摘要:
探讨僵蚕提取液对全脑缺血再灌注(I/R)大鼠行为学改善的作用及可能的机制。全自动血凝仪检测僵蚕提取液干预人血浆凝血四项对提取液进行质控。4周龄雄性SD大鼠60只,分为假手术组,模型组,阳性药物(肝素)组,僵蚕提取液低、中、高剂量组。除假手术组外,其余5组大鼠行双侧颈总动脉反复夹闭-再通手术,构建I/R大鼠模型。僵蚕提取液低、中、高剂量组予僵蚕提取液(0.45、0.9、1.8 mg·g-1·d-1)腹腔注射,阳性药物(肝素)组予肝素注射剂(900 IU·kg-1)腹腔注射,假手术组、模型组予等体积生理盐水腹腔注射,共计7 d;平衡木(BBT)检测大鼠行为学;苏木素-伊红(HE)染色检测脑组织形态学变化,免疫荧光法检测脑皮质(CC)区白细胞共同抗原(CD45)、白细胞分化抗原(CD11b)、精氨酸酶1(Arg-1);酶联免疫吸附试验法(ELISA)检测白细胞介素-1β(IL-1β)、白细胞介素-4(IL-4)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)蛋白表达水平;非靶向代谢组学检测僵蚕提取液、干预后大鼠血浆、干预后大鼠脑皮质代谢物水平。质控结果显示僵蚕提取液有效延长了人血浆活化部分促凝血酶原激酶时间(activated partial thromboplastin time, APTT)、凝血酶原时间(prothrombin time, PT)、凝血酶时间(thrombin time, TT),与往期提取所得僵蚕提取液抗凝作用相似。行为学检测结果显示与假手术组比较,模型组大鼠BBT得分增加;与模型组相比,僵蚕提取液干预后小鼠BBT评分降低。组织形态学结果显示与假手术组比较,模型组大鼠CC脑区可见大量神经细胞形态改变;与模型组相比,僵蚕提取液干预后大鼠CC脑区异常形态神经细胞减少。免疫荧光结果显示与假手术组比较,模型组大鼠CC脑区CD45、CD11b平均荧光强度增加;与模型组相比,僵蚕提取液低剂量组大鼠CC脑区CD11b平均荧光强度减少,Arg-1平均荧光强度增多;僵蚕提取液中、高剂量组大鼠CC脑区CD45、CD11b平均荧光强度减少,Arg-1平均荧光强度增多。ELISA结果显示与假手术组比较,模型组大鼠CC脑区IL-1β、IL-6表达增加,IL-4、IL-10表达减少;与模型组比较,僵蚕提取液低、中、高剂量组IL-1β、IL-6表达不同程度减少,IL-4、IL-10表达不同程度增加。非靶向代谢组学结果显示僵蚕提取液共计鉴定代谢物809个,大鼠血浆中新增代谢物57个,大鼠脑皮质新增代谢物45个。具有抗凝药效的僵蚕提取液改善I/R大鼠行为学功能,其机制可能是促进小胶质细胞向M2型极化,增强其抗炎及吞噬功能,从而降低脑皮质神经细胞受损。
摘要:
Network pharmacology and bioinformatics were used to study puerarin's molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using "Osteoarthritis" as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilβ levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin's anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin's multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.
期刊:
Journal of Clinical Gastroenterology,2023年57(8):782-788 ISSN:0192-0790
通讯作者:
Tian, XF
作者机构:
[Huang, Caizhi; Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;[Huang, Caizhi] Hunan Childrens Hosp, Dept Lab Med, Changsha, Peoples R China.;[Mei, Si] Hunan Univ Chinese Med, Dept Physiol, Changsha, Peoples R China.;[Zhang, Xue] Hunan Univ Chinese Med, Key Lab Tradit Chinese Med Mech Tumor Prevent & Tr, Changsha, Peoples R China.;[Tian, Xuefei; Tian, XF] Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
通讯机构:
[Tian, XF ] H;Hunan Univ Chinese Med, Coll Integrated Chinese & Western Med, Dept Internal Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Univ, Key Lab Oncol Tradit Chinese Med, Changsha, Hunan, Peoples R China.
关键词:
gut microbiota, hepatocellular carcinoma, inflammation, dysbiosis
摘要:
Hepatocellular carcinoma (HCC) is an invasive primary liver cancer caused by multiple pathogenic factors and is a significant global health concern. With few effective therapeutic options, HCC is a heterogeneous carcinoma that typically arises in an inflammatory environment. Recent studies have suggested that dysbiotic gut microbiota is involved in hepatocarcinogenesis via multiple mechanisms. In this review, we discuss the effects of gut microbiota, microbial components, and microbiota-derived metabolites on the promotion and progression of HCC by feeding a persistent inflammatory milieu. In addition, we discuss the potential therapeutic modalities for HCC targeting the inflammatory status induced by gut microbiota. A better understanding of the correlation between the inflammatory milieu and gut microbiota in HCC may be beneficial for developing new therapeutic strategies and managing the disease.
摘要:
ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula Xuefu Zhuyu decoction (XFZYD) is a classic formula in the category of invigorating blood circulation and resolving blood stasis. It has been proven to improve the neurological and ethological prognosis of traumatic brain injury. XFZYD promotes synaptic and axonal regeneration after traumatic brain injury, which is functionally modulated by the N(6)-methyladenosine (m(6)A) modification of RNA. However, the epigenetic effects of XFZYD on m(6)A modification remain unknown. AIM OF THE STUDY: To explore how XFZYD protects against traumatic brain injury induced by controlled cortical impact (CCI) injury by altering RNA m(6)A modification. MATERIALS AND METHODS: The modified neurological severity scoring and Morris water maze were performed to evaluate the neuroprotective effects of XFZYD for 14 days and screen the dose. Then, dot blot, western blotting, and methylated RNA immunoprecipitation sequencing (MeRIP-Seq) were used to explore changes in RNA m(6)A modification in the perilesional cortex. The Metascape platform was used to analyze the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway of the differential m(6)A-tagged genes. Furthermore, MeRIP-qPCR was conducted to quantify differences in the hub differential m(6)A modification gene brain-derived neurotrophic factor (Bdnf). RESULTS: XFZYD significantly ameliorated the neurological deficits, spatial learning, and memory impairments in rats post-CCI on day 14. XFZYD enhanced the m(6)A level, and the expression of METTL14 and YTHDC2 in the perilesional cortex of CCI rats. In all three groups, the 3'-untranslated regions and coding sequence were primarily enriched for m(6)A peaks. XFZYD reversed the increased proportion of 3'-untranslated regions, and the decreased proportion of coding sequence and 5'-untranslated regions post-CCI. Moreover, XFZYD markedly downregulated 41 elevated m(6)A-tagged transcripts and upregulated 119 decreased m(6)A-tagged transcripts following CCI. Gene ontology and KEGG pathway analysis revealed that XFZYD-regulated m(6)A-tagged transcripts were predominantly enriched in synapse assembly, synaptic plasticity, learning or memory, and MAPK signaling pathway. Then, the hub-regulated m(6)A-tagged gene BDNF was identified. Both the m(6)A methylation level and the protein level of BDNF were ascended by XFZYD treatment. CONCLUSION: XFZYD improves neurological deficits, spatial learning and memory impairments in rats post-TBI probably through increasing the expression of METTL14 and BDNF in the cortex. Our study highlights a novel post-transcriptional regulation mechanism mediated by herbal medicine for traumatic brain injury treatment.
期刊:
Frontiers in Pharmacology,2023年14 ISSN:1663-9812
通讯作者:
Zhang, SF
作者机构:
[Ou, Qinling; Zhang, SF; Yan, Haixia; Zhang, Sifang; Chang, Yonglong; Nie, Kechao; Li, Jing] Cent South Univ, Second Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ou, Qinling; Zhang, SF; Zhang, Sifang] Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.;[Zhou, Xuhui] Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Hunan Inst Mental Hlth, Dept Addict Med, Changsha, Peoples R China.;[Liu, Jinhui] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.
通讯机构:
[Zhang, SF ] C;Cent South Univ, Second Xiangya Hosp, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.
摘要:
Background: Colorectal cancer (CRC) is a prevalent malignancy affecting the digestive tract, and its incidence has been steadily rising over the years. Surgery remains the primary treatment modality for advanced colorectal cancer, complemented by chemotherapy. The development of drug resistance to chemotherapy is a significant contributor to treatment failure in colorectal cancer. Nanodrug delivery systems (NDDS) can significantly improve the delivery and efficacy of antitumor drugs in multiple ways. However, there is a lack of visualization of NDDS research structures and research hotspots in the field of colorectal cancer, and the elaboration of potential research areas remains to be discovered.Objective: To comprehensively explore the current research status and development trend of NDDS in CRC research.Methods: Bibliometric analysis of articles and reviews on NDDS for CRC published between 2002 and 2022 using tools including CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel was performed.Results: A total of 1866 publications authored by 9,870 individuals affiliated with 6,126 institutions across 293 countries/regions were included in the analysis. These publications appeared in 456 journals. Abnous Khalil has the highest number of publications in this field. The most published journals are the International Journal of Nanomedicine, International Journal of Pharmaceutics, and Biomaterials. Notably, the Journal of Controlled Release has the highest citation count and the third-highest H-index. Thematic analysis identified "inflammatory bowel disease"," "oral drug delivery," and "ulcerative colitis" as areas requiring further development. Keyword analysis revealed that "ulcerative colitis," "exosomes," and "as1411"have emerged as keywords within the last 2 years. These emerging keywords may become the focal points of future research.Conclusion: Our findings reveal the current research landscape and intellectual structure of NDDS in CRC research which helps researchers understand the research trends and hot spots in this field.
作者机构:
[Long, Chunjiao; Liu, Chi; Qu, Xiangping; Liu, Huijun; Qin, Xiaoqun; Xiang, Yang; Ji, Ming; Liu, Lexin; Wu, Di; Zhu, Jiahui] Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.;[Wu, Di] Foshan Univ, Sch Med, Foshan 528000, Guangdong, Peoples R China.;[Liu, Caixia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.
通讯机构:
[Xiang, Y ] C;Cent South Univ, Sch Basic Med Sci, Dept Physiol, Changsha 410008, Hunan, Peoples R China.
关键词:
CTNNAL1;Glucocorticoid sensitivity;Asthma;House dust mite;Heat shock protein 90
摘要:
AIMS: Adhesion molecules play vital roles in the induction of airway hyperresponsiveness (AHR) or airway inflammation. The down-regulation of catenin alpha-like 1 (CTNNAL1) in the bronchial epithelial cells of asthma patients and mice models has been noted in our previous study. In this work, we further explore the underlying mechanism of CTNNAL1 in asthma. MAIN METHODS: We constructed a house dust mite (HDM)-induced asthma animal model on control mice and applied CTNNAL1-siRNA transfection to create CTNNAL1-deficient mice. KEY FINDINGS: We documented much more severe airway inflammation and increased leukocyte infiltration in the lungs of the CTNNAL1-deficient mice comparing to control mice, along with elevated expression of inflammatory cytokines. Dexamethasone (DEX) treatment led to less reduced inflammation in CTNNAL1-deficient mice compared with control mice. Immunoprecipitation confirmed the interaction between heat shock protein90 (hsp90) and CTNNAL1. The expression of hsp90 was upregulated after CTNNAL1 silencing. Meanwhile, the use of hsp90 inhibitor geldanamycin significantly decreased the expression of NR3C1, ICAM-1 and the ratio of p-p65/p65 in CTNNAL1-silenced 16HBE14o- cells. Both geldanamycin and DEX could function to suppress the expression of ICAM-1 and the phosphorylation level of p65. Nevertheless, the anti-inflammatory effect of DEX proved less potent than geldanamycin in the CTNNAL1-silenced group. The combined therapy of geldanamycin and DEX significantly decreased the inflammatory responses in CTNNAL1-deficient HBE cells than DEX monotherapy. SIGNIFICANCE: Our study corroborates that CTNNAL1 deficiency induced aggravated airway inflammation and rendered insensitivity to glucocorticoids via triggering hsp90 signaling pathway.
作者机构:
[Xiong, Wu] Department of Burns and Plastic Surgery, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China;[Zhang, Xi] Hunan Brain Hospital (Clinical Medical School of Hunan University of Chinese Medicine), Changsha, Hunan Province, China. Electronic address: cmxfyjzx2049@126.com;[Zhou, Jianda] Department of Plastic Surgery, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China;[Chen, Jie] Department of Aesthetic Plastic Surgery, the First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China;[Liu, Yu; Tan, Meixin; Wei, Yang; Huang, Hongyu; Si, Yuqi] College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
通讯机构:
[Zhang, Xi] H;Hunan Brain Hospital (Clinical Medical School of Hunan University of Chinese Medicine), Changsha, Hunan Province, China. Electronic address:
摘要:
BACKGROUND AIMS: Treating chronic non-healing diabetic wounds and achieving complete skin regeneration has always been a critical clinical challenge. METHODS: In order to address this issue, researchers conducted a study aiming to investigate the role of miR-126-3p in regulating the downstream gene PIK3R2 and promoting diabetic wound repair in endothelial progenitor cell (EPC)-derived extracellular vesicles. The study involved culturing EPCs with astragaloside IV, transfecting them with miR-126-3p inhibitor or mock plasmid, interfering with high glucose-induced damage in human umbilical vein endothelial cells (HUVECs) and treating diabetic skin wounds in rats. RESULTS: The healing of rat skin wounds was observed through histological staining. The results revealed that treatment with miR-126-3p-overexpressing EPC-derived extracellular vesicles accelerated the healing of rat skin wounds and resulted in better tissue repair with slower scar formation. In addition, the transfer of EPC-derived extracellular vesicles with high expression of miR-126-3p to high glucose-damaged HUVECs increased their proliferation and invasion, reduced necrotic and apoptotic cell numbers and improved tube formation. In this process, the expression of angiogenic factors vascular endothelial growth factor (VEGF)A, VEGFB, VEGFC, basic fibroblast growth factor and Ang-1 significantly increased, whereas the expression of caspase-1, NRLP3, interleukin-1β, inteleukin-18, PIK3R2 and SPRED1 was suppressed. Furthermore, miR-126-3p was able to target and inhibit the expression of the PIK3R2 gene, thereby restoring the proliferation and migration ability of high glucose-damaged HUVEC. CONCLUSIONS: In summary, these research findings demonstrate the important role of miR-126-3p in regulating downstream genes and promoting diabetic wound repair, providing a new approach for treating chronic non-healing diabetic wounds.
作者机构:
[Huang, Jiawang; Ma, Xinyue; Li, Ling; Liao, Zexuan; Liu, Zhuolin] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;[Feng, Zhiying; Wang, Kangyu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Peoples R China.;[Ning, Yi; Lu, Fangguo] Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.;[Li, Ling; Liu, Zhuolin] Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
通讯机构:
[Li, L ] H;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Hunan Prov Key Lab Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.
摘要:
Influenza is an acute viral respiratory infection that has caused high morbidity and mortality worldwide. Influenza A virus (IAV) has been found to activate multiple programmed cell death pathways, including ferroptosis. Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. However, little is known about how influenza viruses induce ferroptosis in the host cells. In this study, based on network pharmacology, we predicted the mechanism of action of Maxing Shigan decoction (MXSGD) in IAV-induced ferroptosis, and found that this process was related to biological processes, cellular components, molecular function and multiple signaling pathways, where the hypoxia inducible factor-1(HIF-1) signaling pathway plays a significant role. Subsequently, we constructed the mouse lung epithelial (MLE-12) cell model by IAV-infected in vitro cell experiments, and revealed that IAV infection induced cellular ferroptosis that was characterized by mitochondrial damage, increased reactive oxygen species (ROS) release, increased total iron and iron ion contents, decreased expression of ferroptosis marker gene recombinant glutathione peroxidase 4 (GPX4), increased expression of acyl-CoA synthetase long chain family member 4 (ACSL4), and enhanced activation of hypoxia inducible factor-1 alpha (HIF-1 alpha), induced nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) in the HIF-1 signaling pathway. Treatment with MXSGD effectively reduced intracellular viral load, while reducing ROS, total iron and ferrous ion contents, repairing mitochondrial results and inhibiting the expression of cellular ferroptosis and the HIF-1 signaling pathway. Finally, based on animal experiments, it was found that MXSGD effectively alleviated pulmonary congestion, edema and inflammation in IAV-infected mice, and inhibited the expression of ferroptosis-related protein and the HIF-1 signaling pathway in lung tissues.
摘要:
Hepatocellular carcinoma (HCC) has high morbidity and mortality, and effective therapies are lacking. Gallic acid (GA), a natural phenolic compound derived from plants, has been reported to prevent the onset and progression of various cancers. However, there is limited elaboration on the potential mechanisms and anticancer effects of GA on hepatocellular carcinoma. Inducing ferroptosis of tumor cells has become one of the most promising ways to eradicate tumor cells. However, the effect of GA on HCC ferroptosis remains unknown. We evaluated the impact of GA on cell viability, migration, and mitochondrial morphology in HepG2 cells. Our study identified a critical role of GA in inducing ferroptosis in HepG2 cells. Mechanistically, we found that GA could inhibit the expression of a ferroptosis-related protein SLC7A11 and GPX4 in HepG2, by blocking β-catenin transport from nuclear to the cytoplasm, thus inducing the inactivation of the Wnt/β-catenin pathway. Our study has confirmed that GA is a novel ferroptosis inducer of HC, suggesting GA could be a promising candidate for the clinical treatment of HCC.
期刊:
Frontiers in Immunology,2023年14:1209706 ISSN:1664-3224
通讯作者:
Wang, WJ;Kwak-Kim, J
作者机构:
[Chen, Zeyang] Qingdao Univ, Sch Med, Qingdao, Peoples R China.;[Chen, Zeyang; Wang, WJ; Wang, Wenjuan] Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;[Zhang, Yanan] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;[Kwak-Kim, Joanne] Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
通讯机构:
[Kwak-Kim, J ] R;[Wang, WJ ] S;Shanghai Jiao Tong Univ, Reprod Med Ctr, Xinhua Hosp, Sch Med, Shanghai, Peoples R China.;Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Clin Sci Dept, Reprod Med & Immunol,Obstet & Gynecol, Vernon Hills, IL 60064 USA.;Rosalind Franklin Univ Med & Sci, Ctr Canc Cell Biol, Chicago Med Sch, Immunol & Infect, N Chicago, IL 60064 USA.
关键词:
memory regulatory T cells;reproductive immunology;Pregnancy;Recurrent pregnancy loss;gestational diabetes mellitus;Preeclampsia
摘要:
Pregnancy requires the process of maternal immune tolerance to semi-allogeneic embryos. In contrast, an overreactive maternal immune system to embryo-specific antigens is likely to result in the rejection of embryos while damaging the invading placenta, such that the likelihood of adverse pregnancy outcomes can be increased. Regulatory T cells (Tregs) are capable of suppressing excessive immune responses and regulating immune homeostasis. When stimulating Tregs, specific antigens will differentiate into memory Tregs with long-term survival and rapid and powerful immune regulatory ability. Immunomodulatory effects mediated by memory Tregs at the maternal-fetal interface take on critical significance in a successful pregnancy. The impaired function of memory Tregs shows a correlation with various pregnancy complications (e.g., preeclampsia, gestational diabetes mellitus, and recurrent pregnancy losses). However, the differentiation process and characteristics of memory Tregs, especially their role in pregnancy, remain unclear. In this study, a review is presented in terms of memory Tregs differentiation and activation, the characteristics of memory Tregs and their role in pregnancy, and the correlation between memory Tregs and pregnancy complications. Furthermore, several potential therapeutic methods are investigated to restore the function of memory Tregs in accordance with immunopathologies arising from memory Tregs abnormalities and provide novel targets for diagnosing and treating pregnancy-associated diseases.
作者机构:
[Yu Yi-Pin; Sheng Dan; Zhong Li-Qin; Tan Duo-Ting] Hunan Univ Chinese Med, Grad Sch, Changsha 410208, Peoples R China.;[Liang, H; Hu Zhi-Xi; Liang Hao; Yang Liu] Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.;[Huang Ru-Jia] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.
通讯机构:
[Liang, H ] H;Hunan Univ Chinese Med, Inst TCM Diagnost, Changsha 410208, Peoples R China.
摘要:
To investigate the role of miR-140/BCL2L2 axis on the formation of intracranial aneurysms. The expression of miR-140 in the serum of patients with intracranial aneurysms and healthy volunteers was detected. CCK-8 assay and Annexin V-FITC/PI double staining flow cytometry were used to evaluate the effect of miR-140 knockdown on the proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs). Meanwhile, the relationship between miR-140 and BCL2L2 was examined. MiR-140 was found to be upregulation in intracranial aneurysm patients. MiR-140 knock-out significantly inhibited the apoptosis of HBVSMCs and promoted cell proliferation. BCL2L2 was a direct target gene of miR-140 and suppressed its expression. Knockdown of miR-140 alleviates the development of intracranial aneurysms. MiR-140/BCL2L2 axis promotes the progression of intracranial aneurysms by regulating apoptosis of HBVSMCs. Therefore, miR-140 is a potential therapeutic target for intracranial aneurysms.
作者机构:
[Da-Yuan Zhong; De-Liang Liu; Xue-Ming Ou; Ping-Wen Liu; Jia-Rong Li; Xiang-Bo Kong; Jia-Qi Chen] Department of Neurosurgery, Nanhai Hospital of Traditional Chinese and Western Medicine, Jinan University, Foshan 528200, China.;Institute of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China.;[Hong-Sheng Luo] Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.;[Yi-Hui Deng] College of Integrative Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.;[Huan-Jie Li] Preventive Treating Disease Center, Foshan Hospital of Traditional Chinese Medicine, Foshan 528099, China.
通讯机构:
[De-Liang Liu] D;Department of Neurosurgery, Nanhai Hospital of Traditional Chinese and Western Medicine, Jinan University, Foshan 528200, China.
摘要:
Background: Traditional Chinese medicine (TCM) has been shown to be effective in treating ischemic stroke (IS), and the combination of Angelicae Sinensis Radix (ASR) and Astragali Radix (AR) is a core TCM prescription that is widely acknowledged for its efficacy in IS treatment. This study utilized network pharmacology methods to explore the molecular mechanisms underlying the therapeutic effects of Angelicae Sinensis Radix and Astragali Radix in IS treatment, with preliminary validation conducted through molecular docking. Methods: Information on the structure, targets, main biological functions, and pathways of the active components in Angelicae Sinensis Radix and Astragali Radix was collected using databases such as PubChem, PharmMapper, UniProt, and GeneCards. The results were visualized using software such as Cytoscape 3.6.1, Ledock, and pymol. Results: We retrieved 20 active components and 149 targets associated with the compatibility of Angelicae Sinensis Radix and Astragali Radix from various databases, and GeneCards database was used to search 3350 IS-related gene targets, including 78 key targets of Angelicae Sinensis Radix and Astragali Radix for the treatment of IS. Enrichment analysis of these 78 targets using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed the involvement of 48 GO terms in the treatment of IS, mainly in biological processes such as metabolism, biological regulation, and stress response. The composition of biological devices such as supercavitary membrane, cell fluid, and extracellular space was also involved. The biological functions mainly included protein binding, ion binding, hydrolytic enzyme activity, and others. The identified pathways were estrogen signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, PI3K-AKT signaling pathway, RAP1 signaling pathway, P53 signaling pathway, PPAR signaling pathway, FOXO signaling pathway, RAS signaling pathway, prolactin signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway. Molecular docking analysis showed that the 17 key active components of Angelicae Sinensis Radix and Astragali Radix had strong binding activity with 13 IS key targets. Conclusion: Through the application of network pharmacology methods, it was found that the use of Angelicae Sinensis Radix and Astragali Radix for treating ischemic stroke mainly targets the MAPK and PI3K-AKT signaling pathways, involving several crucial compounds and genes. Nevertheless, additional in vitro and in vivo studies are needed to verify these findings.
作者:
Jin Ding;Wen Sheng;Wei Fu;Meixin Lin;Bonan Li;...
期刊:
中医科学杂志(英文),2023年10(4):484-492 ISSN:2095-7548
通讯作者:
Xing Zhou<&wdkj&>Qinghu He
作者机构:
School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China;Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China;[Wei Fu; Meixin Lin] Department of Andrology Clinic, Affiliated Bao'an Hospital of Traditional Chinese Medicine, The Seventh Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518133, China;Hunan University of Medicine, Huaihua, 418000, China;[Jin Ding] School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Department of Andrology Clinic, Affiliated Bao'an Hospital of Traditional Chinese Medicine, The Seventh Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, 518133, China
通讯机构:
[Xing Zhou; Qinghu He] S;School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, 430000, China<&wdkj&>Hunan University of Medicine, Huaihua, 418000, China
关键词:
Male infertility;Oxidative damage;Traditional Chinese medicine;Guilu Erxian glue;Autophagy;Keap1/Nrf2 pathway
摘要:
To explore the effects and underlying mechanisms of Guilu Erxian glue (GLEXG) on oxidative damage in a mouse GC-1 spermatogonial (MGS) cell model.
A cellular model for oxidative damage was created using MGS cells exposed to hydrogen peroxide (H2O2). Cell viability was assessed using the cell counting kit-8 assay, while reactive oxygen species (ROS) and malondialdehyde (MDA) levels were measured via flow cytometry and enzyme-linked immunosorbent assay, respectively. Western blotting and immunofluorescence techniques were employed to quantify the relative expression levels of sequestosome-1 (p62), nuclear factor erythroid 2-related factor 2 (Nrf2), microtubule-associated protein light chain 3β (LC3B), and Kelch-like ECH-associated protein 1 (Keap1). Quantitative real-time PCR was used to evaluate Keap1 mRNA expression. Transmission electron microscopy (TEM) was conducted to observe structural changes in autophagy-related vesicles.
The cellular model of oxidative damage induced by H2O2 showed reduced cell viability along with elevated levels of ROS and MDA. Treatment with 10% GLEXG-enriched serum significantly enhanced cell viability (P = .0002) while decreasing ROS and MDA levels (P = .0105 and P = .0033, respectively). In rapamycin-treated MGS cells, GLEXG treatment substantially upregulated the relative protein expression of p-mTOR, Nrf2, and p62 (all P < .01), and downregulated the expression of Keap1 and the LC3B-II/LC3B-I ratio (P = .002 and P = .0043, respectively). It also lowered ROS and MDA levels. TEM analysis revealed that GLEXG treatment considerably reduced the number of abnormally enlarged autolysosomes in rapamycin-treated MGS cells. In Keap1-siRNA-transfected MGS cells, the siRNA-Keap1-2311 knockdown site demonstrated higher efficiency. Furthermore, GLEXG treatment in these Keap1-siRNA-transfected cells notably upregulated the relative protein expression of Nrf2 and p62, decreased Keap1 expression and the LC3B-II/LC3B-I ratio, and reduced ROS and MDA levels.
GLEXG effectively mitigated oxidative damage in the MGS cell model by inhibiting autophagy through the Keap1/Nrf2 pathway.