BIOMEDICINE & PHARMACOTHERAPY
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2025
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IF 7.5
Yang Yu,Yurong Wang,Ziqi Yang,Zhanqiang Li,Dianxiang Lu,Xingmei Nan
Pulmonary hypertension is divided into five groups, and chronic exposure to hypoxia causes pulmonary hypertension in the third group -- high altitude pulmonary hypertension, which is commonly seen in patients with chronic obstructive pulmonary disease, sleep-disordered breathing, and interstitial lung disease. Its clinicopathological features include right heart overload and right ventricular hypertrophy, with severe patients potentially experiencing right heart failure or even death. The pathogenesis of high altitude pulmonary hypertension is complex; it includes oxidative stress, mitochondrial dysfunction, apoptosis, and pyroptosis. Pharmacological therapy may alleviate the condition if immediate descent to lower altitudes or supplemental oxygen is not possible. Herein, we preliminarily investigated the effect of methyleugenol on high altitude pulmonary hypertension through in vitro and in vivo experiments. Methyleugenol alleviated pulmonary arteriole constriction by acting on potassium ion channels, and inhibited the proliferation of pulmonary artery smooth muscle cells(PASMCs) by decreasing and reactive oxygen species levels, as well as inhibiting the expression of HIF-1α. The cardiac systolic function improved and mitochondrial structure of pulmonary artery smooth muscle cells in rats with high altitude pulmonary hypertension was significantly improved after methyleugenol gavage intervention, and malondialdehyde levels in serum of rats were decreased while those of superoxide dismutase and glutathione increased, suggesting that the reduction of oxidative stress may be one of the mechanisms to improve mitochondrial function. Western blot experiments showed that methyleugenol regulated the oxidative stress level in rats by activating Nrf2/HO-1 signaling pathway, activate p27Kip1, inhibit CDK4/CCND1/ p-ERK1/2 and inhibited HIF-1α/RASSF1/Ras axis to inhibit cell proliferation, thereby improving the occurrence and development of high altitude pulmonary hypertension in rats. The results of this study reveal that methyl eugenol has the potential to alleviate pulmonary vasoconstriction and remodeling in rat models of high-altitude pulmonary hypertension, providing a scientific basis for the application of this compound in improving pulmonary vascular remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
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PubMed
高影响因子
Pharmacognosy Magazine
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2024
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IF 0.6
Zhao Chenghe,Wang Yao,Jing Shu,Lin Huijiao,Li He,Chen Jianguang,Xia Wei
Background: Drug-induced liver injury (DILI) is extremely common in clinical practice and needs to be focused. Anwulignan is a unique lignan monomer of Schisandrae Sphenantherae Fructus and is used as the main active ingredient of Wuzhi tablet, which is used for liver protection in clinical practice. In this study, an acute liver injury mouse model induced by acetaminophen and paracetamol (APAP) was used to observe its effects.Materials and Methods: An acute liver injury mouse model was established by intraperitoneally injecting APAP. Mice were divided into blank control (CON) group, APAP model (MOD) group, Anwulignan CON group, and Anwulignan MOD group. Anwulignan (6 mg/kg) or sodium carboxymethylcellulose (10 mL/kg) was intragastrically given to mice once a day, successively for 14 days. On day 14, 250 mg/kg APAP solution (10 mL/kg) or saline was injected intraperitoneally, and 12 h later, the mice were killed. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum of mice were tested. The liver index of mice was calculated, and the pathology of liver injury was evaluated by HE staining in mice. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as the content of malondialdehyde (MDA) in the liver tissue were tested. The levels of kelch-like ECH-associated protein 1 (Keap-1), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), BCL2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase-3 and tumor suppressor protein (P53) mRNAs in the liver tissues of mice were detected by reverse transcription-PCR (RT-PCR), and the expression levels of Keap-1, Nrf2, HO-1, Bax, Bcl-2, caspase-3 and P53 proteins in the liver tissue of mice were detected by Western blot.Results: Anwulignan can alleviate the acute liver injury of mice. The down-regulation of the cyclophosphamide (CYP2E1) expression in the liver tissue of mice to reduce the hepatotoxicity of APAP, and the regulation of Nrf2-ARE signaling pathway-related gene expressions to play an antioxidant role and apoptosis-related gene expressions to inhibit the liver cell apoptosis may be involved in the mechanism through which Anwulignan can exert its effect.Conclusion: Anwulignan can alleviate the liver injury induced by APAP in mice, and this study may provide evidence for researching and developing some drugs and nutraceuticals used for preventing and treating liver injury.
研究领域:
药理学
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肝脏病学
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分子生物学
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DOI
高影响因子
REDOX REPORT
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2025
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IF 7.4
Tianyi Wang,Jiale Huang,Jian Zhou,Mingjie Xia,Zheng Zhou,Qianqiu Li,Guanhua Xu,Zhanyang Qian,Zhiming Cui
Background: Spinal cord injury (SCI)-induced mitochondrial dysfunction in microglia exacerbates neuroinflammation and neurological deficits. Monoammonium glycyrrhizinate (MAG), a bioactive liquorice-derived compound, exhibits anti-inflammatory and antioxidant properties; however, its effects on microglial mitochondria remain unknown.Methods: Mice received a moderate contusion injury at the T10 spinal segment. Histopathology was assessed using Hematoxylin-Eosin, Nissl staining, and Luxol Fast Blue; locomotor recovery was evaluated via the Basso Mouse Scale, hindlimb flexion scoring, and gait footprint analysis. RNA-Seq and molecular docking identified KEAP1/NRF2 signaling. Verification employed qPCR, Western blot, and immunofluorescence. Mitochondrial function was gauged by JC-1 and MitoSOX.Results: In SCI mice, MAG attenuated neuroinflammation, reduced neuronal tissue loss and demyelination, enhanced neuronal survival, and improved functional recovery. Transcriptomic and molecular docking established that MAG directly activates NRF2, promoting dissociation from KEAP1, nuclear translocation, and induction of NQO1. Pathway enrichment analysis further indicated MAG modulation of mitochondrial regulatory processes. MAG treatment significantly restored mitochondrial function in BV2 cells, improving membrane potential and reducing oxidative stress. Critically, NRF2 inhibition with ML385 abolished MAG's protective effects on anti-inflammatory responses and antioxidant activity.Conclusion: This study identifies MAG as a novel activator of the KEAP1/NRF2/NQO1 axis, alleviating microglial mitochondrial dysfunction and neuroinflammation post-SCI. These findings provide mechanistic insights into MAG's neuroprotective actions and support its therapeutic potential.
研究领域:
神经科学
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药理学
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分子生物学
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炎症研究
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线粒体生物学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2025
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IF 9.6
Huihui Liu,Yilong Hu,Wanting Ji,Sijie Wang,Ying Zhu,Qing Lin,Xiaoqi Zhao,Huanli Zhou,Xuemeng Guo,Yu Liu,Yingying Shi,Junlei Zhang,Zhenyu Luo,Jiaxin Huang,Hang Yin,Lihua Luo,Jian You
Intrinsic skin aging and photoaging induce alterations in skin morphology and increase the risk of skin diseases. Reactive oxygen species (ROS) are key contributors to these processes, and nuclear factor erythroid 2-related factor 2 (Nrf2), a central antioxidant transcription factor, represents a promising therapeutic target for combating oxidative stress. Therefore, activation of Nrf2 is anticipated to alleviate oxidative stress, preserve cellular homeostasis, and restore dermal fibroblast function by upregulating antioxidant enzymes. In this study, the Nrf2 agonist dimethyl fumarate (DMF) is selected as a model drug, and constructed flexible liposome FL@SC by adding anionic surfactants to enhance the skin penetration, and achieved sustained activation of Nrf2 through the controlled release of DMF, while improving the concentration dependence of DMF on cell protection. The results showed that Nrf2 activation ex erted remarkable anti-aging effects in two skin aging models induced by D-galactose and UVB. FL@SC significantly enhanced the penetration and retention of DMF in the dermis, thereby inhibiting hallmarks of skin aging, including structural disorganization, flattening of epidermal rete ridges, and collagen degradation. Collectively, this study presents a viable strategy for delaying skin aging by alleviating oxidative stress in dermal fibroblasts via the targeted delivery of Nrf2 agonists using flexible liposomes.
研究领域:
皮肤病学
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制药纳米技术
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分子生物学
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氧化应激与衰老
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药物递送系统
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PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Jiabing Chen,Xiaoqin Wu,Tingting Chen,Tianqi Cui,Dailin Wu,Min Qiu,Qincheng Yi,Ziyi Zhang,Chenlu Ma,Yong Gao,Yinliang Zhang,Zhuohui Luo,Jiawen Huang
Background : Ginsenoside Rg2 (G-Rg2) is a bioactive saponin derived from Panax ginseng, recognized for its diverse pharmacological activities, which include anti-inflammatory, antioxidant, and hepatoprotective effects. Nevertheless, the therapeutic mechanisms underlying its effects in metabolic dysfunction-associated steatohepatitis (MASH) are still not well understood. Purpose : The current work examined the protective role of G-Rg2 on MASH and elucidate the molecular mechanisms. Methods : Eight-week-old male C57BL/6J mice received a standard diet containing Methionine- and choline-deficient diet (MCD), while LX2 cells were induced by TGFβ, serving as in vivo and in vitro models, respectively. To assess the protective effect of G-Rg2 in alleviating MASH, we conducted histopathological staining, utilized commercial kits, performed qPCR, immunoblotting, and immunofluorescence, as well as executed a cellular thermal shift assay. Additionally, network pharmacology prediction, molecular docking, and molecular dynamics simulation analyses were employed. Results : G-Rg2 reduced body weight loss (p<0.001), AST/ALT (p<0.001), hepatic inflammation (CD68, NFκB, IL1β downregulated, CD206 upregulated; p<0.05), apoptosis (Bcl-2 up, Bax down), oxidative stress (SOD, GSH increased, MDA reduced; p<0.05), and fibrosis (α-SMA decreased). In TGFβ-induced LX2 cells, it suppressed inflammation (IL6, TNFα down; p<0.05), ROS, and fibrosis (COL1A1, α-SMA down; p<0.001) via stabilizing NRF2 binding. In NRF2⁻/⁻ mice or with ML385 (Nrf2 inhibitor), G-Rg2’s effects were abrogated (p>0.05), confirming NRF2 dependency. Conclusion : This study is the first to confirm that G-Rg2 binds to and regulates Nrf2, and further illustrates that it alleviates MASH by activating the NRF2 signaling pathway to inhibit inflammation, cell apoptosis, oxidative stress, and fibrosis. This establishes a conceptual foundation for the future use of G-Rg2 in MASH treatment and supports the development of natural product–based therapeutic strategies derived from dietary sources.
研究领域:
药理学
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肝病学
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分子生物学
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天然产物研究
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生物化学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 6.7
Xiaoxiao Yang,Zhigang Liu,Mengyuan Fang,Tingfeng Zou,Zhen Zhang,Xianshe Meng,Tianxiang Wang,Huawen Meng,Yuanli Chen,Yajun Duan,Qingshan Li
Pterostilbene is a demethylated resveratrol derivative with attractive anti-inflammatory, anti-tumor and anti-oxidative stress activities. However, the clinical use of pterostilbene is limited by its poor selectivity and druggability. Heart failure is a leading cause of morbidity and mortality worldwide, which is closely related to enhanced oxidative stress and inflammation. There is an urgent need for new effective therapeutic drugs that can reduce oxidative stress and inflammatory responses. Therefore, we designed and synthesized a series of novel pterostilbene chalcone and dihydropyrazole derivatives with antioxidant and anti-inflammatory activities by the molecular hybridization strategy. The preliminary anti-inflammatory activities and structure-activity relationships of these compounds were evaluated by nitric oxide (NO) inhibitory activity in lipopolysaccharide (LPS)-treated RAW264.7 cells, and compound E1 exhibited the most potent anti-inflammatory activities. Furthermore, pretreatment with compound E1 decreased reactive oxygen species (ROS) generation both in RAW264.7 and H9C2 cells by increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), as well as downstream antioxidant enzymes superoxide dismutase 1 (SOD1), catalase (CAT) and glutathione peroxidase 1 (GPX1). In addition, compound E1 also significantly inhibited LPS or doxorubicin (DOX)-induced inflammation in both RAW264.7 and H9C2 cells through reducing the expression of inflammatory cytokines by inhibiting nuclear factor-κB (NF-κB) signaling pathway . Moreover, we found that compound E1 improved DOX-induced heart failure by inhibiting inflammation and oxidative stress in mouse model, which is mediated by the potential of antioxidant and anti-inflammatory activities. In conclusion, this study demonstrated the novel pterostilbene dihydropyrazole derivative E1 was identified as a promising agent for heart failure treatment.
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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生物化学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2026
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IF 8.3
XiaoYang Qu,LiJuan Chen,JiangHua He,YuFei Fang,Jing Sun,ZhiYing Yu,Zhen Yang,ZiJing Zhang,JianBo Chen,Ling Dong
Background Epilepsy is a prevalent neurological disorder characterized by recurrent seizures and has limited effectiveness of available clinical treatments. Ferroptosis of neurons is one of the main mechanisms of epilepsy. Arisaema Cum Bile (ACB) is a traditional Chinese medicine that is prepared by fermenting animals bile with Rhizoma Arisaematis rhizomes, has demonstrated therapeutic effects on epilepsy and other nervous system diseases. Furthermore, the active components responsible for the anti-epileptic effects of ACB and the intrinsic mechanisms are still unclear. Purpose This study aims to clarify the principal bioactive constituents of ACB and their mechanisms in the treatment of epilepsy. It also seeks to provide data support for its clinical application in antiepileptic combination therapy. Method Pentylenetetrazol injections were used to induce epilepsy in rats. ACB and brain metabolites were identified via UPLC-Q-Exactive Orbitrap MS/MS, and active components were predicted through bioinformatics analysis. In vivo , ACB and hyodeoxycholic acid (HDCA) were administered by gavage, and the effects on oxidative stress, inflammation, and cognitive impairment were evaluated. Additionally, ferroptosis-related protein and gene expression were analyzed using western blot, PCR, immunofluorescence, and flow cytometry. In vitro , using primary neurons and HT22 cells, with electrophysiology employed to assess neuronal activity and glutamate used to induce ferroptosis in HT22 cells, in order to explore how HDCA alleviates epilepsy by inhibiting neuronal ferroptosis. Result A total of 37 chemical components were identified from the ACB, of which 10 active constituents can cross the blood-brain barrier, including steroids and terpenoids. Bioinformatics analysis suggests that HDCA may be one of the key active components responsible for ACB anti-epileptic effects and ferroptosis may represent a crucial underlying therapeutic mechanism. Studies in animals have demonstrated that treatment with ACB and HDCA reduced the frequency and severity of seizures in epileptic rats, mitigated hippocampal neuronal damage, improved post-epileptic cognitive learning capacity, alleviated neuroinflammatory injury and decreased markers of ferroptosis. This neuroprotective effect likely occurs through activation of the p53/Nrf2/GPX4 signaling pathway. Further in vitro cell experiments demonstrated that HDCA can inhibit the generation of action potentials in primary hippocampal neurons, protects HT22 neurons from glutamate-induced cell death, an effect that is reduced by Nrf2 inhibitors. These findings corroborate earlier bioinformatics analyses, confirming that the neuroprotective effects of HDCA are closely linked to Nrf2-mediated ferroptosis pathways. Conclusion HDCA is a key component of ACB anti-epileptic effects, potentially inhibiting ferroptosis through the p53/Nrf2/GPX4 pathway to reduce epilepsy.
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PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
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2026
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IF 8
Zhan Wang,Cheng Zheng,Wenzhen Li,Kaung Myat Kyaw,Yunmin Zhu,Yihan Lin,Zhen Lin,Di Wu,Zhiqi Hu,Yang Sun,Kaitao Li
Introduction Androgenetic alopecia (AGA), the most common form of hair loss, lacks ideal therapies due to the limitations of current drugs. Natural compounds with low toxicity and good biocompatibility present promising alternatives. Ginkgolide B (GB), a bioactive component of Ginkgo biloba , possesses multiple biological activities, yet its efficacy and mechanism against AGA remain unexplored. Objectives This study aimed to investigate the hair growth-promoting effect of GB in a dihydrotestosterone (DHT)-induced hair loss model and to elucidate the underlying molecular mechanism. Additionally, a novel detachable microneedle delivery system was developed and evaluated to overcome GB's poor transdermal permeability, thereby enhancing its therapeutic efficacy. Methods The AGA microenvironment was first simulated using DHT-stimulated human dermal papilla cells (HDPCs) in vitro. The molecular mechanism by which GB improves the secretory function of HDPCs was investigated through network pharmacology, western blot, transmission electron microscopy, and immunofluorescence. Subsequently, a detachable microneedle system was designed, in which GB was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres and integrated with the sulfobutylether-β-cyclodextrin (SCD)-based matrix (GB@MS-MN). The therapeutic efficacy of this system was evaluated in a DHT-induced hair loss model. Results GB rescued DHT-induced dysfunction in HDPCs, reversing the aberrant secretion of hepatocyte growth factor (HGF) and dickkopf-1 (DKK1). Mechanistically, GB alleviated DHT-induced endoplasmic reticulum stress (ERS) in HDPCs by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. And GB promoted hair growth in DHT-induced hair loss mice. The GB@MS-MN system demonstrated excellent mechanical properties and targeted follicular delivery and showed superior hair growth promotion compared to free GB and minoxidil. It effectively suppressed follicular ERS, with no observed systemic toxicity. Conclusion In summary, this study confirms that GB protects HDPCs function by suppressing DHT-induced ERS through activation of the Nrf2/HO-1 pathway. Furthermore, a detachable microneedle delivery system based on a PLGA-SCD composite effectively overcomes the transdermal barrier of GB and demonstrates superior hair-promoting efficacy.
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高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2026
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IF 4
Haixia Han,Juanjuan Gao,Quan Sun,Dandan Tong,Jian Liu,Xiuli Yang,Jingjing Sun,Yue Cui,Juan Wang,Zuoshan Feng,Mingxi Jia
BACKGROUND Acrylamide (ACR), an environmental neurotoxicant prevalent in thermally processed foods, contributes to brain injury via oxidative stress and neuroinflammation. The cumulative effects of long-term low-dose exposure are particularly alarming. As a traditional food ingredient, the inflorescence of Coreopsis tinctoria Nutt. is rich in polyphenolic compounds that exhibit significant anti-inflammatory and antioxidant properties. This study systematically evaluated the neuroprotective potential of Coreopsis tinctoria Nutt. polyphenols (CTNP) against chronic low-dose ACR exposure in mice. RESULTS Behavioral analyses demonstrated that CTNP (0.25–1.00 g kg −1 ) significantly ameliorated ACR-induced gait abnormalities and restored voluntary activity. CTNP mitigated neuronal misalignment and loss of synaptic density in the hippocampal CA1/CA3 regions and markedly reduced serum levels of brain injury markers MBP and GFAP by 30.6% and 41.7%, respectively. Mechanistic investigations revealed that CTNP attenuated oxidative damage via activation of the Nrf2/HO-1 pathway, leading to decreased brain reactive oxygen species and malondialdehyde levels while enhancing catalase, superoxide dismutase and glutathione peroxidase activities. Furthermore, CTNP suppressed MAPK pathway-mediated neuroinflammation, reducing pro-inflammatory factors such as COX-2, TNF- α and IL-1 β . CONCLUSION These findings demonstrate that CTNP, as diet-derived bioactives, mitigate ACR neurotoxicity through coordinated modulation of Nrf2/HO-1 antioxidant and MAPK anti-inflammatory pathways, supporting their potential as a functional food component for preventing environmental toxicant-associated neural damage. © 2026 Society of Chemical Industry.
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高影响因子
PHYTOMEDICINE
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2026
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IF 11.3
Chunge Zhang,Shuai Huang,Wenxin Zhang,Hongbo Teng,Yuna Shao,Yihua Zhang,Shihang Ren,Qi Wu,Yan Zhao,Zhaowei Yan
Background Acanthopanax sessiliflorus ( A. sessiliflorus ) extract has been used in various traditional Chinese medicines and compound preparations for the treatment of arrhythmia. Our preliminary studies have demonstrated that A. sessiliflorus extract exerts significant protective effects against arrhythmia induced by barium chloride. The present study aims to elucidate the bioactive components of A. sessiliflorus and to investigate the underlying mechanisms by which it mitigates barium chloride-induced arrhythmia. Methods Network pharmacology was employed to predict the pharmacological profiles of chemical constituents from A. sessiliflorus, followed by a systematic screening of their biological activities. Subsequently, a barium chloride-induced arrhythmia model was established, and the potential therapeutic mechanisms were analyzed using transcriptomics. Functional and histopathological analyses of the rat hearts were performed. Western blot was used to detect the expression levels of the Nrf2/HO-1 axis, connexins, ion channels, and autophagy-related proteins in myocardial tissue and NRVMs. Subsequently, PCR, immunofluorescence, co-immunoprecipitation, and molecular docking were employed to verify the involvement of the targets in the intervention of arrhythmia. Results The results showed that after treatment with divaroside, the arrhythmia and redox system imbalance induced by BaCl₂ in rats were significantly restored. Divaroside can inhibit calcium overload by regulating the expression levels of RyR2 and SERCA2a in the sarcoplasmic reticulum, serving as a means to alleviate arrhythmia. In addition, we have confirmed that autophagy plays a crucial role in arrhythmia, and divaroside can activate autophagy, thereby protecting cardiomyocytes from BaCl₂-induced damage. Finally, it was confirmed that divaroside can weaken the interaction between the Keap1-Nrf2 complex and promote the nuclear translocation of Nrf2, activating the Nrf2/HO-1 axis and regulating the aforementioned pathways to counteract arrhythmia. Conclusion This study suggests that divaroside prevents the occurrence of arrhythmia by activating autophagy and reducing abnormal calcium ion homeostasis through the Nrf2/HO-1 axis.
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高影响因子
BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Yu-jia Huo,Miao Wei,Xiao Fan,Li-wen Peng,Jing-chang Yuan,Si-si Tan,Xiao-chen Wang,Ruo-tong Ou-yang,Yi-jing Zhou,Yan-yu Pu,Xi Gao,Jun-qin Lei,Hong Li
Glaucoma is a prominent global cause of irreversible vision loss, fundamentally driven by the continuous degeneration and ultimate death of retinal ganglion cells (RGCs), in which persistent oxidative stress plays a pivotal role. While selenium (Se) offers robust endogenous antioxidant defense, the severe toxicity and narrow therapeutic window of inorganic selenium strictly limit its application. To overcome this critical bottleneck, chitosan-functionalized selenium nanoparticles (CS-SeNPs) are engineered. This strategic nanomodification effectively shields the inherent toxicity of free selenium while conferring improved colloidal stability and biocompatibility. Clinically, systemic Se levels in patients with primary open-angle glaucoma (POAG) are found to be significantly diminished compared to healthy controls. Mechanistically, transcriptome sequencing reveals that CS-SeNPs function through the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway to upregulate the downstream nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) antioxidant axis, reducing intracellular oxidative stress and apoptosis. In vivo, an intravitreal administration strategy for CS-SeNPs is established. In a rat model of acute ocular hypertension (AOH), this targeted local delivery reduces oxidative damage, preserves retinal hierarchical architecture, and restores visual electrophysiological function. These findings identify systemic Se deficiency as a clinical hallmark of POAG and demonstrate that intravitreal CS-SeNPs offer a promising, intraocular pressure-independent nanotherapeutic strategy for glaucomatous neuroprotection.
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高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2026
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IF 4.7
Liu Xiang,Sun Jing-Jing,Mao Chang-Kun,Cao Yong-Sheng,Deng Qi-Fei,Li Guang-Yuan
Cryptorchidism, characterized by the failure of one or both testes to descend into the scrotum, is the most prevalent urogenital malformation in male infants and an important risk element of male infertility and testicular cancer. The purpose of this study was to investigate the molecular mechanisms underlying cryptorchidism-induced testicular damage, with a focus on the role of USP35. Here we established a unilateral experimental cryptorchidism model of Sprague-Dawley rats by resetting the left testis to the abdominal cavity and suturing the inguinal canal, thus preventing its natural descent. The findings indicated that apoptosis and oxidative stress (OS) levels were increased in the undescended testis (UDT) compared to the descended testis (DT) group. Subsequent mRNA sequencing of DT and UDT tissues revealed that ubiquitin specific peptidase 35 (USP35) expression was downregulated in the UDT, implying that USP35 may be an important factor in the pathogenesis of cryptorchidism. To further investigate, an oxidative damage model was constructed using H 2 O 2 -treated GC-1 spermatogonia. USP35 expression was reduced in H 2 O 2 -exposed cells, while overexpression of USP35 attenuated H 2 O 2 -induced oxidative damage by inhibiting apoptosis and OS. Mechanistically, USP35 interacted with nuclear factor erythroid 2-related factor 2 (NRF2) and stabilized its protein expression via deubiquitination. Impairment of NRF2 function abolished the protective effect of USP35 against oxidative damage in H 2 O 2 -treated GC-1 spermatogonia. Overall, these results highlight the significance of the USP35-NRF2 axis in protecting spermatogonia from oxidative injury, suggesting that USP35 may be a potential therapeutic target against cryptorchidism-induced early germ cell damage.
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