JOURNAL OF HAZARDOUS MATERIALS
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2026
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IF 10.6
Xia-Wen Qiu,Jiajun Chen,Jiayan Wang,Yujie Li,Xiaoyan Qi,Xianchang Zeng,Huajun Feng,Xianghui Kong
Respiratory viral infections contribute substantially to global disease burden and mortality. N -(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine quinone (6PPD-Q) has garnered significant attention due to its marked ecotoxicity. However, it remains unclear how this prevalent environmental pollutant impacts host immune defense against respiratory viral infections. This study established a murine model involving 14-day consecutive intranasal administration of environmentally relevant doses of 6PPD-Q coupled with intranasal instillation of influenza A virus (IAV) or tail vein injection of vesicular stomatitis virus (VSV). Our findings revealed that mice pre-exposed to 6PPD-Q exhibited higher mortality during viral infection. Notably, 6PPD-Q exposure resulted in extensive viral dissemination, severe pulmonary pathology, and markedly dysregulated inflammation, characterized by excessive increases in IL-6, TNF-α, IL-1β, and IL-10. Immune profiling demonstrated that 6PPD-Q exposure induced the selective accumulation of neutrophils, monocytes, and monocyte-derived macrophages (MDMs) in the lungs during IAV infection. Interestingly, macrophage depletion unequivocally abolished the differences of survival, viral loads, and cytokine levels between the vehicle- and 6PPD-Q-treated mice. Mechanistically, 6PPD-Q activated NF-κB signaling in pulmonary MDMs, driving excessive inflammatory responses. Our findings confirm that 6PPD-Q significantly increases host susceptibility to viral pneumonia. This underscores the critical significance of environmental health management in the prevention and control of respiratory infectious diseases.
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Qiang Yuan,Yaoke Li,Kaiwen Shen,Ruibo Zhang,Qiang Wang,Shasha Xia,Jun Shen
Background Renal ischemia-reperfusion injury (RIRI) contributes significantly to acute kidney injury (AKI), which is associated with high morbidity and mortality rates. Currently, therapeutic options for RIRI remain limited. Sarsasapogenin (Sar), a steroidal saponin from Anemarrhena asphodeloides, exhibits strong anti-inflammatory properties. However, its renoprotective effects, dose-response characteristics, and tissue-specific benefits in acute RIRI have not been thoroughly explored. This study aimed to determine whether Sar provides protection against RIRI-induced AKI and to investigate the potential signaling pathways involved. Methods Rats underwent 45 min of renal ischemia followed by reperfusion. Sar (20 or 60 mg/kg) was administered daily via gavage for one week prior to surgery. As a positive control, INF39 (7.5 mg/kg), an NLRP3 inhibitor, was injected intraperitoneally 2 h before surgery. Renal function was assessed through serum creatinine and BUN levels, while histopathology was evaluated using H&E and TEM. Tubular injury markers, such as KIM-1, were also assessed. Total cell death was determined using the TUNEL assay, which detects DNA fragmentation but does not specifically identify pyroptosis. The expression of inflammatory factors (IL-1β, IL-6, TNF-α) and key proteins of the NF-κB pathway (p-p65/p65) and NLRP3 inflammasome (NLRP3, Caspase-1, GSDMD) were measured using ELISA, immunohistochemistry, immunofluorescence, and Western blotting. Results RIRI led to severe renal dysfunction, structural damage, and increased KIM-1 expression. These pathological changes were linked to significant activation of the NF-κB pathway, upregulation of NLRP3 inflammasome components, and increased pyroptosis, indicated by elevated levels of cleaved Caspase-1, GSDMD-N, and mature IL-1β. Pretreatment with Sar dose-dependently improved renal function and reduced histopathological injury. Sar provided tissue-specific protection by maintaining mitochondrial integrity in renal tubular epithelial cells. These beneficial effects were accompanied by decreased phosphorylation of p65, reduced expression of NLRP3, cleaved Caspase-1, and GSDMD-N, as well as lower IL-1β production. High-dose Sar exhibited renoprotective effects comparable to INF39, acting as a multi-stage regulator that inhibits both NF-κB priming and NLRP3 inflammasome activation, suggesting advantages over single-target inhibitors. Conclusion Sar effectively attenuated RIRI-induced AKI, demonstrating favorable dose-dependent and tissue-specific renoprotective effects. This protective effect was associated with suppression of the NF-κB/NLRP3 inflammasome axis and reduced pyroptosis, highlighting its potential as a safe, multi-stage, natural candidate for treating ischemia-related renal injury.
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Redox Biology
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2025
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IF 11.9
Ding Liu,Yuanzhi Ye,Zirong Lan,An Chen,Xingchen Zhou,Zhenhao Li,Xin Wen,Jisheng Xiao,Fan Ouyang,Jianyun Yan
Vascular calcification, prevalent in patients with chronic kidney disease, atherosclerosis, and diabetes, is strongly associated with elevated cardiovascular morbidity and mortality, highlighting the urgent need for effective treatments. Oxidative stress is a key contributor to the progression of vascular calcification. Nanozymes, nanomaterials with enzyme-like catalytic properties, exhibit strong reactive oxygen species (ROS) scavenging abilities and good biocompatibility, making them promising therapeutic candidates. This study aims to investigate whether polyvinylpyrrolidone (PVP)-functionalized ultrasmall Cu 2-x Se nanoparticles (CSP NPs) act as nanozymes for treating vascular calcification. In vitro , CSP NPs significantly inhibit calcification of rat and human vascular smooth muscle cells (VSMCs) and reduce the expression of osteogenic markers Runx2 and BMP2. Moreover, CSP NPs alleviate calcification of rat and human arterial rings. In a mouse model, CSP NPs localize to certain areas, such as the aortic arch and abdominal aortas, and are safely metabolized by the liver and kidneys without organ toxicity. Further analyses confirm that CSP NPs inhibit mouse and chronic kidney disease (CKD) rat aortic calcification. Mechanistically, CSP NPs inhibit oxidative stress and mitochondrial dysfunction. Additionally, CSP NPs decrease the expression of NF-κB and NLRP3, thus reducing the levels of inflammatory cytokines IL-1β and IL-6. CSP NPs suppress NLRP3 activator-induced calcification in VSMCs and arterial rings. This study provides the first evidence that CSP NPs alleviate vascular calcification by inhibiting oxidative stress and NF-κB/NLRP3-mediated inflammation, suggesting a promising therapeutic approach.
研究领域:
纳米医学
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心血管研究
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炎症生物学
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氧化应激
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生物医学工程
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iScience
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2025
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IF 4.1
Qian Wang,Jie Chen,Huini Chen,Dongning Liang,Hong Zhou,Juanjuan Chen,Yuan Gui,Fang Yao,Yudan Chen,Xi Zeng,Yaxiang Ma,Dong Zhou,Haiyan Fu
Cisplatin is a commonly used chemotherapy agent for treating various solid tumors, but its clinical application is limited by nephrotoxicity. While the potential for cisplatin to cause chronic kidney disease (CKD) following repeated administration has been underexplored, effective therapeutic strategies for cisplatin-induced CKD are lacking. We found that cisplatin-induced CKD is characterized by renal dysfunction and inflammation, along with intestinal barrier impairment. 16S rRNA and metabolomics revealed that cisplatin disrupts the gut microbiome and raises levels of tryptophan metabolites- Indole-3-propionic acid (IPA). Notably, oral administration of IPA reproduced similar harmful effects in cisplatin-induced CKD. Integrated analyses of the microbiome, metabolomics, Raman spectroscopy and DESI-MSI indicated that IPA supplementation exacerbates the production of uremic toxins linked to tryptophan metabolism and promotes the growth of pathogenic bacteria. Our findings demonstrates that IPA exacerbates renal inflammation and fibrosis by regulating AHR/NF-κB signaling pathways, altering intestinal microbiome composition, and disrupting tryptophan metabolism.
研究领域:
肾脏病学
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肿瘤学
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毒理学
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微生物组研究
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代谢组学
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分子信号通路
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BIOCHEMICAL GENETICS
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2025
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IF 1.6
Yang Min,Ma Yuejiang,Cao Zhu,Zhan Hong,Jin Ye,Huang Xiufeng,Yang Shizhou
Cervical cancer (CC) is one of the most prevalent cancers among women globally. The primary cause of CC is persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16, whose E7 oncoprotein plays a pivotal role in carcinogenesis and the maintenance of stem cell-like characteristics. RTKN2 participates in the progression of various cancers. However, the precise functions of RTKN2 in regulating CC remain unclear. The effects of HPV16 E7 in CC cells were evaluated using MTT, western blotting, Transwell, and sphere formation assays. Transcriptome sequencing and bioinformatics analyses were used to identify the targets of HPV16 E7. The expression levels of the target (RTKN2) in clinical samples were assessed using immunohistochemistry (IHC). The function and mechanism of RTKN2 in CC cells were investigated by the knockdown and overexpression approaches, as well as dual-luciferase reporter assay. HPV16 E7 exhibited a positive correlation on the malignant phenotype and stemness of CC cells. RTKN2 was identified as a target of HPV16 E7, and a reduction in its expression levels was caused by knockdown of HPV16 E7. The high expression of RTKN2 was associated with a poor prognosis in CC. HPV16 E7 may regulate RTKN2 expression by modulating the binding activity of E2F1 to the RTKN2 promoter. Upregulated RTKN2 activates the NF-κB signaling pathway, enhances the stemness of CC cells, and ultimately promotes malignant progression.
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Cardiovascular Toxicology
·
2026
·Vol. 26
·期 2
·27
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IF 3.3
Feng Junkai,Ma Ting,Yang Liu,Li Min,Xiao Dahai,Gong Pengxin,Zhao Ani,Li Pu,Yao Linong
Sepsis-induced cardiomyopathy (SICM) is a life-threatening complication characterized by cardiac dysfunction, inflammation, oxidative stress, and mitochondrial impairment, with limited therapeutic options. Taurine, a naturally occurring amino acid with known anti-inflammatory and mitochondrial-stabilizing properties, may offer therapeutic benefits. However, its role in SICM is not well defined. This study aimed to evaluate the protective effects of taurine against SICM and elucidate its underlying mechanisms. A murine model of SICM was established via cecal ligation and puncture (CLP), and AC16 cardiomyocytes were stimulated with lipopolysaccharide (LPS) to mimic septic injury in vitro. Cardiac function was assessed by echocardiography; inflammatory cytokines and cardiac injury markers were measured via ELISA. Mitochondrial integrity and function were evaluated using transmission electron microscopy (TEM), oxygen consumption rate (OCR), and mitochondrial membrane potential (MMP). Apoptosis was analyzed by TUNEL staining, flow cytometry, and Western blot. Rescue experiments using an NF-κB activator were conducted to validate pathway involvement. The results showed that taurine treatment significantly improved cardiac function and survival rates in SICM mice, attenuated myocardial inflammation and oxidative stress, restored mitochondrial structure and function, and suppressed apoptosis. These beneficial effects were reversed upon NF-κB activation, indicating that taurine exerts its cardioprotective role primarily through inhibition of the NF-κB signaling pathway. In conclusion, this study provides the first evidence that taurine protects against SICM by alleviating NF-κB-driven inflammation, oxidative stress, mitochondrial dysfunction, and apoptosis, suggesting its potential as a therapeutic agent for sepsis-induced cardiac injury. Graphical
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FOOD AND CHEMICAL TOXICOLOGY
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2026
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IF 3.2
Siyan Cao,Runzhi Cai,Shuhua Xi,Yue Wang
Arsenic is a prevalent environmental contaminant found in contaminated drinking water. However, the effects of arsenic exposure on the intestinal tract and the specific mechanisms of action remain unclear. In this study, we utilized subchronic sodium arsenite (NaAsO2)-exposed mice and the NaAsO2-treated human colon mucosal epithelial cell line 460 (NCM460) models to investigate the intestinal damage induced by arsenic. Hematoxylin-eosin (HE) staining revealed that the intestines of mice exposed to arsenic exhibited histological damage, characterized by the destruction of epithelial cells, a reduction in the thickness of the muscularis propria, and an increased infiltration of inflammatory cells within the colonic tissue. Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein, accompanied by elevated concentrations of two biomarkers indicative of intestinal barrier damage: serum diamine oxidase (DAO) and lactate (D-LA). Analysis using 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota. However, it resulted in changes in the abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae increased, while Muribaculaceae decreased. Furthermore, exposure to arsenic led to increased protein levels of IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. Finally, intervention with Pyrrolidine dithiocarbamate (PDTC) significantly attenuated arsenic-induced intestinal inflammation. In conclusion, arsenic exposure compromises the integrity of the intestinal mucosa and disrupts the homeostasis of the intestinal microbiota. Additionally, arsenic mediates intestinal inflammation through the NF-κB signaling pathway.
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ACS Applied Materials & Interfaces
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2026
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IF 8.2
Ling Shuai,Xiaojun Wang,Xudong Wen,Cong Peng,Tian Dong,Jiejuan Lai,Ling Yao,Shijun Fan,Changchun Zhao,Leida Zhang,Yujun Zhang,Xiang Xiong
Hepatic ischemia–reperfusion injury (HIRI), a critical pathological process in surgeries such as liver transplantation and hepatectomy, involves complex mechanisms, including oxidative stress, immune-inflammatory responses, and cell apoptosis. However, universally accepted clinical treatment remains lacking. In this study, an erythrocyte-membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoplatform was constructed to deliver edaravone (Eda) and dexamethasone (Dex), ingeniously transforming the physiological clearance of nanoparticles by the hepatic reticuloendothelial system into a targeted delivery strategy. Edaravone synergizes with the nuclear factor E2-related factor 2 (Nrf2) pathway to scavenge excessive reactive oxygen species (ROS) in damaged hepatocytes, reducing the level of oxidative stress injury during ischemia–reperfusion. Concurrently, dexamethasone regulates the nuclear factor-κB (NF-κB) signaling pathway in neutrophils, thereby suppressing the release of proinflammatory cytokines from activated neutrophils and abrogating the subsequent immune cascade, which, in turn, mitigates the associated immune-mediated liver injury. This multifunctional nanoplatform-based therapeutic strategy can concurrently address short-term oxidative stress and long-term immune damage, which offers a clinically promising approach for the treatment of HIRI.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2026
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IF 5.4
Lili Wu,Siyu Chen,Qiyuan Yang,Xing Li,Lingyan Liu,Shengjun Ji,Shuaiyuan Tang,Sihui Zhang,Yan Wang,Runzhi Chen,Zhikun Zhan
Emodin, a bioactive compound abundant in Chinese medicinal herbs, possesses broad therapeutic potential but raises safety concerns due to conflicting reports of hepatotoxicity. This study investigated the toxicological mechanisms underlying emodin-induced liver injury. Emodin (25-100 μM) elicited dose-dependent cytotoxicity in HepG2 cells, with the cytochrome P450 (CYP) enzymes CYP1A2 and CYP3A4 identified as the primary enzymes metabolizing emodin into hydroxylated products (M1-M3). The comparative cytotoxicity assay of emodin and its metabolites in HepG2 cells indicated that CYP-mediated metabolism functions as a critical detoxification pathway. Moreover, inhibition of CYP with 1-aminobenzotriazole (ABT, 500 μM) markedly enhanced emodin (12.5-100 μM) cytotoxicity in HepG2 cells. Similarly, ABT (50 mg/kg) markedly exacerbated emodin (400 mg/kg)-induced hepatotoxicity in mice following three weeks of co-administration. Transcriptomic profiling and validation experiments demonstrated that activation of the NF-κB/NLRP3 signaling axis contributes to emodin-induced hepatic injury. Metabolomic analyses further revealed perturbations in key pathways, including lipopolysaccharide (LPS) biosynthesis, sphingolipid metabolism, and cholesterol metabolism. Integrated multi-omics analysis identified a significant positive correlation between these metabolites (LPS, sphingosine, cholesterol) and NF-κB/NLRP3 pathway genes. These findings suggest that emodin-mediated upregulation of LPS, sphingosine, and cholesterol activates the NF-κB/NLRP3 pathway, subsequently triggering hepatic injury. Collectively, this study delineates the metabolic detoxification routes of emodin and provides mechanistic insight into its hepatotoxic potential.
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Advanced Science
·
2026
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IF 14.1
Zimei Wu,Yan Xu,Lang Qin,Zemin Ling,Yingjie Mai,Xiong Tian Guo,Jiajia Chen,Leping Yan,Lin Wang,Liming Bian,Fuxin Wei
Intervertebral disc degeneration (IVDD) is driven by persistent inflammation–oxidative stress that disrupts annulus fibrosus (AF) homeostasis. Guided by network pharmacology and docking, we prioritized the NF-κB–LCN2 axis as a druggable target of wedelolactone (WDL). To achieve targeted modulation, we engineered a dual-network ROS-responsive hydrogel (WPG) in which a phenylboronic-ester/PVA redox-cleavable network interpenetrates a covalently crosslinked GelMA–elastin matrix, enabling mechanically robust yet stimulus-triggered WDL release. WDL suppressed NF-κB activation and downregulated LCN2 in both macrophages and AF cells. Conditioned-medium co-culture demonstrated that WDL disrupts macrophage-derived LCN2-mediated paracrine amplification, breaking the self-sustaining inflammatory loop. Bulk RNA-seq across both cell types revealed coordinated downregulation of NF-κB – driven chemokine cascades and restoration of adhesion and ECM gene programs following WPG treatment. In a rat AF-defect model, intradiscal WPG administration preserved disc height and T 2 -weighted MRI signal, reduced MMP13 while increasing Collagen I and Aggrecan expression, suppressed nuclear P-p65 and LCN2, and improved segment biomechanics—without eliciting adverse hematological or organ responses. Collectively, these findings establish that aligning molecular targeting (NF-κB–LCN2 modulation) with the pathophysiological context via ROS-gated delivery provides a synergistic strategy for AF repair and attenuation of IVDD progression.
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MOLECULES
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2026
·Vol. 31
·期 6
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IF 5.1
Leyuan Huang,Xu Zhou,Guanfeng He,Haixin Li,Xiaoying Chen,Jingwen Xu,Lei Zhou
Magnolia officinalisRehder & E.H.Wilson. bark is famous as a traditional herbal medicine used in prescriptions for treating gastrointestinal discomfort, respiratory and inflammatory disorders. Magnolol, one of its principal bioactive constituents, exhibits potent anti-inflammatory and immunomodulatory properties. However, its therapeutic mechanisms in allergic rhinitis (AR) remain to be elucidated. In this study, the anti-allergic effects and molecular mechanisms ofM.officinalisbark aqueous extract (MOAE) and magnolol were investigated using an ovalbumin (OVA)-induced AR mouse model. Nasal symptoms, histopathological alterations, and serum inflammatory mediators, including histamine and immunoglobulins (IgE, IgG1, IgG2a), were evaluated to assess efficacy. Both MOAE and magnolol significantly alleviated nasal rubbing and sneezing, reduced eosinophil infiltration and mucus hypersecretion, and improved tissue morphology in nasal and lung sections. Moreover, treatment markedly decreased serum levels of histamine and OVA-specific antibodies. Integrative network pharmacology, RNA sequencing, and molecular docking analyses revealed 33 co-regulated target genes mainly involved in the NF-κB and MAPK signaling pathways, suggesting that modulation of these pathways underlies the observed anti-inflammatory effects. These findings demonstrate that MOAE and magnolol exert protective effects against AR through the regulation of key inflammatory signaling cascades. This study provides modern pharmacological evidence supporting the traditional use ofM.officinalisbark and highlights its potential as a natural therapeutic candidate for AR.
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Viruses-Basel
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2026
·Vol. 18
·期 5
·567
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IF 3.8
Da Liu,Yan Yan,Xuezhen Fu,Linglong Qin,Jiayu Ma,Hui Zhou,Shiping Sun,Haimin Li,Weiren Dong,Jiyong Zhou
The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) has evolved sophisticated immune-evasion strategies to establish a productive infection in the host, primarily by counteracting the innate antiviral response. Here, we demonstrate for the first time that the PRRSV non-structural protein NSP8 suppresses NF-κB-dependent antiviral signalling by hijacking the host ubiquitin-conjugating enzyme UBE2K and inducing the degradation of IKKα, a pivotal kinase in the NF-κB pathway. PRRSV infection led to significant upregulation of host UBE2K, which in turn facilitated viral replication. Mechanistically, we found that NSP8 interacts directly with IKKα, triggering its degradation by the proteasome. Furthermore, we revealed that this process was facilitated by the host protein UBE2K, which acted as a crucial cofactor by directly interacting with NSP8 and thereby enhancing its activity against IKKα. This disruption blocked the activation of the NF-κB pathway and suppressed the expression of downstream antiviral factors, such as TNF-α, IL-6 and IFN-β, ultimately facilitating PRRSV replication. All of these findings showed that NSP8 is an important part of the process by which the host NF-κB pathway is blocked by viruses. This is a new way in which PRRSV avoids the immune system.
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