MAPK) activation, as evidenced by reduced extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK) phosphorylation in BV2 microglia. In both BV2 microglia and primary astrocytes, HPD1 markedly suppressed the phosphorylation of both the p65 subunit of nuclear factor-κB (NF-κB) and inhibitor of κBα (IκBα), prevented the proteasomal degradation of IκBα, and blocked the nuclear translocation of p65. Consequently, HPD1 attenuated the release of neuroinflammatory mediators while promoting the production of neuroprotective factors, thereby protecting neuronal HT22 cells against neurotoxicity induced by conditioned medium from LPS-activated BV2 microglia. In vivo, HPD1 reduced serum proinflammatory cytokine levels in both an acute intrathecal LPS-induced neuroinflammation model and a chronic constriction injury-induced neuropathic pain model. Collectively, our findings identify the TLR4-MAPK/NF-κB axis as a potential molecular pathway through which sustained H 2 S 2 delivery by HPD1 reprograms glial phenotypic polarization and promotes neuroprotection. This study provides mechanistic insights into H 2 S 2 signaling and supports the therapeutic potential of controllable H 2 S 2 supplementation for neuroinflammatory disorders. Download: Download high-res image (301KB) Download: Download full-size image
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Theranostics
·
2026
·Vol. 16
·期 16
·9295
·
IF 14.9
Jinli Li,Liyao Zhang,Yuanyuan Ren,Junxuan Wang,Pan Zhang,Qianran Shen,Yaqi Wang,Yi Yu,Zi Cheng,Qiang Wang,Haiying Wang,Yuyan Xiong
Rationale Age-associated osteoporosis (AAOP) is characterized by progressive bone loss that can be driven by impaired osteoblast function and increased cellular senescence. However, the molecular mechanisms driving osteoblast senescence during aging remain incompletely understood. In this study, we aim to investigate the role of arginase 2 (ARG2) and its underlying mechanisms in osteoblast senescence and AAOP. Methods AAOP were assessed in D-galactose-induced aging mice, naturally aged mice, and osteoblast-specific ARG2 knockout mice. In vitro , osteoblast senescence was induced by hydrogen peroxide exposure. Bone phenotypes, cellular senescence, mitochondrial function, and mitophagy were examined using histological, molecular, and imaging techniques. Luciferase reporter assays, co-immunoprecipitation (Co-IP), and pharmacological or genetic approaches were employed for molecular mechanistic investigations. Results We observed that ARG2 expression was markedly elevated in senescent osteoblasts and aged mice with osteoporosis. Osteoblast-specific deletion of ARG2 alleviated age-related bone loss, improved trabecular bone microarchitecture, and reduced osteoblast senescence in vivo . Mechanistically, ARG2 promoted mitochondrial oxidative stress and impaired mitophagy, as evidenced by inhibition of the PINK1/Parkin/LC3 pathway and accumulation of p62. Furthermore, we revealed that ARG2 activated IκBα/NF-κB signaling, leading to HDAC9-mediated transcriptional repression of thioredoxin 2 (TXN2), a key mitochondrial antioxidant. Restoration of TXN2 expression, antioxidant treatment, or blockade of NF-κB/HDAC9 signaling rescued mitophagy, attenuated osteoblast senescence, and restored osteogenic function. Moreover, pharmacological inhibition of ARG2 using S-(2-boronoethyl)-L-cysteine (BEC) significantly suppressed osteoblast senescence and protected against age-related osteoporosis. Conclusion ARG2 plays a pivotal role in osteoblast senescence and the development of AAOP by inducing mitochondrial oxidative stress and mitophagy dysfunction through the IκBα/NF-κB/HDAC9/TXN2 signaling axis. Targeting ARG2 may offer a promising therapeutic approach for AAOP prevention and treatment.
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