INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Mingming Sun,Qiuying Wang,Ting Li,Wenzhu Wang,Zihan Li,Yufei Ji,Shuangyue Zhang,Yan Li,Wenshuai Liu,Yan Yu
Pressure ulcers (PUs) have emerged as a significant burden on both individuals and society. Effective treatment of PUs is a significant clinical challenge due to the compromised tissue microenvironment characterized by extracellular matrix (ECM) depletion, increased levels of reactive oxygen species (ROS), excessive inflammation and impaired angiogenesis. To this end, we have developed a glucomannan hydrogel (GM-P gel ) that mimics the skin's extracellular matrix to accelerate wound healing by regulating chronic inflammation in the PUs. This hydrogel not only faithfully replicates the components and nanofibrous architecture of ECM-like glycoproteins but also exhibits remarkable capabilities in enhancing neovascularization, scavenging ROS, and promoting macrophage polarization toward the M2 phenotype. In summary, this ECM-mimetic multifunctional hydrogel emerges as a promising dressing with diverse functionalities, capable of reshaping the compromised tissue environment without the need for additional drugs, exogenous cytokines, or cells. This presents a compelling and effective strategy for the repair and regeneration of chronic cutaneous wounds.
研究领域:
伤口愈合
·
组织工程
·
生物材料
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Hangyi Wu,Zhenhai Zhang,Yanni Cao,Yuhan Hu,Yi Li,Lanyi Zhang,Xinyi Cao,Haitong Wen,Youwen Zhang,Huixia Lv,Xin Jin
Cuproptosis is an emerging cell death pathway that depends on the intracellular Cu ions. Elesclomol (ES) as an efficient Cu ionophore can specifically transport Cu into mitochondria and trigger cuproptosis. However, ES can be rapidly removed and metabolized during intravenous administration, leading to a short half-life and limited tumor accumulation, which hampers its clinical application. Here, the study develops a reactive oxygen species (ROS)-responsive polymer (PCP) based on cinnamaldehyde (CA) and polyethylene glycol (PEG) to encapsulate ES-Cu compound (EC), forming ECPCP. ECPCP significantly prolongs the systemic circulation of EC and enhances its tumor accumulation. After cellular internalization, the PCP coating stimulatingly dissociates exposing to the high-level ROS, and releases ES and Cu, thereby triggering cell death via cuproptosis. Meanwhile, Cu 2+ -stimulated Fenton-like reaction together with CA-stimulated ROS production simultaneously breaks the redox homeostasis, which compensates for the insufficient oxidative stress treated with ES alone, in turn inducing immunogenic cell death of tumor cells, achieving simultaneous cuproptosis and immunotherapy. Furthermore, the excessive ROS accelerates the stimuli-dissociation of ECPCP, forming a positive feedback therapy loop against tumor self-alleviation. Therefore, ECPCP as a nanoplatform for cuproptosis and immunotherapy improves the dual antitumor mechanism of ES and provides a potential optimization for ES clinical application.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Daming Li,Jiao Li,Tao Chen,Xianyan Qin,Lihua Pan,Xin Lin,Wenlang Liang,Qin Wang
Despite the progress in the therapy of ulcerative colitis (UC), long-lasting UC remission can hardly be achieved in the majority of UC patients. The key pathological characteristics of UC include an impaired mucosal barrier and local inflammatory infiltration. Thus, a two-pronged approach aiming at repairing damaged mucosal barrier and scavenging inflammatory mediators simultaneously might hold great potential for long-term remission of UC. A rectal formulation can directly offer preferential and effective drug delivery to inflamed colon. However, regular intestinal peristalsis and frequent diarrhea in UC might cause transient drug retention. Therefore, a bioadhesive hydrogel with strong interaction with intestinal mucosa might be preferable for rectal administration to prolong drug retention. Here, we designed a bioadhesive hydrogel formed by the cross-linking of sulfhydryl chondroitin sulfate and polydopamine (CS-PDA). The presence of PDA would ensure the mucosa-adhesive behavior, and the addition of CS in the hydrogel network was expected to achieve the restoration of the intestinal epithelial barrier. To scavenge the key player (excessive reactive oxygen species, ROS) in inflamed colon, sodium ferulic (SF), a potent ROS inhibitor, was incorporated into the CS-PDA hydrogel. After rectal administration, the SF-loaded CS-PDA hydrogel could adhere to the colonic mucosa to allow prolonged drug retention. Subsequently, sustained SF release could be achieved to persistently scavenge ROS in inflammatory areas. Meanwhile, the presence of CS would promote the restoration of the mucosal barrier. Ultimately, scavenging ROS and restoring the mucosal barrier could be simultaneously achieved via this SF-loaded bioadhesive hydrogel scaffold. Our two-pronged approach might provide new insight for effective UC treatment.
研究领域:
药学
·
生物医学工程
·
胃肠病学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 11
·e70681
·
IF 4.2
Yao Chen,Heqi Dai,Fei Mao,Yangbai Li,Ruizhi Feng,Yun Qian
Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in women of reproductive age. However, the underlying molecular mechanism remains unclear. In this study, we employed RNA sequencing analysis to identify differentially expressed protein‐coding genes and long noncoding RNA (lncRNA) expression profiles in granulosa cells from women with and without PCOS. It was established that the level of NONHSAT233728.1 was diminished in women with PCOS. The present study demonstrated the role of NONHSAT233728.1 in granulosa cells from patients with PCOS and further investigated the potential mechanism of NONHSAT233728.1 in the KGN cell line. Additionally, the knockdown of NONHSAT233728.1 has been observed to promote cell apoptosis, inhibit cell proliferation, promote mitochondrial dysfunction, and inflammation. Western blot analyses confirmed that phospho‐extracellular regulated protein kinases (ERK)1/2 were decreased following lnc‐NONHSAT233728.1 knockdown. Consequently, we propose that ROS accumulation activates the endogenous mitochondrial apoptosis pathway, leading to granulosa cell apoptosis via the MEK/ERK1/2 pathway, which contributes to follicular atresia. We observed a negative correlation between NONHSAT233728.1 and both LH levels and the LH/FSH ratio. These findings indicate that lncRNA NONHSAT233728.1 is linked to the pathogenesis of PCOS and offer new insights into its underlying mechanisms. Through isolation and transcriptomic profiling of granulosa cells, we identified the functional significance of lncRNA NONHSAT233728.1 in polycystic ovary syndrome (PCOS) pathogenesis. Knockdown of lncRNA NONHSAT233728.1 in granulosa cells elevated ROS levels, reduced the Bcl2/Bax ratio, downregulated phospho‐ERK1/2, and increased IL‐8 secretion. These results demonstrate ROS‐mediated mitochondrial apoptosis via MEK/ERK1/2 suppression, alongside inhibited proliferation and enhanced inflammation, consistent with follicular atresia in PCOS. Negative correlations between NONHSAT233728.1 and LH/FSH ratios further support its pathogenic role.
研究领域:
生殖医学
·
分子生物学
·
内分泌学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Lei Yan,Qin Zeng,Wenru Wang,Ying Liang,Rui Lang,Jingyi Zhan,Jiayi Yang,Renhuan Yu,Xinhui Wang
Ethnopharmacological relevance Jianpi Qushi Heluo formula (JQHF) is an evidence-based herbal formula based on "Fangji Huangqi Decoction" in the classic of traditional Chinese medicine (TCM) synopsis of the Golden Chamber. Its effectiveness in reducing idiopathic membranous nephropathy (IMN) proteinuria, edema and other clinical symptoms and improving kidney injury has been confirmed by clinical trials and animal experiments. These results demonstrate the critical significance of reducing podocyte injury by regulating mitophagy through integrating ethnopharmacology. Aim of the study This study aimed to explore the protective effects of JQHF on podocyte injury in IMN, focusing on its role in promoting PINK1-dependent mitophagy to inhibit reactive oxygen species (ROS) mediated activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Materials and Methods The main components of JQHF were identified by ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). Passive Heymann nephritis (PHN) was induced in rats using anti-Fx1A antiserum, while podocyte injury in vitro was stimulated with sublytic complement C5b-9 (sC5b-9). The PHN rats were treated with JQHF, and autophagy inhibitor 3-methyladenine (3-MA) combined with JQHF was used for pathway verification, and Benazepril served as a positive control. In vitro, podocytes were exposed to palmitic acid (PA, a ROS inducer) and N-acetylcysteine (NAC, a ROS scavenger). Further, we silenced the expression of PINK1 in podocytes model and intervened with JQHF-containing serum. Renal function was assessed through biochemical analyses and histopathology. Mitochondrial function was measured by detecting mitochondrial membrane potential (MMP), ROS levels as well as mitochondrial ultrastructure. The expression of podocyte structural proteins (desmin, nephrin, podocin) and inflammasome-related markers (NLRP3, caspase-1, IL-1β, IL-6) was analyzed to assess podocyte injury and inflammasome activation. Results (1) In vitro, in contrast to the control group, PA intervention caused increased ROS accumulation, reduced MMP, upregulated NLRP3 and caspase-1 expression, as well as elevated expression of inflammatory factors IL-1β and IL-6. The expression of nephrin and podocin was notably reduced. By contrast, NAC reversed these effects. (2) In vivo, JQHF effectively ameliorated mitochondrial damage, reduced NLRP3 expression and mitigated podocyte injury in PHN rats. The protective effects of JQHF were diminished by 3-MA, confirming the involvement of autophagy. (3) In vitro, JQHF-containing serum attenuated C5b-9-induced podocyte injury, improved mitochondrial dysfunction, and inhibited ROS-mediated activation of NLRP3 inflammasome. Silencing PINK1 significantly reversed these protective effects. Conclusion JQHF can alleviate podocyte damage, that through inhibiting ROS-mediated NLRP3 inflammasome activation by improving PINK1-mediated mitophagy.
研究领域:
免疫学
·
分子生物学
·
药理学
·
转化医学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-14
·
IF 16.6
Jia Yuanbo,Hu Jiahui,An Keli,Zhao Qiang,Dang Yang,Liu Hao,Wei Zhao,Geng Songmei,Xu Feng
Atopic dermatitis (AD) is a chronic skin disease caused by skin immune dyshomeostasis and accompanied by severe pruritus. Although oxidative stress and mechanical scratching can aggravate AD inflammation, treatment targeting scratching is often overlooked, and the efficiency of mechano-chemically synergistic therapy remains unclear. Here, we find that enhanced phosphorylation of focal adhesion kinase (FAK) is associated with scratch-exacerbated AD. We then develop a multifunctional hydrogel dressing that integrates oxidative stress modulation with FAK inhibition to synergistically treat AD. We show that the adhesive, self-healing and antimicrobial hydrogel is suitable for the unique scratching and bacterial environment of AD skin. We demonstrate that it can scavenge intracellular reactive oxygen species and reduce mechanically induced intercellular junction deficiency and inflammation. Furthermore, in mouse AD models with controlled scratching, we find that the hydrogel alleviates AD symptoms, rebuilds the skin barrier, and inhibits inflammation. These results suggest that the hydrogel integrating reactive oxygen species scavenging and FAK inhibition could serve as a promising skin dressing for synergistic AD treatment.
研究领域:
皮肤病学
·
材料科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Zihe Zhai,Wei Ouyang,Yuejun Yao,Yuqi Zhang,Haolan Zhang,Feng Xu,Changyou Gao
Acute lung injury (ALI) is associated with excessive inflammatory response, leading to acute respiratory distress syndrome (ARDS) without timely treatment. A fewer effective drugs are available currently to treat the ALI/ARDS. Herein, a therapeutic nanoplatform with reactive oxygen species (ROS)-responsiveness was developed for the regulation of inflammation. Dexamethasone acetate (Dex) was encapsulated into poly(thioketal) polymers to form polymeric nanoparticles (NPs) ( [email protected] ). The NPs were composed of poly(1,4-phenyleneacetonedimethylene thioketal) (PPADT) and polythioketal urethane (PTKU), in which the thioketal bonds could be cleaved by the high level of ROS at the ALI site. The [email protected] could accumulate in the pulmonary inflammatory sites and release the encapsulated payloads rapidly, leading to the decreased ROS level, less generation of pro-inflammatory cytokines, and reduced lung injury and mortality of mice. RNA sequencing (RNA-seq) analysis showed that the therapeutic efficacy of the NPs was associated with the modulation of many immune and inflammation-linked pathways. These findings provide a newly developed nanoplatform for the efficient treatment of ALI/ARDS.
研究领域:
药理学
·
纳米技术
·
炎症
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xiaoduo Zhao,Lumin Yang,Licheng Zhang,Le Ji,Shuanhong Ma,Feng Zhou
The early stages of osteoarthritis (OA) in the joints are typically characterized by two key factors: the dysfunction of articular cartilage lubrication and inflammation resulting from the excessive production of reactive oxygen species (ROS). Synthetic injectable macromolecular materials present great potential for preventing the progression of early OA. In this study, to mimic the excellent lubricity of brush-like aggregates found in natural synovial fluid, we develop a novel macromolecular biolubricant (CS-PS-DA) by integrating adhesion and hydration groups onto backbone of natural biomacromolecules. CS-PS-DA exhibits a strong affinity for cartilage surfaces, enabling the formation of a stable lubrication layer at the sliding interface of degraded cartilages to restore joint lubrication performance. In vitro results from ROS scavenging and anti-inflammatory experiments indicate the great advantage of CS-PS-DA to decrease the levels of proinflammatory cytokines by inhibiting ROS overproduction. Finally, in vivo rats OA model demonstrates that intra-cavitary injection of CS-PS-DA could effectively resist cartilage wear and mitigated inflammation in the joints. This novel biolubricant provides a new and timely strategy for the treatment of OA.
研究领域:
生物材料
·
骨科
·
生物医学工程
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 11
·2965-2975
·
IF 5.831
Bin Yang,Kaiyuan Wang,Dong Zhang,Bingjun Sun,Bin Ji,Lin Wei,Zhenbao Li,Menglin Wang,Xuanbo Zhang,Haotian Zhang,Qiming Kan,Cong Luo,Yongjun Wang,Zhonggui He,Jin Sun
In the context of prodrug nanomedicines for cancer therapy, one of the great challenges is the slow and variable release of the parent drug in tumors. Recently, many smart redox-sensitive nanocarriers have been developed to address this problem. However, due to significant tumor heterogeneity, some redox-sensitive nanomedicines still show poor selectivity in drug release. Herein, we report the design and synthesis of a ROS-triggered prodrug nanoplatform fabricated with oxidation-responsive cabazitaxel (CTX) prodrugs for synergistic chemo-photodynamic therapy, thioether-/selenoether-linked conjugates of CTX and oleic acid (OA). These prodrugs can be readily self-assembled into nanoparticles, with pyropheophorbide a (PPa) co-encapsulated into the prodrug-nanosystem for combination therapy. The dual-source ROS-responsive prodrug nanosystems selectively and rapidly release CTX not only in response to endogenous ROS overproduced in tumor cells, but also to exogenous PPa-generated ROS under laser irradiation. Moreover, the selenium-containing linkage demonstrates significant advantages over a sulfur-containing linkage in terms of ROS-triggered drug release and cytotoxicity. The prepared prodrug-nanosystems significantly prolong the systemic circulation and tumor distribution of both CTX and PPa, thereby demonstrating synergistic chemo-photodynamic therapy in vivo. All these drug delivery advantages render the nanosystem extremely promising for cancer treatment.
研究领域:
癌症治疗
·
纳米医学
·
药学科学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2022
·Vol. 36
·期 4
·e22995
·
IF 3.568
Shiqi Li,Jinwen Yuan,Siyan Che,Li Zhang,Zheng Ruan,Xiaoming Sun
Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame retardants as commercial products. PBDEs have been demonstrated to induce hepatic, reproductive, neural, and thyroid toxicity effects. This study aimed to clarify the potential intestinal toxicity effects of decabrominated diphenyl ether (PBDE-209) in vivo and in vitro. First, we investigated the change of PBDE-209 on oxidative stress in the intestine of mice. Subsequently, the potential toxicity mechanism of PBDE-209 in vitro was investigated. Caco-2 cells were treated with different concentrations of PBDE-209 (1, 5, and 25 μmol/L) for 24 and 48 h. We determined the cell viability, reactive oxygen species (ROS) level, multiple cellular parameters, and relative mRNA expressions. The results showed that PBDE-209 significantly injured the colon of mice, increased the intestinal levels of malondialdehyde (MDA), and changed the antioxidant enzyme activities. PBDE-209 inhibited the proliferation and induced cytotoxicity of Caco-2 cells. The change in ROS production and mitochondrial membrane potential (MMP) revealed that PBDE-209 caused oxidative stress in Caco-2 cells. The real-time PCR assays revealed that PBDE-209 inhibited the mRNA expression level of antioxidative defense factor, nuclear factor erythroid 2-related factor 2 (Nrf2). Furthermore, the FAS and Cytochrome P450 1A1 (CYP1A1) mRNA expression levels were increased in Caco-2 cells. These results suggested that PBDE-209 exerts intestinal toxicity effects in vivo and in vitro and inhibits the antioxidative defense gene expression in Caco-2 cells. This study provides an opportunity to advance the understanding of toxicity by the persistent environmental pollutant PBDE-209 to the intestine. Highlights Long-time exposure to decabromodiphenyl ether (PBDE-209) causes oxidative stress and induced intestinal damage in mice. PBDE-209 induces cell apoptosis via upregulation of FAS expression in Caco-2 cells. PBDE-209 inhibits the Keap1-Nrf2 antioxidant defense pathway in Caco-2 cells.
研究领域:
毒理学
·
环境科学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yingwen Lu,Pengfei Shan,Weilin Lu,Xiangping Yin,Haiwei Liu,Xiaoyue Lian,Jiayi Jin,Yuxi Qi,Zhongyu Li,Zhihui Li
Bacterial infection is a serious global health threat, and the clinical abuse of antibiotics has severe systemic toxicity and leads to multidrug-resistant bacteria. Stimuli-responsive polymers represent an encouraging strategy for intelligent treatment; however, inadequate polymer degradation and drug release are still challenging, especially in bacterial infection, where exponential rates of degradation and release are urgently needed. Here, we reported a facile 1,1,3,3-tetramethylguanidine (TMG)-promoted polyesterification method for the preparation of a novel antibiotic-free, PEGylated ROS-responsive polymeric prodrug of cinnamaldehyde (PRPCA), and demonstrated its remarkable intrinsic antibacterial activities and the acceleration of infected wound healing for the first time. The CA was covalently incorporated into the backbone of the polyester by a ROS-responsive thioacetal linkage and can be triggered to release by the ROS generated during bacterial growth. The released CA successively induced more ROS generation and the polymer achieved self-accelerating degradation via the positive feedback. The PRPCA-based nanomedicine possessed great bactericidal effects against both S. aureus and E. coli in vitro . Strikingly, the self-amplifying degradation of PRPCA nanoparticles caused abrupt “self-destruction” of S. aureus . More importantly, PRPCA significantly accelerated the S. aureus -infected wound healing process without systematic toxicity. Collectively, this work opens an avenue to develop novel self-amplifying stimuli-responsive polymers based on natural antimicrobial for superior wound disinfection and healing.
研究领域:
药学
·
材料科学
·
生物医学工程
·
纳米技术
·
传染病学
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Hui Yan,Danping Wang,Chengyin Tian,Long Zhao,Yong Wang,Guoqing Long,Bingjun Sun,Jingming Jia,Anhua Wang
Darutigenol (DL) is an active diterpenoid extracted from the traditional Chinese medicine Sigesbeckia glabrescens (Makino) Makino, widely employed in the treatment of rheumatoid arthritis (RA) for centuries in China. However, the anti-inflammatory mechanism of DL requires further exploration. In this study, we discovered that DL could scavenge reactive oxygen species (ROS) and nitric oxide (NO), and reduce the secretion of proinflammatory cytokines, inducing the M1-to-M2 polarization of macrophages in vitro . In vivo , DL was demonstrated to exert an anti-inflammatory effect via the JAK1, 3/STAT3 and MAPK pathways. It also showed efficacy in repairing cartilage damage via downregulating the proteins MMP2/MMP9 and inhibiting angiogenesis through the CXCL12/CXCR7 system in synovial tissues. However, the application and therapeutic effect of DL was constrained by its poor water solubility and low bioavailability. To address these limitations, ROS-responsive prodrug nanoassemblies were employed, which could be passively transported to the joint inflammation site and decomposed in the inflammatory environment to release DL. The therapeutic effect of prodrug nanoassemblies was superior to that of DL, with negligible toxicity to organs. In summary, we clarified the anti-RA mechanism of DL and constructed an efficient and safe drug delivery system, which provided a strategy for the further application and development of active compounds in traditional Chinese medicine.
研究领域:
药理学
·
纳米技术
·
免疫学
·
传统中药
·
药物递送系统
·
炎症
✓ 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）