International Journal of Biological Sciences
·
2026
·Vol. 22
·期 12
·6363
·
IF 11.7
Ziyang Ding,Sisi Wang,Junhui Chen,Yali Song,Zhou Zhu,Haibo Tong,Ashok Iyaswamy,Peng Chen,Xu Wei,Wei Zhang,Jigang Wang,Chuanbin Yang,Yulin Feng
Oridonin is a bioactive diterpenoid derived from the widely used traditional Chinese medicinal herb Rabdosia rubescens , exhibits broad-spectrum anti-cancer activity, with several derivatives currently in clinical trials. However, the molecular mechanism underlying its anticancer effects, especially its direct target proteins, remain to be fully elucidated. Here, we found that Oridonin promoted intracellular reactive oxygen species (ROS) accumulation, which in turn induced endoplasmic reticulum (ER) stress-mediated apoptosis. Moreover, ER stress was instrumental in inducing autophagy after Oridonin treatment, while blockade of autophagy further exacerbated Oridonin-induced cytotoxicity. Notably, using activity-based protein profiling (ABPP), we identified the anti-oxidant enzyme Peroxiredoxin 1 (PRDX1) as a key direct covalent target of Oridonin. By binding to Cysteine 173 of PRDX1, Oridonin increased intracellular ROS levels. Furthermore, PRDX1 over-expression mitigated, whereas PRDX1 knockdown potentiated, Oridonin-induced ROS accumulation, autophagy, and subsequently apoptosis. Overall, our results indicate that PRDX1 is a direct covalent binding target mediating Oridonin-induced apoptosis. These findings not only provide fresh insights into the core mechanism of Oridonin-induced cytotoxicity, but also highlight PRDX1 as a potential therapeutic target for renal cancer drug development.
✓ 已验证
DOI
PubMed
高影响因子
CELL DEATH AND DIFFERENTIATION
·
2026
·
IF 13.6
Sun Ya-Zhou,Li Xin-Yan,Wang Jia,Zeng Meng-Liu,Qu Wei-Yi,Cheng Xu,Luo Lei,Wang Wei,Yang Juan,Zhang Jun,Tian Han,Zhang Peng,She Zhi-Gang,Li Hongliang,Zhang Xiao-Jing
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions lacking specific pharmacological treatments. Endoplasmic reticulum (ER) stress plays a pivotal role in their pathophysiology, yet the precise regulatory mechanisms remain elusive. In this study, we identify the E3 ubiquitin ligase ring finger protein 5 (RNF5) as a critical driver of ALI/ARDS. RNF5 is markedly upregulated in response to ALI and significantly exacerbates lung injury by stabilizing HSPA5 (heat shock protein family A member 5), a master regulator of the unfolded protein response (UPR). Notably, in vivo Rnf5 ablation effectively attenuated pulmonary edema, inflammatory cell infiltration, and apoptosis, whereas lung-specific Rnf5 overexpression worsened inflammation and cell death in mice. Mechanistically, RNF5 interacts with HSPA5 and competitively blocks its binding to PERK, facilitating PERK release. Furthermore, RNF5 promotes the retro-translocation of HSPA5 from the ER lumen to the cytosol. In the cytosol, RNF5 mediates the K6- and K63-linked polyubiquitination of HSPA5, enhancing its thermal stability and preventing its re-entry into the ER. This spatial sequestration sustains the persistent dissociation of the PERK-HSPA5 complex, leading to the hyperactivation of the pro-apoptotic and pro-inflammatory PERK-eIF2α-CHOP signaling cascade. The ability of RNF5 to promote ALI is strictly dependent on its E3 ligase activity. In conclusion, our findings uncover a compartment-specific regulatory mechanism of HSPA5, suggesting that the RNF5-HSPA5-PERK axis represents a promising therapeutic target for ALI/ARDS.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Quanwei Li,Pan Guo,Shaofeng Wang,Luna Su,Wenlan Yu,Jianying Guo,Liammei Hu,Hui Zhang,Jiaqiang Pan,Zhaoxin Tang,Jianzhao Liao
As an efficient alternative copper (Cu) source, copper nanoparticles (nano-Cu) have been widely supplemented into animal-producing food. Therefore, it is necessary to assess the effect of nano-Cu exposure on the biological health risk. Recently, the toxic effects of nano-Cu have been confirmed but the underlying mechanism remains unclear. This study reveals the impact of nano-Cu on endoplasmic reticulum autophagy (ER-phagy) in chicken hepatocytes and further identifies Drp1 and its downstream gene FAM134B as crucial regulators of nano-Cu-induced hepatotoxicity. Nano-Cu exposure can induce Cu ion overaccumulation and pathological injury in the liver, trigger excessive mitochondrial fission and mitochondria-associated membrane (MAM) integrity damage, and activate ER-phagy in vivo and in vitro. Interestingly, the knockdown of Drp1 markedly decreases the expression of FAM134B induced by nano-Cu. Furthermore, the expression levels of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I induced by nano-Cu exposure are decreased by inhibiting the expression of Drp1. Simultaneously, the inhibition of FAM134B effectively alleviates nano-Cu-induced ER-phagy by downregulating the expression of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I. Overall, these results suggest that Drp1-mediated impairment of MAM integrity leads to ER-phagy as a novel molecular mechanism involved in the regulation of nano-Cu-induced hepatotoxicity. These findings provide new ideas for future research on the mechanism of nano-Cu-induced hepatotoxicity.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Maohui Liu,Jiawei Chen,Zubing Zhou,Jiexin Wang,Guangsen Li,Jinghui Xie,Lingmiao Wen,Huan Wang,Rong Gan,Peihai Zhang,Yanju Gong,Weijun Ding
Ethnopharmacological Relevance Er-Chen Decoction (ECD), a classic traditional Chinese medicine (TCM) formula, is clinically indicated for dispelling dampness and resolving phlegm. It has been widely used in the management of phlegm‒dampness syndrome, including obesity, with a long-standing clinical application history in improving obesity-related male infertility. Although its therapeutic efficacy has been validated through long-term clinical practice, the underlying molecular mechanisms remain incompletely understood. Aim This study aimed to investigate the molecular mechanisms by which ECD ameliorates obesity-related spermatogenic dysfunction (SD) through the SIRT1/p53 signaling axis. Materials and Methods A mouse model of diet-induced obesity was established by feeding a high-fat diet (HFD) for 8 weeks. Subsequently, obese mice were randomly assigned to receive interventions with ECD (low-, medium-, or high-dose) or L-carnitine (positive control) for 3 weeks. Sperm functional parameters were evaluated to assess obesity-related SD. A combination of network pharmacology analysis, molecular docking, biochemical assays, hematoxylin‒eosin (HE) staining, Oil Red O staining, transmission electron microscopy (TEM), quantitative real-time polymerase chain reaction (RT‒qPCR), immunofluorescence (IF) staining, immunohistochemical (IHC) staining, Western blotting (WB), and transcriptomic analysis was employed to dissect the molecular mechanisms underlying the protective effects of the ECD against obesity-related SD. Additionally, the bioactive components of ECD were characterized using extensive targeted mass spectrometry. Results Medium-dose ECD (ECD-M) significantly reduced body weight and lipid accumulation in HFD-induced obese mice. Notably, compared with the HFD group, the ECD-M group presented a 50% reduction in the abnormal sperm percentage (p < 0.01), along with a 60% increase in sperm concentration (p < 0.01), and showed an upward trend in both sperm progressive motility and sperm motility. Furthermore, ECD-M significantly upregulated the expression of the tight junction (TJ) proteins Occludin (p < 0.001) and β-catenin (p < 0.05), thereby restoring the integrity of the blood‒testis barrier (BTB). Mechanistically, ECD not only reversed lipid-induced inhibition of SIRT1 but also suppressed p53 acetylation, leading to a significant decrease in the ratios of cleaved caspase-3/caspase-3 (p < 0.05) and Bax/Bcl-2 (p < 0.0001) in testicular tissues. These effects collectively alleviated mitochondria-mediated apoptosis in the testes of obese mice. Conclusion ECD alleviates mitochondria-mediated apoptosis in testicular tissues by regulating the SIRT1/p53 axis, thereby mitigating obesity-related SD. These findings highlight ECD as a potential therapeutic agent for the management of obesity-related male infertility.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Haoqun Zeng,Xi Chen,Jianyu Ling,Hongpeng Zhang,Yu Tong,Kewei Zhang,Mingzhe Zhang
The enhancement of the spin–orbit torque (SOT) effect through the integration of intrinsic inverse spin galvanic effect spin–orbit torque and spin Hall effect spin–orbit torque is fundamentally dependent on the structural and material properties of the ferromagnets. Consequently, the synthesis of ferromagnets with superior structural integrity and material characteristics is of paramount importance. In this study, a gas–liquid chemical reaction, in conjunction with ultrasonic crushing, was employed to synthesize few-layer MoS2:Er nanosheets. X-ray diffraction, X-ray photoelectron spectroscopy, and energy-dispersive spectroscopy analyses confirm the successful substitution of Mo4+ by Er3+ through doping within the MoS2 lattice. Vibrating sample magnetometry and MT measurements indicate that MoS2:Er exhibits room-temperature ferromagnetism (RTFM), with the underlying mechanism elucidated through first-principles calculations. Furthermore, the unique electron density of states at the Fermi level suggests the presence of ferromagnetism in MoS2:Er. A wedge-shaped Pt/MoS2:Er/Au structure was fabricated and subsequently evaluated for current-induced SOT switching, as well as for its memcapacitor and memristor characteristics. The precession of a magnetic moment in three-dimensional space was successfully simulated by solving the Landau–Lifshitz–Gilbert–Slonczewski equation using the Mumax.
研究领域:
自旋电子学
·
纳米材料
·
凝聚态物理
·
材料科学
·
忆阻器件
·
铁磁半导体
✓ 已验证
DOI
高影响因子
Biology Direct
·
2026
·
IF 5.5
Du Shengwei,Zheng Peisen,Li Wen,Chen Guorong,Chen Hanbin
Hepatocellular carcinoma (HCC) remains a highly aggressive malignancy with a dismal prognosis, largely due to the limited effectiveness of current therapeutic interventions. Although Motesanib (MOT) is a clinically studied VEGFR-centered inhibitor, VEGFR-targeted strategies remain limited by innate or acquired resistance. In this study, we explored a novel pharmacological strategy combining MOT with Auranofin (AF) to enhance therapeutic outcomes in HCC. Our data demonstrate that this dual-targeting approach yields robust synergistic anticancer activity across diverse experimental models. Mechanistically, we discovered that TrxR1 inhibition is critical for this sensitization, which is closely associated with autophagy-related reactive oxygen species (ROS) accumulation. Specifically, genetic depletion of Atg5 effectively suppressed ROS accumulation and attenuated cytotoxicity, suggesting that autophagy contributes to the synergistic oxidative damage. This orchestrated stress response subsequently led to sustained endoplasmic reticulum (ER) stress and JNK pathway activation, culminating in DNA damage, impaired proliferation, and reduced cell viability. Taken together, our results identify the combination of MOT and AF as a promising and mechanistically grounded treatment regimen for advanced HCC (Graphical ). Graphical
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Applied Ceramic Technology
·
2025
·
IF 2.3
Zhenlin Wang,Anze Shui,Hulei Yu,Mei Cai
Photocatalysis presents a promising solution for environmental remediation, though conventional photocatalysts remain constrained to the ultraviolet and partially visible regions of the solar spectrum. To address this limitation, we developed a NaYF 4 :Yb,Er/BiOBr (N/B) composite photocatalyst, leveraging upconversion luminescence to convert near-infrared photons into visible light while utilizing BiOBr's narrow bandgap for enhanced visible-light absorption. The composite photocatalyst was fabricated via a two-step solvothermal approach and evaluated for the degradation of methyl orange (MO). Remarkably, the N/B-120°C sample demonstrated superior photocatalytic activity, achieving degradation rates 2.4- and 5.4-fold higher than those of pristine BiOBr and commercial TiO 2 (P25), respectively. This enhanced performance is attributed to synergistic effects including an increased specific surface area (23.96 m 2 /g for N/B-120°C vs. 16.28 m 2 /g for BiOBr), reduced charge transfer resistance (as evidenced by electrochemical impedance spectroscopy (EIS) Nyquist plots), elevated oxygen vacancy concentration (as verified by x-ray photoelectron spectroscopy [XPS]), and extended solar spectral utilization range (400–980 nm). This work presents a viable strategy to improve the efficiency of photocatalysis.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xinmei Wang,Shanshan Li,Jiayu Yu,Wenlin Wang,Zhuoqi Du,Shuchun Gao,Yin Ma,Ruixin Tang,Ting Liu,Shiping Ma,Qiang Fu,Xueyang Deng
s Ethnopharmacological relevance Saikosaponins B2 (SSB2) is one of the main active components isolated from Radix Bupleuri (Bupleurum chinense DC.), a herb widely used of traditional Chinese medicine. It has been used for the treatment of depression for more than two thousand years. However, the molecular mechanisms remain to be determined. Aim of the study In this study, we evaluated the anti-inflammatory effect and elucidated underlying molecular mechanisms of SSB2 in LPS-induced primary microglia and CUMS-induced mice model of depression. Method The effects of SSB2 treatment were investigated both in vitro and in vivo. The chronic unpredictable mild stimulation (CUMS) procedure was applied to establish the animal model of depression. Behavioural tests were used to evaluate the depressive-like behaviors in CUMS-exposed mice, including sucrose preference test, open field test, tail suspension test, and forced swimming test. The GPX4 gene of microglia was silenced using shRNA, and inflammatory cytokines were determined by Western Blot and immunofluorescence analysis. Endoplasmic reticulum stress and ferroptosis-related markers were detected by qPCR, flow cytometry and confocal microscopy. Result SSB2 reversed depressive-like behaviours in CUMS-exposed mice and relieved central neuroinflammation and ameliorated hippocampal neural damage. SSB2 alleviated LPS-induced activation of microglia through the TLR4/NF-κB pathway. LPS-induced ferroptosis, with increased levels of ROS, intracellular Fe 2+ , mitochondrial membrane potential, lipid peroxidation, GSH, SLC7A11, FTH, GPX4 and Nrf2, and decreased transcription levels of ACSL4 and TFR1, was attenuated with SSB2 treatment in primary microglia cells. GPX4 knockdown activated ferroptosis, induced endoplasmic reticulum (ER) stress, and abrogated the protective effects of SSB2. Further, SSB2 attenuated ER stress, balanced calcium homeostasis, reduced lipid peroxidation and intracellular Fe 2+ content by regulating the level of intracellular Ca 2+ . Conclusions Our study suggested that SSB2 treatment can inhibit ferroptosis, maintain calcium homeostasis, relieve endoplasmic reticulum stress and attenuate central neuroinflammation. SSB2 exhibited anti-ferroptosis and anti-neuroinflammatory effects through the TLR4/NF-κB pathway in a GPX4-dependent manner.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLUSTER SCIENCE
·
2020
·Vol. 32
·期 6
·1683-1691
·
IF 1.731
Liang Xuhua,Fan Jun,Zhao Yanyan,Jin Ruyi
A core–shell-structured composite by combining mesoporous silica with upconversion luminescence (UCL) property had considerable application potentials in the fields of drug delivery, disease diagnosis, and therapy. In this paper, a monodisperse, core–shell-structured NaYF 4 :Yb,Er@ n SiO 2 @ m SiO 2 nanoparticle (UCNP@MSNs-FA) with excellent UCL property was successfully fabricated by a facile two-step sol–gel strategy and by modifying the surface with folic acid (FA) to strengthen its tumor-targeting performance. The properties of the composite were studied extensively, which indicated that UCNP@MSNs-FA possessed good dispersion, typical core–shell-structured with high specific surface area (132.775 m 2 /g), and excellent UCL property that improve cell imaging and drug delivery. The viability of L929 cells and hemolysis assay demonstrated the good biocompatibility of the composite. By using doxorubicin hydrochloride (DOX) as a model drug, the drug loading content and encapsulation efficiency of UCNP@MSNs-FA could reach as high as 11.2% and 37.3%, respectively, which proved the effectiveness to load anticancer drugs. In addition, the DOX-UCNP@MSNs-FA system exhibited sustained drug release and strong pH-dependent performance, in which the drug release would be accelerated at the slightly acidic microenvironment in the tumor. Moreover, experimental results indicated that DOX-UCNP@MSNs-FA exhibited specific cytotoxicity to KB cells but weakened toxicity to FR-negative cells. Therefore, the as-prepared UCNP@MSNs-FA could be used potential for simultaneous targeted anti-cancer drug delivery and cell imaging and enhance the therapeutic efficacy against FR-positive tumor cells.
✓ 已验证
产品关联
DOI
高影响因子
Nutrition & Metabolism
·
2020
·Vol. 17
·期 1
·1-14
·
IF 3.211
Zeng Xin,Zhu Min,Liu Xiaohong,Chen Xuanmin,Yuan Yujia,Li Lan,Liu Jingping,Lu Yanrong,Cheng Jingqiu,Chen Younan
Background Pyroptosis is a novel programmed cell death. It is identified as caspase-1 dependent and characterized by plasma-membrane rupture and release of proinflammatory intracellular contents inculuding IL-1 beta and IL-18. Pyroptosis is distinct from other forms of cell death, especially apoptosis that is characterized by nuclear and cytoplasmic condensation and is elicited via activation of a caspase cascade. In pyroptosis, gasdermin D (GSDMD) acts as a major executor, while NLRP3 related inflammasome is closely linked to caspase-1 activation. Given that pyroptosis has played a critical role in the progression of non-alcoholic steatohepatitis (NASH), here, we investigated whether the regulation of pyroptosis activation is responsible for the protective role of monounsaturated oleic acids in the context of hepatocellular lipotoxicity.Methods Human hepatoma cell line HepG2 cells were exposed to palmitic acid (PA) with or without oleic acids (OA) or/and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA) for 24 h. Besides, the cells were treated with the chemical ER stressor tunicamycin (TM) with or without OA for 24 h as well. The expressions of pyroptosis and ER stress related genes or proteins were determined by real-time PCR, Western blot or immunofluorescence. The morphology of pyroptosis was detected by acridine orange and ethidium bromide (AO/EB) staining. The release of IL-1 beta and tumor necrosis factor alpha (TNF-α) was determined by ELISA. Sprague–Dawley (SD) rats were fed with high fat diet (HFD) for 16 w, then, HFD was half replaced by olive oil to observe the protective effects of olive oil. The blood chemistry were analyzed, and the liver histology and the expressions of related genes and proteins were determined in the liver tissues.Results We demonstrated that PA impaired the cell viability and disturbed the lipid metabolism of HepG2 cells (P < 0.01), but OA robustly rescued cells from cell death (P < 0.001). More importantly, we found that instead of cell apoptosis, PA induced significant pyroptosis, evidenced by remarkably increased mRNA and protein expressions of inflammasome marker NLRP3, Caspase-1 and IL-1beta, as well as cell membrane perforation driving protein GSDMD (P < 0.05). Furthermore, we demonstrated that the PA stimulated ER stress was causally related to pyroptosis. The enhanced expressions of ER stress markers CHOP and BIP were found subcellular co-located to pyroptosis markers NLRP3 and ASC. Additionally,TM was able to induce pyroptosis like PA did, and ER stress inhibitor TUDCA was able to inhibit both PA and TM induced ER stress as well as pyroptosis. Furthermore, we demonstrated that OA substantially alleviated either PA or TM induced ER stress and pyroptosis in HepG2 cells (P < 0.01). In vivo, only olive oil supplementation did not cause significant toxicity, while HFD for 32 w obviously induced liver steatosis and inflammation in SD rats (P < 0.05). Half replacement of HFD with olive oil (a mixed diet) has remarkably ameliorated liver abnormalities, and particularly inhibited the protein expressions of either ER stress and pyroptosis markers (P < 0.05).Conclusion Palmitic acid induced predominant pyroptosis in HepG2 cells, and ER stress may be responsible for the induction of pyroptosis and subsequent cell death. Monounsaturated oleic acids were able to ameliorate hepatocellular lipotoxicity both in vitro and in vivo, and OA mediated inhibition of ER stress and pyroptosis may be the underlying mechanisms.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2019
·
IF 3.743
Xiaohong Xu,Vinothakumar Rajamanicham,Sujing Xu,Zhoudi Liu,Tao Yan,Guang Liang,Guilong Guo,Huiping Zhou,Yi Wang
Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking prognostic and effective therapeutic targets currently. In this study, we evaluated the toxic potential of schisandrin A (SchA), a bioactive phytochemical found in Schisandra chinensis in TNBC. The anti-cancer effect and underlying mechanism of SchA on MDA-MB-231 and BT-549 cells were determined in vitro and in xenograft mouse model. Our data show that SchA markedly inhibited the growth of TNBC cells via induction of cell cycle arrest and cell apoptosis. Moreover, over activation of Wnt signaling was observed in TNBC cells, which was significantly suppressed by the treatment of SchA. Also, SchA treatment activated ER stress in TNBC cells. Finally, we verified these inhibitory effects of SchA in the MDA-MB-231 xenograft mouse model. In conclusion, SchA effectively inhibited TNBC in preclinical models by inducing cell cycle arrest and apoptosis via regulating Wnt/ER stress signaling pathway. All of these data indicate that SchA could be a potential candidate for the treatment of TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2014
·Vol. 43
·期 26
·10202-10207
·
IF 4.097
Min Pang,Xuesong Zhai,Jing Feng,Shuyan Song,Ruiping Deng,Zhuo Wang,Shuang Yao,Xin Ge,Hongjie Zhang
Water-soluble hexagonal NaScF4:Yb/Er nanocrystals have been directly synthesized via a facile one-step hydrothermal route. The as-prepared nanocrystals were monodisperse and could form stable colloidal solutions in polar solvents, such as water and ethanol. The novel NaScF4:Yb/Er nanocrystals exhibited intrinsic intense red upconversion emission, in contrast to other lanthanide-doped fluoride nanocrystals. Remarkably, the upconversion emission intensity was enhanced ∼6.8 times through the coating of an active-shell (containing Yb3+) surrounding the NaScF4:Yb/Er core nanocrystals, owing to surface passivation effect and efficient energy transfer from Yb3+ ions in both the core and the shell to Er3+ ions. These water-soluble hexagonal NaScF4:Yb/Er nanocrystals with intense red emission are ideal for a variety of in vitro and in vivo biological imaging applications.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）