Neural Regeneration Research
·
2017
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IF 1.769
Zhi-fang Zheng,Yi-shu Liu,Xuan Min,Jian-bing Tang,Hong-wei Liu,Biao Cheng
Local sympathetic denervation by surgical sympathectomy is used in the treatment of lower limb ulcers and ischemia, but the restoration of cutaneous sympathetic nerve functions is less clear. This study aims to explore the recovery of cutaneous sympathetic functions after bilateral L 2–4 sympathectomy. The skin temperature of the left feet, using a point monitoring thermometer, increased intraoperatively after sympathectomy. The cytoplasm of sympathetic neurons contained tyrosine hydroxylase and dopamine β-hydroxylase, visualized by immunofluorescence, indicated the accuracy of sympathectomy. Iodine starch test results suggested that the sweating function of the hind feet plantar skin decreased 2 and 7 weeks after lumbar sympathectomy but had recovered by 3 months. Immunofluorescence and western blot assay results revealed that norepinephrine and dopamine β-hydroxylase expression in the skin from the sacrococcygeal region and hind feet decreased in the sympathectomized group at 2 weeks. Transmission electron microscopy results showed that perinuclear space and axon demyelination in sympathetic cells in the L 5 sympathetic trunks were found in the sympathectomized group 3 months after sympathectomy. Although sympathetic denervation occurred in the sacrococcygeal region and hind feet skin 2 weeks after lumbar sympathectomy, the skin functions recovered gradually over 7 weeks to 3 months. In conclusion, sympathetic functional recovery may account for the recurrence of hyperhidrosis after sympathectomy and the normalization of sympathetic nerve trunks after incomplete injury. The recovery of sympathetic nerve function was slower in the limbs than in the torso after bilateral L 2–4 sympathectomy.
研究领域:
医学
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神经科学
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DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2025
·Vol. 25
·期 1
·451
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IF 3.4
Pan Sunfeng,Xiong Lie,Li Jiakun,Wang Zhenjun,Su Yujuan,Fang Gaofeng,Zhu Minda,Shi Hanqiang,Li Jiayan,Liu Zhaoyan,Han Chunmao,Shi Yanbo
Background Venous leg ulcer (VLU) is among the most severe clinical manifestations of chronic venous disease (CVD) and imposes substantial burdens on both patients and society. VLU pathogenesis is closely associated with the impairment of vascular endothelial cells. In this study, tissue samples from the patients’ s skins around wound at different stages of CVD were collected during operation and used to elucidate the involvement of ferroptosis in the pathogenesis of VLU. Also the potential mechanism through which Huoxue Shengji (HXSJ) decoction alleviates ferroptosis in human umbilical vein endothelial cells (HUVECs) was investigated. Methods During surgical procedure such as great saphenous vein high ligation and stripping surgery, matched skin tissues from the normal, hyperpigmentation (HPT), lipodermatosclerosis (LDS), and VLU regions were collected from 10 patients with VLU, and the levels of iron and glutathione peroxidase 4 (GPX4) were quantified to evaluate ferroptosis. In vitro, HUVECs were used to iron overload induction using exogenous 100 µM ferric ammonium citrate (FAC) or 100 µM hemin, or ferroptosis induction with 10 µM erastin, and treated with 10 µg/ml HXSJ decoction for 24 h. Subsequently, lipid peroxidation (LPO) damage, mitochondrial function, and key genes involved in ferroptosis were assessed. Results Iron deposition in the affected skin of patients with CVD gradually increased before progression to VLU and significantly decreased during the VLU stage. Moreover, GPX4 expression increased significantly in the HPT stage but was gradually suppressed with further deterioration of CVD. The in vitro results indicated that in both the iron overload and ferroptosis models, HXSJ decoction effectively upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SLC7A11, xCT), and GPX4, which was accompanied by the inhibition of malondialdehyde and protein carbonylation production, the alleviation of ferrous ion accumulation, and the restoration of mitochondrial function. Conclusions This study demonstrated that iron accumulation-mediated inactivation of GPX4 serves as a crucial mechanism in VLU formation through ferroptosis induction. Notably, the therapeutic mechanism through which HXSJ decoction alleviates ferroptosis involves Nrf2/xCT/GPX4 pathway activation and a reduction in ferrous ion accumulation. These findings may provide novel insights into VLU pathogenesis and give possible reason for developing traditional Chinese medicine therapies targeting ferroptosis and VLUs. Graphical
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2023
·
IF 3.1
Yang Ding,Shengyun Wan,Long Ma,Kaikai Wei,Kun Ye
Hindlimb ischemia (HLI) is an arterial occlusive disease that exposes the patients to the risk of limb gangrene and loss. Polarization of macrophages is related to HLI-induced inflammation. Period circadian regulator 1 (PER1) is a core component of the circadian clock. We first showed, based upon bioinformatics analysis of microarray data, that PER1 expression was reduced in monocytes from patients with critical limb ischemia. The proximal femoral artery in the left hindlimb of male mice was ligated and then the femoral artery and its collateral branches were removed to establish the HLI mouse model. After modeling, a single intramuscular injection of 1 × 10 9 pfu Ad-PER1 was performed at the adductor and gastrocnemius muscles. The gastrocnemius muscle tissues were collected at day 0, 3, 7, 14, 21 post-HLI. There was obvious pathological necrosis, accompanied with reduced expression of PER1 in the muscle tissues of HLI mice. Expression of CD68 and CD31 seemed to be corresponded to PER1 in gastrocnemius muscle, implying the potential of PER1 in regulating macrophage-related inflammation and angiogenesis . PER1 overexpression diminished myocyte damage, promoted blood flow restoration and improved behavioral scores of HLI mice. Immunostaining of CD31 and α-SMA revealed that PER1 upregulation reversed HLI-induced decreases in capillary and arteriole density. In vitro, RAW264.7 cells were cultured in hypoxia (1% O 2 ) for 24 h. The percentage of pro-inflammatory CD86 + macrophages (M1 type) was decreased and that of anti-inflammatory CD206+ macrophages (M2 type) was increased when PER1 was overexpressed. Moreover, the expression levels of TNF-α, IL-6 and M1-type marker iNOS were decreased, and levels of IL-10 and M2-type marker Arg-1 were increased by PER1 in gastrocnemius muscle of HLI mice and hypoxia-treated RAW264.7 cells. PER1 might reduce M1 macrophage polarization and promote M2 macrophage polarization, and thus exert anti-inflammatory and pro-angiogenic actions. Our findings suggest that PER1 overexpression promotes functional recovery of mice with HLI through regulating macrophage polarization.
研究领域:
心脏病学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Junping Zheng,Yanlei Guo,Baifei Hu,Lin Zhu,Yong Yang,Shengrong Li,Na Li,Hongtao Liu
Ethnopharmacological relevance BuZangTongLuo Formula (BZTLF) was the decoction of eight traditional Chinese medicines including Astragalus membranaceus , Dioscorea opposita , Salvia miltiorrhiza , Scrophularia ningpoensis , Ophiopogon japonicus , Panax ginseng , Fritillariae cirrhosae and Whitmania pigra . This formula has been used as an effective remedy for treatment of diabetic ischemia clinically. Aim of the study In previous study, we have reported the therapeutic effect of BZTLF on diabetic vascular dysfunction. However, it remains obscure about the role of metabolic pathways in BZTLF-initiated improvement on hindlimb ischemia. Materials and methods Diabetic mice with hindlimb ischemia were orally administrated with BZTLF by gavage. The serum samples were prepared for untargeted metabolomic analysis by ultra-performance liquid chromatography-mass spectrometer. The metabolic network was built by integrating metabolite data with the Gene Expression Omnibus (GEO) dataset (GSE3313). Further, quantitative PCR was used to confirm the key target genes. Results BZTLF treatment remarkably led to the reversal of changed metabolite levels in serum of diabetic mice with hindlimb ischemia, which mainly derived from bacteria, plant and signaling molecules. Also, BZTLF reshaped the metabolic pathways, especially those responsible for metabolism of lipid, gluthanine and tryptophan . In addition, BZTLF led to the reduction of lysophosphatidic acids (LPAs) and increment of triglycerides (TGs) conjugation with non-saturated fatty acids in serum. BZTLF significantly restored the down-regulation of vascular endothelial growth factor receptor 2 (VEGFR2) and endothelial nitric oxide synthase (eNOS) or the up-regulation of interleukin 4-induced 1 (IL4I1) and cytochrome P450 family 1 subfamily B member 1 (CYP1B1) at mRNA level, which were key regulatory genes located in metabolic pathways of glutamate and tryptophan. Conclusions BZTLF improved hindlimb ischemia in diabetic mice by the positive regulation of metabolome changes in serum.
研究领域:
民族药理学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Jingyu Li,Zhuoting Lu,Liwang Xu,Jing Wang,Shaojie Qian,Qinglian Hu,Yunfen Ge
Hindlimb ischemia is a common disease worldwide featured by the sudden decrease in limb perfusion, which usually causes a potential threat to limb viability and even amputation or death. Revascularization has been defined as the gold-standard therapy for hindlimb ischemia. Considering that vascular injury recovery requires cellular adaptation to the hypoxia, hypoxia-inducible factor 1 α (HIF-1α) is a potential gene for tissue restoration and angiogenesis. In this manuscript, effective gene delivery vector PEI-β-CD (PC) was reported for the first application in the hindlimb ischemia treatment to deliver HIF-1α plasmid in vitro and in vivo. Our in vitro finding demonstrated that PC/HIF-1α-pDNA could be successfully entered into the cells and mediated efficient gene transfection with good biocompatibility. More importantly, under hypoxic conditions, PC/HIF-1α-pDNA could up-regulate the HUEVC cell viability. In addition, the mRNA levels of VEGF, Ang-1, and PDGF were upregulated, and transcriptome results also demonstrated that the cell-related function of response to hypoxia was enhanced. The therapeutic effect of PC/HIF-1α-pDNA was further estimated in a murine acute hindlimb ischemia model, which demonstrated that intramuscular injection of PC/HIF-1α-pDNA resulted in significantly increased blood perfusion and alleviation in tissue damage, such as tissue fibrosis and inflammation. The results provide a rationale that HIF-1α-mediated gene therapy might be a practical strategy for the treatment of limb ischemia.
研究领域:
生物医学工程
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分子生物学
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基因治疗
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药学
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产品关联
DOI
PubMed
高影响因子
Nano Energy
·
2022
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IF 19.069
Weiyan Li,Zhongqian Song,Huijun Kong,Minqi Chen,Shengjie Liu,Yu Bao,Yingming Ma,Zhonghui Sun,Zhenbang Liu,Wei Wang,Li Niu
Biocompatible and reliable temperature monitoring platforms are constantly required to develop wearable electronics for future sophisticated health diagnosis and protection of high-risk individuals. Considering the fact that heat exposures during pregnancy might increase the risk for abortions, premature birth or congenital heart defects, here, we propose a conceptual self-powered temperature monitoring platform for simultaneous real-time tracking of the temperature variation in lower limb of a pregnancy woman and her surrounding environment during exercise. Thanks to the special channel design and local spindle-shaped construction, the single yarn-based temperature (SYBT) sensor exhibits ultrahigh sensitivity, bending resistance, good biocompatibility and integrability with fabrics. A vertical contact-separate mode triboelectric nanogenerator embedded into a shoe extracts energy from body motion to power the SYBT sensors, achieving the self-powered features of the platform. Coupled with wirelessly date transmitting and user interfaces, the temperatures of pregnant volunteer’s lower limb and surrounding ambience are simultaneously and continuously monitored during exercise in a self-powered manner. Such SYBT sensors and self-powered design strategy provides a new avenue for future temperature monitoring electronics.
研究领域:
可穿戴技术
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生物医学工程
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健康监测
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纳米技术
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能量收集
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DOI
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Yiqiong Wang,Yi Tao,Shujing Zhang,Qiuru Wang,Zheting Liu,Shudong Lin,Yaoting Wang,Yunchao Huang,Ting Zhang,Henry Anselmo Mayala,Wenming He,Hui Shen,Ling Zhang,Hui Chai
Background Diabetes mellitus (DM) and its complications pose a significant threat to human health. Diabetes-related lower limb ischemia (DLLI), as a severe complication of diabetic macrovascular disease, presents substantial challenges in clinical management. Purpose The pharmacodynamic profile and mode of action of Pseudostellaria heterophylla polysaccharides (PHP) in DLLI treatment constitute the core investigative objectives herein. Study Design Using complementary in vivo (DLLI murine model) and in vitro (high glucose (HG)-exposed human umbilical vein endothelial cells (HUVECs)) systems, PHP's bioactivity was systematically profiled. Methods In vivo: The effects of PHP on blood perfusion, microvessel density, and PANoptosome assembly in the ischemic limbs of DLLI mice were evaluated. In vitro: HUVECs treated with HG were used to assess PHP’s regulatory effects on angiogenesis functions (cell migration, proliferation, tube formation), PANoptosome/inflammasome formation, key components of the PANoptotic pathway, reactive oxygen species (ROS/mtROS), mitochondrial homeostasis, and autophagy. Transcriptomic analysis was conducted to identify potential target genes. Results In vivo: PHP significantly improved blood perfusion, increased microvessel density, and modulated PANoptosome assembly in ischemic limbs. In vitro: PHP reversed HG-induced angiogenesis dysfunction, inhibited PANoptosis and oxidative stress, restored mitochondrial function, and enhanced autophagic activity. Mechanism: PHP exerted its effects by targeting cytochrome P450 enzyme CYP2E1 through downregulating its expression, thereby alleviating mitochondrial damage and PANoptosis. Additionally, CYP2E1 downregulation promoted endothelial cell migration. Conclusion We pioneered a PANoptosome-centric framework for DLLI, proving that PHP targets CYP2E1 to restore mitochondrial homeostasis, inhibit PANoptosis, and drive angiogenesis, thereby offering a novel natural product-derived therapeutic strategy. Collectively, this work establishes PHP as a promising candidate for DLLI treatment through CYP2E1-mediated restoration of mitochondrial homeostasis and PANoptosis suppression.
研究领域:
药理学
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内分泌学
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心血管研究
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分子生物学
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天然产物
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线粒体生物学
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细胞死亡机制
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Wenxiong Cao,Wei Wei,Bo Qiu,Yuan Liu,Shuang Xie,Qibo Fang,Xiaohong Li
Thrombosis seriously endangers human health with high incidence and mortality worldwide, and the clinical treatment is challenged by low bioavailability of thrombolytic agents, high bleeding risk and thrombosis relapse. Herein, ultrasound-powered Janus micromotors with stimuli-responsive multiple release capabilities are developed for efficient thrombolysis and inhibition of thrombosis recurrence. Resveratrol-loaded hyaluronic acid (HA Res ) nanoparticles (NPs) and urokinase plasminogen activator (uPA) were entrapped into H 2 O 2 -sensitive poly(1,4-cyclohexanedimethanol-co-oxalate) (POX) microparticles (MPs), followed by polydopamine capping and RGD grafting to obtain Janus rJPox@u-HA Res MPs. After RGD-mediated delivery to the thrombus site, the peroxalate ester bonds of POX are oxidized by the elevated H 2 O 2 to produce CO 2 , and the MP collapse accelerates the local release of uPA and HA Res NPs. The resulting CO 2 bubbles amplify the cavitation effect of ultrasound to promote thrombus penetration and site-specific uPA thrombolysis. The endothelial cell targeting and sustained resveratrol release from HA Res NPs dramatically improve endothelial cell viability, nitric oxide production and migration. Compared with free drug administration, the uPA loading into MPs significantly extends the half-life (15 folds) and bioavailability (7 folds), while the resveratrol inoculation into NPs increases the bioavailability 29 times. On an acute lower limb thrombosis model, the thrombus accumulation of MPs is promoted by RGD-mediated interactions with the activated platelets and ultrasound-driven penetration into thrombi, leading to almost full removal of blood clots. The H 2 O 2 -scavenging capability of POX, sustained resveratrol release and efficient thrombolysis alleviate oxidative stresses, eliminate coagulation biomarkers and repair the damaged endothelial layer to effectively inhibit thrombosis relapse. It is demonstrated that rJPox@u-HA Res /US treatment could not only achieve safe and site-specific thrombolytic therapy at the early stage but also restore vascular homeostasis to effectively prevent thrombosis recurrence.
研究领域:
生物医学工程
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药学
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治疗诊断学
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纳米技术
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药物递送系统
·
心血管疾病
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）