ACS Infectious Diseases
·
2023
·
IF 5.3
Zewen Wen,Cong Wang,Bing Bai,Xinyi Cao,Kewei Fan,Chunyou Hu,Peiyu Li,Qiwen Deng,Zhijian Yu
Streptococcus agalactiae is the major cause of invasive neonatal infections and is a recognized pathogen associated with various diseases in nonpregnant adults. The emergence and spread of antibiotic-resistant S. agalactiae necessitate the development of a novel antibacterial agent. Here, the potential antibacterial activities and mechanisms of ginkgolic acid C15:1 (GA (15:1)) from Ginkgo biloba against clinical S. agalactiae are characterized. The MIC50 and MIC90 values for GA (15:1) against 72 clinical S. agalactiae isolates were 6.25 and 12.5 μM, respectively. GA (15:1) showed a strong bactericidal effect against both planktonic bacteria and bacteria embedded in biofilms as well as significant effectiveness in suppressing the growth of S. agalactiae biofilms. Moreover, GA (15:1) possesses intracellular antibacterial activity and could significantly decrease the bacterial burden in the intraperitoneal infection model of S. agalactiae. Mechanistic studies showed that GA (15:1) triggers membrane damage of S. agalactiae through a unique dual-targeting mechanism of action (MoA). First, GA (15:1) targets phospholipids in the bacterial cytoplasmic membrane. Second, by using mass-spectrometry-based drug affinity responsive target stability (DARTS) and molecular docking, lipoprotein signaling peptidase II (lspA) was identified as a target protein of GA (15:1), whose role is crucial for maintaining bacterial membrane depolarization and permeabilization. Our findings suggest a potential therapeutic strategy for developing GA (15:1) to combat S. agalactiae infections.
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JOURNAL OF APPLIED TOXICOLOGY
·
2022
·Vol. 43
·期 5
·662-679
·
IF 3.628
Zhuo-Qing Li,Cai Zhang,Song Fan,Ling-Li Wang,Yan Jiang,Hui-Jun Li
Dictamnine (DTN), a furoquinoline alkaloid isolated from Dictamni Cortex, is responsible for the liver injury caused by Dictamni Cortex and the preparations. Discovering new biomarkers with high specificity and sensitivity for diagnosis and tracing the source of DTN-induced liver injury is urgently needed. Considering that metabolic activation of DTN has been suggested as a primary trigger initiating hepatotoxicity, the present study aimed to investigate the bio-activation process of DTN in vitro and in mice and to explore whether the adducts could be developed as exposure biomarkers. When trapping with N -acetyl-cysteine (NAC) and glutathione (GSH) in mouse liver microsomes and CYP3A4 overexpressed L02 cells, two isomers of DTN-NAC adducts were detected in both systems and one DTN-GSH adduct was found in mouse liver microsomes. As expected, one DTN-NAC adduct was also found in plasma and bile of mice with liver injury after DTN exposure. Moreover, mouse liver microsomes were used to simulate the conjugation of serum albumin with metabolically activated DTN. The sole modified peptide 25 DAHKSEVAHR 34 was found, and the oxidative metabolites of DTN might bind to the side chain amino of albumin at Arg34. The above findings not only provided confirmative evidence that DTN was metabolically activated to induce liver injury but also suggested that the adducts had the potential to be developed as exposure biomarkers of DTN-induced liver injury.
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TOXICOLOGY MECHANISMS AND METHODS
·
2026
·
IF 2.9
Rui Li,Su Zhou,Hongyan Zhu,Jing Fang,Minyang Gu,Zhiwen Ji,Liming Tang,Qingfen Zhu,Zhen Feng
Following the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) multidisciplinary guideline M7 (R2), in silico prediction, in vitro and in vivo genotoxicity evaluations were used to evaluate the potential genotoxic risk of (-)-scopolamine hydrobromide trihydrate (SHT), the main impurity of scopolamine butylbromide in the Chinese Pharmacopoeia (ChP). The 2018 in silico models for genotoxicity (Derek Nexus and Sarah Nexus) predicted SHT to be a Class 4 impurity. Subsequent in vitro and in vivo genotoxicity tests (bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, in vitro mammalian cell gene mutation test and mammalian erythrocyte micronucleus test) showed no positive findings, indicating that SHT has no evidence of genotoxic potential under the tested conditions. Therefore, SHT could be tentatively categorized as a Class 5 impurity according to the ICH multidisciplinary guideline M7 (R2), with a threshold according to ICH quality guideline Q3B (R2). In silico prediction in 2026 confirmed this classification, demonstrating the high reliability of the Nexus software database for classification according to ICH multidisciplinary guideline M7 (R2). In the ChP, the SHT threshold in scopolamine butylbromide falls between the identification thresholds and the qualification thresholds of ICH quality guideline Q3B (R2), which is accurate and reasonable.
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LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Yingjie Zhou,Lijie Zhu,Yingyan Li,Feng Guo,Lei Chen,Guozhen Wang,Qian Shen,Xiuying Liu,Wenping Ding
In this study, soyasaponin (Ssa), corn oil, and soybean protein isolate (SPI) were used to prepare a water-in-oil-in-water (W/O/W) double emulsion system that can protect Lactobacillus plantarum (L.P) in the upper gastrointestinal tract for delivery to the small intestine and colon. Incorporating different amounts of L.P (0.1–0.6% (w/v)) in the W/O/W double emulsion caused the viscoelastic modulus and droplet size of the L.P-embedded emulsion system to change, and the emulsion system transformed from a non-Newtonian fluid to a “solid-like” gel. These results revealed that L.P encapsulation led to significantly improved stability of the W/O/W emulsion. In addition, different concentrations of L.P had different effects on the survival rate of L.P in simulated digestive fluids, and after in vitro digestion, L.P was naturally delivered from the stomach into the intestines. The optimal concentration of L.P for obtaining a stable emulsion was found to be 0.3%, and the survival rate of the encapsulated L.P in the small intestine was as high as 78.96% after 1 h. Thus, choosing an appropriate amount of L.P was crucial. The W/O/W emulsion system effectively maintained the viability of L.P and successfully delivered it to the small intestine and colon.
研究领域:
食品科学
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微生物学
·
生物技术
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Molecular Medicine Reports
·
2023
·Vol. 29
·期 1
·1-17
·
IF 3.4
Yao Zhao,Mirensha Yakufu,Chong Ma,Baicai Wang,Jianhua Yang,Junping Hu
Nonalcoholic steatohepatitis (NASH) is emerging as the primary driver of liver disease‑induced fibrosis. The imperative need for noninvasive biomarkers to ascertain disease progression stage is evident. The present study elucidated the biological roles of hub genes that could potentially serve as diagnostic markers for NASH. Using an in vivo approach, C57BL/6J mice were subjected to a high‑fat and fructose diet (HFFD) for 6, 10, 14, 18 or 22 weeks. Serological biochemical indices were assessed and liver specimens were obtained to identify potential markers linked to the NASH process, employing a comprehensive strategy that combined transcriptomic and histopathological analyses. The HFFD regimen induced hyperlipidemia, obesity and insulin resistance, progressively culminating in NASH with fibrosis over time. The transcriptomic analyses indicated temporal patterns of pivotal gene sets intricately connected to NASH progression, which encompassed processes such as glucose homeostasis, inflammatory responses, reactive oxygen species‑mediated damage, lipid metabolism disruptions and the formation of fibrotic tissue. Among these genes, Serpine1 and Mmp9 demonstrated promising diagnostic potential for NASH, with their intrahepatic mRNA expression levels serving as robust indicators. Moreover, the levels of PAI‑1 (encoded by the Serpine1 gene) and MMP‑9 in the serum of mice demonstrated a parallel increase with the duration of HFFD intervention. In vitro experiments utilizing HepG2 cells further validated these findings, demonstrating a significant elevation in the protein expression levels of both PAI‑1 and MMP‑9 upon exposure to free fatty acids, in agreement with the results of the animal study. Consequently, PAI‑1 and MMP‑9 are promising noninvasive biomarkers for assessing the progression of NASH.
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Scientific Reports
·
2022
·Vol. 12
·期 1
·1-8
·
IF 4.996
Li Hongchuan,Kong Deming,Zhang Borui,Kalkhajeh Yusef Kianpoor,Zhao Yingying,Huang Jieying,Hu Hongxiang
The use of degradable chelating agents to facilitate phytoextraction is a promising low-cost method for the remediation of heavy metal-contaminated soils. However, there are few studies on how plants and soils respond to the chelating agents. In this study, the responses of French marigold ( Tagetes patula L.) and soil cadmium (Cd) to the chelator tetrasodium glutamate (GLDA) was investigated in a 180 d field trial. Five GLDA treatments (0, 292.5, 585, 1170, and 2340 kg hm −2 ) were carried out in a Cd-contaminated soil (0.47 mg kg −1 ) under French marigold plantation. The results showed that the application of GLDA promoted the transformation of other forms of Cd in soil to exchangeable state, and the exchangeable Cd and Fe–Mn oxide bound state increased by 42.13% and 32.97% ( p < 0.05), respectively. The cell wall Cd accumulations significantly increased 9.39% ( p < 0.05) and the percentages of soluble fractions increased by 460.33% ( p < 0.05). Furthermore, increases occurred in soil pH, as well as DOC and DTPA-Cd contents with increasing the total amount of GLDA. The composite application of GLDA (2340 kg hm −2 ) with French marigold reduced the total soil Cd content by 7.59% compared with the soil background. Altogether, results of this study suggested that the application of GLDA can effectively activate soil Cd and enhance the capability of French marigold for the remediation of Cd-contaminated soils.
研究领域:
环境科学
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植物学
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Journal of Environmental Sciences
·
2024
·
IF 5.9
Zheyuan Song,Zheng Ma,Xueshan Feng,Rui Huang,Qiong An,Yunrui Pan,Jing Chang,Bin Wan,Huili Wang,Jianzhong Li
Ethiprole is widely used as a second-generation phenyl pyrazole insecticide. Previous study indicated that ethiprole exhibited thyroid toxicity while two main metabolites (ethiprole sulfone (M1) and ethiprole sulfide (M2)) of ethiprole showed higher acute toxicity than ethiprole. Therefore, assessing the thyroid toxicity of its metabolites is crucial for safety assessment. In this study, the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico, in vitro , and in vivo assays, with the aim of conducting a comparative study on thyroid toxicity. Molecular docking analysis showed that ethiprole, M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3′,5-triiodothyronine (T3). GH3 cell proliferation assays revealed that ethiprole, M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation. Using the zebrafish model, we further investigated that exposure to ethiprole, M1, and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid (HPT) axis-related genes. Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta, M1 mainly through binding with the corticotropin releasing factor receptor-1, and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity. M2 showed the highest developmental toxicity and thyroid disrupting effects, which significantly reducing hatching rates, increasing deformity rates, exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis. This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.
研究领域:
毒理学
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药理学
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环境科学
·
分子生物学
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Nanoscale
·
2025
·
IF 5.1
Xiangming Wang,Yang Zhao,Han Qin,Feng Yan,Tao An,Weimin Liu,Yu Su,Xianbo Yu
Magnesium batteries exhibit promising prospects owing to their high theoretical volumetric capacity, abundant natural reserves, and superior safety. However, their practical applications are hindered by the sluggish diffusion kinetics of Mg2+ in conventional cathode materials. This study innovatively proposes a strategy for the epitaxial growth of imine-linked covalent organic frameworks on the surface of carbon nanotubes (CNTs@COF), thereby effectively balancing electrode conductivity and the density of active sites through precise control of the COF layer thickness. This composite material not only facilitates the efficient diffusion of Mg2+ via axially aligned COF channels and continuous charge transport networks but also enhances electrical conductivity through the incorporation of CNTs, significantly improving the energy storage performance, cycling stability, and utilization efficiency of active sites in magnesium batteries. Furthermore, the Mg2+ storage mechanism in CNTs@COF is hypothesized to involve the storage of six electrons per CN bond within each COF unit. As a result, CNTs@COF exhibits superior discharge capacity, rate capabilities, and cycling performance (e.g., 191.7 mAh g−1 at 20 mA g−1 after 200 cycles and 107.6 mAh g−1 at 500 mA g−1 after 3000 cycles). The synthetic approach paves the way for constructing high-performance multivalent battery systems, bridging the gap from molecular design to macroscopic electrochemical performance.
研究领域:
材料化学
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电化学
·
能源存储
·
纳米材料
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电池技术
·
功能材料
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2019
·Vol. 47
·期 3
·372-382
·
IF 2.336
Ruili Wang,Ying Yang,Hui Wang,Ya He,Chen Li
MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR-29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP-treated mice or MPP + -intoxicated SH-SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR-29c was employed to examine its biological function on PD progress. We found that miR-29c was down-expressed but SP1 was high-expressed in substantia nigra pars compacta (SNpc) of MPTP-induced PD mice. Overexpression of miR-29c attenuated dopaminergic neuron loss and α-synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and TUNEL-positive apoptotic cells in MPTP-treated mice were ameliorated by miR-29c. Similarly, in SH-SY5Y cell models of PD, we also found that miR-29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro-apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR-29c. Luciferase reporter assay confirmed that SP1 was complementary with miR-29c. Knockdown of SP1 with siRNA restored α-synuclein accumulation, inflammation and apoptosis in MPP + -induced SH-SY5Y cells. Collectively, this current work presents that miR-29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.
研究领域:
神经科学
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分子生物学
·
药理学
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2019
·
IF 3.361
Xiao Sun,Yan Liu,Xiuli Feng,Chunyan Li,Siying Li,Zhongxi Zhao
Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo . Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.
研究领域:
免疫学
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药理学
·
呼吸医学
·
细胞生物学
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INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
·
2024
·
IF 5
Yanchi Liu,Lintao Zhao,Hongyang Chen,Zimao Ye,Long Guo,Zhiqin Zhou
The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P. italicum) . The results showed that the minimum inhibitory concentration (MIC) of eugenol nanoemulsion loaded with nobiletin (EGN) was lower than that of pure eugenol nanoemulsion (EG), which were 160 μg/mL and 320 μg/mL, respectively. At the same time, the mycelial growth inhibition rate of EGN nanoemulsion (54.68 %) was also higher than that of EG nanoemulsion (9.92 %). This indicates that EGN nanoemulsion is more effective than EG nanoemulsion. Compared with EG nanoemulsion, the treatment of EGN nanoemulsion caused more serious damage to the cell structure of P. italicum . At the same time, in vitro inoculation experiments found that EGN nanoemulsion has better control and delay the growth and reproduction of P. italicum in citrus fruits. And the results reflected that EGN nanoemulsion may be considered as potential resouces of natural antiseptic to inhibit blue mold disease of citrus fruits, because it has good antifungal activity.
研究领域:
药理学
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微生物学
·
食品科学
·
植物病理学
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JOURNAL OF PHYSICS AND CHEMISTRY OF SOLIDS
·
2026
·
IF 5.9
Xinyang He,Ying Lv,Dapeng Qin,Meixia Xiao,Lei Wang,Weiwei Han
The simultaneous removal of organic dyes and heavy metal ions from complex wastewater remains a formidable challenge due to the competitive redox requirements of different pollutants. In this work, we report a robust in-situ phase transformation strategy to construct a temperature-mediated S-scheme Bi 2 WO 6 /Bi 2 O 2 CO 3 heterojunction. By precisely modulating the hydrothermal temperature, the BiOCOOH phase was strategically transformed into Bi 2 O 2 CO 3 on the Bi 2 WO 6 surface, establishing an intimate interfacial contact. The resulting heterojunction induces a potent internal electric field (IEF), which dictates a high-efficiency S-scheme charge transfer pathway. This mechanism not only maximizes the spatial separation of photogenerated carriers but also preserves the powerful redox potentials of the individual components. Under visible light irradiation, the optimized BCW-2 catalyst exhibited exceptional performance, achieving near-complete removal of Rhodamine B (RhB) and Cr(VI) within 90 min, with reaction rate constants of 0.08911 min −1 and 0.06157 min −1 , respectively. Detailed experimental characterizations and density functional theory (DFT) calculations provided deep mechanistic insights into the band alignment and interfacial electronic behavior, confirming the S-scheme pathway. This study offers a transformative paradigm for the rational design of S-scheme heterojunctions with tailored redox capabilities for advanced environmental remediation.
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