LIFE SCIENCES
·
2021
·
IF 5.037
Zhenjie Sun,Qian Chai,Ziying Zhang,Dexue Lu,Ziang Meng,Weihua Wu
Aims Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. Materials and methods Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. Key findings The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. Significance The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.
研究领域:
内分泌学
·
心脏病学
·
糖尿病
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Xiaozhuo Ba,Tao Ye,Yu He,Yonghua Tong,Haojie Shang,Jian Wu,Wen Deng,Zichen Zhong,Xiaoqi Yang,Kangyang Wang,Yabin Xie,Kehua Jiang,Xiaolin Guo,Kun Tang
Kidney stones are characterized by a high incidence and recurrence rate, leading to kidney injury, which in turn accelerates stone formation and deposition. Increasing evidence have demonstrated that oxidative stress and cell pyroptosis play important role in the calcium oxalate (CaOx) stones induced kidney injury. Currently, treatments related to oxidative stress and inflammation associated with kidney stones are still relatively limited. Here, we designed engineered macrophage cell membrane-coated hollow mesoporous manganese dioxide nanoparticles loaded with NLRP3 inhibitors Mcc950 (KM@M@M). KM@M@M NPs were modified with Kim-1 targeting peptides on M2-polarized macrophage membranes to achieve better targeted delivery to injured kidney tubules. Compared with traditional drugs, KM@M@M NPs reduce systemic toxicity through targeted drug delivery to the kidneys. In vivo and in vitro results demonstrate that KM@M@M NPs reduces the activation of the NLRP3 inflammasome in renal tubular epithelial cells by scavenging ROS, thereby downregulating gasdermin D cleavage and the production of inflammatory cytokines, ultimately inhibiting cell pyroptosis. In addition, bioinformatic analysis revealed that KM@M@M NPs protect against CaOx induced kidney injury via suppressing the NLRP3/GSDMD pathway. This article extending the application of engineered cell membrane-based biomimetic nanotechnology, and providing a promising strategy for dual protection in CaOx stones induced kidney injury. Statement of significance Currently, apart from invasive surgery, there are few pharmacological therapies for CaOx-induced renal injury. This study presents a new strategy using engineered macrophage cell membrane-coated hollow mesoporous manganese dioxide nanoparticles (KM@M@M) to target and treat calcium oxalate (CaOx)-induced kidney injury. The nanoparticles effectively scavenge reactive oxygen species (ROS) and inhibit NLRP3 inflammasome activation, preventing pyroptosis and kidney damage. By delivering NLRP3 inhibitors directly to injured renal tubules, KM@M@M NPs reduce inflammation and stone deposition. This work demonstrates the potential of biomimetic nanotechnology for targeted treatment, offering a promising approach to prevent CaOx-induced renal injury and enhance therapeutic outcomes in kidney stone disease.
研究领域:
医学
·
药理学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2025
·
IF 4.3
Zhishen Xie,Mengmeng Wang,Qingqing Song,Xuan Su,Jenny Jie Chen,Jiangyan Xu,Zhenqiang Zhang,Tongxiang Liu,Xiaowei Zhang,Gai Gao
Diabetic kidney disease (DKD) is widely recognized as the primary cause of end-stage renal disease (ESRD). Activating autophagy is considered a key strategy to improve DKD. Here, through luciferase reporter gene screening of several sesquiterpenoids, it was found that germacrone (GER) significantly activated the transcription factor EB (TFEB), and its effect on DKD and the underlying molecular mechanism was investigated. GER significantly improved renal function impairment and alleviated renal pathological damage. GER inhibited NLR family pyrin domain containing 3 (NLRP3)-mediated inflammatory responses both in vitro and in vivo. Mechanistically, GER activated TFEB to promote autophagy and clear NLRP3 inflammasomes, and the GER-mediated degradation of NLRP3 was reversed by the autophagy inhibitor chloroquine (CQ). Additionally, GER did not affect the expression of TFEB protein but increased its expression in the nucleus. This effect was attributed to the dephosphorylation of p-TFEB (S122) protein caused by the activation of protein phosphatase 2A (PP2A) by GER. This result was further confirmed by supplementing with the PP2A inhibitor okadaic acid (OA). Docking results indicated a stable binding between GER and PP2A. These findings highlighted GER as a potential intervention for treating DKD and clarified the underlying mechanism through which it functions by regulating the PP2A-TFEB pathway.
研究领域:
药理学
·
分子生物学
·
肾病学
·
生物化学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Jiajia Mu,Qiannan Sun,Nanyan Lin,Chenguang Yue,Jiaqiao Zhu,Hui Zou,Hongyan Zhao,Ruilong Song,Zongping Liu,Yonggang Ma
Ketosis in dairy cows is linked to endometritis, but the molecular mechanisms are unclear. We investigated whether P2X7R is crucial in ketosis-induced endometritis. Ketotic cows had higher levels of NLRP3, caspase-1, GSDMD, GSDME, and P2X7R in the uterine tissue. β-Hydroxybutyric acid (BHBA) exposure in bovine endometrial epithelial cells induced pyroptosis, increased pyroptosis protein and gene expression, and raised pyroptosis rates. P2X7R levels rose with BHBA, and BHBA also increased the level of extracellular ATP. Inhibitors of NLRP3, caspase-1, caspase-3, and P2X7R reduced BHBA-induced pyroptosis. P2X7R inhibition suppressed NLRP3, caspase-1, and caspase-3 activation, preventing pyroptosis. In P2rx7–/– mice with a ketosis model, blood BHBA was lower, and uterine tissue showed less pyroptosis-related protein expression compared to ketotic mice. P2X7R appears to regulate BHBA-induced pyroptosis through NLRP3 and caspase-3 signaling, suggesting it is a potential therapeutic target.
研究领域:
兽医学
·
生殖生物学
·
细胞生物学
·
分子生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2017
·Vol. 16
·期 6
·8413-8419
·
IF 1.692
Qian An,Qian Hu,Bing Wang,Wenjun Cui,Fei Wu,Yu Ding
The overexpression of inflammasome components is correlated with diabetes‑associated complications. Oleanolic acid is a triterpenoid compound which is important in arterial injury. The present study evaluated whether oleanolic acid improved diabetic rat carotid artery injury through the inhibition of nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasomes signaling pathways. A diabetic rat model was induced using streptozotocin (60 mg/kg) and underwent carotid artery injury. Morphometric analysis was performed using hematoxylin and eosin staining. The mRNA and protein levels were assayed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. It was found that oleanolic acid (100 mg/kg/day) improved body weight, glucose metabolic disorders, neointimal hyperplasia and endothelial dysfunction in diabetic rats with carotid artery injury. In addition, oleanolic acid administration significantly downregulated the mRNA and protein expression levels of endothelin 1 in diabetic rats. Oleanolic acid decreased the intimal area and the ratio of neointima to media in diabetic rats. Serum levels of tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6 and IL‑18 in the oleanolic acid‑treated diabetic rats were downregulated. Consistent with the serum results, it was demonstrated that oleanolic acid administration caused a significant decrease in the levels of NLRP3, caspase‑1 and IL‑1β in the carotid arteries of diabetic rats. Taken together, these observations suggested that oleanolic acid attenuated carotid artery injury in diabetic rats and the underlying mechanism was mediated, at least partially, through the suppression of NLRP3 inflammasome signaling pathways.
研究领域:
药理学
·
心血管疾病
·
糖尿病
✓ 已验证
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Hong Chen,Yongjie Ding,Wei Chen,Yun Feng,Guochao Shi
Background: Pulmonary fat embolism (PFE) is one of the important causes of acute lung injury (ALI), but its pathogenesis is unclear. In recent years, it has been found that the NLRP3 inflammasome is closely related to inflammatory response. However, there are no reports about the involvement of NLRP3 in PFE- associated ALI. Glibenclamide is a kind of hypoglycaemic drug with anti-inflammatory effect. It has been reported to have the anti-inflammatory effect related to inhibiting NLRP3.Objective: To determine whether NLRP3 inflammasome was involved in ALI induced by PFE or whether glibenclamide had therapeutic effects on such lung injury, we designed this experiment.Materials and methods: The rat model of intravenous injection of oleic acid (OA) was used to simulate PFE. Rats were divided into three groups: control, OA and glibenclamide treatment group. Blood free fatty acid (FFA) concentration was determined by ACS-ACOD. Histopathological examinations were taken to assess the severity of lung injury. The expression of NLRP3 pathway and its downstream products were analyzed by IHC, WB, qPCR and ELISA.Results: Four hours after intravenous OA injection, the typical pathological manifestations of ALI accompanied by elevated levels of plasma FFAs were found. The activity of NLRP3 inflammasomes increased in OA group, too. Pretreatment with glibenclamide partly inhibited the increase in NLRP3, caspase-1 and IL-1β expression induced by OA, simultaneously attenuated the lung injury. But it has little effect on the expression of Toll-like receptor 4 (TLR4) expression in this experiment.Conclusion: NLRP3 inflammasome, one of the main components of innate immune response, involved in ALI induced by OA. Glibenclamide can alleviate this kind of ALI by inhibiting rather the NLRP3/caspase-1/IL-1β signaling pathway than the levels of FFAs or TLR4 pathway.
研究领域:
药理学
·
免疫学
·
肺科学
·
病理生理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Gong Jing,Zhou Min,Huang Yue,Yu Mengjun,Zhou Qiang,Chen Shiwen,Wang Jia,Yang Min,Luo Qing,Zhang Rong,Huang Jingbin
Asthma is a chronic inflammatory respiratory disease worldwide. Its severe phenotypes, particularly the glucocorticoid-resistant ones, pose a major challenge, with neutrophilic inflammation being the key driver. However, no effective treatments are currently available. Herein, we report a macromolecular therapeutic strategy capable of targeting multiple key cells involved in the pathogenesis of neutrophilic asthma. The macromolecular therapy named PMART is constructed by conjugating artesunate and polyethylene glycol to the triazine scaffold. It is highly water-soluble and can self-assemble into nanomicelles, which enables efficient targeting to inflamed lung tissues and localization in inflammatory cells. In a murine model of neutrophilic asthma, PMART has proven to have in vivo efficacy equivalent to or greater than that of two clinically used anti-asthma drugs. Mechanistically, PMART reduces succinate levels by inhibiting branched-chain amino acid transaminase 1 (BCAT1) overexpression, thereby suppressing neutrophilic inflammation via blocking the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and the production of pro-inflammatory cytokines. Notably, PMART exhibits a favorable safety profile in mice. Taken together, these data support the potential of PMART as a novel and highly effective therapeutic agent for neutrophilic asthma and other neutrophil-mediated diseases. Graphical
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2026
·
IF 11
Chu Z,Yang T,Zhang Y,Zhu Q,Wang D,Tang H,Zhang G,Jiang M,Zhou L,Xu L,Fan T,Zhang J,Ma A,Xu C,Wang J,Tang H.
Ulcerative colitis (UC) remains a clinical challenge due to limited efficacy and side effects of conventional therapies, highlighting the need for novel interventions. Here, we investigate the therapeutic potential of naturally derived self-assembled nanoparticles (XDNPs) from the traditional Chinese medicine formula Xiexin Decoction (XXD) and rationally designed carrier-free nanoparticles (RBNPs) composed of berberine (BBR) and rhein. Both formulations effectively mitigated DSS-induced colitis by normalizing gut dysbiosis, reducing the release of pro-inflammatory mediators and facilitating macrophage phenotypic switching. Mechanistically, activity-based protein profiling identified VDAC1 as a direct functional target of BBR. Binding to VDAC1 inhibits its oligomerization, preventing the cytosolic release of oxidized mitochondrial DNA and subsequent activation of the NLRP3 inflammasome in macrophages. Co-assembly with rhein further enhances cellular uptake and bioavailability, amplifying anti-inflammatory efficacy. Proteomic and molecular analyses confirmed broad modulation of immune and metabolic pathways, while in vivo safety assessments demonstrated excellent biocompatibility without detectable organ toxicity. Collectively, this work elucidates a VDAC1-mediated mechanistic axis underlying the potent therapeutic effects of BBR-containing nanoparticles and establishes a rational nanomedicine strategy inspired by traditional herbal formulations. These findings provide a promising platform for the development of targeted, biocompatible nanotherapeutics for UC and other inflammatory disorders.
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2026
·Vol. 24
·期 4
·440-453
·
IF 7.5
Zitong Zheng,Shang Lyu,Meijuan Wang,Peng Liu,Yashi Ou,Junfang Yi,Huajie Yang,Zengrui Liao,Jiangting Sun,Wei Zou,Yulin Feng
Gouty arthritis (GA) is an inflammatory disorder characterized by the deposition of monosodium urate (MSU) crystals in joint tissues. Pulchinenoside B4 (B4) has broad-spectrum anti-inflammatory properties, but its role and potential mechanism in the pathogenesis of GA are still unclear. The purpose of this study is to comprehensively elucidate the therapeutic effect and mechanism of B4 on GA by integrating transcriptome analysis and in vitro and in vivo experiments. In the MSU-induced mouse GA model, B4 treatment significantly improved ankle edema and reduced inflammatory cell infiltration. Through the analysis of transcriptome sequencing results, we identified multiple differentially expressed long non-coding RNAs (lncRNAs), such as Nod1 , Rbck1 and Pycard . In the in-depth exploration of the mechanism, we focused on the NOD-like receptor signaling pathway, NF- κ B signaling cascade, and B4-regulated macrophage polarization. In vitro and in vivo models, we confirmed that B4 significantly inhibited the expression and activation of key components of NLRP3 inflammasome (such as ASC, Caspase-1 and IL-1β) by qPCR, Western blot and immunofluorescence. Flow cytometry and immunofluorescence analysis further showed that B4 could prevent MSU-induced macrophage polarization to pro-inflammatory M1 phenotype. Based on these results, this study elucidated the mechanism of B4 improving MSU-induced GA inflammatory response by inhibiting NLRP3 inflammasome activation and blocking M1 macrophage polarization. These results suggest that B4 has great potential as a candidate drug for the treatment of GA.
✓ 已验证
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Can Wang,Jiayi Liu,Yujuan Zhou,Xiaoqin Shan,Siyi Li,Shuxian Ding,Xingjie Zhuo,Qin Li,Weijun Yang,Xinyue Zhang,Lili Gu
Alzheimer’s disease (AD) is a chronic, low-grade inflammatory neurodegenerative disorder. Inhibiting the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a potential therapeutic strategy for AD, but no approved NLRP3-specific inhibitors are available for clinical use, and current agents often cause significant side effects despite their anti-inflammatory benefits. Acacetin, is a flavonoid compound that can penetrate the blood–brain barrier, with potential for treating AD.The purpose of this study is to clarify the relationship between the anti-AD effect of acacetin and its mechanism of inhibiting NLRP3.acacetin improved cognitive function and reduced neuronal damage in 3xTg mice. Further Acacetin directly binds to sorting nexin-5 (SNX5) and upregulates its expression. This, in turn, activates autophagy to degrade the NLRP3 inflammasome, alleviates inflammationin HT22 cells and BV2 cells. These findings suggest that Acacetin can exert an anti-AD effect by targeting SNX5 to activate autophagy and promote the degradation of the NLRP3 inflammasome, which underscore the importance of targeting SNX5 to suppress NLRP3 inflammasome activation in AD treatment.
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Meng Zhang,Congyao Wang,Ruiqi Zhao,Jiabo Yuan
Background Asthma is a chronic disease characterized by airway remodeling, which results in a progressive decline in lung function. Senkyunolide A is one of the effective components of ligusticum chuanxiong Hort, it shows protective effects on many human diseases. However, the role of Senkyunolide A in asthma remains unclear. Results In our study, we established an asthma mouse model by ovalbumin (OVA) sensitization and challenge, and Senkyunolide A (20 mg/kg and 40 mg/kg) was given by intraperitoneal injection. For in vitro study, lung epithelial BEAS-2B cells were treated with TGF-β1 to induce epithelial mesenchymal transformation. Our study showed that Senkyunolide A (40 mg/kg) alleviated airway injury, inflammatory infiltration and airway remodeling induced by OVA in asthma mice. Meanwhile, Senkyunolide A (40 μM) recovered the high level of cell migration and profibrotic factors expression induced by TGF-β1. Mechanistically, Senkyunolide A abolished the effect of OVA or TGF-β1 on Smad2/3 phosphorylation at site Ser 465/467 /Ser 423/425 in mice or BEAS-2B cells and inhibited the activation of NLRP3 inflammasome induced by OVA. Conclusions In total, our study indicated that Senkyunolide A alleviated airway damage and airway remodeling in asthmatic mice and regulated the progress of asthma by inhibiting the TGF-β/Smad2/3 signaling pathway and NLRP3 activation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2026
·Vol. 63
·期 1
·432
·
IF 5.5
Lin Jinyu,You Bowen,Yang Xin,Li Xue,Sun Wenjuan,Xu Zhongyu,Zhang Yi,Tong Xuhui,Dong Shuying
Cerebral ischemia/reperfusion injury (CIRI) refers to the secondary brain injury that occurs when blood supply is restored to ischemic cerebral tissue, and represents one of the primary causes of adult disability and mortality. Current evidence indicates that aesculin exhibits antioxidative and anti-inflammatory activities; however, its therapeutic effects on CIRI remain to be elucidated. The objective of this study was to investigate the potential role of Esculin (ESCU) in protecting against CIRI and to elucidate its underlying mechanisms. Adult male mice were used to establish the middle cerebral artery occlusion/reperfusion (MCAO/R) model. The mice were administered varying doses of ESCU or a reference positive control drug. To evaluate the neuroprotective effects of ESCU, neurological deficit scores were assessed, and cerebral blood flow was measured. 2,3,5-triphenyltetrazolium chloride staining, H&E staining, and Nissl staining were used to determine neuronal damage. NLRP3-related markers and mitophagy-related markers were determined to investigate the mechanism of action of ESCU. ESCU afforded robust neuroprotection in mice, ameliorating functional deficits, reducing infarct size, and preserving neuronal structure. It potently alleviated oxidative stress and restored mitochondrial function (reduced ROS, improved cristae morphology, and increased mitochondrial membrane potential). Mechanistically, ESCU activated mitophagy (upregulating LC3Ⅱ, PINK1, and Parkin; downregulating p62) and inhibited the NLRP3 inflammasome (downregulating NLRP3, GSDMD-N, cleaved caspase-1, IL-1β, and IL-18). Notably, the mitophagy inhibitor Mdivi-1 abolished ESCU’s inhibition of the NLRP3 pathway, establishing a causal relationship. Thus, ESCU mitigates cerebral ischemia-reperfusion injury by coordinately enhancing mitophagy and suppressing NLRP3 inflammasome activation. Our study demonstrates that ESCU attenuates CIRI mechanistically by promoting PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation. These findings not only elucidate a novel pathway underlying ESCU’s neuroprotection but also position it as a promising therapeutic candidate for CIRI, warranting further investigation into its precise targets and clinical potential.
✓ 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）