作者机构：
[Zeng, Fukang; Liu, Lijuan; Guo, Chun; Zhou, Desheng; Li, Zhong; Zhang, Ying; Zhang, Yuxing] Hunan Univ Chinese Med, Hosp 1, Dept Neurol, Changsha 410007, Peoples R China.;[Zeng, Fukang; Zhang, Yuxing] Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Peoples R China.;[Shao, Le; Zeng, Fukang; Yin, Qian; Zhao, Xin; Zhang, Ying; Zhang, Yuxing] Hunan Univ Chinese Med, Changsha 410006, Peoples R China.;[Shao, Le] Lab Prevent & Transformat Major Dis Internal Med T, Changsha 410007, Peoples R China.
通讯机构：
[Desheng Zhou; Lijuan Liu] D;Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Department of Neurology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
摘要：
Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.
作者机构：
[Liu, Ying-Fei; Yi, Jian; Ou-yang, Yin; Liu, Bai-Yan; Chen, Bo-Wei; Tang, Rong-Mei; Long, Hong-Ping; Tian, Feng-Ming] Hunan Univ Chinese Med, Affiliated Hosp 1, 95 Shaoshan Rd, Changsha, Peoples R China.;[Yi, Jian; Liu, Bai-Yan] Hunan Acad Chinese Med, 58 Lushan Rd, Changsha, Peoples R China.;[Liu, Ying-Fei; Yi, Jian; Ou-yang, Yin; Chen, Bo-Wei; Tang, Rong-Mei; Tian, Feng-Ming] Hunan Univ Chinese Med, 300 Xueshi Rd, Changsha, Peoples R China.;[Tang, Yan] Yiyang Med Coll, 516 Yingbin Rd, Yiyang, Peoples R China.;[Zhang, Wen-Jiang] Shaanxi Univ Chinese Med, Xixian Ave,Xixian New Area, Xianyang, Peoples R China.
通讯机构：
[Bai-Yan Liu] T;The First Affiliated Hospital, Hunan University of Chinese Medicine, 95 Shaoshan Road, Changsha, China<&wdkj&>Hunan Academy of Chinese Medicine, 58 Lushan Road, Changsha, China
摘要：
The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.
摘要：
BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. The aim of this study was to evaluate the efficacy and safety of Fufang Xueshuantong Capsules (FFXST) in combination with conventional drugs in the treatment of glaucoma using meta-analysis and trial sequential analysis (TSA). METHODS: Clinical trials of FFXST for glaucoma were identified in 8 databases until November 2022, and studies were included for meta-analysis and trial sequential analysis. RESULTS: In terms of efficacy endpoints, meta-analysis showed that the combination group of FFXST significantly improved clinical effective rate (RR 1.29, 95% CI 1.20-1.39, P < .00001), visual function (MD 0.04, 95% CI 0.04-0.05, P < .00001), light sensitivity (MD 6.07, 95% CI 4.63-7.51, P < .00001), end-systolic blood flow velocity (MD 2.68, 95% CI 2.19-3.16, P < .00001) and end-diastolic blood flow velocity (MD 2.07, 95% CI 1.86-2.28, P < .00001), and significantly reduced total gray-scale value (MD -64.38, 95% CI -69.08 to -59.68, P < .00001) and defect of visual field (MD -3.40, 95% CI -4.11 to -2.69, P < .00001) compared with the conventional regimen group, while the pulsatility index and resistance index were comparable. The TSA indicated that these benefits were conclusive. In terms of safety endpoints, meta-analysis demonstrated that total drug-related adverse events in the combination group of FFXST were comparable to those in the conventional regimen group, with TSA showing that more studies are needed to validate the current results. CONCLUSION: FFXST may be a safety and effective supplementary strategy for the treatment of glaucoma, which is worthy of further research.
摘要：
Resistin-like molecules (RELMs) are highly cysteine-rich proteins, including RELMα, RELMβ, Resistin, and RELMγ. However, RELMs exhibit significant differences in structure, distribution, and function. The expression of RELMs is regulated by various signaling molecules, such as IL-4, IL-13, and their receptors. In addition, RELMs can mediate numerous signaling pathways, including HMGB1/RAGE, IL-4/IL-4Rα, PI3K/Akt/mTOR signaling pathways, and so on. RELMs proteins are involved in wide range of physiological and pathological processes, including inflammatory response, cell proliferation, glucose metabolism, barrier defense, etc., and participate in the progression of numerous diseases such as lung diseases, intestinal diseases, cardiovascular diseases, and cancers. Meanwhile, RELMs can serve as biomarkers, risk predictors, and therapeutic targets for these diseases. An in-depth understanding of the role of RELMs may provide novel targets or strategies for the treatment and prevention of related diseases.
期刊：
Journal of Cancer Research and Clinical Oncology,2023年149(11):8593-8603 ISSN：0171-5216
通讯作者：
Li, J
作者机构：
[Nie, Duorui; Li, Jing] Hunan Univ Chinese Med, Hosp 1, Dept Oncol, Changsha 410007, Hunan, Peoples R China.;[Zheng, Hao] Guangzhou Univ Chinese Med, Clin Med Coll 1, Guangzhou, Peoples R China.;[An, Guilin] Ningxia Med Univ, Sch Tradit Chinese Med, Yinchuan, Peoples R China.
通讯机构：
[Li, J ] H;Hunan Univ Chinese Med, Hosp 1, Dept Oncol, Changsha 410007, Hunan, Peoples R China.
关键词：
Nomograms;Postoperative survival;SEER database;Signet ring cell carcinoma;Survival analysis
摘要：
BACKGROUND: Gastric signet ring cell carcinoma (GSRCC) is a highly malignant subtype of gastric cancer. We tried to establish and validate a nomogram using common clinical variables to achieve more personalized management. METHODS: We analyzed patients with GSRCC in the Surveillance, Epidemiology, and End Results database between 2004 and 2017. The survival curve was calculated by the Kaplan-Meier method, and the difference in survival curve was tested by log-rank test. We used the cox proportional hazard model to evaluate independent factors of prognosis, and established a nomogram to predict 1-, 3- and 5- overall survival (OS). Harrell's consistency index and calibration curve were used to measure the discrimination and calibration of the nomogram. In addition, we used decision curve analysis (DCA) to compare the net clinical benefits of the nomogram and American Joint Committee on Cancer (AJCC) staging system. RESULTS: The prognosis nomogram predicting 1-, 3- and 5-years OS for patients with GSRCC is established for the first time. The C-index and AUC of nomogram were higher than that of the American Joint Committee on Cancer (AJCC) staging system in the training set. Our model also shows better performance than the AJCC staging system in the validation set, and importantly, DCA shows that our model has a better net benefit than the AJCC stage. CONCLUSIONS: We have developed and validated a new nomogram and risk classification system, which is better than the AJCC staging system. It will help clinicians manage postoperative patients with GSRCC more accurately.
作者机构：
[Zeng, Qiuming; Jiang, Fei; He, Ting; Dong, Xiaohua; Cai, Haobing; Yang, Huan] Cent South Univ, Xiangya Hosp, Dept Neurol, Changsha, Peoples R China.;[Liu, Yu] Second Peoples Hosp Hunan Prov, Brain Hosp Hunan Prov, Changsha, Peoples R China.;[Li, Hongliang] Hunan Univ Chinese Med, Acupuncture & Tuina Rehabil Dept, Hosp 1, Changsha, Peoples R China.;[Ouyang, Song] South China Univ, Hosp Changsha City 1, Med Ctr Neurol, Changsha, Peoples R China.;[Yin, Weifan] Cent South Univ, Xiangya Hosp 2, Changsha, Peoples R China.
通讯机构：
[Qiuming Zeng; Huan Yang] D;Department of Neurology, Xiangya Hospital, Central South University, Changsha, China<&wdkj&>Department of Neurology, Xiangya Hospital, Central South University, Changsha, China
关键词：
Glycoprotein A repetitions predominant;Latency-associated peptide;Neuromyelitis optica spectrum disorders;Regulatory T cells;Transforming growth factor-β1
摘要：
INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a group of antibody-mediated inflammatory demyelinating central nervous system diseases. T lymphocytes participate in NMOSD pathogenesis, with regulatory T cells (Treg) being the core in maintaining immune homeostasis. Studies have revealed that different Treg subsets play different roles in autoimmune diseases. The distribution of LAP(+) or GARP(+) Treg subsets in NMOSD may help us deeply understand their immune mechanism. METHODS: This study reviewed 22 NMOSD patients and 20 normal controls. Flow cytometric analysis was utilized to detect subsets of Treg cells expressing Foxp3, Helios, LAP, or GARP in peripheral blood. ELISA was used to detect plasma TGF-β1 and IL-10. In addition, changes in the proportion of Treg cell subsets before and after glucocorticoid treatment in 10 patients were analyzed. RESULTS: Compared with healthy controls, LAP and GARP expressions were significantly downregulated in the peripheral blood of NMOSD patients. TGF-β1 expression in NMOSD patients was lower and was positively correlated with the ratio of CD4(+)GARP(+) Treg cells. After treatment with glucocorticoid, LAP and GARP expressions in the peripheral blood of NMOSD patients were upregulated. CONCLUSIONS: The proportion of Treg cells expressing LAP and GARP is downregulated, implying that Treg cells with the best inhibitory function are insufficient to maintain autoimmune homeostasis in NMOSD patients. Upregulation of Treg cells expressing LAP and GARP in NMOSD patients may be one of the mechanisms of glucocorticoid treatment.
摘要：
Nearly half of all Asian non-small cell lung cancer (NSCLC) patients harbour epidermal growth factor receptor (EGFR) mutations, and first-generation EGFR tyrosine kinase inhibitors (TKIs) are one of the first-line treatments that have improved the outcomes of these patients. Unfortunately, 20% of these patients can not benefit from the treatment. The basis of this primary resistance is poorly understood. Therefore, overcoming EGFR-TKI primary resistance and maintaining the efficacy of TKIs has become a key issue. β-Elemene, a sesquiterpene compound extracted from Curcuma aromatica Salisb. (wenyujing), has shown potent antitumor effects. In this research, we found that β-elemene combined with erlotinib enhanced the cytotoxicity of erlotinib to primary EGFR-TKI-resistant NSCLC cells with EGFR mutations and that ferroptosis was involved in the antitumor effect of the combination treatment. We found that lncRNA H19 was significantly downregulated in primary EGFR-TKI-resistant NSCLC cell lines and was upregulated by the combination treatment. Overexpression or knockdown of H19 conferred sensitivity or resistance to erlotinib, respectively, in both in vitro and in vivo studies. The high level of H19 enhanced the cytotoxicity of erlotinib by inducing ferroptosis. In conclusion, our data showed that β-elemene combined with erlotinib could enhance sensitivity to EGFR-TKIs through induction of ferroptosis via H19 in primary EGFR-TKI-resistant lung cancer, providing a promising strategy to overcome EGFR-TKI resistance in NSCLC patients.
摘要：
Lipid metabolism disorders are pivotal in the development of various lipid-related diseases, such as obesity, atherosclerosis, non-alcoholic fatty liver disease, type 2 diabetes, and cancer. Celastrol, a bioactive compound extracted from the Chinese herb Tripterygium wilfordii Hook F, has recently demonstrated potent lipid-regulating abilities and promising therapeutic effects for lipid-related diseases. There is substantial evidence indicating that celastrol can ameliorate lipid metabolism disorders by regulating lipid profiles and related metabolic processes, including lipid synthesis, catabolism, absorption, transport, and peroxidation. Even wild-type mice show augmented lipid metabolism after treatment with celastrol. This review aims to provide an overview of recent advancements in the lipid-regulating properties of celastrol, as well as to elucidate its underlying molecular mechanisms. Besides, potential strategies for targeted drug delivery and combination therapy are proposed to enhance the lipid-regulating effects of celastrol and avoid the limitations of its clinical application.
摘要：
BACKGROUND: The association between S100 calcium-binding protein A8 (S100A8) and angiogenesis has been reported in previous reports. This study focuses on the roles of S100A8 in the angiogenesis of human dermal microvascular endothelial cells (HDMECs) and in cutaneous wound healing in mice. METHODS: Candidate genes related to angiogenesis activity were screened using a GSE83582 dataset. The overexpression DNA plasmid of S100A8 was transfected into HDMECs to analyze its effect on cell proliferation, migration, and angiogenesis. Full-thickness skin wounds were induced on mice, followed by adenovirus treatments to analyze the function of gene alteration in wound healing and pathological changes. The upstream regulator of S100A8 was predicted by bioinformatics analysis and verified by luciferase and immunoprecipitation assays. The role of the forkhead box A1 (FOXA1)-S100A8 interaction in p38 MAPK activation and angiogenesis were validated by rescue experiments. RESULTS: S100A8 was identified as a gene significantly correlated with angiogenesis. The S100A8 upregulation promoted the proliferation, migration, and angiogenesis of HDMECs, and it promoted p38 MAPK phosphorylation. Treatment of SB203580, a p38 MAPK inhibitor, blocked the promoting effect of S100A8. FOXA1 was identified as an upstream factor of S100A8 promoting its transcription. FOXA1 overexpression in HDMECs increased p38 MAPK phosphorylation and enhanced the activity of cells, which were blocked by the S100A8 inhibition. Similar results were reproduced in vivo where FOXA1 overexpression accelerated whereas the S100A8 knockdown retarded the cutaneous wound healing in mice. CONCLUSION: FOXA1 mediates the phosphorylation of p38 MAPK through transcription activation of S100A8, thereby inducing angiogenesis and promoting cutaneous wound healing.
摘要：
To explore the mechanism of psoralen synergized with exosomes (exos)-loaded SPC25 on nucleus pulposus (NP) cell senescence in intervertebral disc degeneration (IVDD). IVDD cellular models were established on NP cells by tert-butyl hydroperoxide (TBHP) induction, followed by the treatment of psoralen or/and exos from adipose-derived stem cells (ADSCs) transfected with SPC25 overexpression vector (ADSCs-oe-SPC25-Exos). The viability, cell cycle, apoptosis, and senescence of NP cells were examined, accompanied by the expression measurement of aggrecan, COL2A1, Bcl-2, Bax, CDK2, p16, and p21. After TBHP-induced NP cells were treated with psoralen or ADSCs-oe-SPC25-Exos, cell proliferation and the expression of aggrecan, COL2A1, Bcl-2, and CDK2 were promoted; however, the expression of Bax, p16, p21, and inflammatory factors was decreased, and cell senescence, cycle arrest, and apoptosis were inhibited. Of note, psoralen combined with ADSCs-oe-SPC25-Exos further decelerated NP cell senescence and cycle arrest compared to psoralen or ADSCs-oe-SPC25-Exos alone. Combined treatment of psoralen and ADSCs-oe-SPC25-Exos exerted an alleviating effect on NP cell senescence, which may provide an insightful idea for IVDD treatment.
期刊：
Molecular and Cellular Biochemistry,2023年478(2):241-247 ISSN：0300-8177
通讯作者：
Youliang Zhou
作者机构：
[Zhou, Quan; Zhou, Youliang] Hunan Univ Chinese MedicineYuhua Dist Hunan Prov, Dept Emergency, Hosp 1, 95 Shaoshan Middle Rd, Changsha 410000, Peoples R China.;[Cai, Xu] Hunan Univ Chinese Med, Dept Orthopaed, Hosp 1, Changsha 410000, Hunan, Peoples R China.;[Huang, Ying] Shenzhen Sami Int Med Ctr, Dept Neurosurg, Shenzhen 518038, Guangdong, Peoples R China.
通讯机构：
[Youliang Zhou] D;Department of Emergency, The First Hospital of Hunan University of Chinese MedicineYuhua DistrictHunan Province, No. 95, Shaoshan Middle Road, Changsha, China
摘要：
Curcumin (CUR) is an extract of Curcuma longa Linn., which has various pharmacological activities. The instability, low water solubility and bioavailability of CUR greatly limit its clinical application. This work prepared Pluronic F127-liposome-encapsulated curcumin (CUR-LIP-F127) and explored its functional role in wound healing. Liposome-encapsulated curcumin (CUR-LIP) and CUR-LIP-F127 were prepared. Human keratinocyte cell line (HaCaT) was treated with CUR, Pluronic F127-liposome (LIP-F127) and CUR-LIP-F127, or combined with ML385 (Nrf2 inhibitor). The expression of mRNAs and proteins was detected by quantitative real-time PCR and western blotting. MTT and wound healing assays were performed to detect cell viability and migration. CUR, LIP-F127 and CUR-LIP-F127 all had no influence on cell viability of HaCaT cells. CUR-LIP-F127 treatment significantly accelerated cell migration and enhanced the expression of nuclear factor erythroid-related factor 2 (Nrf2) and kelch-like erythroid cell-derived protein 1 (Keap1) in HaCaT cells with respect to CUR or LIP-F127 treatment. ML385 treatment impaired CUR-LIP-F127-mediated promotion of migration and up-regulation of Nrf2 and Keap1 in HaCaT cells. This work demonstrated that CUR-LIP-F127 activated Nrf2/Keap1 signaling pathway to promote migration of HaCaT cells, suggesting that CUR-LIP-F127 may contribute to wound healing.
作者机构：
[Mi, Yilin; Gong, Zhixian; Kuang, Gaoyan; Xu, Xiaotong; Yan, Ke; Zeng, Fan; Li, Naping; Lu, Min; Yi, Nanxing] Hunan Univ Chinese Med, Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Mi, Yilin; Xu, Xiaotong; Zeng, Fan; Yi, Nanxing] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Tan, Xuyi] Hunan Acad Chinese Med Sci, Affiliated Hosp, Changsha 410006, Hunan, Peoples R China.
通讯机构：
[Gaoyan Kuang; Min Lu] T;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China
摘要：
Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degeneration, subchondral bone sclerosis, synovial hyperplasia and inflammation as the main pathological manifestations. This study aims to investigate the protective effect of prebiotics in post-traumatic osteoarthritic (PTOA) mice by modulating the gut barrier and fecal metabolomics. The results suggested that cartilage degeneration, osteophyte formation and inflammation were significantly reduced by prebiotics in PTOA mice. In addition, the gut barrier was protected by the increased expression of tight junction proteins ZO-1 and occludin in the colon. High-throughput sequencing found that 220 fecal metabolites were affected by joint trauma, 81 of which were significantly recovered after probiotic intervention, and some metabolites (valerylcarnitine, adrenic acid, oxoglutaric acid, etc.) were closely associated with PTOA. Our study demonstrates that prebiotics can delay the progression of PTOA by regulating the metabolites of the gut microbiota and protecting the gut barrier, which is expected to be an intervention method for PTOA.
摘要：
OBJECTIVES: The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. METHODS: AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. RESULTS: AIAM usually occurred 3h to 7days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1-4days after drug discontinuation in all patients. CONCLUSION: Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.
作者机构：
[Tang, Yan-Ran; Choudhary, M. Iqbal; Wang, Wei; Ali, Sajjad; Peng, Cai-Yun; Yi, Pan; Peng, CY; Zhou, Fang; Rahman, Atta-ur; Zafar, Salman; Li, Bin; Sheng, Wen-Bing; Mao, Yu] Hunan Univ Chinese Med, Acad Attaur Rahman Belt & Rd Tradit Med Res Ctr, Sch Pharm, ATCM & Ethnomedicine Innovat Dev Int Lab, Changsha, Peoples R China.;[Tang, Yan-Ran; Yi, Pan] Hunan Food & Drug Vocat Coll, Coll Tradit Chinese Med, Changsha, Peoples R China.;[Zafar, Salman] Univ Peshawar, Inst Chem Sci, Peshawar, Pakistan.;[Ali, Sajjad] Karakoram Int Univ, Dept Chem, Gilgit, Pakistan.;[Zhou, Fang; Chen, Wen-Ming] Hunan Univ Chinese Med, Hosp 1, Changsha, Peoples R China.
通讯机构：
[Peng, CY; Wang, W] H;Hunan Univ Chinese Med, Acad Attaur Rahman Belt & Rd Tradit Med Res Ctr, Sch Pharm, ATCM & Ethnomedicine Innovat Dev Int Lab, Changsha, Peoples R China.
摘要：
Three new constituents: 1,5R-dihydroxy-3,8S-dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3S,4R,16S,17R)-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3-O-beta-D-glucopyranoside (2), and new natural product (S)-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea. Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7, 9 and 14 showed antioxidant activities with IC50 values of 68.9, 50.8 and 48.2 mu M, respectively. [GRAPHICS]
作者机构：
[Luo, Jiamin; Hu, Leihao] Guangzhou Univ Chinese Med, Sch Clin Med 1, Guangzhou 510006, Guangdong, Peoples R China.;[Wang, Lisheng; Wen, Guiqing] Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 510006, Guangdong, Peoples R China.;[Lin, Lizhu; Sun, Lingling; Lin, LZ; Hu, Hao; Hu, Leihao] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Oncol Ctr, Guangzhou 510402, Guangdong, Peoples R China.;[Liu, Wei] Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Guangzhou 510006, Guangdong, Peoples R China.;[Li, Jing] Hunan Univ Chinese Med, Affiliated Hosp 1, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Wang, LS ; Lin, LZ ] G;[Su, WW ] S;Guangzhou Univ Chinese Med, Sch Chinese Mat Med, Guangzhou 510006, Guangdong, Peoples R China.;Guangzhou Univ Chinese Med, Affiliated Hosp 1, Oncol Ctr, Guangzhou 510402, Guangdong, Peoples R China.;Sun Yat Sen Univ, Guangdong Engn & Technol Res Ctr Qual & Efficacy R, Sch Life Sci, Guangdong Prov Key Lab Plant Resources, Guangzhou 510275, Guangdong, Peoples R China.
关键词：
Cell extraction;Network pharmacology;UPLC-MS/MS;Yi-Fei-San-Jie formula
摘要：
BACKGROUND: Chinese herbal formulae has multiple active constituents and targets, and the good clinical response is encouraging more scientists to explore the bio-active ingredients in such complex systems. Yi-Fei-San-Jie formula (YFSJF) is commonly used to treat patients with lung cancer in South China; however, its bio-active ingredients remain unknown. PURPOSE: We investigated the bio-active ingredients of the YFSJF using a novel comprehensive strategy. METHODS: A549 cell extraction coupled with ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was used for the screening of potential bio-active ingredients. Network pharmacology approach and molecular dynamics simulation were performed for the screening of targets. Surface plasmon resonance (SPR) assay and molecular biology techniques were used to verify the targets. RESULTS: Nine A549 cell membrane-binding compounds were identified through cell extraction/UPLC-MS/MS. Five compounds, namely ginsenoside Ro, ginsenoside Rb1, ginsenoside Rc, peimisine, and peimine were cytotoxic to A549 cells, and they were considered the bio-active ingredients of the YFSJF in vitro. Network pharmacology analysis revealed that TGFBR2 is the key target and the TGFβ pathway is the key pathway targeted by YFSJF in non-small cell lung cancer. Peimisine showed an affinity to TGFBR2 using molecular docking and dynamic stimulation, which was confirmed using surface plasmon resonance spectroscopy. The molecular biology-based analysis further confirmed that peimisine targets TGFBR2 and can reverse A549 epithelial-mesenchymal transition by inhibiting the TGFβ pathway. CONCLUSION: Taken together, cell extraction/UPLC-MS/MS, network pharmacology, and molecular biology-based analysis comprise a feasible strategy to explore active ingredients in YFSJF.
期刊：
Pain Research and Management,2023年2023:7711988 ISSN：1203-6765
通讯作者：
Ren, WQ;Long, HP
作者机构：
[Chen, Lei; Zhao, Hongxia; Zeng, Shuiqing; Ren, Weiqiong; Liu, Yeqian; Chen, Chunming; Gong, Shan] Hunan Univ Chinese Med, Dept Pharm, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.;[Li, Hong] Second Peoples Hosp Anhui Prov, Dept Pharm, 1868 Dangshan Rd, Hefei, Anhui, Peoples R China.;[Long, Hongping; Long, HP; Liu, Jian] Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.;[Ma, Danfeng] Childrens Hosp Hunan Prov, Dept Pharm, 86 Ziyuan Rd, Changsha, Hunan, Peoples R China.
通讯机构：
[Ren, WQ ; Long, HP ] H;Hunan Univ Chinese Med, Dept Pharm, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Ctr Med Res & Innovat, Hosp 1, 95 Shaoshan Middle Rd, Changsha, Hunan, Peoples R China.
关键词：
Introduction;Materials and Methods;Results;Discussion;Conclusion;Abstract;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interests;Authors’ Contributions;Funding Statement;Acknowledgements;Acknowledgments;Supplementary Materials;Reference;Dataset Description;Dataset Files;Abstract;Introduction;Introduction and Materials;Introduction and Methods;Materials;Materials and Methods;Methods;Results;Discussion;Results and Discussion;Discussion and Conclusion;Results and Conclusion;Conclusion;Conclusions;Data Availability;Additional Points;Ethical Approval;Consent;Disclosure;Conflicts of Interest;Authors’ Contributions;Funding Statement;Acknowledgements;Supplementary Materials;References;Appendix;Abbreviations;Preliminaries;Introduction and Preliminaries;Notation;Proof of Theorem;Proofs;Analysis of Results;Examples;Numerical Example;Applications;Numerical Simulation;Model;Model Formulation;Systematic Palaeontology;Nomenclatural Acts;Taxonomic Implications;Experimental;Synthesis;Overview;Characterization;Background;Experimental;Theories;Calculations;Model Verification;Model Implementation;Geographic location;Study Area;Geological setting;Data Collection;Field Testing;Data and Sampling;Dataset;Literature Review;Related Works;Related Work;System Model;Methods and Data;Experimental Results;Results and Analysis;Evaluation;Implementation;Case Presentation;Case Report;Search Terms;Case Description;Case Series;Background;Limitations;Additional Points;Case;Case 1;Case 2 etc.;Concern Details;Retraction Details;Copyright;Related Articles
摘要：
OBJECTIVES: Evodia rutaecarpa (ER) is a well-known herbal Chinese medicine traditionally used for analgesia in dysmenorrhea, headaches, abdominal pain, etc. Notably, the analgesic effect of wine-processed Evodia rutaecarpa (PER) was more potent than that of raw ER. This research aimed to investigate the mechanism and pharmacodynamic substance basis of raw ER and PER on smooth muscle cells of dysmenorrhea mice. METHODS: Metabolomics methods based on UPLC-Q-TOF-MS were utilized to analyse the differential components of ER before and after wine processing. Afterwards, the uterine smooth muscle cells were isolated from the uterine tissue of dysmenorrhea and normal mice. The isolated dysmenorrhea uterine smooth muscle cells were randomly divided into four groups: model group, 7-hydroxycoumarin group (1 mmol/L), chlorogenic acid (1 mmol/L), and limonin (50 μmol/L). The normal group consisted of the isolated normal mouse uterine smooth muscle cells, which were repeated 3 times in each group. The cell contraction and the expression of P2X3 and Ca(2+) in vitro were determined using immunofluorescence staining and laser confocal; ELISA was used for detection of PGE2, ET-1, and NO content after 7-hydroxycoumarin, chlorogenic acid, and limonin administered for 24 h. RESULTS: The metabolomics results suggested that seven differential compounds were identified in the extracts of raw ER and PER, including chlorogenic acid, 7-hydroxycoumarin, hydroxy evodiamine, laudanosine, evollionines A, limonin, and 1-methyl-2-[(z)-4-nonenyl]-4 (1H)-quinolone. The in vitro results showed that 7-hydroxycoumarin, chlorogenic acid, and limonin were able to inhibit cell contraction and PGE2, ET-1, P2X3, and Ca(2+) in dysmenorrhea mouse uterine smooth muscle cells and increase the content of NO. CONCLUSION: Our finding suggested that the compounds of the PER were different from those of the raw ER, and 7-hydroxycoumarin, chlorogenic acid, and limonin could improve dysmenorrhea in mice whose uterine smooth muscle cell contraction was closed with endocrine factors and P2X3-Ca(2+) pathway.
摘要：
Respiratory diseases are an emerging public health concern, that pose a risk to the global community. There, it is essential to establish effective treatments to reduce the global burden of respiratory diseases. Astragaloside IV (AS-IV) is a natural saponin isolated from Radix astragali (Huangqi in Chinese) used for thousands of years in Chinese medicine. This compound has become increasingly popular due to its potential anti-inflammatory, antioxidant, and anticancer properties. In the last decade, accumulated evidence has indicated the AS-IV protective effect against respiratory diseases. This article presents a current understanding of AS-IV roles and mechanisms in combatting respiratory diseases. The ability of the agent to suppress oxidative stress, cell proliferation, and epithelial-mesenchymal transition (EMT), to attenuate inflammatory responses, and modulate programmed cell death (PCD) will be discussed. This review highlights the current challenges in respiratory diseases and recommendations to improve disease management.
摘要：
Ethnopharmacological relevance: Intracerebral hemorrhage (ICH) is a central nervous system disease that causes severe disability or death. Even though Annao Pingchong decoction (ANPCD), a traditional Chinese decoction, has been used clinically to treat ICH in China, its molecular mechanism remains unclear. Aim of the study: To study whether the neuroprotective effect of ANPCD on ICH rats is achieved by alleviating neuroinflammation. This paper mainly explored whether inflammation-related signaling pathways (HMGB1/ TLR4/NF-kappa B P65) plays a role in ANPCD treatment of ICH rats.Materials and methods: Liquid chromatography-tandem mass spectrometry was used to analyze the chemical composition of ANPCD. ICH models were established by injecting autologous whole blood into the left caudate nucleus of Sprague-Dawley (SD) rats. Modified neurological severity scoring (mNSS) was used to assess the neurological deficits. The levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 were analyzed using enzyme-linked immunosorbent assay (ELISA). Pathological changes in the rat brains were observed using hematoxylin-eosin, Nissl, and TUNEL staining. The protein levels of HMGB1, TLR4, NF-kappa B p65, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were measured by western blotting and immunofluorescence analysis.Results: Ninety-three ANPCD compounds were identified, including 48 active plasma components. Treatment with ANPCD effectively improved the outcome, as observed by the neurological function scores analysis and brain histopathology. Our results showed that ANPCD exerts its anti-inflammatory effects by significantly downregulating the expression of HMGB1, TLR4, NF-kappa B p65, TNF-alpha, IL-1 beta, and IL-6. ANPCD also exerted anti-apoptotic effects by significantly decreasing the apoptosis rate and Bax/Bcl-2 ratio. Conclusion: We found that ANPCD had neuroprotective effect in clinical work. Here, we also found that the action mechanism of ANPCD might be related to attenuate neuroinflammation and apoptosis. These effects were achieved by inhibiting the expression of HMGB1, TLR4 and NF-kappa B p65.
作者机构：
[方闯; 匡泓俊; 曹洋; 夏叶婉] Postgraduate School of Hunan University of Chinese Medicine, Changsha 410208, China;[钟峰; 章薇; 罗容] Department of Acupuncture and Tuina Rehabilitation, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha 410007;[文钱] Department of Traditional Chinese Medicine, Huaihua Hospital of Traditional Chinese Medicine, Huaihua 418099, Hunan Province
摘要：
Acute lung injury (ALI) is a spectrum of acute and life-threatening pulmonary inflammatory conditions. Treatment of ALI remains a clinical challenge. Recently, intermittent fasting (IF) has been shown to improve health and alleviate many diseases. In this study, we tested whether IF attenuated ALI and investigated the mechanism underlying this process. In vivo , the effects of IF on ALI were evaluated in a lipopolysaccharide (LPS)-induced murine ALI model. We found that two times of 24-h fasting in a week before ALI efficiently ameliorated LPS-induced lung injury in mice, characterized by alleviated lung lesions, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde content, and lower levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta. In vitro, functional assays were conducted to assess IF on the inflammatory response and macrophage polarization of bone marrow-derived macrophages (BMDMs) treated with LPS or IL-4. And PPAR gamma antagonist GW9662 and AMPK siRNA were used to test the role of PPAR gamma and AMPK in the IF-mediated improvement of ALI. The results showed that IF (serum deprivation) suppressed macrophage M1 activation and promoted M2 activation in LPS-treated BMDMs. While, IF also augmented macrophage M2 polarization in IL-4-treated BMDMs. Further mechanistic studies showed that the promotive effect of IF on M2 polarization was related to the activation of the PPAR gamma and AMPK pathways. In conclusion, this study suggests that IF enhances M2 polarization by activating the AMPK and PPAR gamma pathways, thus facilitating anti-inflammatory response and ameliorating ALI. (c) 2022 Elsevier Inc. All rights reserved.
