The proper placement of N6-methyladenosine (m6A) on mRNA is essential for normal cell function, and its disruption is linked to numerous human diseases. The rapid growth of m6A data from diverse sequencing technologies presents challenges for integrative analysis due to technique-specific biases and inconsistent processing. While existing databases provide valuable catalogs, their reliance on aggregating pre-processed results can propagate inconsistencies. To overcome these limitations, we present m6AConquer, a database founded on reproducible quantification. We systematically re-processed raw data from 10 distinct profiling methods, including high-resolution GLORI and eTAM-seq, quantifying methylation at millions of consensus sites across human and mouse. Our rigorous pipeline features uniform site-calling and false-positive calibration with in vitro transcribed (IVT) controls where available. By leveraging a reproducibility-based framework across technically orthogonal methods, we identified over 135300 orthogonally validated m6A sites in human (IDR < 0.05). Beyond this validated methylome, m6AConquer provides matched multi-omics data (gene expression, splicing, variants) and identifies m6A quantitative trait loci (m6A QTLs) to link RNA modification to genetic regulation and disease. Offering intuitive query tools, interactive visualizations, and downloadable, analysis-ready data matrices, m6AConquer provides a standardized resource for rigorous exploration of the roles of m6A in biology and medicine, freely accessible at https://rnamd.org/m6aconquer/.

Background The primary objective of rapeseed breeding is to enhance oil content, which is predominantly influenced by environmental factors. However, the molecular mechanisms underlying the impact of these environmental factors on oil accumulation remain inadequately elucidated. In this study, we used transcriptome data from two higher (HOC) and two lower oil content (LOC) inbred lines at 35 days after pollination (DAP) to investigate genes exhibiting stable expression across three different environments. Meanwhile, a genome-wide association study (GWAS) was utilized to detect candidate genes exhibiting significant associations with seed oil content across three distinct environments. Results The study found a total of 405 stable differentially expressed genes (DEGs), including 25 involved in lipid/fatty acid metabolism and 14 classified as transcription factors. Among these genes, BnBZIP10- A09, BnMYB61 -A06, BnAPA1 -A08, BnPAS2 -A10, BnLCAT3 -C05 and BnKASIII -C09 were also found to exhibit significant associations with oil content across multiple different environments based on GWAS of 50 re-sequenced semi-winter rapeseed inbred lines and previously reported intervals. Otherwise, we revealed the presence of additive effects among BnBZIP10- A09, BnKASIII -C09, BnPAS2 -A10 and BnAPA1 -A08, resulting in a significant increase in seed oil content. Meanwhile, the majority of these stable DEGs are interconnected either directly or indirectly through co-expression network analysis, thereby giving rise to an elaborate molecular network implicated in the potential regulation of seed oil accumulation and stability. Conclusions The combination of transcription and GWAS revealed that natural variation in six environment-insensitive gene regions exhibited significant correlations with seed oil content phenotypes. These results provide important molecular marker information for us to further improve oil content accumulation and stability in rapeseed.

Ethnopharmacological relevance: Poria cocos F.A. Wolf is an edible fungus with forming sclerotia, which has the effects of promoting diuresis, exuding dampness, invigorating the spleen, and regulating the stomach. P. cocos has a high application in the clinic of traditional Chinese medicine, and some studies have indicated that P. cocos has a good effect on tumor diseases. According to ancient records and modern studies, P. cocos wine offers beneficial effects in terms of strengthening tendons and bones and anti-tumor effects.Aim of the study: To understand the substance composition of P. cocos ethanol-soluble extract (PESE) and then further study the effect and potential mechanism of PESE components on gastric cancer.Materials and methods: In vitro and in vivo experiments were performed to detect the cell activity and apoptotic condition. Differential expression analysis and pathway enrichment were performed based on transcriptomics and were verified by real-time polymerase chain reaction and western blotting. The mice of the stomach cancer tumor model were randomly categorized into three groups. The weight and tumor volume of the mice were measured, and the pathological characteristics of tumor tissue and immunohistochemical changes were determined. Then, the main active components of PESE were detected by MKN45 cell fishing. Results: In vitro experiments showed that PESE inhibited the proliferation of MKN45 cells, but it did not induce apoptosis. Based on the transcriptome and western blotting results, the inhibition of MKN45 proliferation by PESE may be influenced by mitogen-activated protein kinase (MAPK) and phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signaling pathways. In vivo experiments showed that PESE inhibited tumor growth in mice and caused partial necrosis of tumor cells but had no toxic effect on mice. Cell fishing identified nine triterpenoids of P. cocos as the major active components of PESE.Conclusions: The results indicated that PESE has a significant inhibitory effect on stomach cancer, and its mechanism probably commonly affects the MAPK and PI3K-Akt signaling pathways, which could be due to the triterpenoid components.

To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

Flowering time is a crucial determinant of both the yield and oil quality of rapeseed as well as a key indicator of plant maturity. We performed a genome-wide association study and transcriptome analysis to identify key genes/loci regulating flowering time in Brassica napus L. Forty-six haplotype regions harboring candidate genes were determined to be significantly associated with flowering time, and 28 of these haplotype regions overlapped with previously reported quantitative trait loci. A further investigation of these haplotype regions revealed nucleotide variations in the genes BnaFT-A02, BnaFRI-A10, and BnaFPA-A09 that correlated with phenotypic variations in flowering time. Furthermore, the co-expression network analysis indicated that BnaFT-A02 is directly linked to BnaFRI-A10 and BnaFPA-A09, in a subnetwork and also associated with 13 vernalization, 31 photoperiod, 33 autonomous pathway, and 10 gibberellin pathway genes, forming a potential network regulating flowering time in rapeseed. These results provide valuable haplotype markers for the breeding of early maturing rapeseed varieties.

目的:利用网络药理学结合指纹图谱技术探讨槐花散抗溃疡性结肠炎(Ulcerative Colitis,UC)的作用机制及潜在质量标志物.方法:采用中药系统药理学数据库与分析平台(TCMSP)检索各药味的活性成分,以UC为疾病背景构建网络图,预测槐花散抗UC药效作用靶点,采用UC动物模型对预测靶点进行实验验证;收集不同厂家共10批次槐花散测定指纹图谱,筛选槐花散潜在质量标志物,并利用分子对接对槐花散潜在质量标志物和预测靶点进行虚拟验证.结果:通过网络药理学预测得到25个槐花散的活性成分和105个共有靶点,通过分析筛选出槐花散共5个潜在药效靶点为白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、IL-1β、蛋白激酶(AKT1)、抑癌基因(TP53).体内实验结果表明槐花散能明显改善UC小鼠的便血症状和疾病活动指数,增加UC小鼠的体质量,降低血清中促炎因子TNF-α、IL-6的含量;下调小鼠结肠组织中的Tnfa、Il1b和Akt1 mRNA的表达,上调Il6、Tp53 mRNA的表达.通过指纹图谱共获得8个共有峰,筛选并指认出5个潜在质量标志物,将其与上述靶点进行分子对接,发现槲皮苷、胡薄荷酮、新橙皮苷及柚皮苷与5个靶点的结合能均小于-4 kJ/mol.结论:槐花散调节IL-6、TNF-α、IL-1β、AKT1及TP53等靶点改善小鼠溃疡性结肠炎,可能与槐花散中质量标志物作用于上述靶点有关.

Background:To investigate the regulation mechanism of hematopoiesis of Siwu paste (SWP) in anemia rats, which is a classic Chinese prescription used for nourishing blood or blood deficiency over 1000 years.Methods:Blood cell and biochemical analysis were used to evaluate the hematopoietic function of SWP in anemia rats. The intestinal microbial composition was analyzed with 16S rRNA gene sequencing, and the metabolites were profiled using UPLC-TripleTOF system nontargeting metabolomics.Results:SWP can improve the levels of red blood cells, hemoglobin, platelet, hematocrit value, white blood cells, lymphocyte, EPO, TPO, and GM-CSF in anemia rats, and significantly change the microbial community and its metabolites. The correlation analysis of intestinal microbiota-hematopoietic efficacy shows that 13 kinds of different intestinal flora were related to hematopoietic efficacy, in which Prevotella_1, Prevotella_9, Lactobacillus, and norank_f__Muribaculaceae were significantly positively correlated with hematopoiesis, nine kinds of intestinal flora are negatively correlated with hematopoietic effect. Compared with anemia rats, 218 potential metabolic biomarkers and 36 metabolites with significant differences were identified in the SWP treatment group, and the key metabolites were mainly amino acids and lipids. An in-depth analysis of metabolic pathways showed that SWP mainly affected 7 metabolic pathways, including aminobenzoic acid degradation and tryptophan metabolism.Conclusion:The study provides novel insights into the regulation of hematopoiesis of SWP in anemia rats that were correlated with gut microbiota and the metabolites, which through the restoration of the firmicutes/bacteroidetes ratio.

Ethnopharmacological relevance: Panax quinquefolius Linn. is one of the most valuable herbal medicine in the world for its broad health benefits, including anti-diabetes. Ginsenoside Rb1, the principal active constituent of Panax quinquefolius Linn., could attenuate insulin resistance and metabolic disorders. The dysfunction of gut microbiota and fecal metabolites plays an important role in the pathogenesis of Type 2 Diabetes mellitus (T2DM). However, whether ginsenoside Rb1's hypoglycemic effect is related to gut microbiota remains elusive. Aim of the study: Our study aimed to explore the insulin-sensitizing and anti-diabetic effects of ginsenoside Rb1 as well as the underlying mechanisms. Materials and methods: The T2DM model were established by high fat diet (HFD)-induced Kkay mice. The anti-diabetic effect of ginsenoside Rb1 (200 mg/kg/day) was evaluated by random blood glucose (RBG), fasting blood glucose (FBG), glucose tolerance test (OGTT), serum insulin level, insulin resistance index (HOMA-IR), pancreatic histology analysis, liver indexes, total triglyceride (TG) and total cholesterol (TC). Subsequently, 16S rRNA sequencing and LC-MS-based untargeted metabolomics were applied to characterize the microbiome and metabolites profile in HFD-induced Kkay mice, respectively. Finally, antibiotic treatment was used to validate the potential mechanism of ginsenoside Rb1 by modulating gut microbiota. Results: Our results showed that ginsenoside Rb1 reduced blood glucose, OGTT, serum insulin level, HOMA-IR, liver indexes as well as pancreatic injury. In addition, the ginsenoside Rb1 reversed the gut microbiota dysbiosis in diabetic Kkay mice, as indicated by the elevated abundance of Parasutterella, decreased population of Alistipes, f_Prevotellaceae_unclassified, Odoribacter, Anaeroplasma. Moreover, ginsenoside Rb1 altered free fatty acid (FFA) levels in fecal metabolites, such as decreased the level of alpha-linolenic acid, 13-OxoODE, oleic acid, 13-HODE, arachidonic acid, palmitic acid, stearic acid, while increased the level of PC (14:0/22:1(13Z)) and PC (16:0/ 16:0). Notably, ginsenoside Rb1 failed to improve HFD-induced diabetes in Kkay mice with antibiotics intervention. Conclusion: These findings suggested that ginsenoside Rb1 may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play essential roles in diabetes-associated metabolic dis-orders and insulin resistance.

BACKGROUND:Type 2 diabetes mellitus (T2DM) has already become a global pandemic. Recently, reports showed its pathogenesis was closely related to a disorder of gut microbiota. In China, the Liu-Wei-Di-Huang Pills (LWDH) have treated T2DM for thousands of years. However, its therapeutic mechanism associated with gut microbiota is worthy of further study.AIMS:This study aims to investigate the effects of LWDH on T2DM by regulating gut microbiota and short-chain fatty acids (SCFAs) in Goto-Kakizaki (GK) rats.METHODS:T2DM models were successfully established based on GK rats and administrated with LWDH. The changes in fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and serum insulin (INS) were determined, and the immunohistochemical (IHC) method was used to test INS expression in pancreas. The 16S-ribosomal DNA (16S rDNA) sequencing analysis assessed gut microbiota structural changes; a gas chromatography-mass spectrometer (GC-MS)-based metabolomics method was adopted to detect SCFA levels. The pathological morphology of jejunum was detected by hematoxylin-eosin (H&E) staining, and the expression of GPR43, GPR41, GLP-1, and GLP-1R was evaluated by qRT-PCR and ELISA, respectively.RESULTS:We observed that GK rats treated with LWDH: (a) has altered the microbial structure and promoted the abundance of bacteria in Firmicutes, including Lactobacillus, Allobaculum, and Ruminococcus_2, (b) increased SCFAs levels involving acetic acid, propionic acid, and butyric acid and (c) alleviated T2DM and jejunum injuries potentially based on SCFAs-GPR43/41-GLP-1 pathway.CONCLUSION:LWDH could improve T2DM by regulating gut microbiota and SCFAs, and the therapeutic mechanism might be related to the SCFAs-GPR43/41-GLP-1 pathway.

In this study, a green and effective extraction method was proposed to extract two main compounds, ginsenosides and polysaccharides, from American ginseng by combining deep eutectic solvents (DESs) with aqueous two-phase systems. The factors of type of DESs, water content in DESs, the solid–liquid ratio, extraction temperature, and extraction time were studied in the solid–liquid extraction. Then, the aqueous two-phase system (DESs-ethylene oxide–propylene oxide (EOPO)) and salty solution exchange (EOPO-salty solution) was applied for the purification of polysaccharides. The content of the polysaccharides and ginsenosides were analyzed by the anthrone–sulfuric acid method and HPLC method, which showed that the extraction efficiency of deep eutectic solvents (DESs) was better than conventional methods. Moreover, the antioxidant activities of ginseng polysaccharides and their cytotoxicity were further assayed. The advantages of the current study are that, throughout the whole extraction process, we avoided the usage of an organic reagent. Furthermore, the separated green solvent DESs and EOPO could be recovered and reused for a next cycle. Thus, this study proposed a new, green and recyclable extraction method for extracting ginsenosides and polysaccharides from American ginseng.

目的:建立不同厂家六味地黄丸(LWDH)HPLC指纹图谱与抗氧化活性间的"谱-效"关系,为其质量控制提供依据.方法:采用HPLC多波长检测方法建立LWDH指纹图谱,进一步采用DPPH自由基清除率来检测抗氧化活性,并通过主成分分析、系统聚类分析、"谱-效"相关性等化学计量学方法对不同厂家的LWDH成分进行鉴别和比较.结果:HPLC指纹图谱共指认14个共有峰,结合抗氧化活性建立谱效关系,其中北京同仁堂LWDH抗氧化活性高,而没食子酸和莫诺苷具有较显著的抗氧化活性相关系数,可作为质量控制成分.结论:本方法简易、快速、准确,可为LWDH质量控制提供一定基础.

Purpose:This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways.Materials:Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH).Results:A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway.Conclusion:The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

Diabetes, and its complications, is a major threat to human health. In this research, we successfully synthesized a new type of glucose-responsive poly(3-acrylamidophenylboronic acid-co-pterostilbene) (p(AAPBA-co-PTE) nanoparticle. The nanoparticles are round in shape with a size between 150 and 200 nm. Insulin-loaded p(AAPBA-co-PTE) nanoparticles can self-adjust according to the changes in glucose concentration in vitro to achieve effective and sustained levels of insulin. P(AAPBA-co-PTE) nanoparticles have good stability, and the drug loading of insulin-loaded p(AAPBA-co-PTE) nanoparticles is up to 16.7%, the encapsulation efficiency is up to 82.4% and the release rate of pterostilbene in vitro is up to 81%. The p(AAPBA-co-PTE) nanoparticles have low toxicity toward cells, and can effectively reduce blood sugar within 24 h. After 14 days of treatment, an animal model of myocardial ischemia-reperfusion injury (MI/RI) was established. After treatment with the insulin-loaded p(AAPBA-co-PTE) nanoparticles, the rat heart function was significantly improved, and the levels of inflammatory factors were significantly reduced. P(AAPBA-co-PTE) nanoparticles were therefore successfully synthesized, and had good performance. P(AAPBA-co-PTE) nanoparticles appear to have the effect of reducing blood sugar and preventing MI/RI, and may be valuable for the development of treatments for MI/RI.

目的:采用网络药理学联合生物信息学的分析方法,探讨便可通片治疗便秘性肠易激综合征(C-IBS)的潜在作用机制.方法:构建便可通片归经络网,分析方中9味药合用的治疗规律.依托中药系统药理学数据库与分析平台(TCMSP)数据库,以口服生物利用度(OB)和类药性(DL)为标准筛选便可通的活性成分及靶点.通过GeneCards,人类孟德尔遗传数据库(OMIM),DrugBank和DisGeNet数据库获得C-IBS治疗相关靶标集,并构建蛋白质-蛋白质相互作用(PPI)网络,利用Cytoscape 3.7.2进行网络可视化,筛选关键靶点,在DAVID平台进行基因本体(GO)注释和京都基因与基因组百科全书(KEGG)富集分析.采用冰水灌胃法制备C-IBS小鼠模型,通过酶联免疫吸附测定法(ELISA)和免疫组化法验证整合分析中便可通片抗C-IBS关键靶点的表达.结果:大肠经为便可通片治疗的主要病位.便可通片中70个潜在活性成分,可作用于227个交集靶点,通过辅助性T细胞17(Th17)细胞分化,Toll样受体,肿瘤坏死因子等多条信号通路参与炎症反应、免疫调控、肠神经调节、激素调节和氧化应激反应,发挥治疗C-IBS的作用.在体实验发现便可通片可显著提高小肠推进率,上调C-IBS小鼠血清和结肠组织血管活性肠肽(VIP)的表达;且便可通片可降低血清及结肠组织中网络预测关键蛋白核转录因子-κB(NF-κB),白细胞介素-6(IL-6),Toll样受体2(TLR2)的表达,证实了整合分析的可靠性.结论:便可通片通过"多成分,多靶点,多途径"发挥协同抗C-IBS的作用,此研究为深入阐释便可通治疗C-IBS的临床研究及进一步实验验证提供了思路.

目的:构建20批杜仲黑茶指纹图谱,联合其抗氧化活性建立"谱-效"相关模型,结合网络药理学方法,预测其潜在抗氧化活性成分及生物通路和机制.方法:采用高效液相色谱(HPLC)法测定杜仲黑茶中主要成分含量;以化学计量学方法建立主要成分与抗氧化活性的相关性;通过TCMSP、Swiss Target Prediction、BATMAN-TCM等数据库获得杜仲黑茶高"谱-效"相关成分及靶点,通过PPI和KEGG分析对杜仲黑茶抗氧化活性成分及其作用机制进行靶向预测,进一步筛选潜在活性标志物.结果:基于杜仲黑茶指纹图谱对其9种主要成分采用Person相关性分析,筛选出7种潜在活性标志物,包括表没食子儿茶素没食子酸酯、芦丁、新绿原酸、绿原酸、原儿茶酸、没食子酸和槲皮素-3-0-桑布双糖苷.利用网络药理学方法构建了杜仲黑茶-特征成分-靶点网络,其中MAPK3、TNF、IL-6、CXCL8、VEGFA、JUN等为关键靶点,而杜仲黑茶抗氧化活性主要涉及氮代谢、TNF信号通路、HIF-1信号通路、VEGF信号通路、Rap1信号通路等.结论:采用"谱-效"相关和网络药理学方法进行杜仲黑茶抗氧化活性研究,为其质量控制提供了新的思路.

Objective: To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang (复方阿胶浆, FFEJJ) on aplastic anemia (AA) using integrated network pharmacology and serum metabolomics. Methods: Traditional Chinese Medicine Systems Pharmacology (TCMSP), Pubmed, integrative pharmacology-based research platform of traditional Chinese medicine (TCMIP), and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) were used to identify the constituents and putative targets of FFEJJ. GeneCards and DisGeNET databases were used to identify AA-associated targets. We constructed a herb-component-target network and analyzed the protein-protein interaction (PPI) network. Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. In addition, an AA model was established using acetylphenylhydrazine (APH) and cetylphenylhydrazine (CTX). Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ. Results: A total of 30 active components of FFEJJ and 24 targets were related to AA. PPI network analysis showed that VEGFA, AKT1, IL-6, CASP3, and ICAM1 were key nodes overlapping with proteins known to be related to AA. KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment. A total of 423 metabolite biomarkers were identified between the control and AA models, which are involved in the development of AA. In contrast, FFEJJ reversed the 79 differential metabolites altered by AA. Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways. Among them, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment, which partially conforms with network pharmacology. The interaction network formed by three key differential metabolites, including hydroxy-eicosatetraenoic acid (HETE), sphingosine 1-phosphate (S1P), and lysophosphati-dylcholine (lysoPC), and three predicted network targets (VEGFA, CASP3, and ICAM1) may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ. Conclusion: FFEJJ could be an alternative treatment option for AA. It acts by promoting hematopoiesis and improving the hematopoietic microenvironment. Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.

Anthocyanins contribute to most colors of plants and play protective roles in response to abiotic stresses. Brassica napus is widely cultivated worldwide as both an oilseed and a vegetable. However, only several high anthocyanin-containing cultivars have been reported, and the mechanisms of anthocyanin accumulation have not been well-elucidated in B. napus. Here, the phenotype, comparative whole-genome identification, and gene expression analysis were performed to investigate the dynamic change of the anthocyanin content and the gene expression patterns of anthocyanin biosynthetic genes (ABGs) in B. napus. A total of 152 ABGs were identified in the B. napus reference genome. To screen out the critical genes involved in anthocyanin biosynthesis and accumulation, the RNA-seq of young leaves of two B. napus lines with purple leaves (PL) or green leaves (GL), and their F1 progeny at 41, 91, and 101 days were performed to identify the differentially expressed genes. The comparative expression analysis of these ABGs indicated that the upregulation of TT8 together with its target genes (such as DFR, ANS, UFGT, and TT19) might promote the anthocyanin accumulation in PL at the early developmental stage (41–91 days). While the downregulation of those ABGs and anthocyanin degradation at the late developmental stage (91–101 days) might result in the decrease in anthocyanin accumulation. Our results would enhance the understanding of the regulatory network of anthocyanin dynamic accumulation in B. napus.

目的:探讨四物膏对再生障碍性贫血(AA)模型大鼠骨髓造血功能和Toll样受体4(TLR4)/核转录因子-KB(NF-κB)信号通路的调控作用.方法:SD大鼠随机分为正常组、模型组、阳性药(复方阿胶浆10.8 g-kg-1)组、四物膏高、低剂量(22.68,5.67 g-kg-1)组,采用乙酰苯肼(APH)联合环磷酰胺(CTX)注射,建立AA大鼠模型,每天灌胃灌胃给予相应药物,连续15 d.检测大鼠外周白细胞(WBC),红细胞(RBC),血红蛋白(HGB),红细胞积压(HCT)和血小板(PLT)水平;计算比较胸腺和脾脏指数;酶联免疫吸附测定(ELISA)检测大鼠血清白细胞介素-3(IL-3)和白细胞介素-6(IL-6)水平,苏木素-伊红(HE)染色观察骨髓病理形态学变化,蛋白免疫印迹法(Western blot)和实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠股骨骨髓细胞中TLR4和NF-κB蛋白及mRNA表达.结果:与正常组比较,模型组WBC,RBC,HGB,HCT和PLT水平明显降低,胸腺指数显著下降,脾脏指数显著增加,血清IL-3水平下降,IL-6水平升高,股骨骨髓中粒细胞和巨核细胞减少,髓腔内充填水肿的血管纤维脂肪组织,纤维化明显,骨髓细胞TLR4和NF-κB蛋白及mRNA表达显著升高(P＜0.01);与模型组比较,四物膏高剂量组大鼠外周血细胞WBC,RBC,HCT和PLT水平增加,胸腺指数增加,脾脏指数减少,IL-3水平升高,IL-6水平下降,股骨骨髓病理形态轻微改善,骨髓细胞TLR4和NF-κB蛋白及mRNA表达明显下降(P＜0.05,P＜0.01).结论:四物膏可能通过调控机体骨髓炎症信号通路TLR4/NF-KB的表达,改善AA模型大鼠骨髓造血功能.

The contamination of soils with cadmium (Cd) has become a serious environmental issue that needs to be addressed. Elucidating the mechanisms underlying Cd accumulation may facilitate the development of plants that accumulate both high and low amounts of Cd. In this study, a combination of phenotypic, physiological, and comparative transcriptomic analyses was performed to investigate the effects of different Cd concentrations (0, 5, 10, 30, 50 mg/kg) on Brassica juncea L. Our results suggest that B. juncea L. seedlings had a degree of tolerance to the 5 mg/kg Cd treatment, whereas higher Cd stress (10–50 mg/kg) could suppress the growth of B. juncea L. seedlings. The contents of soluble protein, as well as MDA (malondialdehyde), were increased, but the activities of CAT (catalase) enzymes and the contents of soluble sugar and chlorophyll were decreased, when B. juncea L. was under 30 and 50 mg/kg Cd treatment. Comparative transcriptomic analysis indicated that XTH18 (xyloglucan endotransglucosylase/hydrolase enzymes), XTH22, and XTH23 were down-regulated, but PME17 (pectin methylesterases) and PME14 were up-regulated, which might contribute to cell wall integrity maintenance. Moreover, the down-regulation of HMA3 (heavy metal ATPase 3) and up-regulation of Nramp3 (natural resistance associated macrophage proteins 3), HMA2 (heavy metal ATPase 2), and Nramp1 (natural resistance associated macrophage proteins 1) might also play roles in reducing Cd toxicity in roots. Taken together, the results of our study may help to elucidate the mechanisms underlying the response of B. juncea L. to various concentrations of Cd.

Chronical hyperuricemia, a severe metabolic disease characterized by increased serum uric acid, urea nitrogen, and creatinine, has a positive correlation with the risks of gouty arthritis, diabetes, hypertension, and kidney damage. Abnormal purine metabolism and reduced uric acid excretion are the major causes of hyperuricemia, which, thus, points to a potential strategy of preventing from or delaying the progress of hyperuricemia-related diseases and its complications by effectively controlling the serum uric acid level. Increasing evidence has revealed that Chinese medicines alleviate hyperuricemia through regulating intestinal flora, which plays a pivotal role in regulating metabolites, including uric acid level. The disease treatment with traditional Chinese medicine is based on syndrome differentiation, and Chinese medicines often have multiple effects and a wide range of targets. In this review, we summarized the anti-hyperuricemia effects and mechanisms of active compounds in Chinese medicines, single Chinese medicinal herbs, and Chinese medicinal prescriptions in regulating the uric acid level via intestinal flora and metabolites, which will be helpful for further study and application of Chinese medicines in hyperuricemia treatment.