Animal Models and Experimental Medicine
·
2024
·
IF 3.8
Bing Zhang,Tingting Fu,Yi Han,Gongke Li,Xianyao Wan,Yong Li
Backgroud Thoracic Trauma and Limb Fractures Are the Two most Common Injuries in Multiple Trauma. However, there Is Still a Lack of Mouse Models of Trauma Combining Tibial Shaft Fracture (TSF) and Thoracic Trauma. In this Study, we Attempted to Develop a Novel Mouse Model of TSF Combined with Blunt Chest Trauma (BCT). Methods A total of 84 C57BL/6J male mice were used as the multiple trauma model. BCT was induced by hitting the chests of mice with heavy objects, and TSF was induced by hitting the tibia of mice with heavy objects after intramedullary fixation. Serum specimens of mice were received by cardiac puncture at defined time points of 0, 6, 12, 24, 48, and 72 h. Results Body weight and body temperature tended to decrease within 24 h after multiple trauma. Hemoglobin analyses revealed a decrease during the first 24 h after multiple trauma. Some animals died by cardiac puncture immediately after chest trauma. These animals exhibited the most severe pulmonary contusion and hemorrhage. The level of lung damage varied in diverse mice but was apparent in all animals. Classic hematoxylin and eosin (H&E)-stained paraffin pulmonary sections of mice with multiple trauma displayed hemorrhage and an immunoinflammatory reaction. Bronchoalveolar lavage fluid (BALF) and serum samples of mice with multiple trauma showed an upregulation of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-1 α (TNF-1 α ) compared with the control group. Microimaging confirmed the presence of a tibia fracture and pulmonary contusion. Conclusions The novel mouse multiple trauma model established in this study is a common trauma model that shows similar pathological mechanisms and imaging characteristics in patients with multiple injuries. This study is useful for determining whether blockade or intervention of the cytokine response is beneficial for the treatment of patients with multiple trauma. Further research is needed in the future.
研究领域:
创伤外科
·
免疫学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Composites and Hybrid Materials
·
2025
·Vol. 8
·期 4
·1-15
·
IF 21.8
Zhang Yicheng,Guo Weijie,Chen Siqi,Fang Yan,Weng Yunxiang,Liu Haiqing,Chen Qinhui
Hemostasis of incompressible trauma has been a challenge in the field of injury first aid, and these wounds are not suitable for the traditional dressings and for applying pressure to stop hemorrhage together. In this study, a Janus sponge of bioactive glass-poly (N-isopropylacrylamide) (PBG-PNIPAM) with mimic tissue structure was prepared by attaching different modified BG nanoparticles to the top and bottom layers of a polyvinyl alcohol sponge to improve hemostasis at incompressible wounds. Upon contacted with blood, the hydrophilic layer which was push into the internal tissue released Ca 2+ and SiO 4 4− to activate the endogenous and exogenous coagulation cascade to accelerate blood coagulation, while the hydrophobic layer with excellent breathability kept in epidermis could block wound to decrease the blood loss and prevent the growth of bacteria. In the rat incompressible model, the blood loss of PBG-PNIPAM Janus sponge was much less than 2.3 times of the commercially available gelatin hemostatic sponge. In vitro results showed that the PBG-PNIPAM Janus sponge exhibited excellent clotting ability, high hemocompatibility and low cytotoxicity. This composite Janus sponge with hemostatic and antibacterial properties is expected to be applied in sharp instrument injuries. Graphical
研究领域:
生物学
·
医学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Theranostics
·
2021
·
IF 11.556
Shaofang Zhang,Ying Liu,Si Sun,Junying Wang,Qifeng Li,Ruijuan Yan,Yalong Gao,Haile Liu,Shuangjie Liu,Wenting Hao,Haitao Dai,Changlong Liu,Yuanming Sun,Wei Long,Xiaoyu Mu,Xiao-Dong Zhang
Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo . The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO 2 (Cr/CeO 2 ) nanozyme increases the reduced Ce 3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO 2 . Furthermore, Cr/CeO 2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO 2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.
研究领域:
神经科学
·
纳米技术
·
药理学
·
材料科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
METHODS
·
2019
·
IF 3.782
Hongshun Hao,Shouchen Hao,Hongman Hou,Gongliang Zhang,Yunxia Hou,Zuowei Zhang,Jingran Bi,Shuang Yan
A novel photoelectrochemical (PEC) immunosensor based on CdSe quantum dots (QDs) sensitized Ho 3+ /Yb 3+ -TiO 2 for the detection of Vibrio parahaemolyticus (VP) was assembled. The working electrode was constructed via the layer-by-layer (LBL) method with the Ho 3+ /Yb 3+ -TiO 2 , CdSe QDs, NHS/EDC, antibody of VP (anti-VP), bovine serum albumin (BSA) modified on the surface of the FTO in sequence. Ascorbic acid (AA) acts as an electron donor to combine photogenerated holes in order to provide a stable current system. Ho 3+ and Yb 3+ co-doping TiO 2 broadened the spectral response range of TiO 2 to the infrared region and improved the photocurrent responsiveness of TiO 2 . The PEC immunosensor, with Ho 3+ /Yb 3+ ratio of 1:5, Ho 3+ /Yb 3+ -TiO 2 of 2 mg/mL and PBS solution of pH 7.4, had an optimal photocurrent responsiveness. Immobilization of anti-VP was by classical NHS/EDC coupling reactions between COOH groups of CdSe QDs and NH 2 groups of the anti-VP. The results indicated that PEC immunosensors had a low detection limit of 25 CFU/mL, a wide detection range of 10 2 –10 8 CFU/mL, high stability, low price, and short detection time. This method could be promising for the rapid and ultrasensitive detection of pathogenic microorganisms in the food.
研究领域:
生物传感
·
食品安全检测
·
微生物学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Bowen Jia,Yuchen Yao,Yejia Xu,Yang Zhao,Jing Li,Yumeng Wu,Xiaofeng Zeng,Shijun Hong,Qianqian Li,Xuexia Liu,Chengliang Luo
Traumatic brain injury (TBI) is a major global health issue, causing blood–brain barrier disruption, neuroinflammation, and neuronal damage. Current therapies are limited and failed to address key pathological mechanisms like ferroptosis, oxidative stress, and inflammation, highlighting the need for novel treatments. Recent advances in nanomedicine, particularly nanozymes, offer promising solutions. Copper-based ultrasmall nanozymes, with excellent catalytic activity and biocompatibility, have shown potential in mitigating ferroptosis and oxidative stress. In this study, we developed polyethylene glycol-modified Cu 5.4 O (Cu 5.4 O-PEG), a nanomaterial with superior blood–brain barrier penetration and biocompatibility. Cu 5.4 O-PEG demonstrated no cytotoxicity and significantly reduced oxidative stress and ferroptosis in both in vitro and in vivo models, improving motor and cognitive functions in murine TBI models. The therapeutic effects were mediated through multiple mechanisms, including inhibition of the Fenton reaction, scavenging of reactive oxygen species (ROS), and reducing iron deposition, effectively limiting tissue damage. Proteomic analysis revealed modulation of ferroptosis-related proteins and activation of protective pathways related to transferrin receptor 1 (TfR1). Furthermore, using AAV-mediated knockdown of TfR1 in mice, we observed significant reductions in lipid peroxidation markers such as ACSL4, COX2, and 4HNE, indicating a decrease in iron-induced damage. Histological analysis showed reduced iron deposition, and improved neuronal morphology in TfR1 knockdown mice underwent TBI, indicating knockdown of TfR1 could alleviate TBI-indued ferroptosis and iron-dependent neurodegeneration. Taken together, these data imply that Cu 5.4 O-PEG presents a neuroprotective strategy for improving cerebral recovery after TBI, at least partly by inhibiting TfR1-mediated ferroptosis.
研究领域:
神经科学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Mingxia Jiao,Xiaoqi Li,Hui Liu,Peng Cai,Xiling Yang,Kevin J. McHugh,Bowen Zheng,Jiachen Sun,Peisen Zhang,Xiliang Luo,Lihong Jing
Surgical intervention is the most common first-line treatment for severe traumatic brain injuries (TBIs) associated with high intracranial pressure, while the complexity of these surgical procedures often results in complications. Surgeons often struggle to comprehensively evaluate the TBI status, making it difficult to select the optimal intervention strategy. Here, we introduce a fluorescence imaging-based technology that uses high-quality silver indium selenide-based quantum dots (QDs) for integrated TBI diagnosis and surgical guidance. These engineered, poly(ethylene glycol)-capped QDs emit in the near-infrared region, are resistant to phagocytosis, and importantly, are ultrastable after the epitaxial growth of an aluminum-doped zinc sulfide shell in the aqueous phase that renders the QDs resistant to long-term light irradiation and complex physiological environments. We found that intravenous injection of QDs enabled both the precise diagnosis of TBI in a mouse model and, more importantly, the comprehensive evaluation of the TBI status before, during, and after an operation to distinguish intracranial from superficial hemorrhages, provide real-time monitoring of the secondary hemorrhage, and guide the decision making on the evacuation of intracranial hematomas. This QD-based diagnostic and monitoring system could ultimately complement existing clinical tools for treating TBI, which may help surgeons improve patient outcomes and avoid unnecessary procedures.
研究领域:
生物医学工程
·
神经外科
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2025
·
IF 5.1
Kaiji Li,Jinchao Wang,Yalong Gao,Xin Chen,Ruilong Peng,Lei Li,Cong Wang,Tuo Li,Shu Zhang,Guili Yang,Jianning Zhang
Aims Traumatic brain injury-induced coagulopathy (TBI-IC) frequently occurs after TBI, exacerbating the severity of TBI and affecting patient prognosis. Benzbromarone (BBR) is commonly used to treat hyperuricemia; however, its protective effects against TBI-IC remain unknown. Therefore, we explored whether BBR could improve TBI. Materials and methods C57BL/6 wild-type mice were subjected to fluid percussion injury to mimic TBI, and BBR was administered intraperitoneally 30 min after TBI. Magnetic resonance imaging (MRI) and Evans blue dye extravasation were used to assess the prognosis, tail bleeding time, ELISA, and coagulation tests assess coagulation function. We further explored the potential mechanism by which BBR alleviates hypercoagulation after TBI using flow cytometry. Key findings The intraperitoneally injected BBR group showed improved survival and neurological severity scores compared to the TBI group. Subsequently, we found that hypercoagulability developed 3 h after TBI and that the administration of BBR improved this hypercoagulability. BBR also reduced the degree of platelet phosphatidylserine (PS) exposure after TBI, platelet activation, and Ca2+ overload, in addition to inhibition of scramblase activity in procoagulant platelets. Significance Our findings indicate that BBR reduces PS externalization by inhibiting TMEM16F expression, thereby improving blood hypercoagulability after TBI.
研究领域:
神经科学
·
药理学
·
血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2022
·
IF 11.322
Ye Li,Min Wang,Meng Sun,Xinxin Wang,Dandan Pei,Bo Lei,Ang Li
Traumatic brain injury (TBI) leads to high rates of morbidity and mortality worldwide with few effective treatments. Excessive oxidative stress and local inflammation at the injury site are considered as the critical factors that determine the therapeutic outcome. In our previous study, stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-Exo) promoted functional recovery of TBI by amelioration of neuro-inflammation. However, the effect was restricted due to unsustainable exosome release and existed oxidative stress that aggravate secondary insult of TBI. To obtain a long-time anti-inflammatory effect of SHED-Exo and attenuate oxidative stress simultaneously, we designed a bioactive antioxidant poly (citrate-gallic acid)-based hybrid hydrogel (FPGEGa) that encapsulate SHED-Exo for treating TBI. The thermosensitive, injectable, self-healing and antioxidant FPGEGa presented ultralong sustained release of SHED-Exo (above 21 days) and significantly decreased the intracellular ROS production of microglia in the central nervous system. FPGEGa carrying SHED-Exo (FPGEGa@SHED-Exo) exhibited better anti-inflammatory potential on microglia, by promoting M2 (anti-inflammatory) polarization and inhibiting M1 (pro-inflammatory) polarization. FPGEGa@SHED-Exo could improve the neuro-regeneration of TBI rats by rescuing damaged motor functions in rats as well as regenerating impaired cortical tissues. The present work suggested that SHED-Exo engineered bioactive antioxidative hydrogel may be promising in achieving satisfactory functional recovery in TBI and other related neurological disorders.
研究领域:
生物材料学
·
神经科学
·
再生医学
✓ 已验证
DOI
高影响因子
Cells
·
2022
·Vol. 11
·期 22
·3588
·
IF 7.666
Tuo Li,Lei Li,Ruilong Peng,Hongying Hao,Hejun Zhang,Yalong Gao,Cong Wang,Fanjian Li,Xilei Liu,Fanglian Chen,Shu Zhang,Jianning Zhang
Background and Purpose: Neuroinflammation has been shown to play a critical role in secondary craniocerebral injury, leading to poor outcomes for TBI patients. Abrocitinib, a Janus kinase1 (JAK1) selective inhibitor approved to treat atopic dermatitis (AD) by the Food and Drug Administration (FDA), possesses a novel anti-inflammatory effect. In this study, we investigated whether abrocitinib could ameliorate neuroinflammation and exert a neuroprotective effect in traumatic brain injury (TBI) models. Methods: First, next-generation sequencing (NGS) was used to select genes closely related to neuroinflammation after TBI. Then, magnetic resonance imaging (MRI) was used to dynamically observe the changes in traumatic focus on the 1st, 3rd, and 7th days after the induction of fluid percussion injury (FPI). Moreover, abrocitinib’s effects on neurobehaviors were evaluated. A routine peripheral blood test was carried out and Evans blue dye extravasation, cerebral cortical blood flow, the levels of inflammatory cytokines, and changes in the numbers of inflammatory cells were evaluated to investigate the function of abrocitinib on the 1st day post-injury. Furthermore, the JAK1/signal transducer and activator of transcription1 (STAT1)/nuclear factor kappa (NF-κB) pathway was assessed. Results: In vivo, abrocitinib treatment was found to shrink the trauma lesions. Compared to the TBI group, the abrocitinib treatment group showed better neurological function, less blood-brain barrier (BBB) leakage, improved intracranial blood flow, relieved inflammatory cell infiltration, and reduced levels of inflammatory cytokines. In vitro, abrocitinib treatment was shown to reduce the pro-inflammatory M1 microglia phenotype and shift microglial polarization toward the anti-inflammatory M2 phenotype. The WB and IHC results showed that abrocitinib played a neuroprotective role by restraining JAK1/STAT1/NF-κB levels after TBI. Conclusions: Collectively, abrocitinib treatment after TBI is accompanied by improvements in neurological function consistent with radiological, histopathological, and biochemical changes. Therefore, abrocitinib can indeed reduce excessive neuroinflammation by restraining the JAK1/STAT1/NF-κB pathway.Keywords:TBI;abrocitinib;neuroinflammation;JAK1/STAT1/NF-κB
研究领域:
神经科学
·
药理学
·
炎症
·
创伤
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2025
·
IF 2.7
Dan Wang,Hui Sun,Kerong Hai,Ningkang Li,Yang Gu,Zengrui Ma
Traumatic brain injury (TBI), a prevalent neurological disorder in clinical practice, is primarily induced by external trauma. Propofol has been reported to alleviate the symptoms associated with TBI. In this study, a TBI model was established in mice using the controlled cortical impact (CCI) method. After treatment with propofol and BML-275, neuronal damage in the TBI model was assessed through the modified Neurological Severity Score (mNSS), Hematoxylin and Eosin (HE) staining, and Nissl staining. To investigate the role of the AMPK/SIRT1 pathway in propofol-regulated TBI, AMPKα-silenced vectors and overexpressed SIRT1 vectors were transfected. Western blot was performed to evaluate the expression of proteins involved in the AMPK/SIRT1 pathway and pyroptosis markers. The regulatory impact of Th17/Treg balance was examined by detecting the key transcription factors RORγt and FOXP3 through immunofluorescent staining and RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-17 and IL-10 concentrations. Results showed that propofol significantly reduced neuronal injury in the TBI model, an effect that was reversed by BML-275. Moreover, propofol mitigated pyroptosis by downregulating Caspase-1 and GSDMD-N expression post-TBI. Propofol inhibited Th17 differentiation while promoting Treg differentiation by modulating RORγt/FOXP3 and IL-17/IL-10 levels. Silencing AMPKα markedly diminished propofol’s effects on Th17 and Treg differentiation, with these effects being reversed upon SIRT1 overexpression. Propofol suppressed neuronal pyroptosis through the regulation of Th17/Treg balance via activation of the AMPK/SIRT1 pathway. These findings suggest propofol exerts a protective effect against neuronal damage following TBI, potentially through the modulation of the Th17/Treg balance and AMPK/SIRT1 signaling pathway.
研究领域:
神经科学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jing Xu,Danyi Shen,Yao Wang,Xingyue Han,Xinning Dong,Xin Chen,Haifeng Shu,Jianwen Hou,Sixun Yu
Traumatic brain injury (TBI) can trigger a series of complex physiological responses, with iron overload and neuronal ferroptosis playing particularly pivotal roles. These processes exacerbate secondary brain injury and significantly deteriorate neurological function. To address this challenge, this study developed an innovative local drug delivery strategy: an injectable, post-traumatic microenvironment-responsive hydrogel. The hydrogel, composed of tannic acid (TA) and quaternized chitosan (QCS), is designed to alleviate neurological deficits secondary brain injury following TBI through its anti-ferroptosis mechanism. In vitro, a ferroptosis model was established using HT22 cells treated with the ferroptosis inducer RSL-3, demonstrating the hydrogel’s antioxidant capacity in the TBI-like conditions. The results showed that the hydrogel significantly restored cell viability, reversed iron accumulation, alleviated lipid peroxidation, and restored mitochondrial function. Further in vivo experiments in the TBI model showed that the TA/QCS hydrogel not only effectively inhibited neuronal degeneration, reduced iron accumulation, and lipid peroxidation but also restored mitochondrial function in neurons. Additionally, the hydrogel significantly attenuated neuroinflammation by inhibiting the activation of microglia and astrocytes, thereby facilitating neurological recovery after TBI. This study offers novel insights into TBI management strategies aimed at preventing the progression of a secondary injury.
研究领域:
神经科学
·
药学
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-20
·
IF 7.5
Zhang Bin,Bai Miao,Yang Mengshi,Wang Yumei,Chen Xiyu,Liu Baiyun,Shi Guangzhi
Background Glucocorticoids (GCs) have been widely used in the treatment of severe traumatic brain injury (TBI) to inhibit neuroinflammation and alleviating brain edema and cannot be replaced by other drugs. However, their systemic application still faces many obstacles, such as the poor blood-brain-barrier (BBB) penetration and severe side effects. Therefore, new treatment strategy or compounds are urgently needed in clinic.Methods Herein, an injectable nanocomposite hydrogel is developed as a biofunctionalized delivery platform for intraoperative administration of dexamethasone (DEX) after TBI. By using a mice TBI model, the safety and efficacy of the nanohydrogels in treating BBB disruption, brain edema and nerve injury were evaluated after TBI.Results The hydrogel is composed of polysaccharide matrix (carboxymethyl chitosan and oxidized dextran) and mesoporous polydopamine (MPDA) nanoparticles loaded with DEX (MPDA@DEX@gel) that could realize in situ injection, self-assembly, a high DEX loading rate and sustained release around the lesion. The MPDA@DEX@gel exhibits excellent antibacterial and hemostatic properties, good biocompatibility and antioxidation, and self-healing capability in vitro. These in vitro and in vivo results show that local application of MPDA@DEX@gel not only alleviates brain edema, promotes neuronal survival, and improves neurological function by restoring the integrity of BBB and inhibiting neuroinflammation after TBI, but also effectively avoids the peripheral and central side effects.Conclusion Our study provides a promising treatment strategy for the rational use of GCs in patients with severe TBI.
研究领域:
神经科学
·
药剂学
·
材料科学
✓ 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）