RSC Advances
·
2017
·Vol. 7
·期 55
·34846-34856
·
IF 3.108
Ye Tian,Zheng Li,Bingyu Shen,Lin Wu,Lu Han,Qiaoling Zhang,Haihua Feng
Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities. However, the protective effects and mechanism of SHK on lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced acute liver injury remain unclear. In this study, LPS/D-GalN caused acute liver injury by intraperitoneal injection. SHK was administrated for 1 h. Then, LPS/D-GalN was given to C57BL/6 mice for 3 h. Our results showed that SHK treatment distinctly decreased serum TNF-α, IL-1β, IL-6 and IFN-γ inflammatory cytokine production, reduced serum ALT, AST, hepatic MPO and ROS production levels, and tissue histology harmful effects, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and suppressed IκBα phosphorylation and degradation. Furthermore, our research showed that SHK could dramatically increase SOD and GSH production, as well as reduce ROS production, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation. These results showed that SHK exerted anti-inflammatory activity, which was associated to the inhibition of inflammatory production via down-regulation of the MAPK and NF-κB signaling pathways, and anti-oxidative effects were connected with GSH and SOD activation through up-regulation of the Nrf2/HO-1 signaling pathways.
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ARCHIVES OF MICROBIOLOGY
·
2024
·Vol. 206
·期 6
·1-11
·
IF 2.3
Zhuang Cuicui,Zhang Ruoqing,Bai Jiangang,Zhang Xinying,Zhao Jinhui
Escherichia coli ( E. coli ) can induce severe clinical bovine mastitis, which is to blame for large losses experienced by dairy farms. Macrophage polarization into various states is in response to pathogen infections. Lycopene, a naturally occurring hydrocarbon carotenoid, relieved inflammation by controlling M1/M2 status of macrophages. Thus, we wanted to explore the effect of lycopene on polarization states of macrophages in E. coli -induced mastitis. Macrophages were cultivated with lycopene for 24, before E. coli inoculation for 6 h. Lycopene (0.5 μmol/L) significantly enhanced cell viabilities and significantly reduced lactic dehydrogenase (LDH) levels in macrophages, whereas 2 and 3 μmol/L lycopene significantly enhanced LDH activities. Lycopene treatment significantly reduced the increase in LDH release, iNOS, CD86, TNF-α, IL-1β and phosphatase and tensin homolog (PTEN) expressions in E. coli group. 0.5 μmol/L lycopene significantly increased E. coli -induced downregulation of CD206, arginase I (ARG1), indoleamine 2,3-dioxygenase (IDO), chitinase 3-like 3 (YM1), PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, jumonji domain-containing protein-3 (JMJD3) and interferon regulatory factor 4 (IRF4) levels. Moreover, Ginkgolic acid C17:1 (a specific PTEN inhibitor), 740YPDGFR (a specific PI3K activator), SC79 (a specific AKT activator) or CHPG sodium salt (a specific NF-κB activator) significantly decreased CD206, AGR1, IDO and YM1 expressions in lycopene and E. coli -treated macrophages. Therefore, lycopene increased M2 macrophages via inhibiting NOTCH1-PI3K-mTOR-NF-κB-JMJD3-IRF4 pathway in response to E. coli infection in macrophages. These results contribute to revealing the pathogenesis of E. coli -caused bovine mastitis, providing the new angle of the prevention and management of mastitis.
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Chemical Biology & Drug Design
·
2024
·Vol. 104
·期 4
·e70003
·
IF 3.2
Xiang Yu,Di Zhang,Chengming Hu,Zejun Yu,Yang Li,Cheng Fang,Yinsheng Qiu,Zhinan Mei,Lingyun Xu
Hepatocellular carcinoma (HCC) is the sixth most prevalent malignant tumor. Hepatocellular carcinogenesis is closely linked to apoptosis, autophagy, and inflammation. Diosmetin and chrysin, are two flavonoid compounds, exhibit anti-inflammatory and anticancer properties. In this study, the TCGA database was utilized to identify differentially expressed genes between normal subjects and HCC patients. Molecular docking and molecular dynamics analyses were employed to assess the binding affinity of chrysin and diosmetin to key proteins in the PI3K/AKT/mTOR/NF-κB signaling pathway. Western blotting and RT-qPCR were used to measure the protein and gene expression within this pathway. The results indicated that HCC patients had elevated levels of PI3K, AKT, mTOR, and P65 proteins compared to normal subjects, which adversely affected patient survival. Molecular docking and dynamics studies demonstrated that diosmetin and chrysin are effectively bound to these four proteins. In vitro experiments revealed that the combination of diosmetin and chrysin could induce apoptosis, enhance autophagy, reduce inflammatory mediator production, and improve the tumor cell microenvironment by inhibiting the PI3K/AKT/mTOR/NF-κB signaling pathway. Notably, the synergy score for the combination of diosmetin (25 μM) and chrysin (10 μM) was 16. Thus, the diosmetin–chrysin combination shows promise as an effective therapeutic approach for hepatocellular carcinoma due to its strong synergistic effect.
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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 6
·e70372
·
IF 4.2
Wang Huikang,Cao Shiya,Pan Di,Faisal Ayub Kiani,Li Hao,Nan Sha,Lin Xuan,Mahmoud M. Abouelfetouh,Zulfiqar Ahmed,Ding Mingxing,Ding Yi
Neuropathic pain (NP), resulting from nerve damage, is difficult to manage and often requires long-term treatment. However, prolonged use of pain medications can lead to addiction and reduced effectiveness over time. Understanding drug tolerance is essential for developing improved pain management strategies. Dexmedetomidine (DEX) is effective in targeting the α2 -adrenergic receptor, providing relief from pain, especially NP. However, its extended use leads to tolerance and hinders its clinical utility. Herein, we investigated tolerance mechanisms and potential applications of this drug in managing NP. Adult C57BL/6 mice (male) were distributed into DEX Dosage Groups ( n = 48), DEX Tolerance Model Groups ( n = 32), SGK1 Inhibitor GSK650394 Groups ( n = 48), and NF - κB Inhibitor PDTC Groups ( n = 32) to explore dexmedetomidine's effects on NP and tolerance mechanisms. NP was established via selective ligation of the sciatic nerve branch (SNI), followed by administration of DEX. The results revealed a dose-dependent analgesic effect of DEX, with significant increases in pain thresholds observed compared to the sham group ( p < 0.05). Optimal efficacy was found at a dose of 30 μg/kg, indicating its potential as an effective treatment for NP ( p < 0.05). However, continuous administration of DEX over 13 days induced analgesic tolerance, evidenced by an initial increase in pain thresholds followed by a gradual decrease ( p < 0.05). Despite an initial efficacy in elevating pain thresholds, the analgesic effect of DEX diminished over time, returning to pre-dose levels after 5 days ( p < 0.05). Transcriptome sequencing of spinal cord samples from mice receiving multiple DEX injections revealed differential gene expression patterns, notably upregulation of SGK1 , NR2A , and NR2B subunits ( p < 0.05). Inhibiting SGK1 mitigated DEX-induced tolerance, suggesting its involvement in tolerance development ( p < 0.05). Moreover, NF - κB inhibition reversed DEX-induced tolerance and implicated the SGK1 - NF - κB pathway in the mediation of analgesic tolerance. To sum up, these findings revealed the molecular mechanism underlying DEX-induced analgesic tolerance in the NP model and offer potential avenues for future therapeutic interventions.
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HISTOLOGY AND HISTOPATHOLOGY
·
2024
·
IF 2.5
Jinfeng Xie,Yonggui Liao,Dile Wang
Background: Deep vein thrombosis (DVT) is the third most prevalent vascular disease worldwide, seriously threatening human health. Baicalin, a flavonoid isolated from the roots of Scutellaria baicalensis , has been identified to play a crucial role in various vascular diseases. The study aimed to explore the efficacy and underlying mechanisms of baicalin in DVT. Methods: Endothelial progenitor cells (EPCs) were differentiated from peripheral blood mononuclear cells isolated from rat bone marrow. Dil-ac-LDL/FITC-UEA-1 double staining and flow cytometry analysis were conducted for the identification of EPCs. The angiogenesis and migration of EPCs in vitro were tested by a tube formation assay and Transwell assay, respectively. DVT rat models were established by stenosis of the inferior vena cava (IVC). After the euthanasia of rats, thrombi in the IVC were collected and weighed, and histological alterations in IVC tissue were measured by H&E staining. The protein levels of SIRT1, p-P65, and p65 in rat IVC tissues were quantified via western blotting. Results: EPCs used in this study displayed a spindle-like shape and were positive for endothelial cell-specific markers, suggesting the phenotypic characteristics of EPCs. Baicalin enhanced the migratory and angiogenetic abilities of EPCs in vitro . For in vivo experiments, baicalin reduced thrombus weight and mitigated DVT formation in model rats. Moreover, baicalin activated SIRT but repressed NF-κB signaling in IVC tissues of DVT rats. Conclusion: Baicalin facilitates migration and angiogenesis of EPCs but impedes thrombus formation via regulation of SIRT1/NF-κB signaling in DVT model rats.
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
·
2024
·
IF 1.5
Chen Jiye,Chen Jiayao,Li Qinxia,Hu Minxia,Zhong Xingxing,Yu Liang,Zhang Xi,Huang Hongyu,Liu Jing,Huang Ziyi,Liu Xinyi,Xiong Wu
This study aimed to explore the potential of using mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) pre-treated with Astragaloside IV (ASIV) to alleviate inflammation in high glucose (HG)-damaged endothelial cells. MSC-Exos were isolated from untreated MSCs and ASIV-pre-treated MSCs, and their characteristics were assessed. The expression of miR-146a-5p in MSC-Exos was determined, and it was found that ASIV treatment enhanced its expression. In order to assess the impact of highly miR-146a-5p-expressing MSC-Exos on HG-injured endothelial cells, we established a model of HG-induced inflammation using human umbilical vein endothelial cells (HUVECs). The study measured cell viability, apoptosis, tube formation, and levels of inflammatory cytokines among the different treatment groups. It was found that transferring MSC-Exos with high miR-146a-5p expression to HG-damaged HUVECs increased cell viability and tube formation ability while reducing the number of apoptotic cells. Additionally, changes in inflammatory factors indicated a reduction in the inflammatory response. Further investigation demonstrated that miR-146a-5p inhibited the expression of TNF receptor associated factor 6 (TRAF6) and phosphorylated NF-κB, which are involved in the inflammatory response. This resulted in the alleviation of inflammation in HG-damaged endothelial cells. In summary, our findings indicate that ASIV treatment stimulated the secretion of MSC-Exos that exhibited increased levels of miR-146a-5p. These exosomes, in turn, regulated the TRAF6/NF-κB pathway. As a result of this modulation, the inflammatory response in HG-damaged endothelial cells was alleviated. These findings offer a fresh approach to addressing vascular complications associated with diabetes, which could lead to novel treatment strategies in the field.
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INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2024
·
IF 8.1
Yun Wu,Jinwei Wang,Weiyi Zhang,Qiang Zhao,Jinping Li,Guang Liu
Highly efficient and economical oxygen evolution reaction (OER) electrocatalysts are instrumental in the utilization and storage of renewable sources. Here, we introduce a straightforward method for the in situ growth of sulfur-doped iron oxide (S-FeO x ) and two-dimensional (2D) zeolitic imidazole framework-67 (ZIF-67) nanoarrays on three-dimensional (3D) nickel foam (NF), yielding a 3D S-FeO x /ZIF-67/NF electrocatalyst. The distinctive sheet-like structure and porous framework of S-FeO x /ZIF-67/NF significantly increase the electrochemical active surface area. The prepared S-FeO x /ZIF-67/NF exhibits outstanding electrocatalytic OER activity, achieving a remarkably low overpotential of 236 mV at a current density of 100 mA/cm 2 . Furthermore, S-FeO x /ZIF-67/NF demonstrates the capability to deliver industrial-level large current densities, requiring overpotentials of merely 291 and 334 mV to attain current densities of 500 and 1000 mA/cm 2 , respectively. Moreover, it maintains stable operation for over 80 h at a current density of 1000 mA/cm 2 , with the sheet-like structure remaining intact and no significant activity decay observed. This investigation offers a strategic approach for the systematic development and fabrication of OER electrocatalysts suitable for large current conditions.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Sheng Li,Shiyi Lu,Jiahui Xiong,Liang Chen,Yanting Lin,Xiaohui Chen,Xinyi Wang,Lijing Lin,Xiaoliang Cai,Xiaoyu Yang
Here, we systematically evaluated the therapeutic efficacy and mechanisms of action of in-house synthesized hydroxyethyl starch-curcumin nanoparticles (HES-CUR NPs) in ulcerative colitis (UC). Using a dextran sodium sulfate (DSS)-induced UC mouse model, we analyzed the effect of HES-CUR NPs on colonic tissue and the gut microbiota through the assessment of organ indices and serum biochemical markers, histopathology, immunohistochemistry, Western blot, and 16S rRNA sequencing. We found that HES-CUR NPs significantly suppressed the TLR4/NF-κB inflammatory pathway (downregulated TLR4, p-IKKβ, IL-1β, IL-6, NFKB, MyD88, and p-IKKB/IKKB; p < 0.01), activated the Nrf2/HO-1 antioxidant pathway (enhanced Nrf2 nuclear translocation and HO-1 expression), and upregulated the expression of tight junction proteins (claudin-1, occludin, ZO-1), thereby restoring intestinal barrier integrity. Microbiota analysis revealed that HES-CUR NPs increased gut microbiota diversity (elevated Chao1, Shannon, and ACE indices) and enriched beneficial bacteria abundance (Ligilactobacillus murinus, Lactobacillus johnsonii). Antibiotic intervention partially attenuated the therapeutic effects of the HES-CUR NPs, confirming that their effects involved microbiota-dependent mechanisms. Compared to CUR and SASP, HES-CUR NPs exhibited significantly enhanced bioavailability and efficacy (p < 0.01), attributed to the targeted delivery and sustained-release properties of the hydroxyethyl starch nanocarrier. No toxicity was observed, as indicated by normal spleen, liver, and thymus indices and stable levels of TP, ALT, AST, ALB, GLB, and ALB/GLB. Our findings indicated that HES-CUR alleviates UC through a synergistic, multi-target mechanism involving inflammatory pathway suppression, antioxidant pathway activation, intestinal barrier repair, and microbiota modulation, providing a theoretical foundation for developing efficient and safe natural nanomedicines targeting UC.
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EXPERIMENTAL EYE RESEARCH
·
2025
·
IF 2.7
Yarong Yan,Shulei Xing,Jinghua Liu,Xinlin Yan,Yi Guan,Zhixin Jiang,Wei Zhang,Xuan Li
Lycium barbarum glycopeptide (LbGp), derived from the Chinese medicinal plant Lycium barbarum, has demonstrated anti-inflammatory properties; however, its precise role and mechanism in corneal repair following injury remain elusive. The present research investigated the mechanisms and effects of LbGp on corneal repair following alkali burn injury using in vivo mouse models of corneal alkali burn and in vitro human keratocyte fibrosis models. Corneal inflammation, opacity, and epithelial defects were assessed via a slit lamp microscope. Results showed that LbGp-treated mice exhibited reduced edema, accelerated re-epithelialization, and decreased corneal opacity compared to the phosphate-buffered saline (PBS)-treated controls. Proteomic analysis revealed altered proteins enriched in the extracellular matrix among the control, injury, and LbGp treatment groups. Moreover, LbGp significantly attenuated TGFβ-1-induced myofibroblasts transdifferentiation from keratocytes. Consistently, LbGp treatment inhibited the upregulation of fibrosis markers (αSMA, fibronectin, and collagen III) at both the protein and mRNA levels after corneal alkali burns. LbGp also effectively suppressed the activation of the NF-κB/NLRP3/IL-1β signaling pathway and neutrophil infiltration following corneal alkali burn injury. Additionally, miR-21 was upregulated in TGFβ-1-stimulated keratocytes and in the alkali-burned mouse cornea. LbGp decreased miR-21 expression, while increasing expression of its target, Smad7, thereby dampening the TGFβ/Smad2/3 signaling pathway. This research demonstrates that LbGp promotes corneal healing by inhibiting inflammation and fibrosis after alkali burns, suggesting its potential as a supplementary therapy for corneal injury repair.
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Human Cell
·
2022
·Vol. 35
·期 5
·1424-1439
·
IF 4.374
Liu Wen,Li Guojuan,Li Jing,Chen Wei
The long-term treatment of glucocorticoids is a common cause of osteoporosis (OP). This study concentrated on inquiring into the regulatory role and potential mechanisms of TRG-AS1 on dexamethasone (Dex)-induced OP in rats. We adopted Dex to treat rat osteoblasts and rats to simulate in-vitro and in-vivo OP models, respectively. Gain-of-function assays of TRG-AS1, miR-802 and CAB39 were constructed in rat osteoblasts to make certain the influence of TRG-AS1, miR-802 and CAB39 on differentiation, proliferation and apoptosis of rat osteoblasts. TRG-AS1 and CAB39 were down-regulated in the Dex-induced OP model in rats, in contrast to miR-802. Overexpression of TRG-AS1 restrained Dex-induced inhibition of osteogenic differentiation, promoted CAB39/AMPK/SIRT-1 and inhibited NF-κB, while overexpression of miR-802 bridled the inhibitory effect of TRG-AS1 on OP. miR-802 was targeted by TRG-AS1, and inhibited CAB39. Inhibition of either AMPK or SIRT-1 abated the osteogenic differentiation-promoting effect of CAB39. Animal experiments displayed that overexpressing TRG-AS1 alleviated Dex-induced OP in rats. In conclusion, up-regulation of TRG-AS1 protected against glucocorticoid-induced OP in rats by modulating the miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yating Hou,Mengmeng Wang,Xinru Wei,Yunmei Du,Dehong Chen,Ruiyong Zhang,Lei Wang
Developing an effective strategy to controllably construct phosphate shells on phosphides remains a challenge because of the sluggish kinetics of the oxygen evolution reaction (OER). In this work, Ni(PO x )@B-Ni 2 P/NF electrodes with an amorphous phosphate shell were fabricated using a phosphorization–quenching strategy. Remarkably, Ni(PO x )@B-Ni 2 P/NF requires only 81 mV and 1.333 V to deliver a current density of 100 mA cm −2 for the hydrogen evolution reaction (HER) and urea oxidation reaction (UOR), respectively—outperforming Pt/C@NF and previously reported Ni-based electrodes. The self-assembled Ni(PO x )@B-Ni 2 P/NF(+)||Ni(PO x )@B-Ni 2 P/NF(−) configuration achieves 1 A cm −2 at only 1.414 V for urea-assisted water splitting, indicating strong potential for industrial application. In situ Raman spectroscopy, combined with theoretical calculations, reveals that the amorphous phosphate shell, which exhibits strong urea adsorption capacity, optimizes the electronic configuration of the Ni(PO x )@B-Ni 2 P heterointerface. It also suppresses the peroxidation of internal Ni active sites into Ni–OOH by-products with high *COO adsorption energy. The resulting low-valent Ni O active species reduce the *COO adsorption energy and promote C N bond cleavage in urea, thereby accelerating UOR kinetics. These findings offer new design strategies for phosphate@phosphide electrodes tailored for industrial hydrogen production coupled with urea degradation.
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LIPIDS
·
2026
·
IF 1.6
Xujiao Hu,Yu Fang
In atherosclerosis (AS), the conversion of vascular smooth muscle cells (VSMCs) to a macrophage-like phenotype is a key contributor to plaque instability. Although retinoic acid receptor responder 2 (RARRES2) has been identified as an adipokine implicated in inflammation and metabolism, its role in VSMC phenotypic transformation remains unknown. This study aimed to investigate whether RARRES2 regulates the macrophage-like transformation and dysfunction of VSMCs. In the in vitro AS model, RARRES2 expression was significantly upregulated. Knockdown of RARRES2 inhibited VSMC proliferation and migration, reduced the secretion of inflammatory factors, decreased lipid accumulation, and the number of CD68-positive cells, and suppressed the activation of key proteins in the NF-κB/NLRP3 pathway. In the AS model, RARRES2 expression was found to be significantly upregulated. Knockdown of RARRES2 inhibited the proliferation and migration of VSMCs, reduced the secretion of TNF-α, IL-6, IL-1β, and MMP-2, reduced lipid accumulation, decreased the number of CD68-positive cells (indicating an acquisition of partial macrophage-like features, though further lineage markers are needed to confirm full partial macrophage-like phenotype), and inhibited the activation of key proteins (p-p65, NLRP3, ASC) in the NF-κB/NLRP3 pathway. RARRES2 knockdown suppresses NF-κB/NLRP3 signaling and attenuates macrophage-like transformation, inflammatory responses, and lipid accumulation in VSMCs, suggesting that RARRES2 may represent a potential therapeutic target for AS.
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