摘要：
Ethnopharmacological relevance: Huang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the study: In the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methods: Observations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflam-matory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-kappa B and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-I kappa B beta, and p-NF-kappa B were evaluated through immunofluorescence analysis. Results: The administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-kappa B and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of I kappa & Vcy;beta, NF-kappa B, JAK, and STAT. Conclusions: The therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-kappa B and STAT signaling pathways.
期刊：
Journal of Ethnopharmacology,2024年318(Pt B):116990 ISSN：0378-8741
通讯作者：
Li, H;Liu, WH
作者机构：
[Li, Hua; Chen, Cong; Zhou, Xiao-qing; Qiu, Shi-wei; Liu, Wang-hua; Li, Jin-xia; Zhou, Chang; Zheng, Cai-xing] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Li, Hua; Liu, Wang-hua; Zhou, Chang] Key Lab TCM Diagnost Hunan Provine, Changsha 410208, Hunan, Peoples R China.;[Zhou, Chang] Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Liu, Wang-hua] Key Lab TCM Heart & Lung Syndrome Differentiat & M, Changsha 410208, Hunan, Peoples R China.;[Liu, Wang-hua] Hunan Engn Technol Res Ctr Med & Funct Food, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Li, H ; Liu, WH ] H;Hunan Univ Tradit Chinese Med, 300 Bachelor Rd,Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, 300 Bachelor Rd,Hanpu Sci & Educ Pk, Changsha, Hunan, Peoples R China.
关键词：
Ischemic stroke;Microglial;Pyroptosis;Inflammation;Glial-vascular unit
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. AIM OF THE STUDY: This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). MATERIALS AND METHODS: Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36g/kg/day), JDHXD-M group (10.71g/kg/day), JDHXD-H group (21.42g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. RESULTS: In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). CONCLUSIONS: Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.
作者机构：
[潘思安] College of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. pansian1989@126.com;[潘思安] College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208. pansian1989@126.com;[刘余; 袁菡钰; 李娟; 汪少华; 薛晓] College of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China;[岳增辉] College of Acupuncture-moxibustion, Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha 410208, China. yue5381316@126.com. LA - eng
作者机构：
[刘梨; 龚志贤] The First Affiliated Hospital /The First Clinical College of Hunan University of Chinese Medicine, Changsha 410007, China;[张亮; 艾坤; 祁芳] College of Acupuncture-Moxibustion and Tuina, Hunan University of Chinese Medicine, Changsha 410208;[李鑫] Hunan Provincial Key Laboratory of Diagnostics of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208;[王文怡; 徐美丽] College of Nursing, Hunan University of Chinese Medicine, Changsha 410208
摘要：
Prolonged exposure of the peritoneum to high glucose dialysate leads to the development of peritoneal fibrosis (PF), and apoptosis of peritoneal mesothelial cells (PMCs) is a major cause of PF. The aim of this study is to investigate whether Astragaloside IV could protect PMCs from apoptosis and alleviate PF. PMCs and rats PF models were induced by high glucose peritoneal fluid. We examined the pathology of rat peritoneal tissue by HE staining, the thickness of rat peritoneal tissue by Masson's staining, the number of mitochondria and oxidative stress levels in peritoneal tissue by JC-1 and DHE fluorescence staining, and mitochondria-related proteins and apoptosis-related proteins such as PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 were measured. We used hoechst staining and flow cytometry to assess the apoptotic rate of PMCs in the PF model, and further validated the observed changes in the expressions of PGC-1α, NRF1, TFAM, Caspase3, Bcl2 smad2 in PMCs. We further incubated PMCs with MG-132 (proteasome inhibitor) and Cyclohexylamine (protein synthesis inhibitor). The results demonstrated that Astragaloside IV increased the expression of PGC-1α by reducing the ubiquitination of PGC-1α. It was further found that the protective effects of Astragaloside IV on PMCs were blocked when PGC-1α was inhibited. In conclusion, Astragaloside IV effectively alleviated PF both in vitro and in vivo, possibly by promoting PGC-1α to enhance mitochondrial synthesis to reduce apoptotic effects.
摘要：
Osteoarthritis (OA) is a chronic joint disease characterized by progressive cartilage degeneration, which imposes a heavy physical and financial burden on the middle-aged and elderly population. As the pathogenesis of OA has not been fully elucidated, it is of great importance to develop targeted therapeutic or preventive medications. Traditional therapeutic drugs, such as non-steroidal anti-inflammatory drugs, steroids and opioids, have significant side effects, making the exploration for safe and effective alternative therapeutic drugs urgent. In recent years, many studies have reported the role of plant-derived polysaccharides in anti-inflammation, anti-oxidation, regulation of chondrocyte metabolism and proliferation, and cartilage protection, and have demonstrated their great potential in the treatment of OA. Therefore, by focusing on studies related to the intervention of plant-derived polysaccharides in OA, including in vivo and in vitro experiments, this review aimed to classify and summarize the existing research findings according to different mechanisms of action. In addition, reports on plant-derived polysaccharides as nanoparticles were also explored. Then, candidate monomers and theoretical bases were provided for the further development and application of novel drugs in the treatment of OA.
作者机构：
[Luo, Min] Cent South Univ, Xiangya Hosp 2, Dept Nephrol, 139 Middle Renmin Rd, Changsha 410011, Hunan, Peoples R China.;[Luo, Min; Hu, Zongren; He, Qinghu] Hunan Univ Med, Dept Rehabil Med & Hlth Care, Huaihua 418000, Hunan, Peoples R China.;[Luo, Min; Hu, Zongren; He, Qinghu] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Hunan, Peoples R China.;[Liu, Ziyu] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Min Luo; Qinghu He] D;Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China<&wdkj&>Department of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan Province, China<&wdkj&>College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China<&wdkj&>Department of Rehabilitation Medicine and Health Care, Hunan University of Medicine, Huaihua, Hunan Province, China<&wdkj&>College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China
关键词：
CI-AKI cell model;HuangKui;cell injury and apoptosis;NEAT1
摘要：
BACKGROUND: Osteoporosis (OP) has emerged as a major global public health issue due to its high prevalence, unknown pathogenesis, and lack of specific drugs for prevention and treatment. Studies have demonstrated that acupuncture in combination with Chinese herbal medicine (CHM) is effective in treating OP. However, there is a scarcity of experience and high-quality evidence. A network meta-analysis and systematic review were used to evaluate the efficacy and safety of acupuncture in combination with CHM for the treatment of OP. METHODS: Comprehensive search of Chinese databases such as China National Knowledge Infrastructure, VIP, Wanfang, China Biomedical Literature Database and English databases for example PubMed, Cochrane Library, EMbase, etc. The search period was extended from the creation of the database to November 2022. All randomized controlled trials on acupuncture in combination with CHM in dealing with OP were collected. After literature analysis and data extraction, the Cochrance system was used to evaluate the high quality of the included articles and Stata 14.0 was used for the network meta-analysis. RESULTS: The current systematic review and network meta-analysis will provide the effectiveness and safety of acupuncture in combination with CHM in dealing with OP. CONCLUSION: The research will provide reliable evidence for the clinical use of acupuncture in combination with CHM in dealing with OP.
摘要：
BACKGROUND: Vascular intimal hyperplasia (IH) is one of the key challenges in the clinical application of small-diameter vascular grafts. Current tissue engineering strategies focus on vascularization and antithrombotics, yet few approaches have been developed to treat IH. Here, we designed a tissue-engineered vascular scaffold with portulaca flavonoid (PTF) composition and biomimetic architecture. METHOD: By electrospinning, PTF is integrated with biodegradable poly(ε-caprolactone) (PCL) into a bionic vascular scaffold. The structure and functions of the scaffolds were evaluated based on material characterization and cellular biocompatibility. Human vascular smooth muscle cells (HVSMCs) were cultured on scaffolds for up to 14days. RESULTS: The incorporation of PTF and preparation parameters during fabrication influences the morphology of the scaffold, including fibre diameter, structure, and orientation. Compared to the PCL scaffold, the scaffolds integrated with bioactive PTF show better hydrophilicity and degradability. HVSMCs seeded on the scaffold alongside the fibres exhibit fusiform-like shapes, indicating that the scaffold can provide contact guidance for cell morphology alterations. This study demonstrates that the PCL/PTF (9.1%) scaffold inhibits the excessive proliferation of HVSMCs without causing cytotoxicity. CONCLUSION: The study provides insights into the problem of restenosis caused by IH. This engineered vascular scaffold with complex function and preparation is expected to be applied as a substitute for small-diameter vascular grafts.
作者机构：
[Qiu, Jingyue; Xiong, Meng; Zhong, Meiqi; Yu, Chang; Peng, Qinghua; Ren, Baoping; Song, Houpan] Hunan Univ Chinese Med, Hunan Prov Key Lab Diagnost Res Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Qiu, Jingyue; Xiong, Meng; Zhong, Meiqi; Yu, Chang; Ren, Baoping; Zeng, Meiyan; Song, Houpan] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Peng, Qinghua] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Ou, Chen; Peng, Qinghua] Hunan Univ Chinese Med, Hunan Prov Key Lab Prevent & Treatment Ophthalmol, Changsha 410208, Hunan, Peoples R China.;[Zeng, Meiyan] Hunan Univ Chinese Med, Coll Tradit Chinese Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Meiyan Zeng] C;[Qinghua Peng] H;College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China<&wdkj&>The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China<&wdkj&>Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with TCM, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
关键词：
Duodenal ulcer;HQJZT;Inflammation;NF-κB;STAT;Traditional Chinese Medicine
摘要：
Huang-Qi-Jian-Zhong-Tang (HQJZT) is a well-known traditional Chinese herbal formulation. This study aimed to investigate the duodenoprotective properties of HQJZT against Indomethacin (IND)-induced duodenal ulceration in rats, and the mechanisms involved, particularly through NF-kappa B and STAT signaling pathways. Our results showed that HQJZT completely protected the duodenal mucosa from ulceration caused by IND, as indicated by improved macroscopic and histological appearances. There was a significant decrease in ulcer index and microscopic score, an increase in villus height and crypt depth, and a normalization of the tissue architecture of the duodenum in rats following HQJZT treatment. Blood flow into the duodenal mucosa was significantly increased after HQJZT administration. HQJZT significantly increased PGE2 and NO levels in the duodenal mu-cosa. A significant reduction in the production of pro-inflammatory cytokines IL-1 beta, IL-6, and TNF-alpha was observed in the duodenal mucosa under treatment with HQJZT. Mechanistically, the administration of HQJZT significantly lowered the duodenal protein expression of inflammation-related genes, including p-NF-kappa B and p-I kappa B beta, compared with the ulcer control group. Furthermore, the STAT signaling pathway-related protein markers p-JAK and p-STAT were significantly reduced in the HQJZT (1.30 and 2.60 g/kg) groups. As a result of these findings, HQJZT alleviates duodenal mucosal ulcers caused by IND. A protective effect of HQJZT on duodenal ulcers is attributed to its ability to improve mucosal blood flow, stimulate the production of cytoprotective mediators, minimize proinflammatory cytokines, and block the activation of NF-kappa B and STAT signaling pathways.
摘要：
In recent years, manganese dioxide (MnO2) nanoparticles with unique physicochemical properties have been widely used in many biomedical fields, such as biosensors, contrast agents, tumor therapy, and drug delivery. From these applications, MnO2 nanoparticles have great clinical translation potential. However, by contrast, the in vitro and in vivo biosafety of MnO2 nanoparticles have been deeply and thoroughly clarified for the clinical translation, which hinders their clinical applications. In this work, we deeply investigated the blood safety of MnO2 nanoparticles by conducting a series of in vitro and in vivo experiments. These included the effects of MnO2 nanoparticles on morphology of red blood cells, activation of platelets, coagulation functions, and toxicity of key organs. The obtained results show that these effects displayed a concentration-dependent manner of MnO2 nanoparticles. Different safe concentration ranges could be found in the different experimental index. This study provides important guidance for the specific biomedical applications of MnO2 nanoparticles, greatly accelerating their laboratory development and clinical translation.
摘要：
To explore the mechanism of Epimedii Folium (HF) and Notoginseng Radix (NR) intervention in vascular dementia (VD). This study used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database to collect the active ingredients and potential drug targets of HF and NR, the Uniprot database to convert drug target names into gene names, GeneCards, Drugbank, Therapeutic Target Database, and Online Mendelian Inheritance in Man database to collect the potential disease targets of VD, and then combined them with the drug targets to construct the HF-NR-VD protein-protein interaction (PPI) network by Search Tool for the Retrieval of Interacting (STRING). Cytoscape (version 3.7.1) was used to perform cluster analysis of the PPI network. Metascape database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The potential interaction of the main components of the HF-NR couplet medicine with core disease targets was revealed by molecular docking simulations. There were 23 predicted active ingredients in HF and NR, and 109 common drug targets that may be involved in the treatment of VD. Through PPI network analysis, 30 proteins were identified as core proteins owing to their topological importance. GO functional analysis revealed that the primary biological processes were mainly related to inflammation, apoptosis, and the response to oxidative stress. KEGG pathway enrichment analysis revealed that TNF and PI3K/Akt signaling pathways may occupy the core status in the anti-VD system. Molecular docking results confirmed that the core targets of VD had a high affinity for the main compounds of the HF-NR couplet medicine. We demonstrated the multi-component, multi-target, and multi-pathway characteristics of HF-NR couplet medicine for the treatment of VD and provided a foundation for further clinical application and experimental research.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. AIM OF THE STUDY: To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study. MATERIALS AND METHODS: Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1. RESULTS: According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P<0.0001). CONCLUSION: The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of XG-1 against COVID-19.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Buyang huanwu decoction (BYHWD) is a classic recipe in traditional Chinese medicine (TCM) to supplement Qi and activate blood. It has been used to recover the neural function after the injury of central nervous system for hundreds of years in China. AIM OF THE STUDY: This study investigated whether Buyang huanwu decoction (BYHWD) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation had synergistic effect on neuroprotection of red nucleus neurons after spinal cord injury (SCI). MATERIALS AND METHODS: Rubrospinal tract (RST) transection model was established and BMSCs were collected. The forelimb locomotor function was recorded using inclined plate test and spontaneous vertical exploration. cAMP level in red nucleus was detected with Enzyme-linked immunosorbent assay (ELISA). Morphology and number of red nucleus neurons was observed using Nissl's staining. Expression of cAMP-response element binding protein (CREB), ras homolog gene family member A (RhoA) and nerve growth factor (NGF) in red nucleus was detected using immunohistochemistry, qRT-PCR and Western-blotting. RESULTS: The combination of BYHWD and BMSCs transplantation could improve the forelimb locomotor function significantly and give the red nucleus somas a better protection. Meanwhile, cAMP level, CREB and NGF increased, while RhoA decreased remarkably in the BYHWD+BMSCs group. CONCLUSIONS: BYHWD combined with BMSCs transplantation had synergistic effect on neuroprotection of red nucleus neurons after SCI; the mechanism may be related to up-regulating cAMP level, activating the cAMP/CREB/RhoA signaling pathway, and promoting expression of NGF.
作者机构：
[Zhang, Mengxia] Hunan Univ Chinese Med, Dept Histol & Embryol, Changsha 410208, Hunan, Peoples R China.;[Tang, Shengsong] Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.;[Zhang, Mengxia; Liu, Qi; Mo, Zhongcheng] Univ South China, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang 421001, Hunan, Peoples R China.;[Tang, Shengsong; Lei, Xiaoyong; Tu, Jian; Li, Lijun] Univ South China, Insitute Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Ning, Jing; Tang, Shengsong] Hunan Univ Med, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.
通讯机构：
[Tang, Shengsong] H;Hunan Univ Med, Hunan Prov Key Lab Antibody Based Drug & Intellig, Huaihua 418000, Hunan, Peoples R China.
关键词：
macrophage colony-stimulating factor;breast cancer;apoptosis;HIF-1 and BINP3
摘要：
Macrophage colony-stimulating factor (M-CSF), a tumour marker, is related to tumour cell anti-apoptosis and drug resistance. However, the role of M-CSF in MCF-7 cells is unknown. In the present study, the effect and mechanism of M-CSF on hypoxia-inducible factor-1 (HIF-1)/BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/Apoptosis Regulator BAX signalling in human breast cancer MCF-7 cells were investigated. Western blotting revealed that the expression of HIF-1, BNIP3, Bax, caspase-3 and caspase-9 was lower in MCF-7-M cells compared to MCF-7 and MCF-7-C cells treated with adriamycin (ADM). Immunoprecipitation combined with western blotting was used to detect the interaction between Bcl-2 and BNIP3 or Bax protein. MCF-7-M cells had a higher amount of Bax binding to Bcl-2 compared to MCF-7 cells or MCF-7-C cells, while the amount of BNIP3 binding to Bcl-2 was decreased in MCF-7-M cells. Hoechst 33342 staining and flow cytometry were utilized to evaluate the effect of M-CSF on apoptosis in MCF-7 cells treated with ADM. Compared to ADM-treated MCF-7 cells, the apoptotic rate of MCF-7-M cells was significantly decreased. These effects were dependent on the concentration of ADM. In conclusion, cytoplasmic M-CSF suppressed apoptosis by inhibiting the HIF-1/BNIP3/Bax signalling pathway, which potentiated the dissociation of Bcl-2 from Bcl-2-BNIP3 compounds and the formation of Bcl-2-Bax compounds.
期刊：
Cellular Physiology and Biochemistry,2018年45(5):1893-1903 ISSN：1015-8987
通讯作者：
Huang, Yongpan;Yi, Minhan
作者机构：
[Zhao, Shuang; Li, Chen; Zhang, Yanyan] Guizhou Med Univ, Key Lab Optimal Utilizat Nat Med Resources, Guiyang, Guizhou, Peoples R China.;[Zhang, Yuan] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China.;[Zhang, Yuan] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA.;[Tang, Jiayu] Brain Hosp Hunan Prov, Dept Neurol, Changsha, Hunan, Peoples R China.;[Huang, Yongpan] Hunan Acad Chinese Med, Inst Chinese Med, Dept Pharmacol, Changsha, Hunan, Peoples R China.
通讯机构：
[Huang, YP; Yi, MH] C;[Huang, YP; Yi, MH] H;Cent S Univ, Informat Secur & Big Data Res Inst, Changsha, Hunan, Peoples R China.;Hunan Acad Chinese Med Changsha, Changsha, Hunan, Peoples R China.
摘要：
Myeloid differentiation factor 88 (MyD88) and Toll or interleukin-1 receptor-domain-containing adaptor-inducing interferon-beta (IFN-beta) (TRIF) are two pivotal downstream adaptors of Toll-like receptors. Activation of MyD88 or TRIF signaling in cardiac immune pathology of severe inflammation negatively influences heart function. In the present study, severe septic cardiac injury was induced in C57BL/6 mice by cecum ligation and puncture (CLP). A total of 64 mice were divided randomly into the following four groups (n=16/group; 8 for observation of survival rate, 8 for heart sample analysis): Sham, CLP, anti-MyD88-CLP and anti-TRIF-CLP. Anti-MyD88 and anti-TRIF antibodies were administered to the respective mice through the tail veins 2 h before CLP. Measurements of cardiac function, including M-modes, velocity vector imaging and cardiac troponin I, were performed. Myocardial inflammatory cytokines were examined by reverse transcription-polymerase chain reaction (RT-PCR), myocardial neutrophil infiltration was measured by a myeloperoxidase activity assay, intracellular adhesion molecule and vascular cell adhesion molecule mRNA expression levels were investigated, and histopathological characteristics were evaluated. Levels of mRNA transcripts encoding genes for apoptosis production and MyD88, TRIF, nuclear factor-kappaB and IFN regulatory factor 3 were investigated by RT-PCR. Mice challenged with CLP demonstrated deleterious cardiac function, increased levels of interleukin-1beta (IL-1beta), IL-6beta, and tumor necrosis factor-alpha mRNA, increased neutrophil infiltration, and increased apoptosis. In contrast, mice in the anti-MyD88 CLP and anti-TRIF CLP groups retained cardiac function with reduced cytokine release, decreased neutrophil infiltration, and reduced apoptosis. In addition, there was no significant difference between the anti-MyD88 CLP and anti-TRIF CLP groups. Thus, the present study indicated that MyD88 and TRIF blockades serve notable and equivalent roles in protecting cardiac deterioration from severe sepsis by attenuating cytokine release, reducing neutrophil infiltration and alleviating apoptosis.
