Journal of Cosmetic Dermatology
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2024
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IF 2.3
Lu Hu,Jiyu Weng,Ziqin Wang,Chujie Huang,Lanyue Zhang
Background Aging is a physiological phenomenon in the process of life, and skin aging has a significant impact on human appearance. Therefore, the search for methods to delay skin aging is of great significance for improving the quality of human life. Materials and Methods This study investigated the anti-photoaging effect of Tricholoma matsutake (T) extract composition combined with bakuchiol (B) and ergothioneine (E), and explored its potential mechanism through transcriptome, metabolomics, and network pharmacology. Results 57 main chemical components are identified from the ethanol extract of T. matsutake (T), including D-carnitine (24.55%), α,α-trehalose (15.56%), DL malic acid (8.99%), D-(−)-quinic acid (7.46%), erucamide (7.04%) and so on. After TBE treatment, inflammation of the mice dorsal skin is significantly minimized. Hematoxylin and eosin (H&E) staining and toluidine blue staining reveal that TBE has an anti-inflammatory effect on the back skin tissue of mice. Masson staining shows that TBE has a repair effect on mice dorsal skin tissue. In addition, the inflammatory factors (IL-1β, IL-6, TNF-α) in the mice dorsal skin tissues are significantly reduced but collagen (COL-1) is significantly increased. By cellular immunofluorescence assay, TBE is shown to promote PPAR-α expression in cells. Transcriptomics, metabolomics, and network pharmacology have revealed that TBE can regulate exogenous stimuli and cancer-related signaling pathways to prevent skin aging. Conclusion The results suggest that TBE can be a beneficial supplement to natural anti-aging.
研究领域:
药理学
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皮肤科学
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分子生物学
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PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2025
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IF 4.3
Yimin Li,Chunnuan Zhang,Zihao Meng,Mengkang You,Huajuan Shi
TBBPA, a ubiquitously distributed brominated flame retardant, poses significant ecological risks due to its bioaccumulative potential and toxicity. Previous investigations have predominantly focused on untargeted metabolomics and lipidomics to characterize the effects of TBBPA on metabolic end products. However, limited data are available regarding the mechanisms underlying TBBPA-induced disruption of lipid metabolism in aquatic organisms. This study systematically investigated the dose-dependent effects of TBBPA on lipid metabolism in common carp through integrated biochemical, histochemical evaluations, and transcriptomic profiling. Fish were exposed to environmentally relevant TBBPA concentrations (0, 0.005, 0.05, and 0.5 mg/L) for a 14-day duration. Serum biochemical analyses revealed dose-dependent hyperlipidemia, manifested by elevated TG and T-CHO levels, suppressed SOD and CAT activities, and increased MDA levels. Oil Red O staining demonstrated hepatic lipid droplet accumulation despite no significant ( P > 0.05) alterations in intrahepatic TG/T-CHO content, with the 0.5 mg/L group exhibited the most severe histopathological phenotype. Transcriptomic profiling identified the AMPK and PPAR signaling pathways as pivotal regulators of TBBPA-induced metabolic dysregulation. Under low-dose TBBPA exposure (0.05 mg/L), lipid accumulation triggered compensatory activation of the AMPK / PPAR-α / CPT1 axis, enhancing fatty acid β-oxidation to partially counteract lipid deposition. Conversely, high-dose TBBPA (0.5 mg/L) disrupted lipid metabolism through coordinated upregulation of genes associated with lipid synthesis, transport, and storage, culminating in pathological lipid deposition. This study provides critical insights into the molecular cascades underlying TBBPA-induced metabolic dysregulation in aquatic species, highlights the dose-dependent disruption of lipid homeostasis.
研究领域:
环境毒理学
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水生毒理学
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分子生物学
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生物化学
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转录组学
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PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2025
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IF 6.1
Yue Zhang,Hui Zhao,Qianxi Feng,Rui Guo,Li Zhong,Shengxian Liang
Benzotriazole ultraviolet stabilizers (BUVSs) are pervasive environmental contaminants that pose significant risks to human health. This study evaluated the effects of three typical BUVSs (UV-328, UV-329, and UV-P) on human mesenchymal stem cells (hMSCs), which play crucial roles in tissue maintenance and repair. hMSCs were exposed to BUVSs across a range of concentrations, and their maintenance and differentiation capacities were assessed. At concentrations below 50 μM, no significant cytotoxicity was observed. However, at non-cytotoxic doses, UV-P exhibited stronger effects on the differentiation of hMSCs compared to UV-328 and UV-329, significantly inhibiting adipogenesis and enhancing osteogenesis. Mechanistically, UV-P was found to significantly enrich the PPAR signaling pathway during both differentiation processes. Dual-luciferase reporter assays confirmed UV-P's interaction with PPARγ_LBD at an alternate binding site outside the canonical pocket. These findings raise concerns about the health impacts of BUVSs, particularly UV-P, and underscore the need for further investigation into their toxicological profiles.
研究领域:
细胞生物学
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毒理学
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环境健康科学
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DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
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IF 12.2
Xun’e Yi,Haiyu Qin,Guangyu Li,Ren Kong,Chunsheng Liu
Tricresyl phosphate (TCP) has received extensive attentions due to its potential adverse effects, while the toxicological information of TCP isomers is limited. In this study, 2 h post-fertilization zebrafish embryos were exposed to tri-o-cresyl phosphate (ToCP), tri-m-cresyl phosphate (TmCP) or tri-p-cresyl phosphate (TpCP) at concentrations of 0, 100, 300 and 600 μg/L until 120 hpf, and the cardiotoxicity and mechanism of TCP isomers in zebrafish embryos/larvae were evaluated. The results showed that ToCP or TmCP exposure induced cardiac morphological defects and dysfunction in zebrafish, characterized by increased distance between sinus venosus and bulbus arteriosis, increased atrium and pericardial sac area, trabecular defects, and decreased heart rate and blood flow velocity, while no adverse effects of TpCP on zebrafish heart were found. Transcriptomic results revealed that extracellular matrix (ECM) and motor proteins, as well as PPAR signaling pathways, were included in the cardiac morphological defects and dysfunction induced by ToCP and TmCP. Co-exposure test with D-mannitol indicated that the inhibition of energy metabolism by ToCP and TmCP affected cardiac morphology and function by decreasing osmoregulation. This study is the first to report the cardiotoxicity induced by TCP in zebrafish from an isomer perspective, providing a new insight into the toxicity of TCP isomers and highlighting the importance of evaluating the toxicity of different isomers.
研究领域:
环境毒理学
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发育生物学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2026
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IF 7.5
Weiqi Zhang,Han Yin,Chenchen Wang,Xiaowei Ma,Dazhuang Miao,Guimiao Li,Wei Chen,Zhiyong Hou,Xianda Gao,Yingze Zhang,Di Zhang
Oxidative stress and apoptosis mediated senescence of nucleus pulposus cells (NPCs) and the degradation of extracellular matrix (ECM), which represent a key mechanism underlying intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes hold therapeutic potential for tissue repair; however, their clinical application is limited by rapid clearance, short half-life, and poor target specificity. To overcome these challenges, this study developed poly(lactic-co-glycolic acid) (PLGA) microspheres as a sustained-release carrier for exosomes derived under either normoxic (Exos, 21% O₂) or hypoxic (H-Exos, 1% O₂) conditions. The PLGA microspheres demonstrated high exosome-loading efficiency and provided controlled release for over four weeks. Released hypoxic exosomes activate PPAR-γ pathway, exerting better effects by reducing NPCs SA-β-gal positive rate by 59.8% and elevates Col II and ACAN levels by 30.7% and 25.5%. Animal experiments confirmed that this system effectively attenuated IVDD progression indicating its potential for clinical translation.
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高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2024
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IF 6.2
Fei Shi,Zhilong Chen,Minshan Yao,Yao Huang,Jin Xiao,Lixin Ma,Jilin Mo,Li Lin,Zhendong Qin
Since disinfectants are used all over the world to treat illnesses in people and other animals, they pose a major risk to human health. The comprehensive effects of disinfectant treatments on fish liver, especially the impacts on oxidative stress, toxicological effects, transcriptome profiles, and apoptosis, have not yet been fully analyzed. In the current investigation, healthy grass carp were exposed to 80 μg/L glutaraldehyde or 50 μg/L povidone-iodine for 30 days. First, the findings of enzyme activity tests demonstrated that the administration of glutaraldehyde could considerably increase oxidative stress by lowering T-SOD, CAT, and GPx and raising MDA. Furthermore, KEGG research revealed that exposure to glutaraldehyde and povidone-iodine stimulated the PPAR signal pathway. To further elucidate the transcriptome results, the relative expressions of related DEGs in the PPAR signal pathway were verified. Glutaraldehyde induced apoptosis in liver tissue of grass carp; however, it activated cytotoxicity and apoptosis in grass carp hepatocytes when exposed to glutaraldehyde or povidone-iodine. According to the current study, disinfectants can cause the impairment of the immune system, oxidative stress, and attenuation of the PPAR signal pathway in the liver of grass carp, making them detrimental as dietary supplements for grass carp, particularly in the aquaculture sector.
研究领域:
水产养殖
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毒理学
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分子生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Cells
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2024
·Vol. 13
·期 3
·206
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IF 5.1
Meng-Yuan Li,Ying Wang,Ying Wu,Xu-Yu Zhao,Zhen-Shan Yang,Bo Li,Si-Ting Chen,Yu-Ying He,Zeng-Ming Yang
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.Keywords:decidualization;implantation;S100A6;RAGE;inflammation
研究领域:
生殖生物学
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分子生物学
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免疫学
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DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
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2024
·Vol. 27
·期 6
·1-12
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IF 2.4
Boyu Tan,Xiaoxu Lan,Yifan Zhang,Pai Liu,Qiyao Jin,Zhiqiang Wang,Zhidong Liang,Wei Song,Ye Xuan,Yunxiao Sun,Youjie Li
The present study aimed to investigate the effect and mechanism of Pulsatilla compounds on lung adenocarcinoma. The representative drug chosen was the compound 23‑HBA. GeneCards, Swiss target prediction, DisGeNET and TCMSP were used to screen out related genes, and MTT and flow cytometry assays were used to verify the inhibitory effect of Pulsatilla compounds on the proliferation of lung adenocarcinoma cells. Subsequently, the optimal target, peroxisome proliferator‑activated receptor (PPAR)‑γ, was selected using bioinformatics analysis, and its properties of low expression in lung adenocarcinoma cells and its role as a tumor suppressor gene were verified by western blot assay. The pathways related to immunity and inflammation, vascular function, cell proliferation, differentiation, development and apoptosis with the highest degree of enrichment and the mechanisms were explored through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Finally, the clinical prognosis in terms of the survival rate of patients in whom the drug is acting on the target was analyzed using the GEPIA database. The results indicated that Pulsatilla compounds can inhibit the proliferation of lung adenocarcinoma cells by blocking the cell cycle at the G1 phase. Subsequently, the related PPAR‑γ gene was verified as a tumor suppressor gene. Further analysis demonstrated that this finding was related to the PPAR signaling pathway and mitochondrial reactive oxygen species (ROS) production. Finally, the clinical prognosis was found to be improved, as the survival rate of patients was increased. In conclusion, Pulsatilla compounds were indicated to inhibit the viability and proliferation of lung adenocarcinoma H1299 cells, and the mechanism of action was related to PPAR‑γ, the PPAR signaling pathway and mitochondrial ROS. The present study provides novel insight to further explore the treatment of lung adenocarcinoma.
研究领域:
肿瘤学
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药理学
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生物信息学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2023
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IF 7.9
Hongkang Zhu,Fanglin Shen,Xiaochen Wang,He Qian,Yu Liu
Background Sleep deprivation (SD) has become a global health concern with serious consequences containing memory deficits and gastrointestinal dysfunctions. The gut-brain axis serves as a crucial link between the brain and gut, and the utilization of chlorogenic acid (CGA) presents a compelling strategy for mitigating or potentially resolving various neuroinflammation-associated disorders. However, it is still unknown how CGA may interact with the gut, microbiota and the brain during SD. Purpose This study aims to explore the therapeutic effect and underlying mechanism of microbiota-gut-brain axis by which CGA prevents SD-induced cognitive deficits. Study design and methods CGA (30, 60 mg/kg.bw.) was gavaged to C57BL/6 mice, and then submitted to 48-h SD. The cognitive and spatial learning abilities were investigated through behavioral tests. Furthermore, we explored the action mechanism of this compound with haematological analysis, histopathological examination, Western blot, ELISA and 16S rRNA gene pyrosequencing from colonic contents. Results The cognitive deficits induced by SD were significantly relieved by administration of CGA in a dose-dependent manner. The H&E staining of hippocampus and colon tissues indicated that pretreatment of CGA not only protected brain tissue from SD, but also maintained intestinal integrity. In the hippocampus, the increased pro-inflammatory neurometabolites were significantly prevented by CGA, and an immune profile capable of hippocampal-dependent spatial memory was improved via Nrf2/PPAR signaling pathways. The observed immunomodulatory effect was concomitant with augmentation of the intestinal barrier, as evidenced by the heightened expressions of tight junction proteins. 16s rRNA analysis of colonic contents revealed that levels of Clostridia_UCG-014 and LPS were significantly inhibited, and those of Lactobacillus and intestinal tight junction proteins were upregulated in the CGA group. Pathways of ko05322 (immune disease) and ko04610 (immune system) were significantly regulated by CGA. Based on PICRUSt2 algorithm, CGA probably influenced gut microbial functions via several metabolism pathways, such as arginine biosynthesis, pyrimidine metabolism and purine metabolism. Conclusion The present study first proved the efficacy and mechanism of CGA in alleviating SD-induced cognitive impairment and neuroinflammatory via creating a systemic protection, a bidirectional communication system connecting the gut with the brain. The intestinal barrier improvement and the reshaped “SD microbiota” profiles restored immunity functions, which were the main contributors to Nrf2/PPAR activation and the neuroprotective effect of CGA. Overall, this work provided novel insights of CGA, which would guide the more reasonable clinical use of CGA in the pathogenesis of sleep-related disorders.
研究领域:
神经科学
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免疫学
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微生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Comparative Biochemistry and Physiology D-Genomics & Proteomics
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2025
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IF 2.4
Bowen Yan,Zhaoshou Ran,Qiang Zhou,Jiaxin Zhu,Fei Kong,Jilin Xu
Docosahexaenoic acid (DHA), an essential omega-3 long-chain polyunsaturated fatty acid, is crucial for the development of marine mollusks. Despite its importance, the molecular mechanisms of DHA action in these organisms are poorly understood, primarily due to the lack of reliable in vitro models. This study utilizes the razor clam Sinonovacula constricta as a model organism, establishing a primary adherent cell culture from various tissues, with mantle tissue identified as the optimal source for its rapid migration and low contamination risk. Cells incubated with varying concentrations of DHA (0–400 μM) for 6 h exhibited a concentration-dependent accumulation of lipid droplets (LDs), highlighting the model's suitability for investigating lipid metabolism. Transcriptomic analysis of cells treated with 50 μM DHA identified 848 differentially expressed genes (DEGs), with 747 upregulated and 101 downregulated, indicating the complex effects of DHA. The top 20 significantly upregulated and downregulated DEGs revealed significant involvement in cell signaling transduction, extracellular matrix organization, and substance transport and metabolism. Particularly, lipid metabolism genes, including perilipin 2 and abhydrolase domain containing 2, as well as pathways such as the PPAR signaling pathway and sphingolipid metabolism, were significantly altered, suggesting a reprograming of fatty acid metabolism contributing to LD accumulation. Additionally, pathways related to immune response were notably affected, potentially enhancing cellular health. Collectively, this study provides the first comprehensive insights into the molecular mechanisms underlying DHA-induced LD accumulation in a marine mollusk model at the cellular level, laying a foundation for developing precise nutritional strategies involving DHA in S. constricta aquaculture.
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PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Yu Wenjing,Luo Rongsiqing,He Chunxiang,Li Ze,Yang Miao,Zhou Jinyong,He Jiawei,Chen Qi,Song Zhenyan,Cheng Shaowu
Background: The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.Methods: The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP)ihb20Tg/+), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin’s effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin’s regulation of PPAR/NF-κB pathway in these three models.Results: 1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.Conclusion: Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.
研究领域:
药理学
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神经科学
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糖尿病
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炎症
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代谢
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行为科学
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DOI
PubMed
高影响因子
CHEMOSPHERE
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2020
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IF 5.778
Jiafeng Zhou,Ruonan Shu,Chunan Yu,Ze Xiong,Qingfeng Xiao,Zezhi Li,Xiaoxian Xie,Zhengwei Fu
Trifluoromethanesulfonic acid (TFMS) is the shortest chain perfluorinated compound . Recently, it has been identified as a persistent and mobile organic chemical with a maximum concentration of 1 μg/L in the environment. However, its toxicological mechanism remains unclear. In this study, to evaluate the liver and intestinal toxicity of TFMS in mammals, male mice were orally exposed to 0, 1, 10 and 100 μg/kg for 12 weeks. Our results showed that TFMS exposure reduced the epididymal fat weight in mice, caused the decrease of serum and liver triglyceride (TG) level and the increase of serum low density lipoprotein (LDL) level. Also, we observed the inflammatory cell infiltration in the liver of mice exposed to 10 μg/kg and 100 μg/kg TFMS, which was coupled with the increased mRNA expression levels of inflammatory factors such as COX2 , TNF-α , IL-1β in the liver. In addition, the mRNA expression levels of lipid metabolism-related genes ( PPAR-α , ACOX , SCD1 , PPAR-γ , etc.) were significantly decreased in the liver of mice after exposure to both doses of TFMS. We also found TFMS exposure caused the imbalance of cecal gut microbiota and change of cecal microbiota diversity. KEGG pathway predictions showed that the exposure of 100 μg/kg TFMS changed the synthesis and degradation of ketone bodies, benzoate degradation and several other metabolic pathways. Our findings indicated that TFMS exposure disturbed the liver lipid metabolism possibly via altering the gut microbiota.
研究领域:
毒理学
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分子生物学
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微生物学
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环境科学
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产品关联
DOI
PubMed
高影响因子
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