期刊:
Annals of Translational Medicine,2022年10(18) ISSN:2305-5839
作者机构:
[Huang, Yalan; Yu, Rong] Hunan Univ Tradit Chinese Med, Coll Grad, Changsha, Peoples R China.;[Cai, Linkun] Guangdong Prov Hosp Tradit Chinese Med, Dept Gastroenterol, Guangzhou, Peoples R China.;[Liu, Xiu] Hunan Univ Tradit Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China.;[Wu, Yongjun] Hunan Univ Tradit Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Xiang, Qin] Hunan Univ Tradit Chinese Med, Sci & Technol Dept, Changsha, Peoples R China.
关键词:
Type 2 diabetes (T2D);RNA-seq;single-cell RNA (sc-RNA)-seq;biomarkers;transcription factors (TFs)
摘要:
Background: Type 2 diabetes (T2D) is a prevalent chronic disease with elusive. Combining transcriptome and single-cell sequencing data to explore biomarkers of T2D could provide new insights into the in-depth understanding of the molecular mechanisms and diagnosis of T2D. Methods: The GSE41762 dataset including RNA-seq data for healthy and T2D patients, was obtained from the Gene Expression Omnibus (GEO) database. The potential functions of the differentially expressed genes (DEGs) were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Moreover, biomarkers were screened out by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and receiver operating characteristic (ROC) analysis. Furthermore, single-cell RNA (sc-RNA)-seq data in the "E-MTAB-5061" dataset was downloaded from the ArrayExpress (European Bioinformatics Institute, EBI) database. Principal components analysis (PCA) and t-distributed stochastic neighbor embedding (tSNE) were used for dimensionality reduction analysis and cell clustering. The FindAllMarkers function was used annotate different cell clusters, and key cell clusters were screened by the expression levels of the biomarkers. Finally, the transcription factors (TFs) of the biomarkers were recognized. Results: A total of 111 DEGs were screened in the GSE41762 dataset, which were mainly related to hormone secretion, specialized postsynaptic membrane, pancreatic secretion, JAK-STAT signaling pathway, and Ras signaling pathway. In addition, SLC2A2, SERPINF1, RASGRP1, and CHL1 were screened out as biomarkers of T2D, which possessed potential diagnostic value as AUC value greater than 0.8. A total of 1,515 T2D group cells and 1,817 healthy cohort cells were screened as core cells in the "E-MTAB-5061" dataset. Following tSNE dimensionality reduction cluster analysis, the core cells were divided into 13 cell clusters. According to the marker genes, the 13 cell clusters were annotated into six types of cells. Notably, SERPINF1 was highly expressed in fibroblasts and might be regulated by NR2F2 (nuclear receptor subfamily2, group F, and member 2). Conclusions: This study identified four biomarkers (SLC2A2, SERPINF1, RASGRP1, and CHL1) for T2D, which provided new markers for the clinical diagnosis of T2D. Among them, SERPINF1 might be regulated by NR2F2, which provides valuable insight into the pathogensis of T2D.
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
期刊:
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS,2022年37(3):270 - 279 ISSN:0393-6155
通讯作者:
Pei Yang<&wdkj&>Hao Liang
作者机构:
[Zhu, Hong; Tan, Fengbo; Yang, Pei] Cent South Univ, Xiangya Hosp, Changsha, Hunan, Peoples R China.;[Zhao, Yu; Jin, Hekun; Wang, Hui; Shi, Yingrui; Jin, Yi; Zhou, Guanzhi; Yang, Pei] Cent South Univ, Hunan Canc Hosp, Affiliate Hosp, Key Lab Translat Radiat Oncol,Xiangya Med Sch, 283 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China.;[Liang, Hao] Hunan Univ Chinese Med, Inst TCM Diagnost, 300 Xueshi Rd,Sci Educ Ind Pk, Changsha 410208, Hunan, Peoples R China.;[Zhao, Yu] Miriam Hosp, Providence, RI 02906 USA.;[Zhou, Guanzhi] Univ South China, Hengyang, Hunan, Peoples R China.
通讯机构:
[Pei Yang] X;[Hao Liang] I;Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China<&wdkj&>Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital, the Affiliate Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, People’s Republic of China<&wdkj&>Institute of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China
关键词:
Neutrophil-to-lymphocyte ratio trend;immune-inflammation response;prognosis;nasopharyngeal carcinoma;radiotherapy
摘要:
Background
Peripheral neutrophil-lymphocyte ratio (NLR), reflecting immune-inflammation status, shows great potential for tumor progression and outcome. Pre-treatment NLR does not fully reflect the immune-inflammatory response to treatment. This study aimed to introduce the NLR trend as a new indicator and to investigate its prognostic value in patients with nasopharyngeal carcinoma receiving radiotherapy.
Methods
This retrospective study evaluated patients with nasopharyngeal carcinoma treated with radiotherapy. The NLR trend value was calculated from the fitted line gradient via the NLRs before, during (at least once), and after each patient's first radiotherapy. The Kaplan–Meier curve and log-rank test were used to calculate and compare survival outcomes of different pretreatment NLRs and NLR trends for progression-free survival, locoregional recurrence-free survival (LRFS), and overall survival at 3 and 5 years. Multivariate Cox regression analyses were performed to assess the association between the NLR trend plus 3- and 5-year overall survival.
Results
The study included 528 patients. A lower NLR trend predicted worse progression-free survival, LRFS, plus 3- and 5-year overall survival. Multivariate Cox regression analysis showed that the NLR trend independently predicted 3- and 5-year overall survival. Sub-group analysis showed that the prognosis of patients with a low pretreatment NLR and a high NLR trend were superior to those of other groups.
Conclusion
The NLR trend independently predicted the prognosis of patients with nasopharyngeal carcinoma receiving radiotherapy. The NLR trend and the pretreatment NLR combination is more precise than pretreatment NLR in predicting prognosis. A high NLR trend may be evidence of a positive immune response to radiotherapy in patients with nasopharyngeal carcinoma.
期刊:
Frontiers in Cell and Developmental Biology,2022年9:792555 ISSN:2296-634X
通讯作者:
He, Quanyuan
作者机构:
[Zuo, Shanru] Cent South Univ, Xiangya Hosp 3, Dept Pharm, Changsha, Peoples R China.;[Zuo, Shanru; Li, Xueguang; Zhou, Junhua; He, Quanyuan; Yang, Yide] Hunan Normal Univ, Sch Med, Key Lab Model Anim & Stem Cell Biol Hunan Prov, Changsha, Peoples R China.;[Yi, Yihu] Wuhan Union Hosp, Dept Orthopaed, Wuhan, Peoples R China.;[Wang, Chen] Cent South Univ, Xiangya Hosp 3, Dept Obstet & Gynecol, Changsha, Peoples R China.;[Zhou, Mingqing] Sun Yat Sen Univ, Zhongshan Peoples Hosp, Zhongshan Hosp, Zhongshan, Peoples R China.
通讯机构:
[He, Quanyuan] H;Hunan Normal Univ, Sch Med, Key Lab Model Anim & Stem Cell Biol Hunan Prov, Changsha, Peoples R China.
关键词:
eccDNA;Circulome;Biogenesis;Cancer;biomarker
摘要:
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA that is derived and free from chromosomes. It has a strong heterogeneity in sequence, length, and origin and has been identified in both normal and cancer cells. Although many studies suggested its potential roles in various physiological and pathological procedures including aging, telomere and rDNA maintenance, drug resistance, and tumorigenesis, the functional relevance of eccDNA remains to be elucidated. Recently, due to technological advancements, accumulated evidence highlighted that eccDNA plays an important role in cancers by regulating the expression of oncogenes, chromosome accessibility, genome replication, immune response, and cellular communications. Here, we review the features, biogenesis, physiological functions, potential functions in cancer, and research methods of eccDNAs with a focus on some open problems in the field and provide a perspective on how eccDNAs evolve specific functions out of the chaos in cells.
摘要:
BackgroundHelicobacter pylori-related gastric ulcer (H. pylori-related GU) is one of the most common digestive system diseases that have received widespread attention from researchers. The purpose of this article was to analyze the research status and hotspots of H. pylori-related GU and to predict its future research directions. MethodsThe article and review papers associated with H. pylori-related GU published from 2012 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The analysis of knowledge maps and bibliometrics was done with CiteSpace 6.1.R2 Basic and VOSviewer 1.6.18. ResultsA total of 2,971 articles were included in the study. Between 2012 and 2022, the number of papers published showed an increasing trend. China was the most prolific country, and the United States was the most influential country. Baylor College of Medicine had the largest number of publications and citations among publishing agencies. World Journal of Gastroenterology published the most articles on the H. pylori-related GU field, and GUT was the journal with the most cited articles. Yamaoka Y from Japan was the most productive author, and Graham DY from the USA was the most influential author. A keyword and reference analysis showed that the hot topics of research were the mechanism of H. pylori and the treatment of H. pylori-related GU. The keywords that emerged in the recent 5 years were oxidative stress, probiotics, competitive acid blocker, vonoprazan, gut microbiota, and neutrophil-activating protein. ConclusionOver the recent 10 years, research on H. pylori-related GU has generally shown an increasing trend. The treatment and pathogenesis of H. pylori-related GU remain a hot topic of research. The treatment of H. pylori by oxidative stress and competitive acid inhibitor mechanisms, the influence of gastrointestinal flora on H. pylori, probiotic adjuvant therapy of H. pylori-related GU, and the immunoprotective effect of neutrophil activator protein could be popular research directions and trends in the future.
摘要:
Cadmium (Cd) is a serious environmental pollutant to human health. Intestinal flora is associated with human health. This study probed into the effects of Cd on the small intestinal mucosal flora in mice by drinking water intake 5 ppm, 20 ppm and 100 ppm cadmium chloride for 50 days respectively. Results indicated that diversity, taxonomic composition and community structure of intestinal mucosal flora were influenced by Cd exposure. Sphingomonas, Microbacterium and Desulfovibrio, as the characteristic bacteria, played vital roles in the different dose groups of Cd. Meanwhile, Cd exposure adjusted the metabolic function of intestinal mucosal flora, mainly involved in the effects on carbohydrate, amino acid and lipid metabolism. Furthermore, different doses of Cd had different effects on the microbial activity of intestinal mucosal. Conclusively, Cd exposure affected the structure and function of intestinal mucosal flora. We screened the Sphingomonas, Microbacterium and Desulfovibrio as the biomarkers of intestinal mucosal flora after Cd exposure.
摘要:
Dry eye disease (DED) is a multifactorial syndrome that commonly occurs with depression. However, therapies targeting depression-related dry eye disease are rare. In the current study, we studied the beneficial effect of a natural flavone, acacetin, in depression-associated dry eye disease by utilizing the chronic unpredictable mild stress (CUMS) depression model. Our data showed that acacetin improved the depressive behaviors in sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST); relieved the dry eye symptoms including corneal epithelial impairments, tear production decrease and goblet cell loss in CUMS mice. Acacetin also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome expression levels and suppressed inflammatory responses via enhancing glycoprotein 78 (gp78)/Insulin induced gene-1 (Insig-1)-controlled NLRP3 ubiquitination in CUMS mice. Furthermore, knockdown of gp78 compromised acacetin-conferred protective efficacy in depression-related dry eye disease. In summary, our findings indicated that acacetin exerts beneficial effect in depression-associated dry eye disease, which is tightly related to gp78-mediated NLRP3 ubiquitination.
作者机构:
[Cao, Jianzhong; Xia, Yu; Long, Piao; Yang, Yuying] Hunan Univ Chinese Med, Hunan Prov Key Lab Diagnost Chinese Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词:
Bupleuri Radix;mechanism of action;molecular docking;network pharmacology;Scutellariae Radix;viral hepatitis B
摘要:
Viral hepatitis B is caused by the hepatitis B virus, which is characterized by liver lesions. Bupleuri Radix and Scutellariae Radix are the main traditional medicine pairs with remarkable efficacy in hepatitis B. However, their molecular mechanisms are incompletely understood. The main active components of Bupleuri Radix and Scutellariae Radix, as well as therapeutic targets for the treatment of hepatitis B, were identified through network pharmacology techniques. We identified viral hepatitis B targets using the GeneCards, online mendelian inheritance in man, and therapeutic target databases. We discovered the active components of Bupleuri Radix and Scutellariae Radix as well as therapeutic targets using the encyclopedia of traditional Chinese medicine, HERB, traditional Chinese medicine systems pharmacology database, and a bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine databases. VENNY obtained the intersections. Cytoscape and STRING were used to create the "active ingredient-potential target" network and protein interaction network. The DAVID database was used to enrich GO and KEGG pathways. The results were confirmed using the molecular docking method. There were 1827 viral hepatitis B targets, and 37 active ingredients for Bupleuri and Scutellariae Radix, with the main components being quercetin, wogonin, baicalein, and kaempferol. Tumor necrosis factor (TNF), mitogen-activated protein kinase 3 (MAPK3), interleukin-6 (IL-6), vascular endothelial growth factor A, cysteinyl aspartate specific proteinase 3, transcription factor AP-1 (JUN), RAC-alpha serine/threonine-protein kinase, and cellular tumor antigen p53 are among the 78 common targets of Bupleuri Radix and Scutellariae Radix intervention in viral hepatitis B. KEGG enrichment resulted in 107 pathways, including cancer, hepatitis B, and TNF signaling pathways. According to the molecular docking technique, quercetin, wogonin, baicalein, and kaempferol had strong binding activities with TNF, MAPK3, and IL-6. In this study, we initially identified various molecular targets and multiple pathways involved in hepatitis B treatment with Bupleuri Radix and Scutellariae Radix.
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.
期刊:
Frontiers in Pharmacology,2022年13:3439 ISSN:1663-9812
作者机构:
[Zhang, Yiwen; Jiang, Ning; Yao, Caihong; Liu, Xinmin; Huang, Hong] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Plant Dev IMPLAD, Res Ctr Pharmacol & Toxicol, Beijing, Peoples R China.;[He, Qinghu] Hunan Univ Med, Sino Pakistan Ctr Tradit Chinese Med, Huaihua, Peoples R China.;[Chen, Fang] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China.;[Lu, Guanghua; Yu, Han] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu, Peoples R China.;[Liu, Xinmin] Ningbo Univ, Inst Drug Discovery Technol, Ningbo, Peoples R China.
关键词:
Chronic restraint stress;Gastrodia elata Blume;learning and memory;animal behavior;Mitochondria
摘要:
Chronic restraint stress (CRS) is a classic animal model of stress that can lead to various physiological and psychological dysfunctions, including systemic neuroinflammation and memory deficits. Fresh Gastrodia elata Blume (FG), the unprocessed raw tuber of Gastrodia elata Blume, has been reported to alleviate the symptoms of headache, convulsions, and neurodegenerative diseases, while the protective effects of FG on CRS-induced cognitive deficits remain unclear. This work aimed to evaluate the effects of FG on CRS-induced cognitive deficits through multiplex animal behavior tests and to further explore the related mechanism by observing the expression of mitochondrial apoptosis-related proteins in the mouse hippocampus. In in vivo experiments, mice were subjected to the object location recognition test (OLRT), new object recognition test (NORT), Morris water maze test (MWMT), and passive avoidance test (PAT) to evaluate the learning and memory ability. In in vitro experiments, the expression of the AKT/CREB pathway, the fission- and apoptosis-related proteins (Drp1, Cyt C, and BAX), and the proinflammatory cytokines' (TNF-alpha and IL-1 beta) level in the hippocampus was examined. Our results demonstrated that in spontaneous behavior experiments, FG significantly improved the cognitive performance of CRS model mice in OLRT (p < 0.05) and NORT (p < 0.05). In punitive behavior experiments, FG shortened the escape latency in long-term spatial memory test (MWMT, p < 0.01) and prolonged the latency into the dark chamber in non-spatial memory test (PAT, p < 0.01). Biochemical analysis showed that FG treatment significantly suppressed CRS-induced Cyt C, Drp1, and BAX activation (p < 0.001, p < 0.01 and p < 0.05), promoted the CREB, p-CREB, AKT, and p-AKT level (p < 0.05, p < 0.01 and p < 0.001), and inhibited the CRS-induced proinflammatory cytokines (TNF-alpha and IL-1 beta, p < 0.05 and p < 0.001) level in the hippocampus. Taken together, these results suggested that FG could attenuate cognitive deficits induced by CRS on multiple learning and memory behavioral tests.
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.
期刊:
Frontiers in Endocrinology,2022年13:2153 ISSN:1664-2392
作者机构:
[Zhang, Ji-Dong; Li, Ling; Sun, Gui-Xiang; Qiu, Li-Ting; Fan, Bo-Yan] Hunan Univ Chinese Med, Coll Tradit Chinese Med, Changsha, Peoples R China.;[Sun, Gui-Xiang] Hunan Univ Chinese Med, Prov Key Lab Tradit Chinese Med TCM Diagnost, Changsha, Peoples R China.;[Sun, Gui-Xiang] Hunan Univ Chinese Med, Inst Chinese Med Diag, Changsha, Peoples R China.;[Wang, Dan] Hunan Univ Technol & Business, Sch Phys Educ & Hlth, Changsha, Peoples R China.
关键词:
eHealth;lifestyle interventions;Overweight and obesity;Children and adolescents;Meta-analysis
摘要:
Objective: To investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes in children and adolescents. Methods: The Medline (via PubMed), Embase, Cochrane Library, Web of Science, CBM, VIP, CNKI, and Wanfang electronic databases were systematically searched from their inception to March 18, 2022, for randomized controlled trials (RCTs). Meta-analyses were performed to investigate the effect of multiple eHealth-delivered lifestyle interventions on obesity-related anthropometric outcomes (body mass index [BMI], BMI Z-score, waist circumference, body weight, and body fat%). Two independent investigators reviewed the studies for accuracy and completeness. All included studies were evaluated using the Cochrane Risk-of-Bias (ROB) Tool. Results: Forty trials comprising 6,403 patients were selected for the meta-analysis. The eligible trials were published from 2006 to 2022. Compared with the control group, the eHealth-intervention group was more effective in reducing BMI (weighted mean difference [WMD] = -0.32, 95% confidence interval [CI]: -0.50 to -0.13, I-2 = 85.9%), BMI Z-score (WMD = -0.08, 95% CI: -0.14 to -0.03, I-2 = 89.1%), waist circumference (WMD = -0.87, 95% CI: -1.70 to -0.04, I-2 = 43.3%), body weight (WMD = -0.96, 95% CI: -1.55 to -0.37, I-2 = 0.0%), and body fat% (WMD = -0.59, 95% CI: -1.08 to -0.10, I-2 = 0.0%). The subgroup analysis showed that parental or school involvement (WMD = -0.66, 95% CI: -0.98 to -0.34), eHealth-intervention duration of > 12 weeks (WMD = -0.67, 95% CI: -0.96 to -0.38), and mobile-based interventions (WMD = -0.78, 95% CI: -1.13 to -0.43) had a significantly greater intervention effect size on BMI. Conclusions: This review recommends that multiple eHealth-delivered lifestyle strategies may be useful for preventing or treating overweight and obesity among children and adolescents. However, our results should be cautiously interpreted due to certain limitations in our study.
摘要:
Objectives: We aimed to estimate the effectiveness and safety of iguratimod (IGU) monotherapy or in combination with methotrexate (MTX) in treating rheumatoid arthritis (RA) to provide an evidence-primarily-based foundation for clinical application. Methods: We conducted a systematic review of the meta-analysis using eight databases and two clinical trial websites searching for randomized controlled trials (RCTs) from conception to 15 March 2022, based on outcomes of patients with RA treated with IGU. The evidence quality assessment of primary outcomes was evaluated by the GRADE tool, and RevMan 5.3 and StataMP 14.0 were used to perform this research. Results: A total of 4302 patients with RA from 38 RCTs was included in this research. Pooled results demonstrated as follows: 1) Compared with methotrexate (MTX) alone, IGU alone was superior in improving ACR20 and DAS28-ESR, while having no significant difference in ACR50 and ACR70 [ACR20: (RR 1.15, 95% CI 1.05-1.27, p = 0.004); ACR50: (RR 0.97, 95% CI 0.66-1.44, p = 0.88); ACR70: (RR 0.92, 95% CI 0.45-1.90, p = 0.83); DAS28-ESR: mean difference (MD) -0.15, 95% CI -0.27 to -0.03, p = 0.01]. 2) Compared with MTX alone, IGU + MTX was more effective in improving ACR20, ACR50, ACR70, and DAS28-ESR. [ACR20: (RR 1.24, 95% CI 1.14-1.35, p < 0.00001); ACR50: (RR 1.96, 95% CI 1.62-2.39, p <0.00001); ACR70: (RR 1.91, 95% CI 1.41-2.57, p < 0.0001)]; [DAS28-ESR: (MD) -1.43, 95% CI -1.73 to -1.12, p < 0.00001]. 3) Compared with MTX + leflunomide (LEF), ACR20, ACR50, ACR70, and DAS28-ESR of IGU + MTX had no significant difference [ACR20: (RR 1.06, 95% CI 0.94-1.19, p = 0.38); ACR50: (RR 1.10, 95% CI 0.66-1.84, p = 0.72); ACR70: (RR 1.20, 95% CI 0.45-3.20, p = 0.71); DAS28-ESR: (MD -0.02, 95% CI -0.13 to -0.10, p = 0.77)]. 4) Compared with MTX + hydroxychloroquine (HCQ), IGU + MTX was superior in improving DAS28-ESR (MD -2.16, 95% CI -2.53 to -1.79, p < 0.00001). 5) Compared with MTX + tripterygium glycosides (TGs), IGU + MTX was more effective in improving DAS28-ESR (MD -0.94, 95% CI -2.36 to 0.48, p = 0.19). 6) There were no significant differences in adverse events (AEs) between the groups of IGU vs. MTX (RR 0.96, 95% CI 0.71-1.31, p = 0.80), IGU + MTX vs. MTX (RR 1.10, 95% CI 0.90-1.35, p = 0.34), IGU + MTX vs. MTX + HCQ (RR 0.64, 95% CI 0.29-1.42, p = 0.27), and IGU + MTX vs. MTX + TGs (RR 0.75, 95% CI 0.28-2.02, p = 0.57). The incidence of AEs in the IGU + MTX group was lower than the MTX + LEF group (RR 0.83, 95% CI 0.71-0.98, p = 0.03). Conclusion: Compared to the MTX alone subgroup, IGU alone offers clear advantages in improving ACR20 and DAS28-ESR, despite the insufficient evidence for DAS28-ESR findings. IGU + MTX shows clear benefits in improving ACR20, ACR50, ACR70, and DAS28-ESR scores compared to standard therapies. When the intervention (IGU alone or IGU + MTX) lasted for 52 weeks, it demonstrated superior efficacy in improving ACR20 of patients without prominent adverse events. Notably, IGU or IGU + MTX has apparent advantages in improving ACR20 of first-visit RA, and IGU + MTX has obvious advantages in improving DAS28-ESR of refractory RA. Furthermore, IGU + MTX does not increase the risk of leukopenia, but it can decrease the risk of liver function tests (LFTs), regardless of the age or the stage of RA.
摘要:
Abstract Dendritic cells (DCs)‐based tumor vaccines have the advantages of high safety and rapid activation of T cells, and have been approved for clinical tumor treatment. However, the conventional DC vaccines have some severe problems, such as poor activation of DCs in vitro, low level of antigen presentation, reduced cell viability, and difficulty in targeting lymph nodes in vivo, resulting in poor clinical therapeutic effects. In this research, magnetic nanoparticles Fe3O4@Ca/MnCO3 were prepared and used to actively and efficiently deliver antigens to the cytoplasm of DCs, promote antigen cross‐presentation and DC activation, and finally enhance the cellular immune response of DC vaccines. The results show that the magnetic nanoparticles can actively and quickly deliver antigens to the cytoplasm of DCs by regulating the magnetic field, and achieve cross‐presentation of antigens. At the same time, the nanoparticles degradation product Mn2+ enhanced immune stimulation through the interferon gene stimulating protein (STING) pathway, and another degradation product Ca2+ ultimately promoted cellular immune response by increasing autophagy. The DC vaccine constructed with the magnetic nanoparticles can more effectively migrate to the lymph nodes, promote the proliferation of CD8+ T cells, prolong the time of immune memory, and produce higher antibody levels. Compared with traditional DC vaccines, cytoplasmic antigen delivery with the magnetic nanoparticles provides a new idea for the construction of novel DC vaccines.
期刊:
Computational and Mathematical Methods in Medicine,2022年2022:9043300 ISSN:1748-6718
通讯作者:
Zhu, M.
作者机构:
[Zhao, Yudong] Chengdu Univ Tradit Chinese Med, Sch Clin Med, Chengdu 610075, Peoples R China.;[Xia, Yu] Hunan Univ Chinese Med, Prov Key Lab TCM Diagnost, Changsha 410208, Peoples R China.;[Kuang, Gaoyan] Hunan Univ Chinese Med, Dept Orthopaed, Affiliated Hosp 1, Changsha 410007, Peoples R China.;[Cao, Jihui] Changshou Dist Hosp Tradit Chinese Med, Dept Orthopaed & Traumatol, Chongqing 400000, Peoples R China.;[Shen, Fu] Yong Zhou Hosp Tradit Chinese Med, Dept Orthopaed, Yongzhou 425000, Peoples R China.
通讯机构:
Department of Orthopaedics, Hospital of Chengdu University of Traditional Chinese Medicine, China
摘要:
<i>Background.</i> Knee osteoarthritis (KOA) is a common degenerative joint disease. In this study, we aimed to identify new biomarkers of KOA to improve the accuracy of diagnosis and treatment. <i>Methods.</i> GSE98918 and GSE51588 were downloaded from the Gene Expression Omnibus database as training sets, with a total of 74 samples. Gene differences were analyzed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and Disease Ontology enrichment analyses for the differentially expressed genes (DEGs), and GSEA enrichment analysis was carried out for the training gene set. Through least absolute shrinkage and selection operator regression analysis, the support vector machine recursive feature elimination algorithm, and gene expression screening, the range of DEGs was further reduced. Immune infiltration analysis was carried out, and the prediction results of the combined biomarker logistic regression model were verified with GSE55457. <i>Results.</i> In total, 84 DEGs were identified through differential gene expression analysis. The five biomarkers that were screened further showed significant differences in cartilage, subchondral bone, and synovial tissue. The diagnostic accuracy of the model synthesized using five biomarkers through logistic regression was better than that of a single biomarker and significantly better than that of a single clinical trait. <i>Conclusions.</i> CX3CR1, SLC7A5, ARL4C, TLR7, and MTHFD2 might be used as novel biomarkers to improve the accuracy of KOA disease diagnosis, monitor disease progression, and improve the efficacy of clinical treatment.
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.
期刊:
International Journal of Biological Macromolecules,2022年203:176-183 ISSN:0141-8130
通讯作者:
Peng, YB;Huang, XK
作者机构:
[Zeng, Yajun; Peng, Yongbo; Peng, Qiyao; Peng, YB; Wang, Junyi; Yu, Chao] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China.;[Peng, Yongbo; Zhou, Rongrong; Wan, Dan; Peng, Qiyao; Zhang, Shuihan] Hunan Acad Tradit Chinese Med, Inst Chinese Med, Changsha 410208, Peoples R China.;[Peng, Yongbo; Zhou, Rongrong; Wan, Dan; Peng, Qiyao; Zhang, Shuihan] Hunan Univ Chinese Med, Changsha 410208, Peoples R China.;[Huang, XK; Huang, Xuekuan; Luo, Hongyu] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cu, Chongqing 410016, Peoples R China.;[Ren, Lingyan] Chongqing Univ Sci & Technol, Sch Safety Engn, Chongqing 401331, Peoples R China.
通讯机构:
[Peng, YB ; Huang, XK ] C;Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Chongqing 400016, Peoples R China.;Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cu, Chongqing 410016, Peoples R China.
关键词:
Function and structure;INO80;NFRKB
摘要:
The INO80 chromatin remodeling complex plays an essential role in the regulation of gene transcription, which participate in a variety of important biological processes in cells including DNA repair and DNA replication. Difference from the yeast INO80 complex, metazoan INO80 complex have the specific subunit G, which is known as nuclear factor related to kappaB binding protein (NFRKB). Recently, NFRKB has been received much attention in many aspects, such as DNA repair, cell pluripotency, telomere protection, and protein activity regulation. To dig the new function of metazoan INO80 complex, a better understanding of the role of NFRKB is required. In this review, we provide an overview of the structure and function of NFRKB and discuss its potential role in cancer treatment and telomere regulation. Overall, this review provides an important reference for further research of the INO80 complex and NFRKB.
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.