JOURNAL OF ETHNOPHARMACOLOGY
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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.
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International Journal of Applied Ceramic Technology
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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.
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JOURNAL OF ETHNOPHARMACOLOGY
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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.
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BIOMEDICINE & PHARMACOTHERAPY
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2019
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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.
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JOURNAL OF CLUSTER SCIENCE
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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.
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Nutrition & Metabolism
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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.
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Journal of Physical Chemistry C
·
2017
·
IF 4.536
Yiru Zhu,Shuwen Zhao,Bin Zhou,Hao Zhu,Youfa Wang
In this work, we report a phenomenon that upconversion emission intensity of Er3+ was enhanced by cadmium. Cd2+ was taken with 0, 3, 10, 20, 30, and 40 mol % as a new dopant to codope LiY0.78Yb0.20Er0.02F4, meanwhile the doping effects on the crystal structure, morphology, and upconversion fluorescence emission are investigated by XRD, Rietveld refinement, TEM, and upconversion spectroscopy analysis methods in detail. The green upconversion emission intensity was enhanced, and the maximum emission intensities were enhanced to twice when 10 mol % Cd2+ was codoped into tetragonal LiYF4, while its decay lifetime was reduced. Additionally, we further designed the synthesis of the homogeneous LiYF4:20%Yb,2%Er,10%Cd@LiYF4 of which the emission intensity is 11 times higher than that of the Cd2+-free nanocrystals, meanwhile an intriguing morphology of core–shell nanocrystals was obtained. This investigation may be useful for the design and improvement of upconversion materials for fulfilling the prerequisite of the practical application.
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MATERIALS RESEARCH BULLETIN
·
2016
·
IF 2.435
Chaoqing Yang,Jing Liu,Liyana Ma,Aoju Li,Zhongxin Liu
Graphene oxide/GdF 3 : Yb, Er (GO/GdF 3 ) nanocomposite have been successfully synthesized via a facile low-temperature hydrothermal route, in which fusiform orthorhombic phase GdF 3 : Yb, Er nanocrystals with uniform size could grow in the graphene oxide substrate. During the annealing of GO/GdF 3 nanocomposites, a structure change from GO/GdF 3 nanocomposites to reduced graphene oxide/NaGdF 4 : Yb, Er (rGO/NaGdF 4 ) nanocomposites was discovered by X-ray powder diffraction, Fourier transform infrared spectroscopy, Thermogravimetric analysis and Scanning electron microscope. Under the excitation of 980 nm, the upconversion luminescence of GO/GdF 3 was completely quenched by the energy receptor in GO substrate, however the black rGO/NaGdF 4 showed improved green upconversion luminescence. Based on the analysis of energy transfer in the nanocomposites, the improvement of the upconversion luminescence of the rGO/NaGdF 4 can be attributed to the structure change of nanocomposites.
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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.
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ACS Applied Nano Materials
·
2024
·
IF 5.3
Barbara Ting Wei Ang,Yin Mei Fong,Chew Beng Soh,Szu-Cheng Chien,Hui An,Ryan Hong Soon Tay
Tropical urban greenhouses are prone to heat trapping due to higher daily temperatures compared to temperate climates, and a high energy cost is required to maintain optimal growth conditions. Lanthanide-based nanoparticles are known for their capability of performing upconversion, a process where lower energy photons are absorbed and converted to a single photon of higher energy. These upconversion nanoparticles (UCNPs) possess the innate ability to convert infrared energy to visible light, thereby facilitating efficient heat removal while simultaneously providing upconverted visible light. Consequently, the incorporation of such material into greenhouse façades presents an attractive zero-energy alternative to commonly used greenhouse cooling technologies. In this study, NaYF4:Yb3+/Er3+ UCNPs were synthesized and coated onto a simulated greenhouse enclosure with Pak Choi plants to observe the effect of such a film coating on actual crop growth. A reduction of the interior temperature, increased sunlight diffusion, and improved crop yield were demonstrated in this work, showing promising results for future urban greenhouse façade applications.
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FERROELECTRICS
·
2024
·
IF 0.6
Zhao Hong,Xu Dan,Yu Taolin,Duan Xiaoyang,Zhou Xinyuan,Zhao Wenjie,He Jun
The effects of Li/Er and Li/Bi co-substitution on the structure, dielectric, and ferroelectric properties of BaTiO3 (BT) ceramics were investigated and analyzed. X-ray diffraction measurements show that the doped samples have a single tetragonal structure without secondary phases. Rietveld refinement results show that the Li/Er and Li/Bi ions tend to replace A-sites of BT lattices at low doping content. As the doping content increases, the Curie temperature moves to the high-temperature region due to the increased tetragonality and internal stress. Compared with the undoped ceramics, the ferroelectric properties of the doped ceramics are improved. The enhanced remnant polarization is attributed to the combined effects of large grain modulation and defect dipole arrangement.
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FASEB JOURNAL
·
2025
·Vol. 39
·期 22
·e71250
·
IF 4.2
Jian Zhao,Yili Chen,Di Lu,Yuanyuan Zeng,Jianjun Li,Jianjie Zhu,Zhe Lei,Jian-an Huang,Zeyi Liu
Copper ionophores such as elesclomol (ES) have been identified as effective agents capable of inducing cuproptosis, a recently characterized form of regulated cell death driven by copper overload. However, the interplay among copper toxicity, endoplasmic reticulum stress, and metabolic rewiring in lung adenocarcinoma (LUAD) remains poorly understood. Here, we demonstrate that ES selectively transports extracellular copper into human LUAD cells, inducing ER stress and upregulating PCK2, a gluconeogenic enzyme with context-dependent roles in cancer. RNA sequencing and functional assays revealed that PCK2 elevation under copper overload affects glucose metabolism and lipid metabolism to suppress malignant phenotypes. Clinically, high PCK2 expression is correlated with favorable prognosis in LUAD patients, as evidenced by analyses of public datasets. Knocking down PCK2 paradoxically increased proliferation and cell motility, suggesting that PCK2 plays a tumor-suppressive role under copper stress. KRAS G12D transgenic mice-derived lung cancer organoids were used to validate the in vitro therapeutic effects of ES + Cu by regulating PCK2 expression. In vivo experiments revealed that ES inhibited tumor growth and upregulated PCK2. Taking together, our findings reveal that the ES-ER stress-PCK2 axis is a critical mediator of copper-induced metabolic disruption, providing a rationale for targeting cuproptosis pathways in LUAD therapy. Graphical Schematic diagram of copper-induced cell death in LUAD. Elesclomol, as a copper ionophore, promotes copper influx into LUAD cells. This copper influx leads to cellular copper overload. Copper overload induces ER stress in LUAD cells. ER stress upregulates PCK2, which in turn inhibits the tricarboxylic acid (TCA) cycle. Collectively, these pathways orchestrate the cellular responses to excessive copper levels in LUAD cells, highlighting the complex interplay between copper homeostasis, metabolic reprogramming, and cell death mechanisms.
研究领域:
肿瘤学
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分子生物学
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癌症代谢
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细胞死亡机制
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药理学
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