INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 16
·7475
·
IF 5.6
Galong Li,Dongyan Li,Bin Lan,Yuanyuan Cheng,Hongxia Liang,Wenli Zhang,Xiaopan Xu,Hongbing Lu
Drug-mediated intravesical therapy is a widely used treatment approach for bladder cancer (BCa), which is limited by poor tumor accumulation and the toxicity of drugs. Herein, a facile approach utilizing magnetic hyperthermia therapy (MHT) for BCa treatment is reported through intravesical instillation of tumor-targeting iron oxide nanoparticles (IONPs), which are coated with anti-FGFR3 antibodies for specific binding to FGFR3 overexpressed on BCa cells. The antibody coating significantly enhanced targeting ability and increased cancer cell uptake. Under an alternating magnetic field (AMF), the IONPs magnetothermally activated TRPV1 on the endoplasmic reticulum (ER) of BCa and induced Ca2+overload in RT4 BCa cells. The magnetothermal treatment significantly upregulated the pro-apoptotic gene expression of Bax, Pro-caspase-3, and Cytc in RT4 cells, and downregulated the anti-apoptotic effector gene Bcl-2, ultimately causing augmented apoptosis in cancer cells. The application of intravesical FGFR3-targeting MHT successfully resulted in greater suppression of tumor growth and improved survival rate of mice, compared to the control, IONP, and AMF-treated groups. These results hold significant potential as a transformative modality toward BCa therapeutic application.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2026
·Vol. 53
·期 9
·e70153
·
IF 2.5
Renchuang Cao,Qingying Meng,Gengyuan Li,Shumei Yuan,Chunmei Li,Xin Zhao,Dongmei Zhang
Heat shock factor 2 (HSF2) and hypoxia‐inducible factor 1α are activated by angiotensin II (ANGII) in cardiomyocytes. The endoplasmic reticulum (ER) stress plays a critical role in cardiac hypertrophy. Moreover, HIF‐1α is known to be regulated by HSF2 in tumour cells. In this study, we hypothesised and clarified whether HSF2 trans‐activated HIF‐1α through initiation of ER stress in hypertrophic cardiomyocytes. Myocardial hypertrophy was induced by the treatment of ANGII. Expression of the gene or protein was assessed by applying RT‐PCR, WB, ICC and IHC. Luciferase and CHIP were applied to detect the transcription of HIF‐1α by HSF2. Both in vitro and in vivo, the expression of HIF‐1α, ER stress markers and HSF2 was increased in ANGII‐treated hypertrophic cardiomyocytes. Blocking ER stress suppressed the expression of HSF2 and HIF‐1α in ANGII‐treated cardiomyocytes. Silencing HSF2 inhibited HIF‐1α, thereby reducing hypertrophy but had no effect on ER stress. Similarly, silencing HIF‐1α reduced hypertrophy without affecting ER stress or HSF2 expression. HSF2 transcriptionally activated HIF‐1α. We concluded that ER stress induced by ANGII activates HSF2, which then trans‐activates HIF‐1α, promoting cardiac hypertrophy.
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Advanced Healthcare Materials
·
2026
·
IF 11
He-Ping Zuo,Jia Yang,Wei Zhao,Min Yang
Sepsis-associated intestinal injury represents a critical pathological event contributing to multiple organ dysfunction, with its pathogenesis closely linked to excessive oxidative stress and hyperactivated endoplasmic reticulum stress. Current clinical interventions lack the capacity for precise modulation of the intestinal microenvironment, while existing nanozyme systems generally face challenges such as low oral delivery efficiency, insufficient stability, and uncertain biosafety. To address these limitations, we developed a novel oral nanozyme delivery system based on 2D V 2 C MXene. Through surface modification with hydroxyethyl cellulose (HEC), we constructed a V 2 C@HEC (CV) nanozyme with enhanced physiological stability and intestinal mucoadhesion. In both in vitro and in vivo studies, the CV nanozyme demonstrated significant reactive oxygen species (ROS)-scavenging capacity. Oral administration of CV effectively mitigated intestinal barrier damage and improved survival in a septic mouse model. Mechanistic investigations suggested that the protective effects of CV may be associated with ROS clearance and modulation of endoplasmic reticulum stress, with inhibition of the ATF6/CHOP signaling pathway potentially serving as one underlying mechanism for its cytoprotective function. In summary, this study not only presents a novel nanozyme material with favorable biocompatibility, excellent stability, and a defined antioxidant mechanism, but also provides an innovative materials-based strategy for the treatment of sepsis.
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MATERIALS RESEARCH BULLETIN
·
2026
·
IF 5.8
Zhiqi Yao,Kejie Li,Jiaqi Zhao,Haicheng Xia,Zuoling Fu,Sung Heum Park
A RE-doped Bi 4 Ti 3 O 12 perovskite-based luminescence material is developed. • Dual NIR-II emissions of Ho 3+ /Er 3+ are achieved under 980 nm excitation. • High performance (Sr=1.3% K-1) phonon-assisted ratiometric thermometer is constructed. High-performance optical thermometers operating in the second near-infrared (NIR-II) window hold great promise for biomedical applications due to their tissue penetration depth and minimal autofluorescence. However, developing reliable NIR-II thermometers with high sensitivity and robust performance across a wide temperature range remains a challenge. Herein, the luminescence properties and NIR-II ratiometric thermometric performance of Er 3+ , Ho 3+ , Yb 3+ co-doped Bi 4 Ti 3 O 12 (BTO) perovskite oxide were investigated. Upon 980 nm excitation, NIR-II emission from Er 3+ at 1560 nm ( 4 I 13/2 → 4 I 15/2 ) and Ho 3+ at 1200 nm ( 5 I 6 → 5 I 8 ) was achieved. A ratiometric thermometer was constructed using the temperature-dependent intensity ratio, I Er /I Ho . Relying on the thermal dependence of this ratio, the BTO system exhibits a relative sensitivity (S r ) of 1.3% at 333 K. Furthermore, the results suggest that phonon characteristics of the BTO host influence energy-transfer processes and NIR-II thermometric performance, highlighting importance of host properties in designing rare-earth-doped NIR-II thermometric materials. Download: Download high-res image (154KB) Download: Download full-size image A high-sensitivity NIR-II ratiometric thermometer is achieved in Bi 4 Ti 3 O 12 : Yb 3+ , Ho 3+ , Er 3+ Perovskites via a unique phonon-assisted energy transfer pathway.
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TALANTA
·
2019
·
IF 4.916
Huihui Wang,Yunyun Lu,Lun Wang,Hongqi Chen
A selective, simple and environment-friendly type fluorescence sensing platform between upconversion nanoparticles (UCNPs) and melanin-like polymer utilizing the photoinduced electron-transfer (PET) mechanism was developed. The effective fluorescence quenching of UCNPs by melanin-like polymers could detect tyramine and tyrosinase (TYR) activity through the bio-catalysed oxidation of tyramine to the melanin-like polymer products. At optimal conditions, the range of linearity in detection was 0.167–33.3 μΜ for tyramine, and the limit of detection of tyramine was 0.026 μΜ. The linear range of TYR was 0.0033–1 U·mL −1 , and the limit of detection of TYR was 0.003 U·mL −1 . Furthermore, the strategy could be applied to real sample analysis with satisfactory results.
研究领域:
生物化学
·
分析化学
·
纳米医学
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Regenerative Therapy
·
2025
·
IF 3.5
Ruixi Luo,Yaqiong Wei,La Wang,Peng Chen,Didong Lou,Weiyi Tian
Introduction Idiopathic pulmonary fibrosis (IPF) is marked by a gradual decline in pulmonary function over time and is associated with a grim prognosis. In the pathogenesis of IPF, persistent endoplasmic reticulum (ER) stress plays a significant role in promoting fibrosis through pathways involving apoptosis. Mesenchymal stem cell-derived exosomes (MSC-Ex) have shown promise in mitigating pulmonary fibrosis by inhibiting apoptosis. Nonetheless, the precise mechanisms underlying this effect remain unclear. In our previous findings, we demonstrated that MSCs alleviate pulmonary fibrosis by regulating ER stress. Building upon this, we sought to investigate whether MSC-Ex could mitigate alveolar epithelial cell apoptosis through the ER stress pathway. We posited that targeting ER stress could represent a crucial mechanism by which MSC-Ex alleviate apoptosis in IPF models. Methods and results In this study, bleomycin (BLM) induced apoptosis in A549 cells, and MSC-Ex treatment reduced apoptotic cells and the Bax/Bcl-2 ratio. ER stress is involved in BLM-induced apoptosis in A549 cells, and MSC-Ex reduced ER stress-related protein (Bip and CHOP) expression and reversed the morphological changes of the ER in A549 cells. Moreover, blockade of ER stress with ER stress inhibitor TUDCA contributed to the amelioration of apoptosis in A549 cells, indicating that MSC-Ex reduced BLM-induced apoptosis at least partly by modulating ER stress. In vivo, MSC-Ex injection decreased BLM-induced pulmonary fibrosis in mice, as well as ER stress and apoptosis in the lung tissues. Conclusions In conclusion, ER stress induced apoptosis in BLM-treated A549 cells, and MSC-Ex treatment mitigated apoptosis via inhibiting ER stress. This study provides a novel mechanism for MSC-Ex-mediated protection on apoptosis in an IPF model and suggests that MSC-Ex could be a promising therapeutic strategy for IPF.
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CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Gan Xin,Xie Jingwen,Dong Zhaojun,Wu Yuna,Zeng Xiaoqing,Yang Zhenzhen,Liu Bo,Zhu Min,Wang Bozhen,Li Wulan,Wang Ledan,Zhang Huajie,Wu Jianzhang,Hu Yue
Background: Pyroptosis, a cell death process triggered by chemotherapy drugs, has
emerged as a highly promising mechanism for combating tumors in recent years. As the lead of
new drugs, natural products play an important role in the discovery of anticancer drugs. Compared
to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior
safety profile. Among a series of MFHNP molecular skeletons, this study found that only
benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity
of 1 remains to be improved.
Aims: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by
modifying the chalcone structure.
Methods: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis,
several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer
activity was tested by MTT assay, and morphological indications of pyroptosis were observed
in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore,
to improve the activity of the chalcone skeleton, the anticancer group 3,4,5-
trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed,
synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally,
a quantitative structure-activity relationship (QSAR) model was established using the
eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore.
Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular
mechanisms of pyroptosis induced by the active compound.
Results: α, β-unsaturated ketone was the functional group of the chalcone skeleton and played a
pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients
(R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these
compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was
found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing
the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft
tumors.
Conclusion: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis
axis and is a kind of promising pyroptosis inducer.
研究领域:
肿瘤学
·
药理学
·
药物化学
·
分子生物学
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Molecular Medicine Reports
·
2021
·Vol. 23
·期 4
·1-1
·
IF 2.952
Guang Chen,Gang Yu,Zheng Yong,Hui Yan,Ruibin Su,Huijun Wang
Drug addiction is a chronic and recurrent disease associated with learning and memory. Shaped by drug use and cues from the environment, drug memory serves a key role in drug‑seeking behaviour. Methamphetamine (MA), a globally abused drug, causes cognitive impairment, and endoplasmic reticulum (ER) stress is one of the mechanisms via which this occurs. In the current study, it was hypothesized that ER stress may serve a role in the disturbance of drug memory. The present study demonstrated that 5 mg/kg MA inhibited conditioned place preference behaviour via ER stress, which caused a disruption in long‑term potentiation in the hippocampus. When mice were pre‑treated with the ER stress inhibitors 4‑phenyl butyric acid or tauroursodeoxycholic acid, drug‑evoked synaptic plasticity was induced. Western blotting results indicated that treatment with 5 mg/kg MA enhanced the expression of cyclin‑dependent kinase‑5 and decreased the expression of Ca2+/calmodulin‑dependent protein kinase II α via ER stress. Collectively, the present results suggested that a large dose of MA inhibited drug‑evoked synaptic plasticity and disrupted drug memory by inducing ER stress.
研究领域:
神经科学
·
药理学
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Oxidative Medicine and Cellular Longevity
·
2021
·
IF 6.543
Peng Li,Changlian Xie,Jiankai Zhong,Zhongzhou Guo,Kai Guo,Qiuyun Tu
Endothelial dysfunction, which is characterized by damage to the endoplasmic reticulum (ER) and mitochondria, is involved in a variety of cardiovascular disorders. Here, we explored whether mitochondrial damage and ER stress are associated with endothelial dysfunction. We also examined whether and how melatonin protects against oxidized low-density lipoprotein- (ox-LDL-) induced damage in endothelial cells. We found that CHOP, GRP78, and PERK expressions, which are indicative of ER stress, increased significantly in response to ox-LDL treatment. ox-LDL also induced mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential, increased mitochondrial ROS levels, and downregulation of mitochondrial protective factors. In addition, ox-LDL inhibited antioxidative processes, as evidenced by decreased antioxidative enzyme activity and reduced Nrf2/HO-1 expression. Melatonin clearly reduced ER stress and promoted mitochondrial function and antioxidative processes in the presence of ox-LDL. Molecular investigation revealed that ox-LDL activated the JNK/Mff signaling pathway, and melatonin blocked this effect. These results demonstrate that ox-LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox-LDL-induced damage.
研究领域:
心血管研究
·
分子生物学
·
药理学
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Materials Research Express
·
2018
·Vol. 5
·期 10
·106203
·
IF 1.151
Tao Pang,Wenbo Peng
Upconversion luminescence of Yb3+/Er3+ and Yb3+/Tm3+ co-doped Y2(MoO4)3 phosphors under 980 nm excitation is investigated. It is demonstrated that Yb3+ co-doping causes a significant thermal effect. For Yb3+ and Er3+ co-doped case, the thermal effect, the long-distance energy migration and the energy transfer from Er3+ to Yb3+ are responsible for the abnormal luminescence quenching. In the case of Yb3+ and Tm3+ co-doped, the thermal effect improves the excited efficiency of Tm3+, and thus the luminescence of Tm3+ continues to strengthen at the Yb3+ concentration that causes Er3+ luminescence quenching. These results contribute to the design of the efficient upconversion materials.
研究领域:
材料科学
·
光学
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JOURNAL OF AUTOIMMUNITY
·
2020
·
IF 6.658
Yingzhen Du,Pingjun Zhu,Xi Wang,Mi Mu,Hongxia Li,Yanhong Gao,Xuebing Qin,Yan Wang,Zhijian Zhang,Geping Qu,Guogang Xu,Christopher Chang,Tianzhi Li,Xiangqun Fang,Senyang Yu
Pirfenidone has been widely used in the treatment of idiopathic pulmonary fibrosis (IPF). However, the role of pirfenidone in LPS-induced acute lung injury (ALI) remains unclear. This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo . Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro . A lower expression level of BAP31, an ER transmembrane protein , was found to be associated with ALI followed LPS challenge. The reintroduction of BAP31 blunted LPS induced ER stress and mitochondrial damage and therefore alleviated ATII cell apoptosis, which correlated with pirfenidone treatment. Knockdown of BAP31 expression in pirfenidone treated ATII cells re-activated ER stress, mitochondrial damage and followed cellular apoptosis. In summary, this study confirms the beneficial effect of pirfenidone on ER stress and mitochondrial dysfunction mediated apoptosis via upregulation of BAP31. Our results demonstrated that pirfenidone may be considered as a potential agent for the treatment of ALI in the future.
研究领域:
药理学
·
肺病学
·
分子生物学
·
细胞生物学
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Journal of Materials Chemistry C
·
2026
·
IF 5.1
Jie Li,Yantao Lou,Ze Wang,V. Balasubramani,Xingchen Zhang,Jiaren Wu,Guodong Lin,Baofeng Zhang,Yuanjie Teng
Surface-enhanced Raman scattering (SERS) enables sensitive molecular detection, yet conventional substrates often exhibit limited stability and poor reproducibility. Semiconductor substrates offer tunable electronic properties and structural robustness, but wide bandgaps and inefficient charge transfer often hinder their performance. Here, we present interface-engineered Er3+-doped ZnSe (Zn1−xErxSe) as a high-performance SERS platform. Controlled Er3+ incorporation, with an optimal doping of 6%, introduces defect states that enhance chemical (charge-transfer) mechanisms while increasing carrier density to strengthen the electromagnetic (plasmonic) response. Using methylene blue as a probe, the substrate achieves a detection limit of 3.24 × 10−8 M with excellent reproducibility. Density functional theory and Mott–Schottky analyses reveal that Er3+ doping reshapes the electronic band structure and enables efficient interfacial plasmon–charge coupling. The substrate also demonstrates potential for environmental sensing, achieving a low detection limit of 5.33 µg mL−1 for PET microplastics, thereby highlighting its suitability for trace-level pollutant monitoring. This work establishes rational interface and carrier engineering in semiconductors as a robust platform for high-performance SERS applications in analytical and environmental chemistry.
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