COMPOSITES PART B-ENGINEERING
·
2024
·
IF 12.7
Zhicun Wang,Cheng Hu,Wen Zhang,Wenqi Liu,Shuyi He,Yang Liu,Li Yang,Yunbing Wang
Following a myocardial infarction (MI) or stroke, the excessive generation of reactive oxygen species (ROS) within a brief timeframe may induce a pronounced inflammatory reaction, which exacerbates the progression of the disease. Thus, there is an urgent need to design a biomaterial to inhibit the inflammatory response associated with MI and stroke. In this study, we designed a reversible extracellular matrix (ECM)-like hydrogel via borate ester crosslinking, which responds to the inflammatory microenvironment affected by MI and stroke. At the same time, we developed a new type of loaded polymer nanoparticle (TK-DA) that can respond to ROS in ischemic regions and release the anti-inflammatory drug dexamethasone. Ultimately, we integrated the nanoparticles and ECM-like hydrogel to fabricate a functional hydrogel. To verify the therapeutic effect of the functional hydrogel, we established two models of typical ischemic diseases, MI and stroke. The results showed that the hydrogel substantially reduced ROS levels and inflammation in vitro. Moreover, the results of the two in vivo animal models demonstrated that this functional hydrogel can effectively treat MI and stroke by suppressing inflammatory responses, mitigating apoptosis, and promoting neovascularization. In conclusion, the functional hydrogel strategy presents a universally applicable treatment approach for ischemic cardiovascular and cerebrovascular diseases, which are not limited solely to the treatment of MI and stroke, but also hold future potential for clinical applications.
✓ 已验证
产品关联
DOI
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Linglian Kong,Peng Sun,Xue Pan,Chuanpi Xiao,Bochen Song,Zhigang Song
ABSTRACT Macrophages play a crucial role in both innate and adaptive immunity. However, their abnormal activation can lead to undesirable inflammatory reactions. This study aimed to investigate the effects of glycerol monolaurate (GML), a natural monoester known for its anti-inflammatory and immunoregulatory properties, on avian macrophages using the HD11 cell line. The results indicated that a concentration of 10 μg/mL of GML enhanced the phagocytic activity of HD11 cells ( P < 0.05) without affecting cell viability ( P > 0.05). GML decreased the expression of M1 macrophage polarization markers, such as CD86 and TNF-α genes ( P < 0.05), while increasing the expression of M2 macrophage polarization markers, such as TGF-β1 and IL-10 genes ( P < 0.05). GML suppressed ROS production, apoptosis, and the expression of proinflammatory genes (IL-1β and IL-6) induced by LPS ( P < 0.05). GML also promoted the expression of TGF-β1 and IL-10 ( P < 0.05), both in the presence and absence of LPS exposure. Moreover, GML suppressed the gene expression of TLR4 and NF-κB p65 induced by LPS ( P < 0.05), as well as the phosphorylation of NF-κB p65 ( P < 0.05). In conclusion, GML exhibited regulatory effects on the polarized state of avian macrophages and demonstrated significant anti-apoptotic and anti-inflammatory properties by suppressing intracellular ROS and the NF-κB signaling pathway.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 21
·11414
·
IF 4.9
Rui-Yi Hu,Si-Min Qi,Ya-Jun Wang,Wen-Lin Li,Wan-Chen Zou,Zi Wang,Shen Ren,Wei Li
Age-related macular degeneration (AMD) is marked by a progressive loss of central vision and is the third leading cause of irreversible blindness worldwide. The exact mechanisms driving the progression of this macular degenerative condition remain elusive, and as of now, there are no available preventative measures for dry AMD. According to ancient records, ginseng affects the eyes by brightening them and enhancing wisdom. Modern pharmacological research shows that the active ingredients in ginseng, ginsenosides, may be used to prevent or improve eye diseases that threaten vision. Some articles have reported that ginsenoside Rg3 can treat diabetic retinopathy in mice, but no reports exist on its effects and mechanisms in AMD. Therefore, the role and mechanism of ginsenoside Rg3 in AMD warrant further study. This study aims to investigate the effects of Rg3 on AMD and its underlying molecular mechanisms. We established a mouse model of AMD to examine the impact of ginsenoside Rg3 on NaIO3-induced apoptosis in the retina and to explore the related intrinsic mechanisms. The in vivo results indicated that ginsenoside Rg3 prevents NaIO3-induced apoptosis in retinal pigment epithelial cells by inhibiting reactive oxygen species production and preventing the reduction in mitochondrial membrane potential. Additionally, we assessed the levels of protein expression within the apoptosis pathway. Ginsenoside Rg3 decreased the expression of Bax, cleaved caspase-3, and cleaved caspase-9 proteins. Additionally, it increased the expression of Bcl-2 by decreasing P-JNK levels. Moreover, our in vivo results showed that ginsenoside Rg3 enhanced retinal structure, increased the relative thickness of the retina, and decreased the extent of disorganization in both the inner and outer nuclear layers. Ginsenoside Rg3 may safeguard the retina against NaIO3-induced cell apoptosis by attenuating reactive-oxygen-species-mediated mitochondrial dysfunction, in which the JNK signaling pathway is also involved. These findings suggest that ginsenoside Rg3 has the potential to prevent or attenuate the progression of AMD and other retinal pathologies associated with NaIO3-mediated apoptosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Non-coding RNA Research
·
2025
·
IF 4.7
Ying Wen,Yitong Li,Danhua Zhang,Ziru Liu,Hong Liu,Xiejia Li,Wei Wu,Liyun Zeng,Qiongyan Zou,Wenjun Yi
The prevalence of secondary hyperparathyroidism (SHPT) in advanced chronic kidney disease (CKD) exceeds 80%. Our previous study indicated that photodynamic therapy (PDT) has potential for treating SHPT. Long noncoding RNA (lncRNA) is involved in various oxidative stress and apoptotic processes, but the molecular mechanism remains unreported. In this study, we found that PDT induced apoptosis in SHPT through reactive oxygen species (ROS) accumulation. The expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and heme oxygenase 1 (HO-1) within SHPT was upregulated after PDT. Inhibition of MALAT1 increased PDT-induced ROS, which promoted the apoptosis. Pearson correlation analysis confirmed that there was a positive correlation between MALAT1 and HO-1, and MALAT1 inhibition down-regulated HO-1, whereas concomitant overexpression of HO-1 was able to eliminate the PDT-induced ROS and inhibit apoptosis. The direct binding of MALAT1 to Kelch-like ECH-associated protein 1 (Keap1) protein was confirmed by high-throughput sequencing, RNA pulldown, silver staining and western blotting assays. Si-Keap1 was able to rescue the down-regulation of HO-1 caused by MALAT1 inhibition, restoring the elimination of ROS by HO-1 and attenuating the effect of PDT. In addition, PDT effectively reduced parathyroid hormone (PTH) secretion in SHPT rats, and this effect was further enhanced in combination with MALAT1 inhibitors. Overall, MALAT1 activates downstream HO-1 expression by binding to Keap1, thereby reducing ROS and inhibiting apoptosis, which in turn mediates PDT resistance in SHPT. Inhibition of MALAT1 significantly enhanced the efficacy of PDT, suggesting a potential therapeutic target for improving PDT for SHPT outcomes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
JunWei Feng,Xia Deng,Peng Hao,ZongDong Zhu,Tao Li,XinWei Yuan,Jiang Hu,Yue Wang
Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Hao Zhou,Jinpeng He,Renfeng Liu,Jun Cheng,Yuhao Yuan,Wanpu Mao,Jun Zhou,Honghui He,Qianqi Liu,Wei Tan,Cijun Shuai,Youwen Deng
Intervertebral disc degeneration (IVDD) can be caused by aging, injury, and genetic factors. The pathological changes associated with IVDD include the excessive accumulation of reactive oxygen species (ROS), cellular pyroptosis, and extracellular matrix (ECM) degradation. There are currently no approved specific molecular therapies for IVDD. In this study, we developed a multifunctional and microenvironment-responsive metal-phenolic network release platform, termed TMP@Alg-PBA/PVA, which could treat (IL-1β)-induced IVDD. The metal-phenolic network (TA-Mn-PVP, TMP) released from this platform targeted mitochondria to efficiently scavenge ROS and reduce ECM degradation. Pyroptosis was suppressed through the inhibition of the IL-17/ERK signaling pathway. These findings demonstrate the versatility of the platform. And in a rat model of IVDD, TMP@Alg-PBA/PVA exhibited excellent therapeutic effects by reducing the progression of the disease. TMP@Alg-PBA/PVA, therefore, presents clinical potential for the treatment of IVDD.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2024
·
IF 4.2
Hongmin Lu,Yue Zhang,Xin Zhang,Ruoqi Wang,Tiantian Guo,Qi Wang,Hongjing Zhao,Mingwei Xing
Environmental pollution caused by arsenic or its compounds is called arsenic pollution. Arsenic pollution mainly comes from people mining and smelting arsenic compounds. In addition, arsenic compounds' widespread use and production of arsenic-containing pesticides, arsenic-rich water used to irrigate farms, or high arsenic levels in foods caused by coal burning are all sources of arsenic contamination. Arsenic contamination poses a significant threat to global public health. It is reported that exposure to arsenic can induce severe renal injury. However, the underlying mechanism needs to be clarified. In this study, the arsenic exposure model in vivo and in vitro was used to explore the mechanism of arsenic-induced renal injury, especially the role of ferroptosis and its regulatory mechanism, and then to evaluate its anti-pollution effect by supplementing zinc. The results showed that arsenic significantly induced ferroptosis, characterized by up-regulating the expression of YAP and TFR in kidney and CIK cells and then increasing the levels of Fe 2+ and ROS, lipid peroxidation, and iron metabolism. Microscopic observation revealed the shrinkage of mitochondria and the increase in membrane density. In addition, molecular docking and inhibitor experiments further confirmed that arsenic is involved in the process of ferroptosis by activating YAP and TFR. These results clarify the harmful effects of arsenic on carp kidneys and its mechanism and highlight the critical interactions between the YAP-TFR pathway, ROS, and ferroptosis. Importantly, this study found that zinc can reduce ferroptosis caused by the arsenic-activated YAP-TFR pathway by inhibiting YAP activation and lipid peroxidation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Mingtao Tan,Hong Jiang,Rusong Chai,Miao Fan,Zengting Niu,Guotong Sun,Shanchun Yan,Dun Jiang
Heavy metal pollutants are important abiotic environmental factors affecting pest habitats. In this study, Cd pre-exposure significantly increased the tolerance of Lymantria dispar larvae to β-cypermethrin, but did not significantly alter their tolerance to λ-cyhalothrin and bifenthrin. The activation of P450 by Cd exposure is the key mechanism that induces insecticide cross-tolerance in L. dispar larvae. Both before and after β-cypermethrin treatment, Cd exposure significantly increased the expression of CYP6AB224 and CYP6AB226 in L. dispar larvae. Silencing CYP6AB224 and CYP6AB226 reduced the tolerance of Cd-treated L. dispar larvae to β-cypermethrin. Transgenic CYP6AB224 and CYP6AB226 genes significantly increased the tolerance of Drosophila and Sf 9 cells to β-cypermethrin, and the recombinant proteins of both genes could significantly metabolise β-cypermethrin. Cd exposure significantly increased the expression of CnCC and Maf . CnCC was found to be a key transcription factor regulating CYP6AB224 - and CYP6AB226 -activated insecticide cross-tolerance in Cd-treated larvae. Decreasing reactive oxygen species (ROS) levels in the Cd-treated larvae or increasing ROS levels in the untreated larvae reduced or enhanced the expression of CnCC , CYP6AB224 and CYP6AB226 and β-cypermethrin tolerance in L. dispar larvae, respectively. Collectively, Cd exposure confers β-cypermethrin tolerance in L. dispar larvae through the ROS/ CnCC signalling pathway-mediated P450 detoxification. Environmental Implication Heavy metals have been reported to produce cross-tolerance in agricultural insects to insecticides. The growing demand for chemical pest control necessitates expanding research on the widespread occurrence of cross-tolerance to insecticides among pests, particularly forest pests, in areas polluted with heavy metals. In this study, Cd pre-exposure enhanced the cross-tolerance of Lymantria dispar larvae to β-cypermethrin. Cd pre-exposure activated the P450 detoxification system of L. dispar larvae. CYP6AB224 and CYP6AB226 were key detoxify genes to the formation of cross-tolerance. ROS-CnCC signaling pathway was proved to be responsible for activation of detoxify genes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Bo Wang,Jiquan Shen,Xinggao Wang,Ruixing Hou
Previous study has indicated that Celastrol (Cel) has various physiological and pharmacological effects, including antibacterial, antioxidant, pro-apoptotic, anticancer and anti-rheumatoid arthritis (RA) effects. However, low water solubility, low oral bioavailability, narrow treatment window, and high incidence of systemic adverse reactions still limit the further clinical application of Cel. Here, aiming at effectively overcome those shortcomings of Cel to boost its beneficial effects for treating RA, we developed the leukosome (LEUKO) coated biomimetic nanoparticles (NPs) for the targeted delivery of Cel to arthritis injury area in RA. LEUKO were synthesized using membrane proteins purified from activated J774 macrophage. LEUKO and Cel-loaded LEUKO (Cel@LEUKO) were characterized using dynamic light scattering and transmission electron microscopy. Our results demonstrated that Cel@LEUKO can inhibit the inflammatory response of lipopolysaccharide (LPS) induced mouse monocyte macrophage leukemia cells (RAW264.7 cells) and human rheumatoid arthritis synovial fibroblasts (MH7A) cells through the inhibition of reactive oxygen species (ROS)-NF-κB pathway. In addition, research has shown that LEUKO effectively targets and transports Cel to the inflammatory site of RA, increased drug concentration in affected areas, reduced systemic toxicity of Cel, and reduced clinical symptoms, inflammatory infiltration, bone erosion, and serum inflammatory factors in collagen-induced arthritis (CIA) rats.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Natural Medicines
·
2024
·
IF 2.5
Chen Ping,Zhang Xueer,Fang Qiaomiao,Zhao Zhongxiang,Lin Chaozhan,Zhou Yuan,Liu Fangle,Zhu Chenchen,Wu Aizhi
Betulinic acid (BA), a naturally occurring lupane-type triterpenoid, possesses a wide range of potential activities against different types of cancer. However, the molecular mechanisms involved in anti-cervical cancer about BA were rarely investigated. Herein, the role of BA in cervical cancer suppression by ROS-mediated endoplasmic reticulum stress (ERS) and autophagy was deeply discussed. The findings revealed that BA activated Keap1/Nrf2 pathway and triggered mitochondria-dependent apoptosis due to ROS production. Furthermore, BA increased the intracellular Ca 2+ levels, inhibited the expression of Beclin1 and promoted the expression of GRP78, LC3-II, and p62 associated with ERS and autophagy. Besides, BA initiated the formation of autophagosomes and inhibited autophagic flux by the co-administration of BA with 3-methyladenine (3-MA) and chloroquine (CQ), respectively. The in vivo experiment manifested that hydroxychloroquine (HCQ) enhanced the apoptosis induced by BA. For the first time, we demonstrated that BA could initiate early autophagy, inhibit autophagy flux, and induce protective autophagy in HeLa cells. Thus, BA could be a potential chemotherapy drug for cervical cancer, and inhibition of autophagy could enhance the anti-tumor effect of BA. However, the interactions of signaling factors between ERS-mediated and autophagy-mediated apoptosis deserve further attention. Graphical abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Xinyue Zhang,Yawen Huang,Tao Luo,Chen Hu,Haihang Li,Xiaoju Fan,Kefeng Wang,Jie Liang,Yafang Chen,Yujiang Fan
Excessive fibrotic scar formation during skin defect repair poses a formidable challenge, impeding the simultaneous acceleration of wound healing and prevention of scar formation and hindering the restoration of skin integrity and functionality. Drawing inspiration from the structural, compositional, and biological attributes of skin, we developed a hydrogel containing modified recombinant human collagen type III and thiolated hyaluronic acid to address the challenges of regenerating skin appendages and improving the recovery of skin functions after injury by reducing fibrotic scarring. The hydrogel displayed favorable biocompatibility, antioxidant properties, angiogenic potential, and fibroblast migration stimulation in vitro. In a rat full-layer defect model, it reduced inflammation, promoted microvascular formation, and significantly enhanced the wound healing speed and effectiveness. Additionally, by upregulating fibrosis-associated genes, such as TGFB1, it facilitated collagen accumulation and a beneficial balance between type I and type III collagen, potentially expediting skin regeneration and functional recovery. In conclusion, the utilization of rhCol III-HS demonstrated considerable potential as a wound dressing, offering a highly effective strategy for the restoration and rejuvenation of complete skin defects.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2025
·Vol. 15
·期 9
·3750
·
IF 13.3
Ziliang Xiu,Yujing Zhu,Xiaofeng Li,Xiaoxi Jiang,Yunru Feng,Li He,Chunhui Li,Rui Cai,Gang Tao
Background: Pathogenic bacteria and activated immune cells in periodontal tissues continuously generate reactive oxygen species (ROS) and inflammatory mediators, creating an oxidative stress microenvironment that causes damage to cells and tissues. Antimicrobial strategies and ROS scavenging are crucial for treating periodontitis. Methods: This study encapsulated iron-curcumin nanoparticles (Fe-Cur NPs) within GelMA microspheres using microfluidic technology. The microsphere surface was then modified with a polydopamine (PDA) layer, and minocycline hydrochloride (MH) was attached to it to form multifunctional composite microspheres (GM@Fe-Cur/PDA/MH). Results: The GM@Fe-Cur/PDA/MH microspheres exhibited excellent adhesion, allowing them to remain in periodontal pockets for prolonged periods to maintain their functionality. Benefiting from the photothermal properties of PDA combined with MH, these microspheres effectively kill bacteria and mitigate excessive immune responses. Additionally, they regulate the M1/M2 polarization of macrophages, suppress the expression of inflammatory factors, and promote osteogenic protein expression under oxidative stress conditions in vitro . In a rat model of periodontitis, GM@Fe-Cur/PDA/MH effectively controlled inflammation progression and reduced alveolar bone loss. Further studies indicated that GM@Fe-Cur/PDA/MH may promote ROS scavenging by modulating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway while inhibiting the activation of the nod-like receptor protein-3 (NLRP3) inflammasome. Conclusions: In summary, GM@Fe-Cur/PDA/MH represents an effective therapeutic approach that integrates antibacterial, antioxidant, anti-inflammatory, and bone loss mitigation properties, demonstrating significant potential for application in the treatment of periodontitis.
✓ 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）