LABORATORY INVESTIGATION
·
2020
·Vol. 100
·期 9
·1223-1237
·
IF 4.197
Kong Huimin,Wang Huaili,Zhuo Zhihong,Li Zhenbiao,Tian Peichao,Wu Jing,Liu Jian,Chen Zheng,Zhang Jiyao,Luo Qiang
MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.
研究领域:
神经科学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF BIOTECHNOLOGY
·
2026
·
IF 4
Mengjun Sun,Chunliu Mi,Tiantian Dong,Jingwen Xue,Yan Lin,Shaolei Geng,Qiuli Sun,Xinjian Chang,Tianyun Wang
7,8-DHF enhances recombinant protein expression 1.5-1.6 fold and reduces antibody aggregation by 6.0% in CHO cells. • 7,8-DHF elevates NAD+ to activate SIRT1-PGC-1β, improving mitochondrial energy synthesis and reducing lactate. • 7,8-DHF upregulates BCL-2 and downregulates BAX/cleaved caspase-3, inhibiting apoptosis in CHO cells. • 7,8-DHF acts as a metabolic modulator to overcome aerobic glycolysis limitations in biopharmaceutical production. Chinese hamster ovary (CHO) cells serve as a critical mammalian system for producing therapeutic proteins in biopharmaceuticals. However, these cells exhibit highly active aerobic glycolysis during culture, which leads to reduced energy conversion efficiency and excessive lactic acid accumulation. This metabolic dysregulation can further impair cell growth and recombinant protein expression. Enhancing the endogenous NAD⁺ level is critical for improving cellular metabolism; however, current technical approaches face significant challenges. In the present study, we found that 7,8-dihydroxyflavone increased the expression of recombinant proteins in CHO cells by 1.6- and 1.5-fold, respectively, while reducing antibody aggregation by approximately 6.0%. Transcriptome and metabolic pathway analyses revealed that the elevated intracellular NAD⁺ content activated the SIRT1-PGC-1β pathway, which modulates mitochondrial energy synthesis and enhances antioxidant capacity while mitigating lactate accumulation in the glycolytic pathway. Furthermore, 7,8-dihydroxyflavone significantly inhibited apoptosis by upregulating BCL-2 expression and downregulating BAX and cleaved caspase-3 expression. Taken together, these findings indicate that 7,8-dihydroxyflavone may serve as a promising metabolic modulator for recombinant protein production.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2026
·
IF 17.1
Jiaxin Su,Lingcheng Wu,Huiru Zhu,Haoru Wang,Xiaoya He,Bing Liang,Jinhua Cai
Introduction Acute kidney injury (AKI) is a devastating global health burden. Its pathogenesis, particularly in ischemia/reperfusion (I/R) injury, centers on a vicious cycle between a reactive oxygen species (ROS)-driven inflammatory storm and severe mitochondrial dysfunction in renal tubular cells. While activation of the SIRT1/PGC-1α pathway is a promising therapeutic target for mitochondrial recovery, its potent agonist resveratrol (Rsv) suffers from poor bioavailability, and monotherapy fails to address the concomitant inflammatory pathology. Objective This study aimed to develop a kidney-targeted theranostic nanoplatform that synergistically breaks this pathological cycle. We hypothesized that a nanoplatform co-delivering Rsv and a ROS-scavenging component could concurrently suppress inflammation via direct ROS elimination and restore mitochondrial homeostasis via SIRT1/PGC-1α activation, with integrated magnetic resonance imaging (MRI) capability for monitoring. Methods We engineered a theranostic nanoplatform designated Rsv@HMnO 2 -HA (HMRH NPs). The platform was constructed by loading Rsv into hollow mesoporous manganese dioxide (HMnO 2 ) nanozymes, followed by surface coating with hyaluronic acid (HA) for active targeting to CD44 receptors over expressed on injured renal tubules. The system’s physicochemical properties were thoroughly characterized. Its therapeutic efficacy and theranostic performance were systematically evaluated in a well-established murine model of renal I/R-induced AKI, using a combination of biochemical assays, histological analysis, molecular biology techniques, and in vivo MRI. Results HMRH NPs successfully accumulated in injured kidneys and disassembled in situ. The HMnO 2 shell effectively scavenged excess ROS, attenuating the inflammatory response. The co-released Rsv activated the SIRT1/PGC-1α pathway, restored mitochondrial biogenesis, and improved cellular energy homeostasis. The released Mn 2+ ions enabled clear T 1 -weighted MRI contrast, allowing real-time visualization of renal targeting and therapeutic progression. Conclusion The results conclusively demonstrate that the HMRH NPs successfully implements a synergistic two-pronged therapeutic strategy. By co-delivering a ROS-scavenger and a mitochondrial-regenerative agent directly to the site of injury, the platform effectively disrupts the critical pathological crosstalk between inflammation and mitochondrial damage in AKI. This work presents a holistic, targeted, and image-guided nanomedicine strategy, offering a promising approach for the effective treatment and monitoring of AKI.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APOPTOSIS
·
2023
·Vol. 28
·期 3
·607-626
·
IF 7.2
Yu Li-Ming,Dong Xue,Huang Tao,Zhao Ji-Kai,Zhou Zi-Jun,Huang Yu-Ting,Xu Yin-Li,Zhao Qiu-Sheng,Wang Zhi-Shang,Jiang Hui,Yin Zong-Tao,Wang Hui-Shan
Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2023
·Vol. 13
·期 1
·1-13
·
IF 4.6
Li Shaocong,He Qi,Chen Baihao,Zeng Jiaxu,Dou Xiangyun,Pan Zhaofeng,Xiao Jiacong,Li Miao,Wang Fanchen,Chen Chuyi,Lin Yuewei,Wang Xintian,Wang Haibin,Chen Jianfa
Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Yongjian Guo,Chengju Luo,Yuening Sun,Wenjing Guo,Ruitian Zhang,Xin Zhang,Xue Ke,Libin Wei
Mitochondria dynamically change their morphology via fusion and fission, a process called mitochondrial dynamics. Dysregulated mitochondrial dynamics respond rapidly to metabolic cues, and are linked to the initiation and progression of diverse human cancers. Metabolic adaptations significantly contribute to tumor development and escape from tissue homeostatic defenses. In this work, we identified oroxylin A (OA), a dual GLUT1/mitochondrial fusion inhibitor, which restricted glucose catabolism of hepatocellular carcinoma cells and simultaneously inhibited mitochondrial fusion by disturbing SIRT1/PDK2/PARL axis. Based the dual action of OA in metabolic regulation and mitochondrial dynamics, further results revealed that mitochondrial functional status and spare respiratory capacity (SRC) of cancer cells had a close correlation with mitochondrial metabolic plasticity, and played important roles in the susceptibility to cancer therapy aiming at glucose restriction. Cancer cells with healthy mitochondria and high SRC exhibit greater metabolic flexibility and higher resistance to GLUT1 inhibitors. This phenomenon is attributed to the fact that high SRC cells fuse mitochondria in response to glucose restriction, enhancing tolerance to energy deficiency, but undergo less mitochondrial oxidative stress compared to low SRC cells. Thus, inhibiting mitochondrial fusion breaks mitochondrial metabolic plasticity and increases cancer cell susceptibility to glucose restriction therapy. Collectively, these finding indicate that combining a GLUT1 inhibitor with a mitochondrial fusion inhibitor can work synergistically in cancer therapy and, more broadly, suggest that the incorporations of mitochondrial dynamics and metabolic regulation may become the targetable vulnerabilities bypassing the genotypic heterogeneity of multiple malignancies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2021
·
IF 4.932
Xinrui Li,Peiquan Yu,Yinghua Yu,Ting Xu,Jiao Liu,Yuan Cheng,Xia Yang,Xiaoying Cui,Cui Yin,Yi Liu
Hyperglycemia-induced neuroinflammation promotes the progression of diabetic encephalopathy. Hydrogen sulfide (H 2 S) exerts anti-inflammatory and neuroprotective activities against neurodegenerative diseases. However, the effects of H 2 S on hyperglycemia-induced neuroinflammation has not been investigated in neurons. Herein, by using HT-22 neuronal cells, we found that high glucose decreased the levels of endogenous H 2 S and its catalytic enzyme, cystathionine-β-synthase (CBS). The administration of sodium hydrosulfide (NaHS, a H 2 S donor) or S-adenosylmethionine (SAMe, an allosteric activator of CBS) restored high glucose-induced downregulation of CBS and H 2 S levels. Importantly, H 2 S ameliorated high glucose-induced inflammation in HT-22 cells, evidenced by NaHS or SAMe inhibited the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) expression in HT-22 cells exposed to high glucose. Furthermore, NaHS or SAMe restored the SIRT1 level and the phosphorylation of mTOR and NF-κB p65 disturbed by high glucose in HT-22 cells, suggesting H 2 S reversed high glucose-induced alteration of SIRT1-mTOR/NF-κB signaling pathway. Our results demonstrated that exogenous H 2 S treatment or enhancing endogenous H 2 S synthesis prevents the inflammatory processes in the neurons with the exposure of high glucose. Therefore, increasing the H 2 S level using NaHS or SAMe might shed light on the prophylactic treatment of diabetic encephalopathy.
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2021
·Vol. 24
·期 6
·1-9
·
IF 2.952
Juanjuan Huang,Xianfeng Chen,Aihua Xie
Formononetin has proven to be anti‑inflammatory and able to alleviate symptoms of certain allergic diseases. The present study aimed to determine and elucidate the potential effects of formononetin in allergic rhinitis. JME/CF15 cells were pretreated with formononetin at different doses, followed by stimulation with IL‑13. Cell Counting Kit‑8 assay was performed to determine the cytotoxicity of formononetin. The expression levels of inflammation‑related proteins, histamine, IgE, TNF‑α, IL‑1β, IL‑6, granulocyte‑macrophage colony‑stimulating factor and eotaxin in IL‑13‑stimulated JME/CF15 cells were detected using ELISAs. The expression levels of phosphorylated‑NF‑κB p65, NF‑κB p65 and cyclooxygenase‑2 (Cox‑2) were analyzed using western blotting. Reverse transcription‑quantitative PCR, western blotting and immunofluorescence were performed to measure the levels of mucin 5AC oligomeric mucus/gel‑forming. Expression levels of sirtuin 1 (SIRT1) and nuclear erythroid factor 2‑related factor 2 (Nrf2) proteins were also measured using western blotting. The results of the present study revealed that formononetin exerted no cytotoxic effect on the viability of JME/CF15 cells. Following stimulation of JME/CF15 cells with IL‑13, formononetin suppressed the upregulated expression levels of proinflammatory cytokines. IL‑13‑induced formation of mucus was also attenuated by formononetin treatment. Furthermore, it was found that the SIRT1/Nrf2 signaling pathway was activated in formononetin‑treated JME/CF15 cells, whereas treatment with the SIRT1 inhibitor, EX527, reversed the effects of formononetin on IL‑13‑induced inflammation and mucus formation in JME/CF15 cells. In conclusion, the findings of the current study indicated that formononetin may activate the SIRT1/Nrf2 signaling pathway, thereby inhibiting IL‑13‑induced inflammation and mucus formation in JME/CF15 cells. These results suggested that formononetin may represent a promising agent for the treatment of allergic rhinitis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Yin Zhihui,Geng Xinyue,Zhang Zhengyi,Wang Ying,Gao Xiaoyan
Neuronal mitochondrial oxidative stress induced by β-amyloid (Aβ) is an early event of Alzheimer’s disease (AD). Emerging evidence has shown that antioxidant therapy represents a promising therapeutic strategy for the treatment of AD. In this study, we investigated the antioxidant activity of rhein against Aβ1-42 oligomer-induced mitochondrial oxidative stress in primary neurons and proposed a potential antioxidant pathway involved. The results suggested that rhein significantly reduced reactive oxygen species (ROS) level, reversed the depletion of mitochondrial membrane potential, and protected neurons from oxidative stress-associated apoptosis. Moreover, further study indicated that rhein activated mitochondrial biogenesis accompanied by increased cytochrome C oxidase (CytOx) and superoxide dismutase (SOD) activities. CytOx on the respiratory chain inhibited the production of ROS from electron leakage and SOD helped to eliminate excess ROS. Finally, western blot analysis confirmed that rhein remarkedly increased the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) together with its upstream deacetylase sirtuin 1 (SIRT1), and activated downstream transcription factor nuclear respiratory factor 1, promoting mitochondrial biogenesis. In conclusion, our results demonstrate that rhein activates mitochondrial biogenesis regulated by the SIRT1/PGC-1α pathway as an antioxidant defense system against Aβ1-42 oligomer-induced oxidative stress. These findings broaden our knowledge of improving mitochondrial biogenesis as an approach for relieving neuronal oxidative stress in AD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2019
·
IF 5.515
Yin Ying,Cheng Jiang,Meiling Zhang,Jiye Jin,Shuyu Ge,Xiaodong Wang
Diabetic cardiomyopathy increases the risk of heart failure independent of coronary artery disease and hypertension. Phloretin (PHL) shows anti-inflammatory effects in macrophages. In this study, we explored the protective effects of PHL on high glucose (HG)-induced injury in diabetic cardiomyopathy in vivo and in vitro . Using streptozotocin-induced diabetic mouse model and incubating cardiac cells line under a HG environment, PHL were evaluated of the activities of anti-inflammation and anti-fibrosis. In the study, PHL treatment ameliorated cardiomyocyte inflammation injury, and reduced fibrosis in vivo and in vitro . PHL also improved cardiac biochemical criterions after 8 weeks of induction of diabetes in C57BL/6 mice. Molecular docking results indicated that silent information regulator 2 homolog 1 (SIRT1) bound to PHL directly and that SIRT1 expression was upregulated in the PHL-treated group in HG-induced H9C2 cells. Protective effect of PHL was been eliminated in silence SIRT1 H9C2 cells. Taken together, these results suggested that PHL suppressed HG-induced cardiomyocyte injury via restoring SIRT1 expression.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Xueping Liu,Rongxia Li,Zi Xiu,Siling Tang,Yancang Duan
Acrolein (ACR), an unsaturated, highly reactive aldehyde, is a widespread environmental toxin. ACR exerts permanent and irreversible side effects on ovarian functions. Granulosa cells play a crucial role in supporting ovarian function. Thus, in this study, we investigated the toxicity effects of granulosa cells induced by ACR. Following treatment with varying ACR concentrations (0, 12.5, 25, 50, and 100 μM), we observed that ACR exposure induced reactive oxygen species accumulation, mitochondrial energy metabolism disorder, and apoptosis in KGN cells (a human ovarian granulosa cell line) in a dose-dependent manner. In addition, mitochondrial biogenesis in KGN cells displayed biphasic changes after ACR exposure, with activation at a low ACR dose (12.5 μM), but inhibition at higher ACR doses (≥50 μM). SIRT1/PGC-1α-mediated mitochondrial biogenesis is crucial for maintaining intracellular mitochondrial homeostasis and cellular function. The inhibition/activation of the SIRT1/PGC-1α pathway in KGN cells validated its role in ACR-induced damage. The results indicated that the inhibition of the SIRT1/PGC-1α pathway aggravated ACR-induced cell damage, whereas its activation partially counteracted ACR-induced cell damage. This study attempted to uncover a novel mechanism of ACR-induced ovarian toxicity so as to provide an effective treatment option for safeguarding female reproductive health from the adverse effects of ACR.
研究领域:
毒理学
·
生殖生物学
·
细胞生物学
·
环境健康
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xiaoqian Ding,Jieliang Shen,Jindong Tan,Fan Wang,Weiwei Yi,Zijie Wang,Xinhe Li,Xinyu Zhang,Yi He,Wang Han,Mengtong Guan,Bo Liao,Juan Wang,Xiaoyu Han,Dingqun Bai
The disruption of endogenous electric field (EF) and subsequent degradation of the extracellular matrix (ECM) and joint wear are the fundamental pathological mechanisms underlying Osteoarthritis (OA). The key to reversing OA and promoting cartilage repair lies in restoring the endogenous electric field, improving lubrication performance between articular cartilage, and achieving a catabolic balance of ECM. In this study, we utilized short fiber fabrication technology and one-step surface dopamine grafting technology to construct a “PLA/ G@β-Gly /GO/PMPC” lubricated electroactive short fiber. By utilizing an “ultrasonic piezoelectric transducer” to generate electrical signals, we promoted ECM synthesis, restored endogenous EF, repaired hydration lubrication layer, and stabilized the endogenous electric field. This approach enables regeneration and optimization of articular cartilage while breaking free from the detrimental cycle associated with OA. Under ultrasonic stimulation at 1 W, 650 KHz frequency, and 50 % duty cycle, the lubricated electroactive short fiber generated a significant electrical signal of 1.31 V which upregulated Sirt1 expression in OA chondrocytes. It improved mitochondrial function and increased ATP capacity to 23.074 ± 1.87 pmol/min. Furthermore, incorporating different proportions of lubricating molecules (1:1, 1:4, and 1:8) into the material reduced the coefficient of friction (COF) between articular cartilages from approximately 0.725–0.693 to about 0.235. This improvement enhanced lubrication performance between articular cartilages by inhibiting ECM degradation and stabilizing endogenous EF. The innovative composite electrospun material exhibits great potential in promoting OA cartilage repair.
研究领域:
生物医学工程
·
组织工程
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）