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：
[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[He, Chunxiang; Li, Ze; Song, Zhenyan; Cheng, Shaowu; Song, ZY; Zhong, Dayuan; Yu, Jingping; Cheng, SW; Yang, Miao; Yu, Wenjing; Deng, Sisi] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Yu, Jingping] Baoshan Coll Tradit Chinese Med, Baoshan 678000, Yunnan, Peoples R China.;[Zhong, Dayuan] Guangdong Prov Hosp Integrated Tradit Chinese & We, Foshan 528000, Guangdong, Peoples R China.
通讯机构：
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.
关键词：
Alzheimer’s disease;RAGE;TLR4/NF-κB signaling pathway;neuroinflammation;traditional Chinese medicine
摘要：
The purpose of this study is to investigate the therapeutic effect of Qi Fu Yin (QFY) on Alzheimer's disease (AD) both computationally and experimentally. Network pharmacology analysis and molecular docking were conducted to identify potential targets and signaling pathways involved in QFY treating AD. Streptozotocin-induced AD rat model was used to verify important targets and predicted pathways. The components of QFY were identified using liquid chromatography-tandem mass spectrometry. The results indicate that the potential targets of QFY are highly enriched for anti-inflammatory pathways. Molecular docking analysis revealed stable structures formed between QFY's active compounds, including stigmasterol, β-sitosterol, and isorhamnetin, and the identified targets. In vivo, QFY improved cognitive memory in AD rats and reduced the mRNA expression levels of toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (AGER), and the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brains of AD rats. Furthermore, QFY effectively reduced nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited NF-κB and microglia activation. In conclusion, QFY can ameliorate neuroinflammation in AD model rats, partly via the inhibition of TLR4 and RAGE/NF-κB pathway and microglia activation, thereby enhancing learning and memory in AD model rats.
作者机构：
[Ma, Xinwei; Meng, Mingfang; Xie, Xi] Heilongjiang Univ Tradit Chinese Med, Clin Med Coll 1, Harbin, Peoples R China.;[Gao, X; Lou, Hongjun; Gao, Xi] Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 1, Harbin 150040, Heilongjiang, Peoples R China.;[Shi, Ye; Gan, Guang] Hunan Univ Tradit Chinese Med, Coll Integrated Chinese & Western Med, Changsha, Peoples R China.;[Deng, Hanqing] Hunan Univ Tradit Chinese Med, Clin Med Coll 1, Changsha, Peoples R China.
通讯机构：
[Gao, X ] H;Heilongjiang Univ Tradit Chinese Med, Affiliated Hosp 1, Harbin 150040, Heilongjiang, Peoples R China.
关键词：
chronic kidney disease;Liuwei Dihuanng pill;mechanism of action;molecular docking;network pharmacology
摘要：
BACKGROUND: Chronic kidney disease (CKD) is a progressive disease that poses a huge economic burden to society. Liuwei Dihuanng pill is an effective treatment for chronic kidney disease, but its treatment mechanism is unclear. The rapid development of network pharmacology has provided new strategies for studying Chinese medicine. METHOD: The traditional Chinese medicine systems pharmacology database and analysis platform was used to obtain the bioactive components and targets of Liuwei Dihuanng pill. The sources for the CKD-related targets were then obtained from the Genecards, OMIM, TTD, and DisGeNET databases. R was used to identify the intersecting genes for Liuwei Dihuang pill and CKD-related targets. Analysis of protein-protein interactions (PPI) was performed using STRING, and PPI networks and drug-component-target networks were constructed using Cytoscape software. Kyoto encyclopedia of genes and genomes pathway and gene ontology enrichment analyses were performed using R. Finally, molecular docking was performed to determine the binding activity between bioactive components and the targets. RESULT: After screening and data de-duplication of 74 active components, 209 drug targets, and 14,794 disease targets, a total of 204 drug-disease targets were acquired. Subsequently, a drug-component-target network and PPI network were established. The primary components of Liuwei Dihuang pill included quercetin, stigmasterol, kaempferol, beta-sitosterol, tetrahydroalstonine, kadsurenone, hederagenin, hancinone C, diosgenin, and sitosterol. In addition, JUN, AKT1, TP53, RELA, MAPK1, FOS, TNF, IL6, ESR1, and RXRA were identified as the main targets. Gene ontology function enrichment analysis revealed that these targets were involved in reactive oxygen species metabolic processes, responses to metal ions and to chemical stimuli, G protein-coupled amine receptor activity, and nuclear factor receptor activity. Kyoto encyclopedia of genes and genomes enrichment analysis showed that these targets were involved in the AGE-RAGE signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. Molecular docking results indicated good binding activity between the core targets and core components. CONCLUSION: The potential mechanism of Liuwei Dihuanng pill in the treatment of CKD was preliminarily discussed in this study, providing a theoretical basis and evidence for further experimental research.
摘要：
BACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work. OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH. METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25mg/kg, 50mg/kg, and 100mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri‑hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits. RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage. CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.
摘要：
Background: Evidence indicates that chronic stress promotes progression of colorectal liver me-tastases (CLM). Mangiferin is the active chemical constituent of the rhizomes of Anemarrhena asphodeloides Bunge. Mangiferin (MGF) exerts anti-inflammatory, anti-proliferative, anti-angiogenic, anti-fibrotic and antioxidant effects in a variety of cancers. Its mechanism in chronic stress and tumor growth is still poorly understood. Methods: To investigate the effects of MGF on the CLM and tumor-associated depression, activated hepatic stellate cells (a-HSCs), HT-29 CRC cells, were used in chronic unpredictable mild stress (CUMS) of tumor-bearing models. Potential antidepressant activity was determined by FST, TST, SIT and serum cytokine (IL-6, IL-18 and TNF-alpha) examination. Downstream signaling molecules were detected by Western blot, immunohistochemistry and fluorescence microscopy. Results: CUMS induced depression behavior and depression-related cytokines and promoted tumor growth in CLM. MGF-treated mice significantly improved chronic stress behaviors by reducing depression-related cytokines. In addition, MGF treatment inhibits WAVE2 signaling pathway, leading to TGF-beta 1 induced HSC inhibition, thereby reducing depressive behavior and tumor growth in CLM. Conclusion: MGF can alleviate CUMS induced tumor growth and the treatment of CLM patients with MGF may be beneficial.
作者机构：
[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Song, ZY; Luo, Rongsiqing; He, Chunxiang; He, Jiawei; Xia, Xiaofang; Lin, Fan; Hou, Mirong; Cheng, SW; Pan, Ying] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan; Cheng, Shaowu; Wang, Yuke; Li, Ping; Song, ZY; Luo, Rongsiqing; He, Chunxiang; He, Jiawei; Cheng, SW] Hunan Univ Chinese Med, Coll integrated Chinese & western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Song, Zhenyan; Song, ZY] Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.;[He, Pan] Res Inst Zhong Nan Grain & Oil Foods, Changsha 410208, Hunan, Peoples R China.
通讯机构：
[Song, ZY ; Cheng, SW] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Coll integrated Chinese & western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;Natl Key Lab Cultivat Base Chinese Med Powder & In, Changsha 410208, Hunan, Peoples R China.
摘要：
The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.
作者机构：
[Lu, Baowei; Li, Bonan; Sheng, Wen; Wang, Neng; Liu, Lumei; Ding, Jin; He, Qinghu; Zhong, Zixuan] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;[Ding, Jin] Guangzhou Univ Tradit Chinese Med, Affiliated Baoan Hosp Tradit Chinese Med, Clin Med Coll 7, Dept Androl Clin, Shenzhen, Peoples R China.;[Lu, Baowei; Li, Bonan; Sheng, Wen; Wang, Neng; Liu, Lumei; Ding, Jin; He, Qinghu; Zhong, Zixuan] Hunan Univ Chinese Med, Androl Lab, Changsha, Peoples R China.;[He, Qinghu] Hunan Univ Med, Huaihua, Peoples R China.
通讯机构：
[Wen Sheng; Qinghu He] C;College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Andrology Laboratory, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>Hunan University of Medicine, Huaihua, China
摘要：
Context Guilu-Erxian-Glue (GLEXG) is a traditional Chinese formula used to improve male reproductive dysfunction. Objective To investigate the ferroptosis resistance of GLEXG in the improvement of semen quality in the oligoasthenospermia (OAS) rat model. Materials and methods Male Sprague-Dawley (SD) rats were administered Tripterygium wilfordii polyglycoside, a compound extracted from Tripterygium wilfordii Hook F. (Celastraceae), at a dose of 40 mg/kg/day, to establish an OAS model. Fifty-four SD rats were randomly divided into six groups: sham, model, low-dose GLEXG (GLEXGL, 0.25 g/kg/day), moderate-dose GLEXG (GLEXGM, 0.50 g/kg/day), high-dose GLEXG (GLEXGH, 1.00 g/kg/day) and vitamin E (0.01 g/kg/day) group. The semen quality, structure and function of sperm mitochondria, histopathology, levels of oxidative stress and iron, and mRNA levels and protein expression in the Keap1/Nrf2/GPX4 pathway, were analyzed. Results Compared with the model group, GLEXGH significantly improved sperm concentration (35.73 +/- 15.42 vs. 17.40 +/- 4.12, p < 0.05) and motility (58.59 +/- 11.06 vs. 28.59 +/- 9.42, p < 0.001), and mitigated testicular histopathology. Moreover, GLEXGH markedly reduced the ROS level (5684.28 +/- 1345.47 vs. 15500.44 +/- 2307.39, p < 0.001) and increased the GPX4 level (48.53 +/- 10.78 vs. 23.14 +/- 11.04, p < 0.01), decreased the ferrous iron level (36.31 +/- 3.66 vs. 48.64 +/- 7.74, p < 0.05), and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway. Discussion and conclusions Ferroptosis resistance from GLEXG might be driven by activation of the Keap1/Nrf2/GPX4 pathway. Targeting ferroptosis is a novel approach for OAS therapy.
期刊：
Frontiers in Medicine,2023年9:1042015 ISSN：2296-858X
作者机构：
[Gong, Yuanxun; Tang, Qianli] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Gong, Yuanxun; Tang, Qianli] Youjiang Med Univ Nationalities, Affiliated Hosp, Baise, Peoples R China.;[Jiang, Yan] Youjiang Med Univ Nationalities, West Guangxi Key Lab Prevent & Treatment High Inci, Baise, Peoples R China.;[Huang, Jinmei] Guangxi Univ Chinese Med, Grad Sch, Nanning, Peoples R China.;[He, Zuofen] YouJiang Med Univ Nationalities, Grad Sch, Baise, Peoples R China.
摘要：
BackgroundThe incidence of diabetes-related wounds is widespread, and the treatment is challenging. We found that Moist Exposed Burn Ointment (MEBO) promotes the healing of diabetes-related wounds, but the mechanism is not clear. MethodsThis study aimed to explore the mechanism of MEBO on diabetic wound healing, which may be related to the promotion of re-epithelialization. A full-thickness skin resection model was established in streptozotocin (STZ)-induced diabetic mice. MEBO and Kangfuxin (KFX) were applied to the wound area, and the wound healing rate was analyzed by photographing. The granulation tissue and epidermal thickness, the collagen remodeling rate, and the expression of cytokeratin 10 (CK10), cytokeratin 14 (CK14), Ki67, Collagen I, and Collagen III in the regenerated skin were detected by H&E staining, Masson staining, and immunofluorescence staining, respectively. MEBO and KFX were applied to human immortalized keratinocytes (HaCaT), mouse dermal fibrolasts (MDF) cells, and cell viability, cell migration, and differentiation were determined by CCK-8, scratching assay, RT-qPCR, and Western blot (WB), respectively. ResultsWe found that MEBO significantly promoted the formation of wound granulation tissue and collagen remodeling in diabetic mice. The application of MEBO to diabetic wounds not only promoted the formation of hair follicles and sebaceous glands but also promoted the expression of Ki67, CK10, and CK14 in epidermal cells. MEBO had no significant effect on the differentiation process of keratinocytes. ConclusionOur study further proved that MEBO plays a positive role in diabetic wound healing, and its excellent ability to promote re-epithelialization may be an important reason for promoting wound healing.
摘要：
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.
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.
摘要：
Purpose This study aimed to investigate the association between macronutrient intake and biological age.Methods Data were collected from 26,381 adults who participated in the United States National Health and Nutrition Examination Survey (NHANES). Two biological ages were estimated using the Klemera-Doubal method (KDM) and PhenoAge algorithms. Biological age acceleration (AA) was computed as the difference between biological age and chronological age. The associations between macronutrient intakes and AA were investigated.Results After fully adjusting for confounding factors, negative associations were observed between AA and fiber intake (KDM-AA: beta - 0.53, 95% CI - 0.62, - 0.43, P < 0.05; PhenoAge acceleration: beta - 0.30, 95% CI - 0.35, - 0.25, P < 0.05). High-quality carbohydrate intake was associated with decreased AA (KDM-AA: beta - 0.57, 95% CI - 0.67, - 0.47, P < 0.05; PhenoAge acceleration: beta - 0.32, 95% CI - 0.37, - 0.26, P < 0.05), while low-quality carbohydrate was associated with increased AA (KDM-AA: beta 0.30, 95% CI 0.21, 0.38, P < 0.05; PhenoAge acceleration: beta 0.16, 95% CI 0.11, 0.21, P < 0.05). Plant protein was associated with decreased AA (KDM-AA: beta - 0.39, 95% CI - 0.51, - 0.27, P < 0.05; PhenoAge acceleration: beta - 0.21, 95% CI - 0.26, - 0.15, P < 0.05). Long-chain SFA intake increased AA (KDM-AA: beta 0.16, 95% CI 0.08, 0.24, P < 0.05; PhenoAge acceleration: beta 0.11, 95% CI 0.07, 0.15, P < 0.05). omega-3 PUFA was associated with decreased KDM-AA (beta - 0.18, 95% CI - 0.27, - 0.08, P < 0.05) and PhenoAge acceleration (beta - 0.09, 95% CI - 0.13, - 0.04, P < 0.05).Conclusion Our findings suggest that dietary fiber, high-quality carbohydrate, plant protein, and omega-3 PUFA intake may have a protective effect against AA, while low-quality carbohydrate and long-chain SFA intake may increase AA. Therefore, dietary interventions aimed at modifying macronutrient intakes may be useful in preventing or delaying age-related disease and improving overall health.
期刊：
Naunyn-Schmiedeberg's Archives of Pharmacology,2023年396(6):1187-1203 ISSN：0028-1298
通讯作者：
Dan Zhou<&wdkj&>Wei Zhang
作者机构：
[Li, Junxi; Ding, Huang; Zhou, Dan; Zhang, Wei; Liu, Jingze; Yan, Fanchen] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410208, Hunan, Peoples R China.;[Sun, Zhengji] Hunan Univ Chinese Med, Yueyang Tradit Chinese Med Hosp, Changsha 414021, Hunan, Peoples R China.
通讯机构：
[Dan Zhou; Wei Zhang] T;The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China<&wdkj&>The Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine On Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
摘要：
Buyang Huanwu decoction (BYHWD) is a classical traditional prescription. Glycosides are effective extracts of BYHWD, which have been proven to protect blood vessels and prevent atherosclerosis (AS). However, the mechanism of glycosides in inhibiting abnormal angiogenesis in atherosclerosis is still unclear. The specific amygdalin (AG), paeoniflorin (PF), and astragaloside IV (ASV) contents in the BYHWD-containing serum were detected using mass spectrometry. Network pharmacology and molecular docking are used to screen the targets of glycosides for treating atherosclerosis. The predicted targets were validated in an AS model of rat thoracic aortic endothelial cells (RTAEC) induced by oxidized low-density lipoprotein (ox-LDL). According to the mass spectrometry data, the specific contents of AG, PF, and ASV in the serum were 24.11ng/ml, 20.94ng/ml, and 69.87ng/ml, respectively. Results of bioinformatics analysis show that signal transducer and activator of transcription (STAT)-3, hypoxia-inducible factor (HIF)-1, and vascular endothelial-derived growth factor (VEGF) may be involved in the treatment of AS with glycosides. The results of cell experiments revealed that glycoside combinations could treat atherosclerosis by inhibiting STAT3, HIF-1, and VEGF. AG, PF, and ASV are the effective ingredients of BYHWD. Glycoside combinations significantly ameliorate atherosclerosis by inhibiting STAT3, HIF-1, and VEGF.
期刊：
FRONTIERS IN IMMUNOLOGY,2023年14:1205445 ISSN：1664-3224
通讯作者：
Zhang, SF
作者机构：
[Ou, Qinling; Zhang, SF; Zhang, Sifang; Chang, Yonglong; Nie, Kechao] Cent South Univ, Xiangya Hosp 2, 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] Hunan Inst Mental Hlth, Brain Hosp Hunan Prov, Peoples Hosp Hunan Prov 2, Dept Addict Med, Changsha, Peoples R China.;[Liu, Jinhui] Hunan Univ Tradit Chinese Med, Coll Integrated Tradit Chinese & Western Med, Changsha, Hunan, Peoples R China.
通讯机构：
[Zhang, SF ] C;Cent South Univ, Xiangya Hosp 2, Dept Integrated Tradit Chinese & Western Med, Changsha, Peoples R China.;Natl Clin Res Ctr Metab Dis, Changsha, Peoples R China.
摘要：
Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability rate. The neutrophil extracellular trap network (NETs) is a newly discovered mechanism that allows neutrophils to capture and kill pathogens. Multiple studies in recent years have highlighted its relevance to the progression of rheumatoid arthritis. Despite the growing number of studies indicating the crucial role of NETs in RA, there has been no bibliometric review of research hotspots and trends in this area. In this study, we retrieved articles related to NETs in RA from the Web of Science Core Collection (WoSCC) database from 1985 to 2023 and used visualization tools such as Citespace, VOSviewer, Tableau Public, and Microsoft Office Excel 2021 to analyze the data. After screening, we included a total of 416 publications involving 2,334 researchers from 1,357 institutions in 167 countries/regions, with relevant articles published in 219 journals. The U.S., China, and Germany are the top 3 countries/regions with 124, 57, and 37 publications respectively. Mariana J. Kaplan is the most published author, and journals such as Frontiers in Immunology and International Journal of Molecular Sciences have had a significant impact on research in this field. The clinical application of PAD enzymes and their inhibitors, and the drug development of NETs as therapeutic targets for RA is a trend for future research. Our study provides a comprehensive bibliometric analysis and summary of NETs in RA publications, which will aid researchers in conducting further scientific research.
摘要：
Objective: The use of immune checkpoint inhibitors (ICIs) provides promising strategies for hepatocellular carcinoma (HCC) treatment. This study aimed to explore impact and underlying mechanism of the combination therapy of quercetin and anti-programmed cell death 1 (anti-PD-1) antibody on HCC. Methods: Orthotopically transplanted HCC tumors in mice were treated with quercetin, anti-PD-1 antibody, or a combination of both therapies. Histopathological changes and programmed cell death ligand 1 (PD-L1) expression were characterized by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining. The diversity and differences of gut microbiota (GM) were evaluated through 16S rRNA sequencing. Levels of macrophage immunity-related cytokines were quantified by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), and Western blot. Results: Combination therapy reduced necrosis, fibrosis, and PD-L1 expression in liver tissues. Additionally, combination therapy reduced GM imbalance and increased abundance of Firmicutes, Actinobacteria, and Verrucomicrobiota at the phylum level as well as Dubosiella and Akkermansia at the genus level. Combination therapy improved macrophage immunity, raised the expressions of CD8a, CD4, CD11b, interleukin (IL)-10, and interferon (IFN)--y , and declined the expressions of IL-4, IL-6, toll-like receptor 4 (TLR4), an inhibitor of nuclear factor kB alpha (IkB alpha), and the NFkB subunit p65. Upon combination therapy, expressions of M2 macrophage-related genes arginase-1 (Arg-1), IL-10, transforming growth factor-beta (TGF-beta), and matrix metalloproteinase-9 (MMP-9) were upregulated. Instead, M1 macrophage-related genes IL-6, IL-12a, IL-1 beta, and tumor necrosis factor-alpha (TNF-alpha) were downregulated. Conclusions: Quercetin/anti-PD-1 antibody combination therapy reshaped HCC tumor microenvironment in mice in parallel with regulating the GM and macrophage immunity.
期刊：
Frontiers in Public Health,2023年11:1293134 ISSN：2296-2565
通讯作者：
Song, Zhenyan;Cheng, SW
作者机构：
[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;[Song, Zhenyan; Guo, Minhua; Cheng, Shaowu; Song, ZY; He, Jiawei; Cheng, SW; Wang, Shiwei] Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.;[Wang, Weijie] Hunan Univ Chinese Med, Sch Informat, Changsha, Peoples R China.
通讯机构：
[Song, ZY; Cheng, SW ] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Peoples R China.;Hunan Univ Chinese Med, Coll Integrated Tradit Chinese & Western Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha 410128, Peoples R China.
关键词：
Barthel Index (BI);activities of daily living;machine learning algorithm;memory-related diseases;the China health and retirement longitudinal survey
摘要：
INTRODUCTION: Memory-related diseases (MDs) pose a significant healthcare challenge globally, and early detection is essential for effective intervention. This study investigates the potential of Activities of Daily Living (ADL) as a clinical diagnostic indicator for MDs. Utilizing data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS), encompassing 10,062 Chinese individuals aged 45 or older, we assessed ADL using the Barthel Index (BI) and correlated it with the presence of MDs. Statistical analysis, supplemented by machine learning algorithms (Support Vector Machine, Decision Tree, and Logistic Regression), was employed to elucidate the relationship between ADL and MDs. BACKGROUND: MDs represent a significant public health concern, necessitating early detection and intervention to mitigate their impact on individuals and society. Identifying reliable clinical diagnostic signs for MDs is imperative. ADL have garnered attention as a potential marker. This study aims to rigorously analyze clinical data and validate machine learning algorithms to ascertain if ADL can serve as an indicator of MDs. METHODS: Data from the 2018 national baseline survey of the China Health and Retirement Longitudinal Study (CHARLS) were employed, encompassing responses from 10,062 Chinese individuals aged 45 or older. ADL was assessed using the BI, while the presence of MDs was determined through health report questions. Statistical analysis was executed using SPSS 25.0, and machine learning algorithms, including Support Vector Machine (SVM), Decision Tree Learning (DT), and Logistic Regression (LR), were implemented using Python 3.10.2. RESULTS: Population characteristics analysis revealed that the average BI score for individuals with MDs was 70.88, significantly lower than the average score of 87.77 in the control group. Pearson's correlation analysis demonstrated a robust negative association (r = -0.188, p < 0.001) between ADL and MDs. After adjusting for covariates such as gender, age, smoking status, drinking status, hypertension, diabetes, and dyslipidemia, the negative relationship between ADL and MDs remained statistically significant (B = -0.002, β = -0.142, t = -14.393, 95% CI = -0.002, -0.001, p = 0.000). The application of machine learning models further confirmed the predictive accuracy of ADL for MDs, with area under the curve (AUC) values as follows: SVM-AUC = 0.69, DT-AUC = 0.715, LR-AUC = 0.7. Comparative analysis of machine learning outcomes with and without the BI underscored the BI's role in enhancing predictive abilities, with the DT model demonstrating superior performance. CONCLUSION: This study establishes a robust negative correlation between ADL and MDs through comprehensive statistical analysis and machine learning algorithms. The results validate ADL as a promising diagnostic indicator for MDs, with enhanced predictive accuracy when coupled with the Barthel Index. Lower levels of ADL are associated with an increased likelihood of developing memory-related diseases, underscoring the clinical relevance of ADL assessment in early disease detection.
期刊：
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY,2023年13:1323674 ISSN：2235-2988
通讯作者：
Song, ZY;Cheng, Shaowu
作者机构：
[Jin, Yijie; Song, Zhenyan; Zhou, Yujia; Song, ZY; He, Chunxiang; Jin, Jing; Liang, Si; Yu, Wenjing; Deng, Sisi; Qiu, Jiakang] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;[Song, Zhenyan; Cheng, Shaowu; Song, ZY; He, Chunxiang; Huang, Yaqi; Yu, Wenjing; Cheng, SW; Deng, Sisi] Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.
通讯机构：
[Song, ZY ; Cheng, SW] H;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha, Hunan, Peoples R China.;Hunan Univ Chinese Med, Key Lab Hunan Prov Integrated Tradit Chinese & Wes, Changsha, Hunan, Peoples R China.
关键词：
Alzheimer's disease;Danggui-Shaoyao-San;intestinal flora;cognitive dysfunction;Traditional Chinese Medicine
摘要：
Background: Alzheimer's disease (AD), characterized by a severe decline in cognitive function, significantly impacts patients' quality of life. Traditional Chinese Medicine (TCM) presents notable advantages in AD treatment, closely linked to its regulation of intestinal flora. Nevertheless, a comprehensive exploration of the precise role of intestinal flora in AD remains lacking. Methods: We induced an AD model through bilateral intracerebroventricular injection of streptozotocin in rats. We divided 36 rats randomly into 6 groups: sham-operated, model, Danggui Shaoyao San (DSS), and 3 DSS decomposed recipes groups. Cognitive abilities were assessed using water maze and open field experiments. Nissl staining examined hippocampal neuron integrity. Western blot analysis determined synaptoprotein expression. Additionally, 16S rDNA high-throughput sequencing analyzed intestinal flora composition. Results: DSS and its decomposed recipe groups demonstrated improved learning and memory in rats (P<0.01). The open field test indicated increased central zone residence time and locomotor activity distance in these groups (P<0.05). Furthermore, the DSS and decomposed recipe groups exhibited reduced hippocampal neuronal damage and increased expression levels of synapsin I (P<0.05) and PSD95 (P<0.01) proteins. Alpha and Beta diversity analyses showed that the intestinal flora species richness and diversity in the DSS and decomposed recipe groups were similar to those in the sham-operated group, signifying a significant restorative effect (P<0.05). Conclusion: The combination of DSS and its decomposed recipes can reduce the abundance of harmful gut microbiota, leading to improvements in cognitive and learning abilities.
摘要：
Autoimmune diseases are affected by complex pathophysiology involving multiple cell types, cytokines, antibodies and mimicking factors. Different drugs are used to improve these autoimmune responses, including nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antibodies, and small molecule drugs (DMARDs), which are prevalent clinically in the treatment of rheumatoid arthritis (RA), etc. However, low cost-effectiveness, reduced efficacy, adverse effects, and patient non-response are unattractive factors driving the development of new drugs such as iguratimod. As a new disease-modifying antirheumatic drug, iguratimod has pharmacological activities such as regulating autoimmune disorders, inflammatory cytokines, regulating immune cell activation, differentiation and proliferation, improving bone metabolism, and inhibiting fibrosis. In recent years, clinical studies have found that iguratimod is effective in the treatment of RA, SLE, IGG4-RD, Sjogren ‘s syndrome, ankylosing spondylitis, interstitial lung disease, and other autoimmune diseases and rheumatic diseases. The amount of basic and clinical research on other autoimmune diseases is also increasing. Therefore, this review systematically reviews the latest relevant literature in recent years, reviews the research results in recent years, and summarizes the research progress of iguratimod in the treatment of related diseases. This review highlights the role of iguratimod in the protection of autoimmune and rheumatic bone and related immune diseases. It is believed that iguratimod’s unique mode of action and its favorable patient response compared to other DMARDs make it a suitable antirheumatic and bone protective agent in the future.
期刊：
Cancer Cell International,2023年23(1):1-15 ISSN：1475-2867
通讯作者：
Sheng, W;Li, YQ
作者机构：
[Xu, Wenjing] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Dermatol, Changsha 410021, Peoples R China.;[Ding, Jin] Guangzhou Univ Chinese Med, Shenzhen Baoan Tradit Chinese Med Hosp, Dept Androl, Shenzhen 518133, Peoples R China.;[Li, Bonan; Sheng, W; Sheng, Wen; Kuang, Shida; Zhu, Congxu; Sun, Tiansong] Hunan Univ Chinese Med, Androl Lab, Changsha 410208, Peoples R China.;[Kuang, Shida] Hunan Univ Chinese Med, Sch Tradit Chinese Med, Changsha 410208, Peoples R China.;[Li, Bonan; Sheng, W; Sheng, Wen; Zhu, Congxu; Sun, Tiansong] Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.
通讯机构：
[Sheng, W ; Li, YQ ] H;Hunan Univ Chinese Med, Androl Lab, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Sch Integrated Chinese & Western Med, Changsha 410208, Peoples R China.;Hunan Univ Chinese Med, Med Sch, Changsha 410208, Peoples R China.
摘要：
Docetaxel (DTX) resistance reduces therapeutic efficacy in prostate cancer (PCa). Accumulating reports support the role of phytochemicals in the reversal of DTX resistance. This study aimed to determine whether Epimedium brevicornu and Curcuma zedoaria extracts (ECe), specially icariin-curcumol, attenuates DTX resistance and explore their potential mechanisms. Regulatory pathways were predicted between ECe active ingredients and PCa using network pharmacology. DTX-resistant cell LNCaP/R were established based on DTX-sensitive LNCaP, and xenograft models were further established. Active ingredients in ECe by HLPC-MS were identified. The binding of icariin and curcumol to the target was analyzed by molecular docking. Biochemical experiments were applied to determine the possible mechanisms by which Icariin-Curcumol regulates DTX sensitivity. Akt1 and the PI3K-Akt signaling pathway were predicted as the primary functional target between drug and PCa. ECe and DTX inhibited xenograft tumor growth, inflammation, cell viability and promoted apoptosis. Icariin and curcumol were detected in ECe, and icariin and curcumol docked with Akt1. ECe, Icariin-Curcumol and DTX downregulated AR, PSA, PI3K, Akt1, mTOR, and HIF-1ɑ. Moreover, ECe, Icariin-Curcumol and DTX increased glucose and PDH, decreased lactic acid, ATP and LDH, and downregulated c-Myc, hnRNPs, VEGF, PFK1, and PKM2. Notably, the anti-PCa effect of DTX was attenuated compared to ECe or Icariin-Curcumol in the LNCaP/R model. The combined effect of Icariin-Curcumol and DTX was superior to that of DTX. Our data support that Icariin-Curcumol reverses DTX resistance by inhibiting the PI3K-Akt signaling and the Warburg effect, providing new ideas for improving therapeutic measures for PCa.
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.
