MOLECULAR NEUROBIOLOGY
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2025
·Vol. 63
·期 1
·335
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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.
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MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Yu Zhong,An-Yang Li,Jun-Bin Dai,Chen Guo,Shan-Shan Chen,Li-Li Su,Qin-Ying Liu,Yang Sun
Sensitive and rapid quantification of chemotherapeutic drug paclitaxel (PTX) in human serum is crucial for enabling personalized dosing and minimizing severe toxicity. In this approach, an ultrasensitive electrochemical sensor was developed via facile one-step deposition method for rapid determination of PTX. The nitrogen-doped carbon quantum dots-multiwalled carbon nanotubes (NCQDs-MWCNT) nanocomposite, which modified on the screen-printed carbon electrode (SPCE), synergistically enhanced the active surface area, boosted the electrical conductivity and improved the detection sensitivity. Under the optimized conditions, the prepared NCQDs-MWCNT/SPCE exhibited good linearity in both 0.2 M phosphate buffer (pH 7.4) and human serum, and the limit of detection (LOD) reached as low as 1.0 nM and 2.3 nM, respectively. Additionally, the developed sensor possessed satisfactory repeatability, long-term storage property and anti-interference capability. The recovery rates were in the range of 107.73–114.05 % in human serum, indicating its accuracy of PTX measurement. In depth, the electrochemical behaviors of PTX at NCQDs-MWCNT/SPCE were examined. Collectively, the proposed ultrasensitive and facile sensor displays potential applications in therapeutic drug monitoring for PTX, facilitating individualized treatment in precision medicine.
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Materials Today Bio
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2025
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IF 10.2
Yanhui Cui,Xueqin Wang,Caiyang Lu,Liling Ran,Zirui Guo,Jiayu Yao,Tian Yu,Xuanxi Liu,Fang Li,Changqi Li,Yingcai Meng,Wenhu Zhou
Acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition marked by severe inflammatory responses and disruption of the alveolar-capillary barrier, leading to high mortality rates and lack of effective treatments. Recent research has underscored the crucial role of programmed cell death pathways-pyroptosis, apoptosis, and necroptosis-in exacerbating inflammation and barrier dysfunction in ALI/ARDS. However, effective therapeutic agents targeting this process remain scarce. In this study, we reveal that PANoptosis, which integrates these cell death pathways through the PANoptosome complex, plays a central role in the pathogenesis and progression of ALI/ ARDS. The levels of PANoptosis-related molecules were significantly elevated in both the ALI mice and the clinical ARDS patient samples, highlighting it as a novel therapeutic target. Building on this insight, we developed a multifunctional nanomedicine, TPNs/Sal B, which integrates tea polyphenol-based nanoparticles (TPNs), a bioactive nanomaterial with anti-pyroptotic and anti-necroptotic properties, with salvianolic acid B (Sal B), known for its anti-apoptotic effects. Our results demonstrate that the nanomedcine TPNs/Sal B effectively inhibit PANoptosis, thereby attenuating lung tissue pathological damage, reducing inflammation, and improving lung epithelial barrier function in ALI models. Moreover, we identified LIM and SH3 protein 1 (LASP1) which may play an critical role in modulating alveolar epithelial barrier function during ALI/ARDS progression, and treatment with TPNs/Sal B effectively restored LASP1 levels. Our findings underscore the therapeutic potential of TPNs/Sal B as a targeted treatment for ALI/ARDS, offering a promising strategy for modulating PANoptosis and preserving lung function.
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Diabetes & Metabolism Journal
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2025
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IF 8.5
Lei Zhou,Yuwen Jiao,Jiaming Xue,Xiaoqiang Zhan,Dongmei Wang,Liming Tang
Background: To investigate the biological functions of the transcription factor LRR binding FLII interacting protein 1 (LRRFIP1) in white adipocyte differentiation (WAD) and elucidate the underlying molecular regulatory mechanisms involved. Methods: Consensus clustering, differential gene expression screening, and intersection analysis were used to identify transcription factors involved in WAD. Adipogenic differentiation experiments were conducted using C3H10T1/2 cells, and a diet-induced obesity model in C57BL/6J mice was established to investigate the function of LRRFIP1 in WAD in vitro and in vivo. Molecular mechanisms were examined through quantitative real-time polymerase chain reaction, Western blotting, luciferase assays, and chromatin immunoprecipitation. Results: Bioinformatics analyses identified LRRFIP1 as a transcription factor associated with WAD. LRRFIP1 expression was downregulated in white adipose tissues from obese patients and in mature white adipocytes. Silencing LRRFIP1 significantly inhibited WAD in C3H10T1/2 cells and reduced differentiation biomarker expression; in contrast, overexpressing LRRFIP1 had the opposite effects. Mechanistically, LRRFIP1 bound to the E2F transcription factor 6 (E2F6) promoter to suppress E2F6 transcription, thereby downregulating a key differentiation regulator, CCAAT enhancer binding protein alpha (C/EBPα). Furthermore, in a diet-induced obesity model, LRRFIP1 could regulate the differentiation and maturation of inguinal white adipose tissue. Conclusion: Our findings reveal that LRRFIP1 plays a crucial inhibitory role in WAD by negatively regulating the E2F6/C/EBPα axis. This discovery not only enriches our understanding of the molecular networks governing WAD but also holds great promise for creating targeted therapies for obesity and associated metabolic conditions.
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Frontiers in Medicine
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2025
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IF 3
Leidong Lian,Dingli Xu,Chaonan He,Zhe Luo,Han Yu,Botao Liu,Ke Zhou,Liangjie Lu,Kaifeng Gan
Introduction The natural polysaccharide-based injectable hydrogels have showed significant interest to use as 3D scaffolds for critical-sized bone defect repair. Methods Here, we incorporated ZnO nanoparticles (NPs) into a newly synthesized water-soluble phosphocreatine-functionalized chitosan (CSMP) water solution to form an injectable hydrogel (CSMP-ZnO) via supramolecular combination between phosphate groups in CSMP and Zinc in ZnO NPs. Results The phosphocreatine in this hydrogel not only provides sites to combine with ZnO NPs form supramolecular binding but also serves as the reservoir to control Zn 2+ release. The results show that the lyophilized CSMP-ZnO hydrogels presented a porous structure with some small holes in the pore wall, as shown by scanning electron microscopy. Rheological characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of ZnO NPs. In vitro experiments showed that the CSMP-ZnO hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CSMP hydrogel. The as-released Zn 2+ ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP2/SMAD signaling pathway. In vivo , the as-released Zn 2+ ions promot osteoblastic proliferation and the mineralization of osteoblasts inside the CSMP-ZnO scaffolds. Immunofluorescence for RUNX2, COL-1, and CD31, showed that stable vasculature could be formed inside the CSMP-ZnO scaffolds. Discussion Both the in vitro and in vivo results demonstrate that CSMP-ZnO hydrogel shows promise for bone regeneration, suggesting a new strategy for tissue engineering and regeneration in the future.
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JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Mengze Ding,Xiaohan Wei,Changshun Liu,Xiaomei Tan
Ethnopharmacological relevance Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. Aim of this study This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. Methods MFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1β) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 μg/mL). Pyroptosis-related protein expression was measured by western blotting. Results Thirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 μg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. Conclusion MFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.
研究领域:
药理学
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免疫学
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民族药理学
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炎症
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中医
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CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Chenghao Wu,Dongsheng Shen,Zhixiang Bian,Ming Yang,Shasha Zhang,Shunjie Chen
Acute kidney injury (AKI) is a severe renal dysfunction syndrome mainly associated with the overproduction of endogenous reactive oxygen species (ROS) in complex inflammatory processes driven by innate immune cells and lymphocytes. Herein, we reported the targeted enrichment of nanoparticles into the kidney that can effectively scavenge ROS and manipulate immune cells including macrophages, neutrophils, T cells (Th17/Treg cells) to suppress inflammation of AKI. The nanoparticle-based platform employs mesoporous polydopamine nanoparticles (PDA) as a porous core loaded with dexamethasone (Dex), coated by M2 macrophage membrane, could induces effective ROS scavenging, to prevent renal tubular epithelial cell from apoptosis. These nanoparticles have enhanced adhesion to inflammatory endothelial cells with the assistance of the cell membrane, thereby promoting their enrichment to the kidney. In addition, the nanoparticles further reduce inflammatory cell infiltration, promote M2 macrophage polarization, decrease the ratio of Th17 cells and increase the ratio of Tregs to improve AKI. These results suggest that this nanoparticular drug delivery system can effectively alleviate AKI and is expected to be of clinical application in the treatment of AKI.
研究领域:
医学
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药学
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INTERNATIONAL JOURNAL OF OBESITY
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2024
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IF 4.2
Yan Zheng,Luo Jia,Wang Ying,Yang Jie,Su Mingli,Jiang Lei,Yang Julin,Dai Manyun,Liu Aiming
Background As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear. Methods In this study, male wild-type (WT) and Pparα -null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues. Results The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells. Conclusion Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis.
研究领域:
环境健康
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内分泌学
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营养学
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分子生物学
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Peihong Lin,Rui Gao,Wenjing Yang,Zhengyu Fang,Zhouru Wang,Mengdie Yu,Lihua Xu,Zhen Ma,Jie Fang,Wenying Yu
Acute lung injury (ALI) is a medical condition characterized by significant morbidity and elevated mortality rates; however, to date, there are no clinically approved pharmacological interventions that are both safe and effective for its treatment. In the pathophysiology of ALI, a robust inflammatory response is a critical factor. Dexamethasone (Dex), a potent glucocorticoid, is commonly employed in clinical settings to manage inflammatory conditions. However, the frequent or high-dose administration of corticosteroids can result in significant adverse effects and long-term complications. In this study, we have developed a biomimetic anti-inflammatory nanosystem, designated PM-LPs@Dex, aimed at treating ALI. This system leverages the inherent affinity of platelets for sites of inflammation, alongside the advantageous drug encapsulation properties of liposomes (LPs). By harnessing the suitable physicochemical characteristics of LPs and the distinctive biological functions of platelet membranes (PM), PM-LPs@Dex is capable of stable and sustained drug release in vitro. Experimental results regarding cellular uptake and biodistribution reveal that PM-LPs@Dex is preferentially internalized by inflammatory cells and exhibits enhanced accumulation in inflamed lung tissue compared to LPs@Dex. Pharmacokinetic studies displayed that PM-LPs@Dex showed prolonged circulation time in blood. Additionally, pharmacodynamic assessments demonstrate that PM-LPs@Dex significantly mitigates the severity of ALI, as evidenced by reductions in pulmonary edema, tissue pathology, bronchoalveolar lavage cell counts, protein concentration, and levels of inflammatory cytokines. Notably, PM-LPs@Dex also exhibits favorable biocompatibility. This research is anticipated to contribute novel strategies for the safe and effective targeted management of inflammatory diseases.
研究领域:
药理学
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纳米医学
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肺科学
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炎症研究
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CHEMICAL PHYSICS LETTERS
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2025
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IF 3.1
Guozheng Zhao
In this study, a sandwich-type immunoassay was employed for the simultaneous detection of four glucocorticoids (cortisone, clobetasol 17-propionate, triamcinolone, and dexamethasone) using graphene (GNP)-chitosan (CHI)\nanogold\glucocorticoid receptor (GR) bioimmunosensor. A novel strategy was developed, which involved the integration of surface modification technology, electrochemical detection technology, and immunoassay technology. The electrochemical characteristics of the modified bioimmunosensor were investigated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) methods. The GR concentration and incubation time were optimized to achieve the best detection effect. The differential pulse voltammetry (DPV) response sequence based on the identical concentration level was found to be cortisone > clobetasol 17-propionate > triamcinolone > dexamethasone. The bioimmunosensor demonstrated excellent performance characteristics with a wider linear range of 0.5–7000 ng⋅mL −1 , lower detection limit of 0.071–0.106 ng⋅mL −1 , better stability and repeatability. Cortisone and clobetasol 17-propionate were detected in skincare samples and achieved satisfactory test results.
研究领域:
分析化学
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生物医学工程
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免疫学
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NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2025
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IF 3.1
Li Yue,Li Hailan,Sun Minhui,Chen Hong,Xiao Yao,Wang Jieman,Zhang Yuanyuan,Fang Shuhua,Kou Junping
Silibinin (Sil) is a major bioactive component of silymarin, extracted from the fruit and seeds of Silybum marianum . Silibinin meglumine (SM) is a water-soluble derivative of silibinin that has shown significant potential in liver fibrosis. However, the potential effects and underlying mechanisms of SM on acute liver failure (ALF) are still not fully understood. This study aims to find the likely mechanism. An ALF mouse model and a cell model were established with GalN/LPS. SM was administered to mice via the tail vein or to a hepatocyte line (alpha mouse liver 12, AML12). The results showed that SM particularly lowered the mortality and improved liver pathological lesions in ALF mice. Meanwhile, SM improved the levels of GSH, SOD, TNF-α, IL-6, IL-1β, and IL-10 in the liver tissues and serum. Additionally, SM enhanced cell viability and reduced oxidative stress in vitro. In the AKT/GSK3β/Nrf2/GPX4 pathway, the subpathway of AKT/GSK3β was inhibited, and the subpathway of Nrf2/GPX4 was activated by SM both in vivo and in vitro. In addition, ferrostatin-1, a ferroptosis inhibitor, and the silencing of AKT using siRNA weakened the protective effect of SM, indicating that this process is mediated in an AKT-dependent manner. All the results suggested that SM inhibits inflammation and oxidative stress by modulating the AKT/GSK3β/Nrf2/GPX4 pathway.
研究领域:
药理学
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肝脏病学
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分子生物学
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iScience
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2024
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IF 4.6
Kai Yang,Ying-yi Luan,Shan Wang,You-sheng Yan,Yi-peng Wang,Jue Wu,Yong-qing Sun,Jing Zhang,Wen-qi Chen,Yu-lan Xiang,Ze-lu Li,Dong-liang Zhang,Cheng-hong Yin
Mesenchymal stem cell (MSC)-mediated coupling of osteogenesis and angiogenesis is a critical phenomenon in bone formation. Herein, we investigated the role and mechanism of SGMS1 in the osteogenic differentiation of MSCs and, in combination with osteogenesis and angiogenesis, to discover new therapeutic targets for skeletal dysplasia and bone defects. SGMS1 addition accelerated MSC osteogenic differentiation, whereas SGMS1 silencing suppressed this process. Moreover, SGMS1 overexpression inhibited ceramide (Cer) and promoted sphingomyelin (SM) levels. SM treatment neutralized the suppressive effect of shSGMS1 on osteogenesis. SGMS1 restrained PP2A activity by regulating Cer/SM metabolism and thus enhanced the levels of phosphorylated Akt, Runx2, and vascular endothelial growth factor (VEGF). Furthermore, SGMS1 transcription was regulated by Runx2. SGMS1 increased MSC-mediated angiogenesis by promoting VEGF expression. SGMS1 addition promoted rat bone regeneration in vivo . In conclusion, SGMS1 induces osteogenic differentiation of MSCs and osteogenic-angiogenic coupling through the regulation of the Cer/PP2A/Akt signaling pathway.
研究领域:
细胞生物学
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骨再生医学
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