Drug Design Development and Therapy
·
2021
·
IF 4.162
Shuo Wang,Ping Zhao,Ying Zhang,Lianhua Zhu,Jianing Zhu,Yukun Luo,Qiuyang Li
Purpose Sepsis is the leading condition associated with acute kidney injury (AKI) in the hospital and intensive care unit (ICU), sepsis-induced AKI (S-AKI) is strongly associated with poor clinical outcomes. Curcumin possesses an ability to ameliorate renal injury from ischemia-reperfusion, but it is still unknown whether they have the ability to reduce S-AKI. The aim of this study was to investigate the protective effects of curcumin on S-AKI and to assess its therapeutic potential on renal function, inflammatory response, and microcirculatory perfusion.Methods Male Sprague-Dawley (SD) rats underwent cecal ligation and puncture (CLP) to induce S-AKI and immediately received vehicle (CLP group) or curcumin (CLP+Cur group) after surgery. At 12 and 24h after surgery, serum indexes, inflammatory factors, cardiac output (CO), renal blood flow and microcirculatory flow were measured.Results Serum levels of creatinine (Scr), cystatin C (CysC), IL-6 and TNF-α were significantly lower in the CLP+Cur group than those in the CLP group (P < 0.05). Treatment with curcumin improved renal microcirculation at 24h by measurement of contrast enhanced ultrasound (CEUS) quantitative parameters [peak intensity (PI); half of descending time (DT/2); area under curve (AUC); P < 0.05]. In histopathological analysis, treatment with curcumin reduced damage caused by CLP.Conclusion Curcumin can alleviate S-AKI in rats by improving renal microcirculatory perfusion and reducing inflammatory response. Curcumin may be a potential novel therapeutic agent for the prevention or reduction of S-AKI.
研究领域:
药理学
·
肾脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Hao Zhang,Xianzhen Dong,Yuhang Liu,Ping Duan,Changjiang Liu,Kun Liu,Yifeng Yu,Xinyue Liang,Honglian Dai,Aixi Yu
The combined effects of persistent chronic inflammation, oxidative stress, microcirculation disorders, and dysregulated cellular energy metabolism often hinder the repair of diabetic skin wounds. Traditional treatment methods are typically insufficient in simultaneously addressing these complex factors, resulting in delayed wound healing and a high propensity for recurrence and chronic ulceration. This study developed an innovative strategy based on reactive oxygen species (ROS)–responsive nanoparticles loaded with an ultraviolet (UV)-light-responsive hydrogen sulfide (H 2 S) donor. This approach leverages the endogenous ROS present in diabetic wounds and external UV light as dual triggers to facilitate the controlled and stepwise release of H 2 S. The material design explicitly targets the critical challenges in diabetic wound repair, including the inhibition of chronic inflammation, oxidative stress reduction, microcirculation improvement, and support of cellular energy metabolism, thereby significantly accelerating wound healing. This adaptive release of signaling molecules effectively modulates the wound regeneration microenvironment, enhancing the repair process and offering a promising solution for diabetic skin wound management. Statement of Significance This study developed an innovative strategy based on reactive oxygen species (ROS)–responsive nanoparticles loaded with an ultraviolet (UV)-light-responsive hydrogen sulfide (H 2 S) donor. This approach leverages the endogenous ROS present in diabetic wounds and external UV light as dual triggers to facilitate the controlled and stepwise release of H 2 S. The material design explicitly targets the critical challenges in diabetic wound repair, including the inhibition of chronic inflammation, oxidative stress reduction, microcirculation improvement, and support of cellular energy metabolism, thereby significantly accelerating wound healing. This adaptive release of signaling molecules effectively modulates the wound regeneration microenvironment, enhancing the repair process and offering a promising solution for diabetic skin wound management.
研究领域:
生物材料学
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再生医学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SURGICAL RESEARCH
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2009
·
IF 1.875
Ole Goertz,Stefan Baerreiter,Andrej Ring,Birger Jettkant,Tobias Hirsch,Adrien Daigeler,Hans U. Steinau,Stefan Langer
Background The breakdown of skin microcirculation and the leukocyte–endothelium interaction are assumed to play a key role in the pathophysiology of frostbite injuries. However, little is known as yet. The aim was to develop an in vivo frostbite model to monitor microcirculatory changes and angiogenesis after frostbite injury. Materials and Methods Deep partial thickness frostbite injuries were inflicted with a no-touch-technique to the ears of hairless mice ( n = 9). To this end, a gas jet of nitrogen vapor (T = –195,8 ± 2.7°C) was delivered onto an area of 1.9 mm 2 for 1,5 s. Intravital fluorescent microscopy in combination with FITC-dextran and Rhodamin 6 G as fluorescent dyes was used to assess microcirculatory changes, leukocyte behavior, and angiogenesis during the 14 d of wound healing. Results The area of no perfusion decreased significantly over the observed period, and perfusion was almost completely restored due to angiogenesis by d 14 (day 1: 1.89 [mm 2 ] ± 0.44SEM, d 14: 0.02 ± 0.01). No post-traumatic extension of the trauma could be observed. Edema formation increased significantly up to d 7. The number of adherent leukocytes showed a significant increase during the first 7 d. Functional vessel density showed a significant post-frostbite decrease to 60% of the baseline value. Conclusions This novel frostbite model provides a simple and nonetheless highly effective technique of creating locally limited reproducible frostbite injuries using a no touch technique. Tissue damage can be fully attributed to the thermal trauma, and the model allows repetitive intravital fluorescent microscopy of the microcirculation, leukocyte–endothelium interaction, and angiogenesis.
研究领域:
医学
·
生物学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Hui Li,Shuangshuang Chen,Yumei Li,Zelin Sang,Zhenhua Chen,Xifan Mei,Xiuli Ren
In the pathogenesis of inflammatory bowel disease (IBD), overstimulation of inflammatory factors can trigger a coagulation cascade, increase the risk of intestinal micro-thrombosis and lead to microcirculation disorders. However, prevention of microcirculation pathways has not received enough attention. Heparin is commonly used in anticoagulant therapy, but oral delivery does not have an excellent anticoagulant effect. To improve the stability of heparin (HEP) in the gastrointestinal tract, zein/tea polyphenol nanospheres with a core-shell structure (EGNs@Z) were developed for oral administration of heparin (HEGNs@Z). The Zein shell has pH-responsive properties and is effective in preventing premature dissolution of heparin. At the same time, EGCG nanospheres (EGNs) play an anti-inflammatory role, jointly improve the vicious cycle between inflammation and microthrombosis. The results of SEM, TEM and FTIR showed that EGNs successfully encapsulated heparin and formed zein shells on the surface of microspheres with a thickness of 50-100 nm. In vitro simulated digestion experiments showed that zein shells prevented the breakdown of microspheres and heparin in a simulated gastric environment, whereas EGNs and HEP were slowly degraded and released in a simulated intestinal environment. Coagulation analysis showed that HEGNs@Z was effective in delaying clotting time. A mouse model of acute colitis has also shown that HEGNs@Z robust promotes colonic epithelial regeneration, inhibits malignant microcirculation, and reduces bleeding risk. These findings reveal that this orally bioavailable multifunctional material may provide a novel, effective and convenient treatment for inflammatory bowel disease.
研究领域:
药学
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生物医学工程
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Yuanfang Sun,Shasha Li,Lijing Du,Xiaopeng Ren,Huizi Jin,Shikai Yan,Xue Xiao
Background: Microcirculatory dysfunction leads to a number of diseases and worsen prognosis. Blood-activating drugs like Xinnaoning capsule may improve circulation, but its pharmacological effects in microcirculatory dysfunction remain unclear.Objective: The purpose of this study is to determine the pharmacological effect of Xinnaoning capsules in treating microcirculatory dysfunction.Methods: Adrenaline and icy water stimuli were used to establish a rat model of acute microcirculatory dysfunction. Detecting laser speckle contrast imaging, coagulation function, hemorheology, and the Elisa assay were conducted to investigate the effect of Xinnaoning capsule on microcirculation in rats. In addition, the untargeted metabolomics was applied to character the therapeutic effect of Xinnaoning systematically from the perspective of endogenous terminal metabolites.Results: Laser speckle contrast imaging showed that model rats suffered low perfusion in ears, feet and tails, and Xinnaoning capsule treatment increased microcirculatory blood flow. Xinnaoning capsule diminished the reduction of thrombin time, prothrombin time, activated partial thromboplastin time and the elevated fibrinogen level caused by acute microcirculatory dysfunction. Xinnaoning capsule could recover the increased blood viscosity as well as the abnormal vasomotor and microcirculation function in model rats. Furthermore, Xinnaoning capsule intervention could alter metabolic state in model rats, which was characterized by the abnormality metabolites mainly in pathway of phospholipids and arachidonic acid metabolism.Conclusion: The macroscopic image and microscopic indicators elucidated that Xinnaoning capsule was highly effective against microcirculatory dysfunction. The present study provided a new perspective on the clinical application of Xinnaoning capsule, and contributed to explore novel therapeutic drug against microcirculatory dysfunction.
研究领域:
药理学
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生物医学工程
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代谢组学
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微循环
·
血液学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Neurotherapeutics
·
2024
·
IF 5.6
Zhiyuan Shen,Yuxuan Lu,Yingying Ren,Zhaoxia Wang,Jianwen Deng,Ding Nan,Jingjing Jia,Weiwei Yu,Yunyi Jin,Wei Sun,Yining Huang,Xiaozhong Qu,Haiqiang Jin
The precise oxygen content thresholds of ischemic deep parenchymal (OCIDP) and that in cortical microcirculation (OCCM), which leads to ischemic penumbra converting into the infarcted core, remain uncertain. This study employed an invasive fiber-optic oxygen meter and a newly developed oxygen-responsive probe called RuA 3 -Cy5-rtPA (RC-rtPA) based on recombinant tissue-type plasminogen activator (rtPA) to examine the oxygen content thresholds. A mouse model of middle cerebral artery occlusion was generated and animals were randomly divided into a sham, 24-h reperfusion after 3-h ischemia (IR 3-h), and IR 6-h groups, all of which were sacrificed following reperfusion. Stroke severity was evaluated based on the infarction area, neurological symptoms, microcirculation perfusion, and microemboli in microcirculation. OCIDP was characterized based on its extent and distribution, whereas OCCM was measured using RC-rtPA. During ischemia, stroke severity escalation manifested as increasing infarction area, severe neurologic symptoms, and poorer microcirculation perfusion with more microthrombi depositions. OCIDP presented rapid decline following artery occlusion along with a gradual increase in the hypoxic area. Within 3 h following ischemia induction, the ischemic tissue that experienced hypoxia could be rescued, and this reversibility would disappear after 6 h. Within 6 h, OCCM continued to decrease. A significant decrease in oxygen content in cortical venules and cortical parenchyma was observed. These findings assist in establishing the extent of the ischemic penumbra at the microcirculation level and offer a foundation for assessing the ischemic penumbra that could respond positively to reperfusion therapy beyond the typical time window.
研究领域:
神经科学
·
中风
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微循环
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氧测量
·
动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Xilin Li,Junjiang Pan,Mingjie Liu,Enning Zhang,Yan Li,Yang He,Guang Yang,Shaobing Zhou
Frostbite is a prevalent form of acute cold injury that can cause extensive tissue damage, often requiring amputation. However, most clinical interventions face the challenge of preventing or mitigating reperfusion injury while restoring the blood supply. In this study, a fiber patch is developed with reperfusion injury prevention and thermal stimulation capabilities for frostbite treatment. Encapsulating itaconic acid (ITA) within the surface knots of the fabricated necklace-like polymer fibers optimizes its release kinetics, effectively inhibiting the generation of reactive oxygen species (ROS) through metabolic pathways. Localized thermal stimulation from the fiber matrix modulates cytokine secretion and promotes microcirculation remodeling in frostbitten tissues. In a study involving a third-degree frostbite model, the fiber patch demonstrates superior therapeutic efficacy in accelerating tissue repair, outperforming conventional pharmaceutical treatments. Hence, this study provides a portable, effective, and preventive solution for frostbite management.
研究领域:
生物医学工程
·
材料科学
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急诊医学
·
热疗
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
Oxidative Medicine and Cellular Longevity
·
2020
·
IF 5.076
Xing Li,Dan Luo,Yu Hou,Yonghui Hou,Shudong Chen,Jiheng Zhan,Jiyao Luan,Le Wang,Dingkun Lin
Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Mingrui Xiong,Hong Chen,Yu Fan,Muchuan Jin,Dong Yang,Yuchen Chen,Yu Zhang,Robert B. Petersen,Hua Su,Anlin Peng,Congyi Wang,Ling Zheng,Kun Huang
Rationale: Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating injury. Exogenous application of elabela (ELA) peptides has been demonstrated by us and others to alleviate AKI, partly through its receptor APJ. However, the endogenous role of ELA in renal I/R remains unclear. Methods: Renal tubule specific ELA knockout ( Apela Ksp KO) mice challenged with bilateral or unilateral I/R were used to investigate the role of endogenous ELA in renal I/R. RNA-sequencing analysis was performed to unbiasedly investigate altered genes in kidneys of Apela Ksp KO mice. Injured mice were treated with ELA32 peptide, Nω-hydroxy-nor-L-arginine (nor-NOHA), prostaglandin E2 (PGE2), Paricalcitol, ML221 or respective vehicles, individually or in combination. Results: ELA is mostly expressed in renal tubules. Aggravated pathological injury and further reduction of renal microvascular blood flow were observed in Apela Ksp KO mice during AKI and the following transition to chronic kidney disease (AKI-CKD). RNA-seq analysis suggested that two blood flow regulators, arginine metabolizing enzyme arginase 2 (ARG2) and PGE2 metabolizing enzyme carbonyl reductases 1 and 3 (CBR1/3), were altered in injured Apela Ksp KO mice. Notably, combination application of an ARG2 inhibitor nor-NOHA, and Paricalcitol, a clinically used activator for PGE2 synthesis, alleviated injury-induced AKI/AKI-CKD stages and eliminated the worst outcomes observed in Apela Ksp KO mice. Moreover, while the APJ inhibitor ML221 blocked the beneficial effects of ELA32 peptide on AKI, it showed no effect on combination treatment of nor-NOHA and Paricalcitol. Conclusions: An endogenous tubular ELA-APJ axis regulates renal microvascular blood flow that plays a pivotal role in I/R-induced AKI. Furthermore, improving renal blood flow by inhibiting ARG2 and activating PGE2 is an effective treatment for AKI and prevents the subsequent AKI-CKD transition.
研究领域:
肾病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Zhao Zhang,Si-Yuan Ma,Xin Yin,Yu-Sang Li,He-Bin Tang
Ethnopharmacological relevance The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. Aim of the study To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. Materials and methods The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. Results FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. Conclusions FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy.
研究领域:
药理学
·
中医
·
伤口愈合
·
微循环
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2019
·
IF 2.929
Zhuoyu Wen,Yongjun Jiang,Linyuan Zhang,Xiaomeng Xu,Nan Zhao,Xiaohui Xu,Fang Wang,Jie Gao,Guo-Yuan Yang,Xinfeng Liu
Background Previous studies have estimated that the risk of recurrent stroke was nearly 20% shortly after a transient ischemic attack (TIA) or minor stroke. A missing or hypoplastic (<0.5 mm) anterior communicating artery can have deleterious effects on the brain. Our study aimed to investigate the effect of anterior communicating artery flow on neurovascular injury and neurobehavioral outcomes in mice with recurrent stroke and to identify its underlying mechanisms. Methods A recurrent stroke model was established by an initial cortical infarction followed by a corticostriatal infarction 3 days later. The vascular structure was visualized using synchrotron radiation angiography & magnetic resonance angiography in vivo and transparent endovascular perfusion imaging in vitro . Microvessel perfusion was assessed via fluorescein isothiocyanate perfusion. The infarct volume was measured by magnetic resonance imaging. Results The finding that anterior communicating artery flow facilitates pial artery patency in the ipsilateral hemisphere in mice with recurrent stroke suggests that compensatory collateral patency contributes to increased regional cerebral blood flow, enhanced microcirculatory perfusion, improved neurological function and reduced infarct volume. Conclusions The results of this study demonstrate that anterior communicating artery flow alleviates recurrent stroke-induced neurovascular injury and improves neurobehavioral outcomes by promoting the establishment of collateral circulation.
研究领域:
神经科学
·
实验性中风研究
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脑血管疾病
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神经影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Ge Xie,Nuoya Zhou,Yujie Gao,Shuo Du,Hongyao Du,Juan Tao,Lianbin Zhang,Jintao Zhu
Acceleration of skin wound healing is an important aspect of wound treatment. The use of carbon dioxide (CO 2 ) has been recognized as one of the most effective ways to improve microcirculation and to benefit wound healing, while the need of the specialized equipment and the uncontrollable delivery of gas CO 2 might restrict such strategy in wide applications. Herein, we develop a photothermal hydrogel for the on-demand and localized delivery of CO 2 to accelerate skin wound healing by combining thermoresponsive block copolymer (BCP) of Pluronic F127 and carbon nanoparticles (CNPs) with amino groups, which can be used for loading CO 2 precursor of bicarbonate for controlled release. We show that by rationally optimizing the content of the thermoresponsive BCP in the photothermal hydrogel, a liquid-to-solid transition triggered by the body temperature can be achieved. Under light irradiation, the CNPs can convert light into heat, triggering the decomposition of the bicarbonate, and the photothermal hydrogel can thus locally release CO 2 in the wound site. Wound healing can be accelerated by improving local microcirculation disturbance and increasing tissue oxygen concentration. This study provides a new opportunity for local CO 2 supplement for accelerating wound healing.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
·
纳米技术
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）