FOLIA HISTOCHEMICA ET CYTOBIOLOGICA
·
2023
·Vol. 61
·期 2
·109-122
·
IF 1.5
Jiahui Han Di Jia Hao Yao Ting Lv Xi Xu Xin Ge
Introduction. Hemorrhagic shock (HS) is an important cause of high mortality in traumatized patients. Cryptotanshinone (CTS) is a bioactive compound extracted from Salvia miltiorrhiza Bunge (Danshen). The current study aimed to explore the effect and underlying mechanism of CTS on the liver injury induced by HS. Material and methods. Male Sprague-Dawley rats were used to establish the HS model by hemorrhaging and monitoring mean arterial pressure (MAP). CTS was intravenously administered at concentration of 3.5 mg/kg, 7 mg/kg, or 14 mg/kg 30 minutes before resuscitation. Twenty-four hours after resuscitation, the liver tissue and serum samples were collected for the following examinations. Hematoxylin and eosin (H&E) staining was used to evaluate hepatic morphology changes. The myeloperoxidase (MPO) activity in liver tissue and the serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined to reveal the extent of liver injury. The protein expression of Bax and Bcl-2 in liver tissue was detected by western blot. The TUNEL assay determined the apoptosis of hepatocytes. Oxidative stress of liver tissue was assessed by the examination of reactive oxygen species (ROS) generation. The content of malondialdehyde (MDA), glutathione (GSH), and adenosine triphosphate (ATP), the activity of superoxide dismutase (SOD) and oxidative chain complexes (complex I, II, III, IV), as well as cytochrome c expression in cytoplasm and mitochondria, were also used to determine the extent of oxidative injury in the liver. Immunofluorescence (IF) was employed to estimate nuclear factor E2-related factor 2 (Nrf2) expression. The mRNA and protein levels of heme oxygenase 1 (HO-1), NAD(P)H: quinone oxidoreductases 1 (NQO1), cyclooxygenase-2 (COX-2), and nitric oxide synthase (iNOS) were assessed by real-time qPCR, western blot to investigate the mechanism of CTS regulating HS-induced liver injury. Results. H&E staining and a histological score of rat liver suggested that HS induced liver injury. The activity of ALT, AST, and MPO was significantly increased by HS treatment. After CTS administration the ALT, AST, and MPO activities were suppressed, which indicates the liver injury was alleviated by CTS. The HS-induced upregulation of the TUNEL-positive cell rate was suppressed by various doses of CTS. HS-induced ROS production was decreased and the protein expression of Bax and Bcl-2 in the HS-induced rat liver was reversed by CTS administration. In the liver of HS-induced rats, the upregulation of MDA content and the downregulation of GSH content and SOD activity were suppressed by CTS. Additionally, CTS increases ATP content and mitochondrial oxidative complexes activities and suppressed the release of cytochrome c from mitochondria to the cytoplasm. Moreover, IF and western blot demonstrated that the activation of Nrf2 blocked by HS was recovered by different doses of CTS in liver tissue. The expression of downstream enzymes of the Nrf2 pathway, including HO-1, NQO1, COX-2, and iNOS, was reversed by CTS in the HS rat model. Conclusions. The current study for the first time revealed the protective effect of CTS in HS-induced liver injury. CTS effectively recovered hepatocyte apoptosis, oxidative stress, and mitochondria damage induced by HS in the rat liver partly via regulating the Nrf2 signaling pathway.
研究领域:
药理学
·
病理生理学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
3 Biotech
·
2021
·Vol. 11
·期 12
·1-13
·
IF 2.406
Tang Miaolong,Cai Jimin,Wang Yan,Huan Zhirong,Yao Hao,Xu Ce,Ge Xin,Song Sheng
Hemorrhage shock (HS) is a major threat to patients with trauma and spontaneous bleeding, resulting in multi-organ failure including the kidney. Tyrosine kinase nonreceptor 1 (TNK1) has been shown to be upregulated in the kidney of experimental HS and patients with severe trauma . The study aims to investigate the role of TNK1 and the underlying mechanism in HS-induced kidney injury. A model of HS was established with femoral artery bloodletting, followed by resuscitation in Sprague–Dawley rats. Renal expression of TNK1 was abnormally induced by HS in rats. Knockdown of TNK1 alleviated HS-induced cell apoptosis and the level of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) in the kidney. The expression of M1 macrophage markers (CD86 and iNOS) and the activation of STAT1 were inhibited by TNK1 knockdown in HS rats. In vitro, human monocyte THP-1 cells were treated with 20 ng/mL interferon-gamma plus 100 ng/mL lipopolysaccharide to induce M1 polarization. TNK1 knockdown exerted inhibitory effect on macrophage M1 polarization, M1-type inflammatory cytokine production and STAT1 activation in THP-1 cells. In conclusion, downregulation of TNK1 alleviates HS-induced kidney injury by suppressing macrophage M1 polarization, inflammation and kidney cell apoptosis, in which the deactivation of STAT1 signaling may be involved.
研究领域:
医学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
·
IF 9.078
Cai Long,Yongquan Qing,Songhe Li,Miao Cui,Mengxue Han,Kai An,Xiao Long,Chen Liu,Changsheng Liu
Wound dressings are of great importance in trauma medicine. However, such dressings are poor in hemostatic effect, and they easily adhere to the wound skin, leading to their unsatisfactory effects for clinical application. Herein, we developed a new concept of creating an asymmetric composite wound nanodressing (ACWN) with unique structure consisting of superhydrophilic/superhydrophobic alternate inner layer and superhydrophobic outer layer. Compared to traditional hemostatic materials, our fabricated material consisted of integration of alternate micropattern wettability of the inner layer and the asymmetric wettability of the inner/outer layers into simple gauze. This ACWN was verified to overcome the challenge of reducing blood loss and simultaneously reducing adhesion based on the results of rat experiments both in in vivo and in vitro . Importantly, the resulting ACWN exhibited efficient blood absorption and clotting abilities on the zone of superhydrophilic inner layer. Moreover, the zone of superhydrophobic inner layer with blood repellency could avoid pain and secondary injuries caused by forced removal of dressings, and its outer layer could further prevent blood extravasation and reduce the risk of infection. Undoubtedly, this effective strategy provides new insight into the practical application of hemostatic materials.
研究领域:
创伤医学
·
生物材料学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Rong-Xin Song,Xiao-Yi Ma,Ting-Ting Zhou,Zhi-Fang Yu,Jun Wang,Bao-Dong Li,Yu-Mo Jing,Han Wang,Yue Fu,Rui-Zhao Lv,Shi-Yan Jia,Xiao-Ming Li,Li-Min Zhang
Objective Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H 2 S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H 2 S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl- d -Aspartate (NMDA) receptor function. Methods Mice were immediately administered dl -propargylglycine (PAG) intragastrically as an H 2 S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. Results Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H 2 S-induced intestinal and cerebral injury. Conclusion This experimental data suggests that H 2 S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.
研究领域:
神经科学
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药理学
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病理生理学
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行为科学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jinnan Guo,Yuanyuan Zhao,Guanqun Peng,Tong Ye,Xiaohui Zhu,Runtian Li,Jintao Shen,Lina Du,Shanshan Wang,Zhiyun Meng,Hui Gan,Ruolan Gu,Wenzhong Sun,Guifang Dou,Shuchen Liu,Yunbo Sun
Severe bleeding from deep and irregular wounds poses a significant challenge in prehospital and surgical settings. To address this issue, we developed a novel chitosan-based hemostatic dressing with a magnetic targeting mechanism using Fe 3 O 4 , termed bovine serum albumin-modified Fe 3 O 4 embedded in porous α-ketoglutaric acid/chitosan (BSA/Fe 3 O 4 @KA/CS). This dressing enhances hemostasis by magnetically guiding the agent to the wound site. In vitro, the hemostatic efficacy of BSA/Fe 3 O 4 @KA/CS is comparable to that of commercial chitosan (Celox™) and is not diminished by the modification. In vivo, BSA/Fe 3 O 4 @KA/CS demonstrated superior hemostatic performance and reduced blood loss compared to Celox™. The hemostatic mechanism of BSA/Fe 3 O 4 @KA/CS includes the concentration of solid blood components through water absorption, adherence to blood cells, and activation of the endogenous coagulation pathway. Magnetic field targeting is crucial in directing the dressing to deep hemorrhagic sites. Additionally, safety assessments have confirmed the biocompatibility and biodegradability of BSA/Fe 3 O 4 @KA/CS. In conclusion, we introduce a novel approach to modify chitosan using magnetic guidance for effective hemostasis, positioning BSA/Fe 3 O 4 @KA/CS as a promising candidate for managing various wounds.
研究领域:
生物材料
·
止血
·
伤口愈合
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Min Zhou,Jiaxing Liao,Guobing Li,Zhijie Yu,Dandan Xie,Huyue Zhou,Fengling Wang,Yukun Ren,Rufu Xu,Yue Dai,Jie Wang,Jingbin Huang,Rong Zhang
Uncontrolled hemorrhage poses a severe life-threatening situation. However, traditional hemostats still have various limitations. It is urgent to develop a material with excellent biocompatibility and hemostatic ability. Evidence has shown that carboxymethyl chitosan (CMCS) has hemostatic properties and good compatibility. Herein, we develop an expandable hemostatic sponge by modifying CMCS with cellulose nanofibrils (CNFs) through the CO-NH cross-linking method. We verified its potential as a hemostatic agent both in vivo and in vitro . The results demonstrated that the prepared carboxymethyl chitosan/cellulose nanofiber composite (CNF-CMCS) sponges could absorb blood, quickly expand to exert pressure in the wound, and exhibit an excellent coagulation ability. The CNF-CMCS sponges significantly decreased the bleeding time and blood loss in several hemorrhage models and possessed a significant advantage in treating the deep penetrating injury hemorrhage. Therefore, the sponges provide a unique application prospect and potential as a penetrating trauma hemostatic agent.
研究领域:
生物材料
·
止血
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Zhicheng Liu,Hao Zhang,Huining Su,Yang Chen,Xunan Jing,Daquan Wang,Shaohui Li,Hao Guan,Lingjie Meng
Developing porous hemostatic sponges that are both biosafe and multifunctional remains a complex challenge. Conventional hemostatic techniques often fall short in managing bleeding effectively, leading to severe critical cases such as suboptimal hemostasis, increased infection risk, and complications arising from profuse bleeding. To address these deficits, our study introduces a novel multifunctional nanocomposite sponge that synergistically incorporates chitosan (CS), cellulose (Cel), graphene oxide (GO), and silver (Ag) nanoparticles. The resulting CS/Cel/GO/Ag developed demonstrates a swelling rate exceeding 3000 %, an absorption rate of over 2100 %, and the lowest stress surpassing 20 kPa at an initial 80 % strain. In vitro analyses reveal that the CS/Cel/GO/Ag sponge has excellent cytocompatibility, non-hemolytic nature, and competence in blood cell adherence and bacterial inhibition. In vivo evaluations further demonstrate that compared to conventional hemostatic methods, the sponge substantially enhances hemostatic efficacy, as evidenced by the marked reductions in clotting times and diminished blood loss compared to conventional hemostatic methods. Specifically, the test results of the CS/Cel/GO/Ag sponge across three different models are as follows: for the rat tail amputation model, the clotting time was 99 s, while blood loss was 222 mg; for the rat liver injury model, the clotting time was 129 s. while blood loss was 812 mg; for the rat femoral artery laceration model, the clotting time was 96 s, while blood loss was 758 mg. The compelling attributes of the CS/Cel/GO/Ag sponges position them as a promising solution for the acute management of bleeding. Their excellent performance indicates they have potential role to play in trauma care.
研究领域:
材料科学
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生物医学工程
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止血
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纳米技术
·
组织工程
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2024
·
IF 4.8
Bo Li,Wuming Zhou,Jiacheng Zhang,Nan Wang,Xingguan Yang,Xin Ge
Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae , exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. However, the effect of Sch A on HS-caused cardiac injury and its underlying mechanism still lack research. In this study, we established an HS rat model through blood loss from the femoral artery and monitoring mean arterial pressure (MAP) followed by fluid resuscitation. Our findings suggested that cardiac dysfunction and pathological injury were induced by HS and attenuated by Sch A treatment in a dose-dependent manner. Apoptosis in cardiac tissue was promoted by HS, but suppressed after administration of Sch A by decreasing the protein expressions of cleaved-caspase-3 and -9. Moreover, excessive ROS production induced by HS was mitigated by Sch A, and the levels of oxidative stress indicators were improved by Sch A. Additionally, HS triggered the reduction of mitochondrial membrane potential (MMP), and led to mitochondrial dysfunction. Sch A reversed this effect of HS on mitochondria. The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.
研究领域:
药理学
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心脏病学
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急诊医学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xiao Yang,Wen Liu,Guanghui Xi,Mingshan Wang,Bin Liang,Yifen Shi,Yakai Feng,Xiangkui Ren,Changcan Shi
It is important to control immediate hemorrhage and prevent infection simultaneously in the wound management. However, most of hemostatic materials are associated with low efficiency of hemostasis, poor biocompatibility and lack of antimicrobial properties. A kind of starch-based macroporous sponges (KR-Sps) immobilized covalently with antimicrobial peptide KR12 using highly efficient thiol-ene photo click reaction were developed. The physical properties of these sponges could be fine-tuned by varying the ratio of modified starch/HS-PEG-SH and the polymer concentration. The in vitro and vivo results demonstrated that KR-Sps induced thrombosis, shortened clotting time and reduced the blood loss at bleeding site. Besides, KR12 immobilized sponge exhibited inherent antimicrobial properties against Gram (+) and (−) bacteria and methicillin-resistant Staphylococcus aureus ( MRSA ), which could maintain at least 5 days. Therefore, KR-Sps were believed to be an excellent candidate as hemostatic and antimicrobial product for the intraoperative wound management.
研究领域:
生物材料
·
生物医学工程
·
伤口愈合
·
抗菌材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2022
·
IF 3.662
Jiayi Guo,Qun Liu,Jun Cheng,Xin Fu,Yucang Zhang,Huan Yang
Fish skin collagen has attracted a wide range of attention in the field of hemostatic materials due to its excellent biocompatibility and hemostatic performance. In this work, the hemostatic cotton based on poly(vinyl alcohol)/soluble starch-fish skin collagen (PVA/SS-FSC) composites was prepared by solvent displacement followed by lyophilization. The experimental results showed that the PVA/SS enabled the composite material to have 3-D porous structures. When compounding with FSC, PVA/SS-FSC(1) composite cotton (mass ratio 1:1:1) possessed 3-D porous structures, good water absorption, and no cytotoxicity or hemolytic properties. In vitro and in vivo experiments demonstrated that the PVA/SS-FSC(1) hemostatic cotton accelerated the coagulation rate, reduced blood loss, and improved the hemostatic efficiency. Furthermore, arterial hemostasis tests in rats confirmed that the PVA/SS-FSC(1) hemostatic cotton afforded a shorter hemostasis time (64 ± 7 s) and lower blood loss (323 ± 38 mg) compared with commercial hemostatic gauze (210 ± 12 s and 840 ± 41 mg, respectively), thus indicating promising applications in rapid wound hemostasis.
研究领域:
材料科学
·
生物材料
·
止血
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·
IF 5.7
Xingguan Yang,Jiahui Han,Zhirong Huan,Ce Xu,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is defined as a reduction in tissue oxygenation and organ dysfunction due to severe blood loss. Lung injury is a frequent complication of HS. Baicalin, isolated from Radix Scutellariae , has been reported to profile the antitumor, anti-oxidative, anti-inflammatory, and antibacterial roles in various pathological processes. Nevertheless, the effects of baicalin on HS-induced lung injury are unclear. This study aims to examine the therapeutic effects of baicalin on lung injury. We first established the lung injury rat models by withdrawing blood in the femoral artery followed by resuscitation. A pathological analysis showed that HS-administrated rats presented severe capillary leakage and pulmonary edema, while baicalin therapy alleviated the symptoms. Baicalin therapy reduced the number of macrophages and neutrophils in bronchoalveolar lavage fluid and decreased the expression and activity of myeloperoxidase (neutrophile infiltration marker) in the lung tissues of HS rats, indicating that baicalin alleviated HS-induced infiltration of inflammatory cells. The secretion of inflammatory cytokines, including interleukin (IL)-1 β , IL-6, IL-18, and tumor necrosis factor α (TNF- α ), as well as the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome, were inhibited by baicalin administration. Furthermore, we found that the NF- κ B pathway, a canonical pro-inflammatory pathway, was also blocked after treatment with baicalin in HS-evoked rats, as indicated by the decreased expression of p65 and p65 phosphorylation in the lung tissues. In summary, we infer that baicalin may exert a protective role in HS-induced lung injury by suppressing the activation of NLRP3 inflammasome via the NF- κ B pathway.
研究领域:
药理学
·
免疫学
·
病理生理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
研究领域:
药理学
·
免疫学
·
心脏病学
·
病理生理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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