Nanomedicine
·
2018
·
IF 5.005
Huanan Li,Deping Zeng,Zhenyu Wang,Liaoqiong Fang,Faqi Li,Zhibiao Wang
Aim: To build up a combined therapy strategy to address limitations of the enhanced permeability and retention (EPR) effect and improve the efficiency of tumor therapy. Materials & methods: A pH-sensitive nanocomplex for co-delivery of doxorubicin (DOX) and all-trans retinoic acid (ATRA) was developed based on nanodiamonds (DOX/ATRA-NDs) to enhance intracellular retention of drugs. Meanwhile, ultrasound was employed to enhance tumor vascular penetration of DOX-ATRA-NDs. Results: The distribution of DOX/ATRA-NDs in the tumor tissues increased threefold when ultrasound was applied at 1 MHz and 0.6 W/cm2. Comparing with unmodified chemotherapeutics, the combined therapy induced more tumor cells apoptosis and greater tumor growth inhibition in both liver and breast tumor models. Conclusion: DOX-ATRA-NDs demonstrate great potential in clinical applications.
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高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
·
2021
·Vol. 298
·期 2
·
IF 5.157
Binxiang Cai,Chunyan Liao,Danxue He,Jingmeng Chen,Jiahuai Han,Jiaying Lu,Kaiqi Qin,Wenxu Liang,Xiaoling Wu,Zuguo Liu,Yalin Wu
The breakdown of all-trans-retinal (atRAL) clearance is closely associated with photoreceptor cell death in dry age-related macular degeneration (AMD) and autosomal recessive Stargardt's disease (STGD1), but its mechanisms remain elusive. Here, we demonstrate that activation of gasdermin E (GSDME) but not gasdermin D promotes atRAL-induced photoreceptor damage by activating pyroptosis and aggravating apoptosis through a mitochondria-mediated caspase-3-dependent signaling pathway. Activation of c-Jun N-terminal kinase was identified as one of the major causes of mitochondrial membrane rupture in atRAL-loaded photoreceptor cells, resulting in the release of cytochrome c from mitochondria to the cytosol, where it stimulated caspase-3 activation required for cleavage of GSDME. Aggregation of the N-terminal fragment of GSDME in the mitochondria revealed that GSDME was likely to penetrate mitochondrial membranes in photoreceptor cells after atRAL exposure. ABC (subfamily A, member 4) and all-trans-retinol dehydrogenase 8 are two key proteins responsible for clearing atRAL in the retina. Abca4−/−Rdh8−/− mice exhibit serious defects in atRAL clearance upon light exposure and serve as an acute model for dry AMD and STGD1. We found that N-terminal fragment of GSDME was distinctly localized in the photoreceptor outer nuclear layer of light-exposed Abca4−/−Rdh8−/− mice. Of note, degeneration and caspase-3 activation in photoreceptors were significantly alleviated in Abca4−/−Rdh8−/−Gsdme−/− mice after exposure to light. The results of this study indicate that GSDME is a common causative factor of photoreceptor pyroptosis and apoptosis arising from atRAL overload, suggesting that repressing GSDME may represent a potential treatment of photoreceptor atrophy in dry AMD and STGD1.
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高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2021
·
IF 3.196
Zechun Li,Changjin Yang,Yanchan Wei,Yuanbing Zhou,Shuangquan Liao
Natural rubber (NR) has excellent mechanical properties due to its unique molecular chain structure. In previous studies, the signal of the cis- and trans -isoprene units was deduced by 13 C-NMR spectrum of the low molecular weight fraction of NR. In this study, through investigating the 1 H-NMR spectra of ribbed smoked sheet 1 (RSS-1) and standard Chinese rubber whole fraction (SCR-WF), and Eucommia ulmoides gum (EUG), trans -1,4-polyisoprene (TPI), found that the methyl-proton in the cis- and trans -isoprene units in 1 H-NMR spectra of NR showed signals at 1.61 and 1.53 ppm, respectively. Further, the content of trans -structure in the molecular chain of NR of different producing areas was calculated. The results show that the content of trans -structure in the molecular chain structure of RSS-1 and SCR-WF were 1.500 and 1.054%, respectively.
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JOURNAL OF BIOLOGICAL CHEMISTRY
·
2020
·Vol. 295
·期 20
·6958-6971
·
IF 4.238
Chunyan Liao,Binxiang Cai,Yufeng Feng,Jingmeng Chen,Yiping Wu,Jingbin Zhuang,Zuguo Liu,Yalin Wu
Disrupted clearance of all-trans-retinal (atRAL), a component of the visual (retinoid) cycle in the retina, may cause photoreceptor atrophy in autosomal recessive Stargardt disease (STGD1) and dry age-related macular degeneration (AMD). However, the mechanisms underlying atRAL-induced photoreceptor loss remain elusive. Here, we report that atRAL activates c-Jun N-terminal kinase (JNK) signaling at least partially through reactive oxygen species production, which promoted mitochondria-mediated caspase- and DNA damage-dependent apoptosis in photoreceptor cells. Damage to mitochondria in atRAL-exposed photoreceptor cells resulted from JNK activation, leading to decreased expression of Bcl2 apoptosis regulator (Bcl2), increased Bcl2 antagonist/killer (Bak) levels, and cytochrome c (Cyt c) release into the cytosol. Cytosolic Cyt c specifically provoked caspase-9 and caspase-3 activation and thereby initiated apoptosis. Phosphorylation of JNK in atRAL-loaded photoreceptor cells induced the appearance of γH2AX, a sensitive marker for DNA damage, and was also associated with apoptosis onset. Suppression of JNK signaling protected photoreceptor cells against atRAL-induced apoptosis. Moreover, photoreceptor cells lacking Jnk1 and Jnk2 genes were more resistant to atRAL-associated cytotoxicity. The Abca4−/− Rdh8−/− mouse model displays defects in atRAL clearance that are characteristic of STGD1 and dry AMD. We found that JNK signaling was activated in the neural retina of light-exposed Abca4−/−Rdh8−/− mice. Of note, intraperitoneal administration of JNK–IN-8, which inhibits JNK signaling, effectively ameliorated photoreceptor degeneration and apoptosis in light-exposed Abca4−/−Rdh8−/− mice. We propose that pharmacological inhibition of JNK signaling may represent a therapeutic strategy for preventing photoreceptor loss in retinopathies arising from atRAL overload.
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高影响因子
Microorganisms
·
2025
·Vol. 13
·期 11
·2554
·
IF 4.2
Yong-Lan Ma,Min Li,Qian Lei,Hai-Jun Ma,Ya-Jing An
Auxenochlorella pyrenoidosa , a promising edible bioresource, can be efficiently and safely cultivated using exogenous phytohormones to enhance its productivity. This study employed multi-omics analysis to systematically investigate the effects and mechanisms of exogenous trans-Zeatin (tZ) on the growth and metabolism of A. pyrenoidosa . Results demonstrated that 10 mg/L tZ significantly promoted algal growth, increasing biomass by 166 ± 3.35% at 72 hours (h), while concurrently elevating cellular soluble protein (SP), carbohydrate (CHO), and chlorophyll a (Chla) content. tZ also strengthened the antioxidant defense system, evidenced by reduced reactive oxygen species (ROS) levels, enhanced activities of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), upregulation of glutathione metabolism, and decreased lipid peroxidation product (malondialdehyde (MDA)). Furthermore, tZ activated key metabolic pathways, including nitrogen metabolism, photosynthetic carbon fixation, and porphyrin biosynthesis, leading to the accumulation of arginine and polyamines, etc. This study reveals that tZ promotes microalgal growth by coordinately regulating carbon–nitrogen metabolic networks and antioxidant systems, providing a theoretical foundation for phytohormone-augmented microalgae cultivation technologies.
研究领域:
藻类学
·
植物生理学
·
代谢组学
·
分子生物学
·
生物技术
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ACS Nano
·
2025
·
IF 16
Jingkai Wang,Jiangjie Chen,Jinyang Chen,Kaishun Xia,Pengcheng Yuan,Xiaopeng Zhou,Ronghao Wang,Chao Yu,Yi Li,Kesi Shi,Yuang Zhang,Haibin Xu,Tengfei Zhao,Hao Li,Qixin Chen,Shiqing Feng,Chengzhen Liang
The central nervous system (CNS) barrier obstructs therapeutic component entrance and hinders the therapy efficiency of CNS diseases. An ideal delivery system should penetrate and concentrate in the CNS without safety concerns. Nanovesicles (NVs) are a popular delivery tool, because of their biological homology, inherent homing effects, and capacity to penetrate barriers. However, the delivery efficacy of NVs is insufficient for CNS disease therapy, and the mechanism for barrier penetration remains elusive. Herein, nanovesicles (NVs) were extruded from mesenchymal stem cells and modified by a lesion tissue affinity peptide (CAQK) for spinal cord injury (SCI) therapy. The NVs penetrated endothelial barriers effectively in vitro. Subsequently, the CNS barrier penetration capacity of the CAQK-conjugated NVs (CNVs) was verified in vivo in spinal cord injury (SCI) and the temporary middle cerebral artery occlusion (t-MCAO) mouse models. Furthermore, the endothelial barrier penetration of CNVs depended on the active endocytosis by endothelial cells. After endocytosis, the Rab11+ endosome was identified to mediate a transcellular transcytosis to transport CNVs across the barrier. In the SCI model, CNVs promoted the lesion tissue accumulation, leading to improvement in the neural functional recovery. In summary, we developed a natural NV tool for SCI therapy, employing the inherent CNS barrier penetration capacity and enhanced lesion tissue homing characteristics of NVs. The NVs crossed the CNS barriers via active endocytosis, followed by Rab11+ endosome-mediated transcytosis. The CNV exhibited good delivery efficacy and therapeutic effects in CNS diseases and has the potential for clinical translation.
研究领域:
纳米医学
·
神经科学
·
药物递送系统
·
再生医学
·
生物医学工程
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高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Jun Zhang,Wenxing Yang,Zhuo Li,Feijun Huang,Kui Zhang
Cadmium is a naturally existing heavy metal and a notorious environmental pollutant. While its toxic outcomes and underlying mechanisms remain largely elusive. To explore the behavioral change caused by multigenerational exposure of cadmium to C. elegans , we challenged the C. elegans with cadmium for six generations and observed its impact on animal behaviors. Wild-type worms were randomly divided into two groups, the control and cadmium exposure groups. Locomotive and chemotactic behaviors were observed across six generations. Head thrashing frequency, chemotaxis index, and fold change index were used to evaluate the neurotoxicity of multigenerational cadmium exposure. Multigenerational cadmium exposure can trans -generationally increase the head thrashing frequency of C. elegans during swimming, and impair the chemotactic behaviors to isoamyl alcohol, diacetyl, and 2-nonanone. Our findings proposed a trans -generationally behavioral impact induced by multigenerational cadmium exposure.
研究领域:
毒理学
·
环境科学
·
神经科学
·
发育生物学
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高影响因子
LIPIDS
·
2016
·Vol. 52
·期 1
·27-35
·
IF 1.892
Pan Yao,Liu Benxin,Deng Zeyuan,Fan Yawei,Li Jing,Li Hongyan
The effects of two fatty acids, oleic acid (OLA) and elaidic acid (ELA) on normal human umbilical vein endothelial cells (HUVEC) and non-rafts HUVEC were investigated in this study. The expression levels of inflammatory cytokines (ICAM-1, VCAM-1 and IL-6) were analyzed. Western blot was used to analyze the expression levels of inflammation-related proteins (NF-κB, ERK1/2) and toll-like receptors 4 (TLR4). The results showed that the levels of nuclear translocation of NF-κB p65 and phosphorylated ERK1/2 were significantly decreased only in non-lipid rafts cells pretreated with trans fatty acid (TFA). The expression of TLR4 in the ELA-treated normal cells was higher than that in non-lipid rafts HUVEC. When the lipid rafts was destroyed by methyl-β-cyclodextrin, the levels of nuclear translocation of NF-κB p65, phosphorylated ERK1/2 and TLR4 were decreased significantly. Therefore, lipid rafts may be involved in TFA induced-inflammation in HUVEC through blocking the inflammatory signal pathway. Lipid rafts might be a platform for specific receptors such as TLR4 for TFA to activate the pro-inflammation on cell membranes.
研究领域:
细胞生物学
·
分子生物学
·
心血管研究
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高影响因子
RSC Advances
·
2017
·Vol. 7
·期 57
·35917-35927
·
IF 3.108
Jun Wang,Aimin Shi,Dominic Agyei,Qiang Wang
Resveratrol is a high-value bioactive polyphenolic compound with vast applications in functional foods; as such, effective and scalable delivery strategies for this compound are worthy of study. In this research, W/O/W emulsions were successfully prepared using polyglycerol polyricinoleate (PGPR) as a lipophilic emulsifier and Tween 80 as a hydrophilic emulsifier with the goal of developing biocompatible carriers to improve the bioavailability of resveratrol. The effects of the type of emulsifier, the concentration of emulsifier, the ratio of the oil phase to the internal water phase, and homogeneous pressure on the physical properties of the W/O/W emulsions (such as microstructure, droplet size, distribution, zeta potential, viscosity and encapsulation efficiency) were investigated. The optimum processing conditions for preparing W/O/W emulsions are as follows: the ratio of the oil phase to the internal water phase is 80 : 20, the concentrations of lipophilic and hydrophilic emulsifiers are 10 wt% and 5 wt%, and the homogeneous pressures in the first and second steps are 30 MPa and 10 MPa. The optimal preparation process of the W/O/W emulsions was used to encapsulate resveratrol. The results showed that at up to 0.040 wt% in the internal water phase (ethanol), resveratrol could be successfully encapsulated in W/O/W emulsions with an encapsulation efficiency of 99.97 ± 0.001%. Moreover, resveratrol was successfully encapsulated in the internal water phase and oil phase together; thus, it was not necessary to increase the amount of carrier materials. This study provides a novel encapsulation formulation to increase the delivery efficacy of resveratrol.
研究领域:
食品科学
·
药物递送
·
生物技术
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高影响因子
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
·
2015
·
IF 2.495
Yaping Wang,Song Zhang,Simei Sun,Kai Liu,Bing Zhang
The ultrafast dynamics of S 2 -excited trans -4-diethylaminoazobenzene ( trans -4-DEAAB) is investigated in solution by femtosecond transient absorption spectroscopy combined with quantum chemical calculations. Following excitation, the internal conversion from the S 2 state to the S 1 state occurs directly with time constant of ∼0.10 ps. The cis isomer is observed by the partial recovery of ground-state bleach in 450–480 nm and the permanent positive absorption in 480–550 nm. The time constant of <1 ps is assigned to the lifetime of the S 1 state which decays by isomerization to the cis -isomer hot S 0 state and internal conversion to the trans -isomer hot S 0 state. The photoisomerization is deduced by inversion mechanism because of the independence between the viscosity and the S 1 -state lifetime. The vibrational cooling of the hot S 0 state of cis -4-DEAAB occurs with ∼15 ps in acetone but is shortened to ∼6 ps in alcohols solvents. This shortening is due to the H-bond which forms easily in protic solvent and accelerates the flow of vibrational energy between solute and solvent.
研究领域:
物理化学
·
光化学
·
超快光谱学
·
分子动力学
·
量子化学计算
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Yuling Dong,Changjian Xie,Beibei Du,Hongliang Liu,Shujing Zhang,Qiuxiang Pang,Desheng Zhang
Sodium benzoate (SB) is a widely used synthetic food preservative with broad-spectrum antimicrobial activity. Although generally recognized as safe at regulated levels, concerns persist regarding its potential toxicity at high concentrations. Our previous study demonstrated that chronic exposure to high-dose SB (2000 ppm) significantly delayed pupation and adult emergence timing while altering gut microbiota composition in Drosophila melanogaster . However, whether these developmental and microbial disruptions will be vertically transmitted to the next generation remains unknown. Therefore, in this study, we investigated the trans-generational effects of SB on F1 offspring development and gut microbiota dynamics. Notably, larval pupation and adult emergence time were significantly delayed in offspring derived from SB-exposed parents (2000 ppm). Strikingly, the gut microbiota dysbiosis observed in parental flies was partially attenuated in the F1 generation. However, F1 offspring exhibited significantly higher Shannon and Simpson diversity indices, suggesting a profound restructuring of the microbial community that may reflect over-compensation or an alternative dysbiotic state rather than complete normalization. Gene expression analysis further revealed that while most SB-induced transcriptional changes were normalized in offspring, four key genes, Yp2 , TOR , E74B and CAT , remained persistently upregulated, indicating sustained trans-generational dysregulation. Collectively, these findings provide novel evidence that SB exposure can induce trans-generational developmental toxicity, potentially mediated by persistent gene dysregulation despite recovery of the gut microbiota. These findings highlight the need for further mechanistic investigations in future work.
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CHEMOSPHERE
·
2024
·
IF 8.1
Anlin Xu,Ziyan Yang,Zhiyi Zhou,Pu Yang,Yang Yu,Jiayang Liu,Yunhai Zhang
Hydrogen peroxide (H 2 O 2 ) synthesis by electrochemical two-electron oxygen reduction has garnered increasing interest as a wide range of potential applications. Gas diffusion electrodes (GDEs) can effectively promote the H 2 O 2 production efficiency by overcoming the oxygen mass transfer limitations but strongly influenced by the electrowetting process along the long-term operation. In this study, the effect of trans -electrode pressure (TEP) of GDE cathode on the electrowetting process was further elucidated. We controlled the TEP values of four types of GDEs: two Ni-based GDEs and two carbon cloth GDEs prepared by hot-pressing or brushing carbon black. SBA-15 was further used to regulate the microstructure of one Ni-based GDE. It was found that an optimal range of TEP occurred for all tested GDEs in terms of the max. concentration, the yield efficiency, the energy consumption, and the stability because TEP may change the triple-phase interface and influence the anti-electrowetting effect. The porosity of hot-pressed Ni GDE can maintain the TEP window and thus enhance the production of H 2 O 2 , likely via creating oxygen-containing functional groups and a bimodal pore structure on the electrode, revealed with several characterization techniques including SEM, CA, XPS , Raman spectra, CV and EIS . The porous Ni GDE presented an efficient and stable production of H 2 O 2 for 10 cycles: yielding H 2 O 2 at 4393.2–4602.2 mmol m −2 h −1 with current efficiencies of 94.2–98.7%. The best accumulated H 2 O 2 concentration can reach up to 3.58 ωt% H 2 O 2 at 10 h. The results provide an important reference for the industrial scaleup of electro-production of H 2 O 2 with GDEs.
研究领域:
电化学
·
材料科学
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高影响因子
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