WORLD JOURNAL OF GASTROENTEROLOGY
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2024
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IF 4.3
Kai-Di Chen,Kui-Ling Wang,Chen Chen,Yi-Jia Zhu,Wen-Wen Tang,Yu-Ji Wang,Ze-Peng Chen,Lin-Hai He,Yu-Gen Chen,Wei Zhang
BACKGROUND Constipation, a highly prevalent functional gastrointestinal disorder, induces a significant burden on the quality of patients' life and is associated with substantial healthcare expenditures. Therefore, identifying efficient therapeutic modalities for constipation is of paramount importance. Oxidative stress is a pivotal contributor to colonic dysmotility and is the underlying pathology responsible for constipation symptoms. Consequently, we postulate that hydrogen therapy, an emerging and promising intervention, can serve as a safe and efficacious treatment for constipation. AIM To determine whether hydrogen-rich water (HRW) alleviates constipation and its potential mechanism. METHODS Constipation models were established by orally loperamide to Sprague-Dawley rats. Rats freely consumed HRW, and were recorded their 24 h total stool weight, fecal water content, and charcoal propulsion rate. Fecal samples were subjected to 16S rDNA gene sequencing. Serum non-targeted metabolomic analysis, malondialdehyde, and superoxide dismutase levels were determined. Colonic tissues were stained with hematoxylin and eosin, Alcian blue-periodic acid-Schiff, reactive oxygen species (ROS) immunofluorescence, and immunohistochemistry for cell growth factor receptor kit (c-kit), PGP 9.5, sirtuin1 (SIRT1), nuclear factor-erythroid-2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Quantitative real-time PCR and western blot analysis were conducted to determine the expression level of SIRT1, Nrf2 and HO-1. A rescue experiment was conducted by intraperitoneally injecting the SIRT1 inhibitor, EX527, into constipated rats. NCM460 cells were induced with H 2 O 2 and treated with the metabolites to evaluate ROS and SIRT1 expression. RESULTS HRW alleviated constipation symptoms by improving the total amount of stool over 24 h, fecal water content, charcoal propulsion rate, thickness of the intestinal mucus layer, c-kit expression, and the number of intestinal neurons. HRW modulated intestinal microbiota imbalance and abnormalities in serum metabolism. HRW could also reduce intestinal oxidative stress through the SIRT1/Nrf2/HO-1 signaling pathway. This regulatory effect on oxidative stress was confirmed via an intraperitoneal injection of a SIRT1 inhibitor to constipated rats. The serum metabolites, β-leucine (β-Leu) and traumatic acid, were also found to attenuate H 2 O 2 -induced oxidative stress in NCM460 cells by up-regulating SIRT1. CONCLUSION HRW attenuates constipation-associated intestinal oxidative stress via SIRT1/Nrf2/HO-1 signaling pathway, modulating gut microbiota and serum metabolites. β-Leu and traumatic acid are potential metabolites that upregulate SIRT1 expression and reduce oxidative stress.
研究领域:
胃肠病学
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药理学
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分子生物学
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微生物学
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代谢组学
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DOI
PubMed
高影响因子
JOURNAL OF BIOLOGICAL CHEMISTRY
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2025
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IF 3.9
Juncheng Zhong,Xuebo Liu,Jiawei Wang,Huaming Liu,Geng Liu,Xiaobo Wen,Kun Wu
Very-long-chain fatty acids (VLCFAs), are vital for growth, development, and overall health. Zinc oxide nanoparticles (ZnO NPs), recognized for their high bioavailability and wide use in medicine and nutrition, have an unclear impact on lipid metabolism. This study explores how ZnO NPs impact VLCFA metabolism using yellow catfish ( Pelteobagrus fulvidraco ) as a model organism. In vivo , 240 yellow catfish were divided into a control group and a group fed 10 mg/kg ZnO NPs diet for 10 weeks. ZnO NPs administration significantly increased hepatic VLCFA content, accompanied by elevated triglyceride (TG) and total cholesterol (T-CHO) levels. Additionally, ZnO NPs reduced peroxisomal β-oxidation and peroxisome-ER (Po-ER) contacts. In vitro studies with yellow catfish hepatocytes confirmed these findings and explored the underlying mechanisms. ZnO NPs reduced Po-ER attachment and significantly decreased peroxisomal β-oxidation levels. ZnO NPs markedly decreased the expression and localization of ACBD5, a key protein involved in Po-ER interactions and VLCFA degradation. Overexpression of ACBD5 counteracted these effects, whereas knockdown mimicked them. Further experiments revealed that FOXO3 directly regulates ACBD5 by binding to its promoter. ZnO NPs increased the acetylation level of hepatocytes, inhibited the nuclear entry of FOXO3, and reduced the protein level of SIRT1. SIRT1 directly regulates FOXO3 deacetylation at lysine 243. Overall, ZnO NPs disrupt lipid homeostasis by downregulating ACBD5 via the SIRT1/FOXO3 axis, impairing peroxisomal function and Po-ER contacts. This study highlights the significance of the SIRT1 - FOXO3 - ACBD5 axis in managing VLCFA-related metabolic disorders.
研究领域:
纳米毒理学
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脂质代谢
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细胞生物学
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分子生物学
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环境毒理学
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营养科学
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2020
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IF 4.679
Rili Hao,Xinyu Song,Feng Li,Xintong Tan,Dongxiao Sun-Waterhouse,Dapeng Li
Exposure to nonbiodegradable cadmium (Cd) causes many health problems including the damage to the nervous system. This study aimed to increase knowledge about its neurotoxic effects and the neuroprotective potential of caffeic acid phenethyl ester (CAPE, a polyphenol abundant in honeybee propolis). In mice, CAPE (10 μmol/kg/day body weight) attenuated significantly learning and memory deficits induced by CdCl 2 (1.5 mg/kg/day body weight). For the CdCl 2 -treated mice, CAPE increased crossing number in open field test, decreased the alternation in Y-maze test, and increased the latency time and error number in step down test. CAPE also inhibited CdCl 2 -initiated Aβ accumulation and activation of pro-inflammatory factors and microglia in the brains. Therefore, CAPE could be a food-derived neuroprotective agent against Cd-induced neurotoxicity and neurodegenerative disorders, through attenuating neuronal apoptosis and neuroinflammation via the AMPK/SIRT1 pathway and amyloid-tau-neuroinflammation axis.
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PubMed
高影响因子
Food & Function
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2022
·Vol. 13
·期 5
·2647-2661
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IF 6.317
Yongfeng Ren,Dongxiao Sun-Waterhouse,Fangxin Ouyang,Xintong Tan,Dapeng Li,Longhua Xu,Bo Li,Yongli Wang,Feng Li
Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.
研究领域:
神经毒理学
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药理学
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行为神经科学
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分子生物学
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DOI
PubMed
高影响因子
Redox Biology
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2025
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IF 11.9
Jing Fu,Congping Su,Yin Ge,Zhou Ao,Li Xia,Yingxiang Chen,Yizheng Yang,Shiwei Chen,Rui Xu,Xiaoyan Yang,Kai Huang,Qin Fu
Cyclic adenosine monophosphate (cAMP) plays a major role in normal and pathologic signaling in the heart. Phosphodiesterase 4 (PDE4) is a major PDE degrading cAMP in the heart. There are inconsistencies concerning the roles of the PDE4 isoforms 4B and 4D in regulation of cardiac function. Cardiac PDE4B overexpression is beneficial in remodeling and heart failure (HF), however, the effect of PDE4D and PDE4 inhibitor in HF remains unclear. We generated global and conditional cardiac-specific heterozygous PDE4D knockout mice and adeno-associated virus serotype 9-PDE4D overexpression to determine the role of PDE4D in cardiac hypertrophy and HF. PDE4D upregulation was observed in failing hearts from human and isoproterenol injection and TAC mice. In vitro , isoproterenol stimulation increased PDE4D expression via PKA but had no effect on PDE4B expression in cardiomyocytes. PDE4D overexpression per se induced oxidative stress, mitochondrial damage and cardiomyocyte hypertrophy by decreasing PINK1/Parkin-mediated mitophagy through inhibiting cAMP-PKA-CREB-Sirtuin1 (SIRT1) signaling pathway, while PDE4B overexpression did not affect CREB-SIRT1 pathway and mitophagy but exhibited a protective effect on isoproterenol-induced oxidative stress and hypertrophy in cardiomyocytes. PDE4D silencing or inhibition with PDE4 inhibitor roflumilast ameliorated isoproterenol-induced mitochondrial injury and cardiomyocyte hypertrophy. In vivo , ISO injection or TAC inhibited cardiac mitophagy and caused cardiac hypertrophy and HF, which were ameliorated by roflumilast or cardiac-specific PDE4D haploinsufficiency. Conversely, cardiac PDE4D overexpression suppressed cardiac mitophagy and abolished the protective effects of global PDE4D haploinsufficiency on TAC-induced cardiac hypertrophy and HF. In conclusion, these studies elucidate a novel mechanism by which sustained adrenergic stimulation contributes to cardiac hypertrophy and HF by increasing PDE4D via cAMP-PKA signaling, which in turn reduces cAMP-PKA activity, resulting in cardiomyocyte hypertrophy and mitochondrial injury via inhibition of CREB-SIRT1 signaling-mediated mitophagy . PDE4D inhibition may represent a novel therapeutic strategy for HF.
研究领域:
心血管研究
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药理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2019
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IF 4.784
Qiang Chu,Ruoyi Jia,Wen Chen,Yangyang Liu,Yonglu Li,Xiang Ye,Yong Jiang,Xiaodong Zheng
Ethyl Carbamate (EC), as a carcinogen widely found in fermented foods, was verified that its cytotoxicity was associated with oxidative stress. Polysaccharides from natural sources due to their antioxidative capacity have attracted great attention in the past time. In this study, purified polysaccharide from Tetrastigma hemsleyanum vines (TVP) with 64.89 kDA was extracted and conducted multiple analysis to identify its structural information. It could be discovered that TVP was composed of mannose, rhamnose, glucuronic acid, glucose, galactose, and arabinose. In vitro , TVP could inhibit cytotoxicity and genotoxicity, attenuate oxidative damage and mitochondrial dysfunction induced by EC in Caco-2 cells. Meanwhile, TVP could suppress apoptosis by mTOR and Bcl-2 signaling pathways, ameliorate oxidative via Sirt1-FoxO1 and Nrf2-Keap1 signaling pathways. In vivo , EC as well triggered the decline of survival and athletic ability in Caenorhabditis elegans ( C. elegans ) and TVP could reverse the decline. In the meantime, TVP could ameliorate oxidative damage in N2 and daf-2 (-) mutant but fail in daf-16 (-) mutant, which suggested that DAF-16 (FOXO) might affect the antioxidative protection of TVP in C. elegans . In brief, our results manifested that TVP could attenuate EC-induced cytotoxicity both in vitro and in vivo .
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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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
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生物材料
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组织工程
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免疫学
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糖尿病研究
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产品关联
DOI
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
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2026
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IF 11.3
Jinchen Jiang,Haixia Meng,Zhenhao Shu,Nannan Zhao,Xiaojun Lin,Jianglan Li,Minjun Qin,Siyu Wu,Lianglin Qiu
As an emerging alternative to perfluorooctanesulfonate (PFOS), 6:2 chlorinated polyfluoroalkyl ether sulfonate (6:2 Cl-PFAES) is associated with male reproductive disorders, yet its testicular targets and mechanisms remain unclear. This study combined in vivo exposure of male C57BL/6J mice (0, 4, 40, and 400 μg/L for 18 weeks) and in vitro assays in primary Leydig cells to demonstrate that 6:2 Cl-PFAES dose-dependently reduced sperm count and serum/testicular testosterone, accompanied by testicular interstitial vacuolation. Transcriptomics and metabolomics demonstrated the concurrent significant enrichment of autophagy pathways and disruption of lipid metabolism. Mechanistically, 6:2 Cl-PFAES suppressed expressions of Sirtuin 1 (SIRT1), ras-related GTP binding protein 7 (RAB7), and deacetylation of forkhead box class O1 (FOXO1), thereby impairing lipophagy flux and promoting lipid droplets accumulation. Molecular docking indicated comparable binding affinity of 6:2 Cl-PFAES and PFOS to SIRT1 (−10.4 kcal/mol), and further research demonstrated that 6:2 Cl-PFAES reduced the deacetylation activity of SIRT1. Crucially, Sirt1 overexpression in transgenic mice (Sirt1TG) or pharmacological activation of SIRT1 (SRT1720) and RAB7 (ML-098) rescued testosterone synthesis and restored lipophagy flux. This study identifies the SIRT1–FOXO1–RAB7 axis as a core target for 6:2 Cl-PFAES-induced suppression of testosterone biosynthesis via lipophagy dysregulation, providing critical molecular insights for assessing the reproductive risks of PFOS alternatives.
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Shiyao Guo,Mingyue Zhang,Ke Zhang,Xiaotong Lu,Peiran Chen,Bangliu Yang,Xueqian Wang,Yuhong Zhuo,Dongqin Yu,Chao Qi,Kaiyong Cai
Osteoporosis compromises bone repair by generating a dysregulated microenvironment marked by excessive accumulation of reactive oxygen species (ROS) and a reduced pH. This pathological state leads to mitochondrial dysfunction, impaired osteogenic differentiation, and excessive activation of osteoclasts. In this study, a ROS-responsive titanium implant coating composed of calcium carbonate-mineralized nicotinamide mononucleotide (NMN) nanoparticles, lipoic acid-modified gelatin (LAMG), and sodium alginate (SA) is developed, designed to enhance osseointegration through dual synergistic mechanisms. First, the LAMG hydrogel effectively scavenges excess ROS, while calcium carbonate neutralizes H + ions and restores physiological pH levels, thereby reducing acid-induced bone resorption and inhibiting osteoclast activity. Second, ROS and H + ions-triggered release of NMN enhances the intracellular NAD⁺/NADH ratio in bone marrow mesenchymal stem cells, activates the SIRT1 signaling pathway, restores mitochondrial function, and promotes osteogenic differentiation. By concurrently remodeling the pathological bone microenvironment and repairing mitochondrial dysfunction, this multifunctional coating suppresses osteoclast-mediated bone resorption while facilitating osteoblast formation, thereby enhancing peri-implant osseointegration under osteoporotic conditions. This strategy not only presents a promising therapeutic approach for functionalizing titanium implants but also offers a potentially translatable platform for treating osteoporotic bone defects.
研究领域:
生物材料
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组织工程
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骨科
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再生医学
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纳米医学
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骨骼生物学
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生物医学工程
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Lei Huang,Shihao Zhang,Mengxuan Bian,Xingdong Xiang,Lan Xiao,Jiayi Wang,Shunyi Lu,Weisin Chen,Cheng Zhang,Guokang Mo,Libo Jiang,Yulin Li,Jian Zhang
The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo . Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significance Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro . Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.
研究领域:
生物医学工程
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材料科学
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组织工程
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骨科
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生物材料
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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）