Endocrine Metabolic & Immune Disorders-Drug Targets
·
2025
·Vol. 26
·期 1
·E18715303382831
·
IF 2
Yuting Chen,Jie Min,Xiali Yu,Haixiang Ni,Yamei Jin
IntroductionAn increase in the intraorbital adipose tissue is the main pathological feature of thyroid-associated ophthalmopathy (TAO). IGF-1R activates PI3K/AKT signaling and accelerates adipogenesis. Pingmu decoction has been demonstrated to promote orbital adipocyte apoptosis; however, less is reported regarding the action mechanism of Danshenol A (DA), a single active ingredient of Salvia miltiorrhiza (Danshen). Accordingly, this study aimed to investigate the role and association of DA and IGF-1R in the proliferation and lipid accumulation of orbital adipocytes.MethodsPrimary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.ResultsOrbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.DiscussionThis study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.ConclusionThis study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.
研究领域:
内分泌学
·
眼科学
·
分子生物学
·
信号转导
·
脂肪代谢
·
中药药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Tao Sheng,Shuai Xia,Jia-Min Li,Ruo-bin Peng,Pingbo Yan,Bing-Feng Zhang
The activation and inflammation of hepatic stellate cells (HSCs) promoted the progression of liver fibrosis. The antioxidant and anti-inflammatory therapy can effectively alleviate liver fibrosis. Here, dual prodrug nanoassemblies modified with chitosan (CS/HS-HD NPs) was constructed. The particle size of CS/HS-HD NPs was about 200 nm, which was uniformly dispersed spherical particles, and Zeta potential was positive. The CS/HS-HD NP loaded SLB 3.66 ± 0.04 % and DEX 0.52 ± 0.01 %. In vitro stability and release investigation showed CS/HS-HD NPs had good stability and sustained release characteristics without burst release. These results of in vivo pharmacokinetics, intestinal absorption and in vivo distribution showed that CS/HS-HD NPs had longer t l/2 and larger AUC than other groups (Free drug, HS-HD NPs), which significantly enhanced intestinal absorption and specific accumulation in the liver. In CCl 4 -induced liver fibrosis, CS/HS-HD NPs significantly inhibited the secretion of pro-inflammatory cytokines TNF-α, IL-6 and IL-12, and increased anti-inflammatory cytokines IL-10 level, and then reduce the infiltration of inflammatory cells. The image of liver, HE staining, Masson staining showed CS/HS-HD NPs reduced collagen deposition and liver pathological damage, effectively improved liver fibrosis. Taken together, these findings suggested chitosan coated hybrid prodrug-nanoassemblies could adjust inflammatory cytokines and improve therapeutic effect on liver fibrosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR NEUROBIOLOGY
·
2025
·Vol. 63
·期 1
·335
·
IF 4.3
Pan Gaowei,Liu Xiaoling,Zhang Xiaoyue,Gao Hao,Xu Ting,Li Kemin,Wang Lei,Ji Shangrong,Li Ting,Zhang Shengxiang
Monomeric C-reactive protein (mCRP) is a key acute phase reactant involved in inflammatory responses. Cerebral ischemia triggers persistent neuroinflammation. However, the effects of mCRP on global cerebral ischemia are poorly understood. In present study, mCRP was intracerebroventricularly injected to brain, and a bilateral common carotid artery ligation (BCAL) model was established in CX3CR1 GFP/+ mice. Behavioral tests were employed to evaluate spontaneous activity, rotarod performance (latency to fall), and forelimb grasping strength in mice. Nissl and Fluoro-Jade C (FJ-C) staining were used to assess neuronal injury. Skeletonization analysis and CD16/32, CD206 staining were used to assess microglial activation. RT-qPCR was applied to evaluate the changes of inflammatory factors and complement system. Primary cultured microglia and oxygen–glucose deprivation (OGD) model were used to verify the effects of mCRP on microglia in vitro . Results showed that mCRP treatment exacerbated behavioral performance post-ischemia. Nissl staining showed that mCRP caused a significant decrease in neuronal density. Additionally, FJ-C staining indicated an increase in degenerative cells after mCRP treatment. Immunofluorescence analysis revealed an increase in CD16/32 and CD206-positive microglia, and skeletonization analysis showed increased de-ramification of microglia following mCRP administration. RT-qPCR results further demonstrated that mCRP treatment upregulated the expression of pro-inflammatory and anti-inflammatory factors, as well as complement system components, in both brain tissue and primary cultured microglia following ischemia or OGD. These findings suggest that mCRP significantly enhances microglial activation, increases the level of inflammatory response, exacerbates neuronal loss and degenerative damage, and impairs behavioral performance after ischemia.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2026
·Vol. 40
·期 4
·e71580
·
IF 4.3
Liujie Zheng,Yinhua Ni,Suyao Xie,Yitian Ji,Jiahong Dong,Lanjun Fu,Zhengwei Fu,Juan Jin,Qiang He
Acute kidney injury (AKI) is a serious complication of cisplatin chemotherapy, requiring new preventive therapies. Germacrone, a sesquiterpenoid derived from Rhizoma Curcuma , has multiple pharmacological effects, including anti-inflammatory, antiapoptotic, and antioxidant effects. The current study aimed to investigate the effect and mechanism of germacrone on AKI. Single high-dose and multiple low-dose cisplatin-induced AKI and AKI-chronic kidney disease (CKD) transition mouse models were used to determine the preventive effect of germacrone, with the mechanism explored in HK-2 and Raw264.7 cells. A breast cancer tumor-bearing model was developed to determine whether the nephron-protective effects of germacrone affect the anticancer properties of cisplatin. Here, we found that germacrone significantly alleviated AKI and fibrosis in cisplatin-treated mice, as demonstrated by decreased serum creatinine and blood urea nitrogen (BUN) levels and improved renal pathology. Germacrone attenuated cisplatin-induced apoptosis and inflammation in vivo and in vitro. RNA sequencing revealed that germacrone restored cisplatin-induced gene dysregulation and regulated inflammation and apoptosis through the PI3K/AKT and Ras/MAPK pathways. Inhibition of these pathways abrogated the renoprotective effect of germacrone in vitro. Moreover, germacrone reduced macrophage activation and induced an M2-dominant shift in macrophage polarization in the kidneys and Raw264.7 cells via similar pathways. Furthermore, germacrone protected the kidneys without affecting the chemotherapeutic effects of cisplatin on a mouse model of breast cancer. Therefore, germacrone is expected to have universal renoprotective effects across different AKI models and a tumor-bearing model through similar signaling pathways, suggesting its potential as a clinical adjuvant therapy for reducing nephrotoxicity in patients receiving cisplatin chemotherapy. Graphical Germacrone alleviates inflammation and apoptosis in cisplatin-injured kidneys by activating PI3K/AKT and suppressing Ras/MAPK signaling, thereby protecting against acute kidney injury (AKI) in mice. This renoprotection is reinforced by its ability to drive an M2-dominant macrophage shift both in vivo and in vitro, ultimately restoring tubular integrity and renal function.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2026
·
IF 18.1
Mao Congyang,Jin Wanyu,Dou Limeng,Guo Tong,Huang Jin,Wang Yi,Liu Xiangmei,Wu Shuilin,Qiao Wei,Xiang Yiming,Zhu Yizhou,Wu Jun,Yeung Kelvin Wai Kwok
The pandemic-scale progression of type 2 diabetes mellitus (T2DM) necessitates innovative interventions targeting the pathogenic triad of insulin resistance, dysregulation of lipid metabolism, and gut microbiome dysbiosis. Here, we report a synthetically bioengineered probiotic consortium (REcN-F/Ca) developed through directed metabolic adaptations of Escherichia coli Nissle 1917 (EcN) under iterative hydrogen peroxide selection, subsequently functionalized with fructooligosaccharide-calcium carbonate composites. REcN-F/Ca exhibits enhanced reactive oxygen species tolerance through upregulated antioxidant enzymes and hydrogen sulfide-mediated redox balancing, alongside improved gastrointestinal survivability. In high-fat diet-induced obese male mice, REcN-F/Ca restores gut microbiota diversity, enriches butyrogenic taxa (Lachnospiraceae and Blautia ), and rescues short-chain fatty acids depletion. Transcriptomic profiling reveals PPAR signaling activation, driving lipid metabolism and suppressing adipose inflammation. These effects translate to systemic metabolic improvements with attenuated weight gain (−25.4%), restored glucose homeostasis, and reduced insulin resistance (HOMA-IR: −73.2%) in the obesity and T2DM murine model. Our findings establish REcN-F/Ca as a synthetically engineered probiotic that simultaneously corrects intestinal ecological perturbations and reverses host metabolic dysfunction, proposing a paradigm for metabolic syndrome management.
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2026
·
IF 6
Jie Bai,Ying Bao,Shan Li,Zicheng Guo,Jie Xu,Rong Huang,Jing Yang,Cunqin Lv,Jianhong Liu,Dinglin Zhang
Reactive oxygen species (ROS) exert critical influence in inflammatory bowel disease (IBD). Metal–polyphenol nanoparticles (MPNs) have exhibited a promising ability to regulate ROS levels and restore homeostasis in the context of IBD. However, the relationship between therapeutic efficacy and the type of MPNs requires further investigation. In this research, we synthesized tailorable MPNs by using epigallocatechin gallate (EGCG) and Mg2+, Zn2+, Ca2+, and Cu2+ and investigated their therapeutic efficacy for IBD. In vitro experiments confirmed that these MPNs exhibited pH and ROS responsiveness, increased the stability of EGCG, and improved ROS elimination. In vivo experiments demonstrated that these MPNs can effectively accumulate at sites of colonic inflammation after intraperitoneal injection and can continuously scavenge ROS, downregulate inflammatory factors, and restore the intestinal barrier integrity. Compared with other MPNs, Zn-EGCG nanoparticles (NPs) significantly alleviate symptoms of DSS-induced acute colitis in mice. Our work provides strong evidence to support the rational design of MPNs to regulate inflammation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2026
·
IF 26.8
Weikang Lv,Tuya Naren,Abdellah Aazmi,Haoran Yu,Yujun Wang,Jie Ying Lee,Mengfei Yu,Junjun Jia,Xiuxiu Jiang,Huayong Yang,Liang Ma
Hepatic fibrosis, as the common pathological endpoint of chronic liver diseases, is characterized by a self-perpetuating vicious cycle comprising extracellular matrix (ECM) driven liver tissue stiffening and sustained hepatic stellate cell (HSC) activation. Although existing studies have simulated fibrotic microenvironments using 2D models with tunable matrix stiffness or static 3D cultures, these models lack engineered hepatic sinusoidal vasculature and dynamic mechanical stimulation within 3D ECM contexts. This study employed embedded sacrificial bioprinting to construct functional liver sinusoid-mimetic vascular networks within hydrogel matrix of precisely tunable elastic modulus, establishing a dynamically perfused in vitro liver fibrosis model. Experimental validation demonstrated that matrix stiffness directly drives HSC activation, inducing marked myofibroblastic transdifferentiation. Furthermore, compared to static models, 3D dynamic perfusion significantly enhanced hepatocyte sensitivity to high-stiffness matrix, more accurately replicating the functional decline of hepatocytes in fibrotic microenvironments observed in vivo. More critically, the biomimetic in vitro platform established in this study presents a potential avenue for evaluating pharmacotherapeutic interventions against liver fibrosis. Through targeted inhibition of key signaling hubs, we achieved partial reversal of HSC activation on stiff matrix and partial recovery of liver tissue function. Overall, by simultaneously integrating matrix stiffness modulation, 3D multicellular interactions, and hemodynamic stimulation, this work effectively addresses the insufficient responsiveness of hepatocytes to mechanical cues in conventional models due to inadequate mechanical stimulation. This approach provides a robust framework for faithfully recapitulating the pathophysiological progression of liver fibrosis in vitro through precise tuning of ECM mechanical properties, thereby offering a promising platform for future drug screening and therapeutic assessment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2026
·
IF 8.3
Xueling He,Chen Wang,Ruihao Zhang,Yuanyuan Wang,Ying Zhang,Tong Yang,Junzhe Zhang,Shuan Rao,Huan Tang,Xin Peng,Jigang Wang
Background Sepsis, a life-threatening condition, arises from an aberrant or uncontrolled immune response of the host to severe infection. Timely and precise control of this inflammatory response is of paramount importance in sepsis prevention and constitutes the core of sepsis prevention efforts. Parthenolide (PA), recognized as an NF-κB inhibitor, has previously demonstrated its capacity to mitigate the inflammatory response. This study aimed to investigate whether and how PA can inhibit inflammation, thereby alleviating sepsis, and to profile functional target proteins using chemoproteomics strategy. Methods The cecal ligation and puncture (CLP) procedure was performed to induce a mouse model of sepsis, and lipopolysaccharide (LPS) was employed to establish a model of cellular inflammation in mouse mononuclear macrophage cells (RAW264.7) in vitro . Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin (H&E) staining were utilized to evaluate the therapeutic effects of PA on septic mice. In the in vitro experiments, streamlined cysteine activity-based protein profiling (SLC-ABPP) and proteomics techniques were employed to identify potential protein targets and molecular pathways responsible for the anti-inflammatory properties of PA. Results We demonstrated that PA could enhance the survival rate, reduce inflammatory cytokines release, ameliorate histopathological changes, and balance macrophage polarization in a sepsis model. Similarly, PA could effectively alleviate the inflammatory response in LPS-stimulated RAW264.7 cells. Chemoproteomics profiling revealed that Trim33 protein was a potential covalent target of PA via cysteine engagement, and the expression changes of global proteins indicated by proteomics analysis suggested that PA mitigated inflammation by inhibiting the NF-κB pathway. Finally, through a series of molecular biology experiments, we confirmed that PA suppresses the NF-κB pathway by functionally binding to Trim33 and subsequently reducing the ubiquitin dependent degradation of Smad4, thereby exhibiting anti-inflammatory activity. Conclusion Our findings demonstrated that PA significantly mitigated inflammation in sepsis by targeting the Trim33 protein and consequently suppressing ubiquitination on Smad4 as well inhibiting the NF-κB pathway, thus providing new insights into the clinical use of PA in treatment of inflammation related diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2026
·
IF 5.2
Junhua Xu,Haochen Wang,Kaizhi Li,Shulei Pan,Gang Guo,Kaiyun Liu,Ning Wang,Lin Xiang
Oral ulcers are a common and painful condition. Current treatments, including topical corticosteroids like dexamethasone, are hindered by poor drug penetration and systemic side effects. To address these challenges, we developed a dissolving microneedle patch incorporating protease-responsive gelatin nanoparticles encapsulating dexamethasone (DEX@GNPs) for localized delivery to the oral mucosa. This system is engineered to penetrate the mucosal barrier and release dexamethasone in response to the inflammatory microenvironment, thereby enhancing drug deposition at the ulcer site. In a rat buccal ulcer model, the DEX@GNP-loaded microneedles effectively delivered dexamethasone to the target tissue layers, significantly reduced ulcer size and promoted tissue regeneration. Moreover, the responsive release of dexamethasone in the presence of elevated protease levels was associated with a marked reduction in inflammation, as evidenced by decreased levels of key pro-inflammatory cytokines. These findings indicate that DEX@GNP-loaded microneedles provide a promising approach for the localized treatment of oral ulcers and may help to improve therapeutic outcomes by enabling efficient localized corticosteroid delivery.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2026
·
IF 8.4
Li Shuo,Xu Bing,Lu Ming-jun,Wu Qian-wen,Qin Wen-qing,Dai Zi-qi,Li Xiao-jiao-yang,Bai Jin-zhao,Lei Hai-min,Liu Run-ping
The severe inflammation associated with infectious or inflammatory diseases significantly contributes to mortality. Interferon regulatory factor 3 (IRF3) represents a potential anti-inflammatory target, but the development of IRF3 inhibitors has not yielded satisfactory results to date. In this study, we established a phenotype-based high-throughput screening system to conduct activity-guided hierarchical screening of clinical frequently used anti-inflammatory and anti-rheumatic herbal extracts and compounds. Employing a Gaussia-luciferase reporter system driven by the IFNB1 promoter, we identified sinomenine as a potent type I interferon (IFN) inhibitor from a set of 28 anti-inflammatory herbal products. Furthermore, among 24 synthesized sinomenine derivatives modified by various electrophilic groups, Sim-9 (2.5–10 μM) dose-dependently inhibited IFN responses triggered by TLRs, RLRs, and STING activation in mouse RAW264.7 cells and in human THP-1 cells, HT-29 cells and A549 cells. We demonstrated that Sim-9, by covalently binding to Cys222, induced a conformational change in the p LxIS motif-binding surface of IRF3, thus blocking its interaction with upstream adapters, including TRIF, MAVS and STING, and subsequent homodimerization of IRF3 itself, which were all essential for activation of type I IFN responses. In in vivo experiments, we showed that injection of Sim-9 (30, 60 mg/kg, i.p.) effectively protected against devastating inflammation in cecal ligation and puncture (CLP)-induced sepsis in mice, and improved cerulein-induced pancreatitis by inhibiting IRF3. Our study discovers Sim-9 as a novel covalent allosteric inhibitor of IRF3 and reveals that the p LxIS motif binding surface represents a previously uncharacterized druggable target for IRF3 activation, providing a promising therapeutic strategy for the treatment of severe inflammatory injuries.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2026
·
IF 5.4
Xiaoxuan Xue,Buwen Jiang,Zhuoya Li,Yufu Jiang,Kewei Zhang,Zhijian Ji,Guojun Song,Chao Yang
The efficient degradation of organic pollutants remains a significant challenge in the field of catalysis, and the recycling of granular catalysts remains a persistent challenge during repeated usage. Herein, a ZnO@PVDF(Polyvinylidene Fluoride)-Nanopillar membrane has been prepared by combing the template and hydrothermal method and was applied in degrading methyl orange(MO) dye. The catalytic degradation rate attained 98.05 % at 360 min under the condition of ultrasonication and ultraviolet light being attributed to the composition and the bionic pine branch structure under a synergistic mechano(contactelectric & piezoelectric)-photocatalytic tri-catalysis. The PVDF-Nanopillar substrate as a dielectric material served as the reservoir of electron hole pair and prolonged their recombination by engineering a PVDF/ZnO nanorod heterojunction. Furthermore, the robust and reusability of this composite membrane were detected and the results indicated the membrane could also catalyze the degradation of dexamethasone, and its morphology and composition changed little comparing that in the recycling experiment after with before. Remarkably, the designed ZnO@PVDF-nanopillar membrane achieves ≈ 100 % organic pollutant degradation efficiency and enables facile catalyst recovery, offering a practical solution for sustainable water treatment applications, improving the catalytic convenience. This work provides new design principles for constructing organic-inorganic heterojunctions in environmental catalysis, offering fresh insights into hybrid material engineering.
✓ 已验证
产品关联
DOI
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2026
·
IF 4.3
Mengzhu Lv,Zheng Lu,Xiaoyu Mao,Jiangtao Huang,Qianqian Zheng,Dashuang Mo,Liping Shu
N-(1,3-dimethylbutyl)- N ′-phenyl- p -phenylenediamine (6PPD), a widespread tire-derived contaminant, has drawn increasing concern for its environmental persistence and toxicity. However, its specific effects on early liver development remain poorly understood. In this study, we investigated the hepatotoxicity of 6PPD using zebrafish larvae and human L02 hepatocyte models. A novel exposure strategy was employed, initiating 6PPD treatment at 48 h post-fertilization, after liver budding, to minimize interference from early-stage developmental defects. 6PPD exposure led to a marked reduction in liver size without obvious morphological abnormalities, alongside downregulation of hepatocyte marker genes. Importantly, liver growth gradually recovered after 6PPD removal, suggesting acute and reversible toxicity. Mechanistically, 6PPD induced DNA damage and apoptosis in hepatocytes, as evidenced by elevated γ-H2AX, baxa , and casp3a expression, while hepatocyte proliferation remained unaffected. Transcriptomic and qPCR analyses revealed activation of inflammatory pathways and increased macrophage infiltration. Co-treatment with the anti-inflammatory agent dexamethasone rescued liver size and reduced DNA damage, indicating inflammation as a key mediator of 6PPD-induced toxicity. Similarly, 6PPD exposure in human hepatocytes reduced viability and increased apoptotic markers, which were alleviated by dexamethasone. These results demonstrate that 6PPD causes acute, inflammation-mediated liver toxicity during embryogenesis, with conserved mechanisms across species.
✓ 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）