TOXICOLOGY LETTERS
·
2020
·
IF 3.569
Jianxin Ye,Kangnan Zhang,Xindi Yuan,Haosen Ji,Miner Hu,Tongliang Huang,Ren-Shan Ge
Di -n- hexyl phthalate (DNHP) is commonly used as a plasticizer. However, whether DNHP influences Leydig cell development during puberty remains unexplored. In this study, DNHP (0, 10, 100, and 1000 mg/kg) was administered via gavage to 35-day-old male Sprague-Dawley rats for 21 days. Serum levels of testosterone, luteinizing hormone, follicle-stimulating hormone, Leydig cell number, the expression of Leydig and Sertoli cell genes and proteins were investigated. DNHP significantly increased serum testosterone levels at 10 mg/kg but lowered its level at 1000 mg/kg. DNHP significantly increased luteinizing hormone levels at 1000 mg/kg without affecting follicle-stimulating hormone levels. DNHP increased Leydig cell number at all doses but down-regulated the expression of Lhcgr , Hsd3b1 , Hsd17b3 , and Hsd11b1 in Leydig cell per se at 1000 mg/kg. DNHP elevated phosphorylation of ERK1/2 and GSK-3β at 10 mg/kg but decreased SIRT1 and PGC-1α levels at 1000 mg/kg. In conclusion, DNHP exposure causes Leydig cell hyperplasia possibly via stimulating phosphorylation of ERK1/2 and GSK-3β signaling pathways.
研究领域:
毒理学
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内分泌学
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生殖生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Bao-Feng Zhao,Fan Wang,Jia-Chen Sun,Jin-Peng Gao,Li-Juan Zhao,Zhao-Liang Shen,Zhi-Peng Li,Yi-Xuan Wang,Yuan Wang,Dan Li,Xi-Fan Mei
Spinal cord injury (SCI) inflicts devastating consequences for health. While drugs have been employed to alleviate SCI symptoms, their complex synthesis procedures and the need for specialized drug delivery raise concerns regarding administration. Herein, we utilize a green synthesis protocol to produce polymer quantum dots (Pdots) from polyvinylpyrrolidone precursors, empowered by the catalytic prowess of copper. These Copper-catalyzed Pdots (CPdots) not only offer enhanced improved fluorescence properties but also exhibit remarkable antioxidant, anti-inflammatory, and mitochondrial function repair effects. An intriguing finding emerged from our research as CPdots were observed to activate the AMPK/PGC-1α/Sirt3 pathway-a distinctive molecular mechanism that combats mitochondrial dysfunction, and mitigates calcium overload associated with acute SCI. Furthermore, the rapid metabolism and exceptional biocompatibility of our CPdots reinforce their safety and efficacy.
研究领域:
神经科学
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材料科学
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生物医学工程
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药理学
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DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Meimei Shan,Xingrui Xu,Chuanqi Chu,He Wang,Chengting Zhang,Shengbao Cai
Fatigue is an intricate physiological phenomenon, causing serious secondary concerns and bioregulation disorders. The objective of this research was to look into the anti-fatigue effect and potential mechanisms of natural ingredients in methanol extract of edible oil from Rhus chinensis Mill. fruits (PMRO). Results showed that a total of 18 fatty acids and 9 anacardic acids were identified by GC-MS and UHPLC-ESI-HCES/MS in PMRO. PMRO significantly increased the weight-bearing swimming time. Further investigations showed that PMRO significantly improved physiological indexes related to fatigue and regulated the oxidative stress (Keap1/Nrf2) and energy metabolism (AMPK/PGC-1α)-related proteins expression to exert anti-fatigue effects. The 16S rRNA sequence analysis indicated that a potential role of PMRO in modulating the abundance of gut bacteria and influencing the short-chain fatty acids content, thereby exerting an anti-fatigue effect. Therefore, the natural ingredients in PMRO may hold promise as a dietary supplement capable of delaying body fatigue.
研究领域:
营养学
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药理学
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微生物学
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生物化学
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产品关联
DOI
高影响因子
Molecular Medicine Reports
·
2025
·Vol. 31
·期 3
·1-12
·
IF 3.5
Xiangli Yan,Siqi Quan,Roujia Guo,Zibo Li,Ming Bai,Baoying Wang,Pan Su,Erping Xu,Yucheng Li
Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.
研究领域:
神经科学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2024
·
IF 3.5
Wang Liwei,Zhang Lu,Yun Yang,Liang Tingting,Yan Chaoqun,Mao Zhuoya,Zhang Jingfang,Liu Baoshe,Zhang Jian,Liang Taigang
Occupational and unintentional exposure of zinc oxide nanoparticles (ZnONPs) raises concerns regarding their neurotoxic potential and there is an urgent need for the development of effective agents to protect against the toxic effects of ZnONPs. Astragalus memeranaceus (AM), a famous Traditional Chinese Medicine, as well as its bioactive components, showing a potential neuroprotective function. This study aims to investigate the neuroprotective effects of bioactive components of AM against ZnONPs-induced toxicity in human neuroblastoma SH-SY5Y cells and its underlying mechanisms. The cell apoptosis, ROS generation, MMP changes, mitochondrial fission/fusion, biogenesis, and mitophagy were assessed. In this study, AM treatment inhibited ZnONPs-induced cell apoptosis and ROS overproduction in SH-SY5Y cells. And astragaloside IV (ASIV) played a dominant role in the attenuation of cytotoxicity after ZnONPs exposure, rather than flavonoids and polysaccharides. ASIV treatment significantly reduced ROS generation and MMP collapse in ZnONPs-exposed cells. Furthermore, the protein expressions of mitochondrial biogenesis (PGC-1α), fusion (Mfn1 and Mfn2), and fission (Drp1) were markedly increased. Meanwhile, the PINK1/Parkin-mediated mitophagy was activated after ASIV administration, which ameliorated ZnONPs-induced SH-SY5Y cell death. Collectively, ASIV administration mitigated ZnONPs-induced cytotoxicity in SH-SY5Y cells through restoring mitochondrial quality control process, which hinted the protective role of ASIV in ZnONPs-induced neurotoxicity. Graphical abstract
研究领域:
药理学
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毒理学
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神经科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
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2018
·Vol. 8
·期 65
·37117-37128
·
IF 2.936
Guixin Wu,Min Wen,Lin Sun,Huitao Li,Yubei Liu,Rui Li,Feihua Wu,Rong Yang,Yining Lin
Geniposide (GE) is a major component isolated from Gardenia jasminoides Ellis, which has been used to treat cholestasis liver diseases. Our previous study has shown that GE could notably increase mRNA and protein expressions of BSEP in cholestatic rats. BSEP plays a critical role in maintenance of the enterohepatic circulation of bile acids. BSEP could be regulated by the transactivation pathway of farnesoid X receptor (FXR) and nuclear factor erythroid 2-related factor (Nrf2). Here the mechanisms for BSEP regulation by GE were investigated. GE induced the mRNA levels of BSEP in HepG2 cells and cholestatic mice, and knockdown of FXR and Nrf2 reduced the mRNA expression of BSEP at varying degrees after treatment of GE. FXR acts as the major regulator of BSEP transcription. The involvement of FXR regulated BSEP expression by GE was further investigated. An enhancement was observed in FXR-dependent BSEP promoter activation using luciferase assay. ChIP assay further confirmed the interaction between FXR and BSEP after GE treatment. Using siRNA and ChIP assays, we demonstrated that peroxisome-proliferator-activated receptor γ co-activator-1α (PGC-1α) and co-activator-associated arginine methyltransferase 1 (CARM1) were predominantly recruited to the BSEP promoter upon FXR activation by GE. In conclusion, GE regulated the expression of BSEP through FXR and Nrf2 signaling pathway. The FXR transactivation pathway was enhanced by increasing recruitment of coactivators PGC-1α and CARM1 upon GE treatment, coupled with an increased binding of FXR to the BSEP promoter.
研究领域:
药理学
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分子生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Han Xiaoying,Zhang Yi,Qiao Ou,Ji Haixia,Zhang Xinyu,Wang Wenzhe,Li Xia,Wang Juan,Li Dekun,Ju Aichun,Liu Changxiao,Gao Wenyuan
Yiqi Fumai lyophilized injection (YQFM) is the recombination of Sheng mai san (SMS).YQFM has been applied clinically to efficaciously and safely treat chronic heart failure (CHF). However, the mechanism of YQFM is still not fully elucidated. The purpose of our study was to investigate the protective mechanism of YQFM against abdominal aortic coarctation (AAC) in rats by proteomic methods. After YQFM treatment, the cardiac function were obviously meliorated. One hundred and fifty-seven important differentially expressed proteins (DEPs) were identified, including 109 in model rat compared with that in control rat (M:C) and 48 in YQFM-treated rat compared with that in model rat (T:M) by iTRAQ technology to analyze the proteomic characteristics of heart tissue. Bioinformatics analysis showed that DEPs was mainly involved in the body’s energy metabolism and was closely related to oxidative phosphorylation. YQFM had also displayed efficient mitochondrial dysfunction alleviation properties in hydrogen peroxide (H2O2)-induced cardiomyocyte damage by Transmission Electron Microscope (TEM), Metabolic assay, and Mitotracker staining. What’s more, the levels of total cardiomyocyte apoptosis were markedly reduced following YQFM treatment. Furthermore, Western blot analysis showed that the expressions of peroxisome proliferator activated receptor co-activator-1α(PGC-1α) (p < 0.01 or p < 0.001), perixisome proliferation-activated receptor alpha (PPAR-α) (p < 0.001)and retinoid X receptor alpha (RXR-α) were upregulated (p < 0.001), PGC-1α as well as its downstream effectors were also found to be upregulated in cardiomyocytes after YQFM treatment(p < 0.001).These results provided evidence that YQFM could enhance mitochondrial function of cardiomyocytes to play a role in the treatment of CHF by regulating mitochondrial biogenesis-related proteins.
研究领域:
心脏病学
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药理学
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蛋白质组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Wenshuai Hao,Ruitao Cha,Mingzheng Wang,Juanjuan Li,Hongbo Guo,Ran Du,Fengshan Zhou,Xingyu Jiang
Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.
研究领域:
纳米技术
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药理学
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胃肠病学
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2021
·Vol. 12
·期 10
·4582-4590
·
IF 5.396
Xue-Yan Dai,Yi Zhao,Jing Ge,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Jin-Long Li
Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. Di(2-ethylhexyl) phthalate (DEHP) is regarded as a universal environmental pollutant. To clarify the potential protective effect of Lyc on DEHP-induced splenic injury, 140 male mice were randomized into seven groups: control (distilled water), vehicle control (corn oil per day), Lyc (5 mg per kg BW per day), DEHP (500 or 1000 mg per kg BW per day), and DEHP combined Lyc group, respectively. All experimental animals were treated by oral gavage for 28 days. The results that showed DEHP exposure significantly up-regulated the mRNA and protein expression of the sirtuin family (except SIRT4-5), PGC-1α, OPA1, Drp1, MFN1/2, NRF1, TFAM, Parkin and PINK in DEHP-treated alone groups and the SOD2 and LC3-II protein expression were also in accordance with the above changes. These were accompanied with an increase of the number of inflammatory cells and rate of mitochondrial damage, and autophagosome formation in the spleen. Notably, Lyc supplementation facilitated all these changes to effectively return to the normal level, indicating that Lyc exerts protective effects against DEHP-induced splenic toxicity. Altogether, the protective effects of Lyc may be a strategy to ameliorate DEHP-induced spleen damage.
研究领域:
毒理学
·
药理学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Sijia Chen,Wanzhen Lei,Qi Liu,Xiaoting Wang,Kehan Chen,Xiaoyu Lin,Xuejiu Wang
Patients with diabetes frequently experience impaired wound healing, a challenge commonly attributed to immune imbalance and oxidative stress; notably, these issues arise from mitochondrial dysfunction. In this study, we fabricate a naturally derived bioactive hydrogel by incorporating resveratrol-loaded mesoporous polydopamine nanoparticles into silk microfibers-reinforced methacrylated silk network (SS/MPDA@RES), which exhibits appropriate injectability, light-curable performance and mechanical strength. It effectively scavenges excessive ROS to protect mitochondria, restore ATP production and remodel redox homeostasis. More importantly, it promotes mitochondrial biogenesis, respiratory capacity and oxidative phosphorylation via the AMPK/SIRT1/PGC-1α signaling axis, thereby reprogramming macrophages to the anti-inflammatory phenotype. In vivo , SS/MPDA@RES hydrogel promotes wound healing in diabetic rats by modulating immunity, inhibiting early inflammation, and accelerating angiogenesis and collagen deposition. Targeting mitochondria to regulate immune and redox homeostasis provides a novel avenue for the design of future tissue regeneration materials, with SS/MPDA@RES emerging as a potential treatment strategy for diabetic wounds.
研究领域:
材料科学
·
生物材料
·
组织工程
·
免疫学
·
糖尿病研究
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产品关联
DOI
高影响因子
Advanced Science
·
2024
·
IF 14.3
Junpeng Xu,Peng Dai,Chen Zhang,Na Dong,Caiyan Li,Chonghui Tang,Zhihao Jin,Shih-Ho Lin,Luyang Ye,Tianmiao Sun,Yukai Jin,Fenzan Wu,Lihua Luo,Ping Wu,Shengcun Li,Xiaokun Li,Shan-hui Hsu,Dawei Jiang,Zhouguang Wang
Parkinson's disease (PD) is one of the most common long-term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly translational and challenging. Here, a hierarchical bioactive hydrogel (OACDP) is designed with asynchronous release based on PD pathology. The hydrogel with caffeic acid-grafted polymer main chain is crosslinked using a micellar nanocrosslinker, with sufficient modulus (≈167 Pa), antioxidant activity (> 50%), injectability (30-gauge syringe needle), and shape-adaptability. Each of the three drugs (caffeic acid, fibroblast growth factor 21, and Edaravone) is separately engaged in different micro- or nanostructures of the hydrogel and released with asynchronous kinetics of first-order release, zero-order release, or matching Korsmeyer–Peppas model. The triple-loaded hydrogel is injected into the brains of PD rats, showing behavioral improvement. Histological analysis revealed that the triple-loaded OACDP hydrogels are effective in achieving immediate neuroprotection, i.e., reduction the loss of tyrosine hydroxylase in substantia nigra compacta and striatum (retained ≈10-fold versus control), decreasing oxidative stress, reducing astrocyte and microglia activation, and stimulating the AMPK/PGC-1α axis to regulate the mitochondrial function, providing a multi-dimensional PD therapy. The asynchronous release of OACDP hydrogel provides a new conception for PD treatment and other neurodegenerative diseases.
研究领域:
神经科学
·
药学
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生物材料
·
神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Siming Wang,Yuchu Zhao,Junjie Yang,Shichao Liu,Weifeng Ni,Xueyuan Bai,Ze Yang,Daqing Zhao,Meichen Liu
Ethnopharmacological relevance Panax ginseng C.A. Mey (PG) is famous for “Qi-tonifying” effect, which has a medicinal history of more than 2 millennia. Modern pharmacology has confirmed that the “Qi-tonifying” effect of PG may be closely related to its pharmacological properties such as anti-oxidation, antineoplastic and treatment of cardiovascular disease. As one of the earliest cells affected by oxidative stress, RBCs are widely used in the diagnosis of diseases. Ginseng polysaccharide (GPS), is one of the major active components of PG, which plays an important role in resisting oxidative stress, affecting energy metabolism and other effects. However, the molecular mechanism explaining the “Qi-tonifying” effect of GPS from the perspective of RBCs oxidative damage has not been reported. Aim of the study This study aimed to investigate the protective effect of GPS on oxidatively damaged RBCs using in vitro and in vivo models and explore the molecular mechanisms from the perspective of glycolysis and gluconeogenesis pathways. To provides a theoretical basis for the future research of antioxidant drugs. Materials and methods Established three different in vitro and in vivo research models: an in vitro model of RBCs exposed to hydrogen peroxide (H 2 O 2 ) (40 mM), an in vivo model of RBCs from rats subjected to exhaustive swimming, and an in vitro model of BRL-3A cells exposed to H 2 O 2 (25 μM). All three models were also tested in the presence of different concentrations of GPS. Results The findings showed that GPS was the most potent antagonist of H 2 O 2 -induced hemolysis and redox inbalance in RBCs. In exhaustive exercise rats, GPS ameliorated RBVs hemolysis, including reducing whole-blood viscosity (WBV), improving deformability, oxygen-carrying and -releasing capacities, which was related to the enhancing of antioxidant capacity . Moreover, GPS promoted RBCs glycolysis in rats with exhaustive exercise by recovering the activities of glycolysis-related enzymes and increasing band 3 protein expression, thereby regulating the imbalance of energy metabolism caused by oxidative stress. Furthermore, we demonstrated that GPS improved antioxidant defense system, enhanced energy metabolism, and regulated gluconeogenesis via activating PPAR gamma co-activator 1 alpha (PGC-1α) pathway in H 2 O 2 -exposed BRL-3A cells. Mechanistically, GPS promoted glycolysis and protected RBCs from oxidative injury was partly dependent on the regulation of gluconeogenesis, as inhibition of gluconeogenesis by metformin (Met) attenuates the regulation of antioxidant enzymes and key enzymes of glycolytic by GPS in exhaustive exercise rats. Conclusion This study demonstrates that GPS protects RBCs from oxidative stress damage by promoting RBCs glycolysis and liver gluconeogenesis pathways. These results may contribute to the study of new RBCs treatments to boost antioxidant capacity and protect RBCs against oxidative stress.
研究领域:
药理学
·
生物化学
·
细胞生物学
·
民族药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）