Potential mechanisms of formononetin against inflammation and oxidative stress: a review.

Formononetin (FMNT) is a secondary metabolite of flavonoids abundant in legumes and graminaceous plants such as Astragalus mongholicus Bunge [Fabaceae; Astragali radix] and Avena sativa L. [Poaceae]. Astragalus is traditionally used in Asia countries such as China, Korea and Mongolia to treat inflammatory diseases, immune disorders and cancers. In recent years, inflammation and oxidative stress have been found to be associated with many diseases. A large number of pharmacological studies have shown that FMNT, an important bioactive metabolite of Astragalus, has a profoundly anti-inflammatory and antioxidant potential. This review focuses on providing comprehensive and up-to-date findings on the efficacy of the molecular targets and mechanisms involve of FMNT and its derivatives against inflammation and oxidative stress in both in vitro and in vivo. Relevant literature on FMNT against inflammation and oxidative stress between 2013 and 2023 were analyzed. FMNT has antioxidant and anti-inflammatory potential and shows mild or no toxicity in various diseases. Moreover, in the medical field, FMNT has shown potential in the prevention and treatment of cancers, neurological diseases, fibrotic diseases, allergic diseases, metabolic diseases, cardiovascular diseases, gastrointestinal diseases and autoimmune diseases. Thus, it is expected to be utilized in more products in the medical, food and cosmetic industries in the future.

[Mechanism of Ganke Granules intervening acute lung injury based on network pharmacology and experimental verification].

This study aims to explore the potential mechanism of action in the intervention of acute lung injury(ALI) based on the blood entry components of Ganke Granules in rats and in conjunction with network pharmacology, molecular docking, and animal experimental validation. The blood entry components of Ganke Granules in rats were imported into the SwissTargetPrediction platform to predict drug targets, and ALI-related targets were collected from the disease database. Intersections were taken, and protein-protein interaction(PPI) networks were constructed to screen the core targets, followed by Gene Ontology(GO) functional and Kyoto encyclopedia of genes and gnomes(KEGG) pathway enrichment analyses. A "blood entry components-target-pathway-disease" network was constructed, and the core components for disease intervention based on their topological parameters were screened. Molecular docking was used to predict the binding ability of the core components to key targets. The key targets of Ganke Granules in the intervention of ALI were verified by the lipopolysaccharide(LPS)-induced ALI mouse model. Through PPI topological parameter analysis, the top six key targets of STAT3, SRC, HSP90AA1, MAPK3, HRAS, and MAPK1 related to ALI were obtained. GO functional analysis showed that it was mainly related to ERK1 and ERK2 cascade, inflammatory response, and response to LPS. KEGG analysis showed that the main enrichment pathways were MAPK, neutrophil extracellular trap(NET) formation, and so on. Six core components(schizantherin B, schisandrin, besigomsin, harpagoside, isotectorigenin, and trachelanthamine) were filtered out by the "blood entry components-target-pathway-disease" network based on the analysis of topological parameters. Molecular docking results showed that the six core components and Tectoridin with the highest content in the granules had a high affinity with the key targets of MAPK3, SRC, MAPK1, and STAT3. In vivo experiment results showed that compared with the model group, Ganke Granules could effectively alleviate LPS-induced histopathological injury in the lungs of mice and reduce the percentage of inflammatory infiltration. The total protein content, nitric oxide(NO) level, myeloperoxidase(MPO) content, tumor necrosis factor-α(TNF-α), gamma interferon(IFN-γ), interleukin-1ß(IL-1ß), interleukin-6(IL-6), vascular endothelial growth factor(VEGF), and chemokine(C-X-C motif) ligand 1(CXCL1) chemokines in bronchoalveolar lavage fluid(BALF) were decreased, and the expression levels of lymphocyte antigen 6G(Ly6G), citrullinated histones 3(Cit-H3), and phosphorylated proteins SRC, ERK1/2, and STAT3 in lung tissue were significantly down-regulated. In conclusion, Ganke Granules could effectively inhibit the inflammatory response of ALI induced by LPS, protect lung tissue, regulate the release of inflammatory factors, and inhibit neutrophil infiltration and NET formation, and the mechanism of action may be related to inhibiting the activation of SRC/ERK1/2/STAT3 signaling pathway.

Ischemic stroke pathophysiology: A bibliometric and visualization analysis from 1990 to 2022.

Background: Pathophysiology plays a significant role in the scientific study of ischemic stroke, and has attracted increasing interest from researchers in the field. However, a comprehensive bibliometric analysis is lacking in this field. The purpose of this study is to identify the current research status and hotspots of ischemic stroke pathophysiology from a bibliometric perspective. Methods: The Web of Science Core Collection database was searched for articles published from 1990 to 2022. CiteSpace, VOSviewer, and R package "bibliometrix" software were used to analyze countries/regions, institutions, journals, authors, papers, and keywords to predict the latest trends in ischemic stroke pathophysiology research. Results: This analysis collected 7578 records of ischemic stroke pathophysiology. China and America emerged as the leading countries in this field, with Harvard University being the most active institution. Among journals and authors in this field, journal Stroke and author Gregory YH Lip published the most papers, while Nature Medicine was the journal with the highest citation per article. Keywords and co-citation clusters were closely related to "central nervous system", "mechanisms", "biochemistry & molecular biology" and "radiology, nuclear medicine & medical imaging", while other related fields, such as peripheral organs damage induced by the central nervous system and rehabilitation after ischemic stroke, require further research efforts. Conclusion: This is the first bibliometric study that comprehensively mapped out the knowledge structure and development trends of ischemic stroke pathophysiology in recent 32 years, which may provide a reference for scholars to explore ischemic stroke pathophysiology.

Salicylic acid regulates phenolic acid biosynthesis via SmNPR1-SmTGA2/SmNPR4 modules in Salvia miltiorrhiza.

Phenolic acids are the main active ingredients in Salvia miltiorrhiza, which can be used for the treatment of many diseases, particularly cardiovascular diseases. It is known that salicylic acid (SA) can enhance phenolic acid content, but the molecular mechanism of its regulation is still unclear. Nonexpresser of PR genes 1 (NPR1) plays a positive role in the SA signaling pathway. In this study, we identified a SmNPR1 gene that responds to SA induction and systematically investigated its function. We found that SmNPR1 positively affected phenolic acid biosynthesis. Then, we identified a novel TGA transcription factor, SmTGA2, which interacts with SmNPR1. SmTGA2 positively regulates phenolic acid biosynthesis by directly up-regulating SmCYP98A14 expression. After double-gene transgenic analysis and other biochemical assays, it was found that SmNPR1 and SmTGA2 work synergistically to regulate phenolic acid biosynthesis. In addition, SmNPR4 forms a heterodimer with SmNPR1 to inhibit the function of SmNPR1, and SA can alleviate this effect. Collectively, these findings elucidate the molecular mechanism underlying the regulation of phenolic acid biosynthesis by SmNPR1-SmTGA2/SmNPR4 modules and provide novel insights into the SA signaling pathway regulating plant secondary metabolism.

The SmNPR4-SmTGA5 module regulates SA-mediated phenolic acid biosynthesis in Salvia miltiorrhiza hairy roots.

Phenolic acids are the main bioactive compounds in Salvia miltiorrhiza, which can be increased by salicylic acid (SA) elicitation. However, the specific molecular mechanism remains unclear. The nonexpresser of PR genes 1 (NPR1) and its family members are essential components of the SA signaling pathway. Here, we report an NPR protein, SmNPR4, that showed strong expression in hairy root after SA treatment, acting as a negative moderator of SA-induced phenolic acid biosynthesis in S. miltiorrhiza (S. miltiorrhiza). Moreover, a basic leucine zipper family transcription factor SmTGA5 was identified and was found to interact with SmNPR4. SmTGA5 activates the expression of phenolic acid biosynthesis gene SmTAT1 through binding to the as-1 element. Finally, a series of biochemical assays and dual gene overexpression analysis demonstrated that the SmNPR4 significantly inhibited the function of SmTGA5, and SA can alleviate the inhibitory effect of SmNPR4 on SmTGA5. Overall, our results reveal the molecular mechanism of salicylic acid regulating phenolic acid biosynthesis in S. miltiorrhiza and provide new insights for SA signaling to regulate secondary metabolic biosynthesis.

Unlocking Migratory Insertion in Gold Redox Catalysis.

Exploration of elementary reactions in organometallic catalysis is an important method with which to discover new reactions. In this article, we report a gold(I)-catalyzed iodo-alkynylation of benzyne involving the merging of challenging migratory insertion and an oxidative addition process in gold catalytic cycle. A wide range of structurally diverse alkynyl iodides are good coupling partners in this iodo-alkynylation transformation. Both aliphatic and aromatic alkynyl iodides can react with benzynes smoothly to afford highly functionalized 1,2-disubstituted aromatics in moderate to good yields. Its good functional group compatibility and late-stage application of complex molecules demonstrate its synthetic robustness. Studies of the mechanism reveals the feasibility of oxidative addition and the DFT calculations demonstrate the possible migratory insertion of benzyne into AuIII -carbon bonds in the AuI /AuIII redox catalytic cycle, representing an important step towards an elementary reaction in gold chemistry research.

MAPKK2/4/5/7-MAPK3-JAZs modulate phenolic acid biosynthesis in Salvia miltiorrhiza.

Phenolic acids are the major bioactive metabolites produced in Salvia miltiorrhiza, a traditional Chinese medicine called Danshen. Many phytohormone elicitor treatments induce phenolic acid biosynthesis, even though the underlying mechanism remains obscure. Expression pattern analysis showed that SmMAPK3 was highly expressed in leaves, and SmMAPK3 was significantly induced by salicylic acid (SA) and methyl jasmonate (JA). Bioinformatics analysis revealed that SmMAPK3 belongs to group A and contains a TEY motif in the activation loop together with three conserved regions (P-loop, C-loop and CD-domain). A previous study speculated that SmMAPK3 is likely a positive regulator in the biosynthesis of phenolic acids in S. miltiorrhiza. In this study, overexpression of SmMAPK3 increased phenolic acid biosynthetic gene expression and enhanced the accumulation of phenolic acids in S. miltiorrhiza plantlets. Yeast two-hybrid (Y2H) analysis and firefly luciferase complementation imaging (LCI) assays revealed that SmMAPKK2/4/5/7-SmMAPK3-SmJAZs form a cascade that regulates the accumulation of phenolic acids. In summary, this work deepens our understanding of the posttranscriptional regulatory mechanisms of phenolic acid biosynthesis and sheds new light on metabolic engineering in S. miltiorrhiza.

Streptococcus pneumoniae promotes migration and invasion of A549 cells in vitro by activating mTORC2/AKT through up-regulation of DDIT4 expression.

Introduction: Dysbiosis of the lower airway flora is associated with lung cancer, of which the relationship between Streptococcus, especially pathogenic Streptococcus pneumoniae (S. pneumoniae), and the progression of lung cancer are unclear. Methods: Bronchoalveolar lavage fluid (BALF) samples were prospectively collected from patients with pulmonary nodules during diagnostic bronchoscopy, and finally included 70 patients diagnosed with primary lung cancer and 20 patients with benign pulmonary nodules as the disease control group. The differential flora was screened by 16S ribosomal RNA (rRNA) gene amplicon sequencing. An in vitro infection model of lung adenocarcinoma (LUAD) cells exposed to S.pneumoniae was established to observe its effects on cell migration and invasion ability. Exploring the molecular mechanisms downstream of DDIT4 through its loss- and gain-of-function experiments. Results: 16S rRNA sequencing analysis showed that the abundance of Streptococcus in the lower airway flora of lung cancer patients was significantly increased. After exposure to S. pneumoniae, A549 and H1299 cells significantly enhanced their cell migration and invasion ability. The results of DDIT4 loss- and gain-of-function experiments in A549 cells suggest that up-regulation of DDIT4 activates the mTORC2/Akt signaling pathway, thereby enhancing the migration and invasion of A549 cells while not affecting mTORC1. Immunofluorescence (IF) and fluorescence in situ hybridization (FISH) showed that S. pneumoniae was enriched in LUAD tissues, and DDIT4 expression was significantly higher in cancer tissues than in non-cancerous tissues. The increased expression of DDIT4 was also related to the poor prognosis of patients with LUAD. Discussion: The data provided by this study show that S. pneumoniae enriched in the lower airway of patients with lung cancer can up-regulate DDIT4 expression and subsequently activate the mTORC2/AKT signal pathway, thereby increasing the migration and invasion abilities of A549 cells. Our study provides a potential new mechanism for targeted therapy of LUAD.

Antigen Epitope Developed Based on Acinetobacter baumannii MacB Protein Can Provide Partial Immune Protection in Mice.

Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen widely present in medical environment. Given its complex drug resistance, A. baumannii poses a serious threat to the safety of critically ill patients. Given the limited alternative antibiotics, nonantibiotic-based functional anti-A. baumannii infection proteins must be developed. In this study, we firstly used a series of biological software to predict potential epitopes in the MacB protein sequence and verified them by antibody recognition and lymphocyte proliferation tests. We finally screened out B cell epitope 2, CD8+ T cell epitope 7, and CD4+ T cell epitope 11 and connected them to construct a recombinant antigen epitope (RAE). The determination of IgG in the serum of immunised mice and cytokines in the supernatant of lymphocytes showed that the constructed epitope induced an immune response mediated by Th-1 cells. Finally, the challenge experiment of A. baumannii infection in mice confirmed that the epitope developed based on MacB, especially RAE, provided incomplete immune protection for mice.

Genome-wide characterization and expression profiling of MAPK cascade genes in Salvia miltiorrhiza reveals the function of SmMAPK3 and SmMAPK1 in secondary metabolism.

BACKGROUND: The contribution of mitogen-activated protein kinase (MAPK) cascades to plant growth and development has been widely studied, but this knowledge has not yet been extended to the medicinal plant Salvia miltiorrhiza, which produces a number of pharmacologically active secondary metabolites. RESULTS: In this study, we performed a genome-wide survey and identified six MAPKKK kinases (MAPKKKKs), 83 MAPKK kinases (MAPKKKs), nine MAPK kinases (MAPKKs) and 18 MAPKs in the S. miltiorrhiza genome. Within each class of genes, a small number of subfamilies were recognized. A transcriptional analysis revealed differences in the genes' behaviour with respect to both their site of transcription and their inducibility by elicitors and phytohormones. Two genes were identified as strong candidates for playing roles in phytohormone signalling. A gene-to-metabolite network was constructed based on correlation analysis, highlighting the likely involvement of two of the cascades in the synthesis of two key groups of pharmacologically active secondary metabolites: phenolic acids and tanshinones. CONCLUSION: The data provide insight into the functional diversification and conservation of MAPK cascades in S. miltiorrhiza.

MPA-CdTe quantum dots as "on-off-on" sensitive fluorescence probe to detect ascorbic acid via redox reaction.

Mercaptopropionic acid (MPA) capped CdTe quantum dots (MPA-CdTe QDs) were synthesized in aqueous medium by hydrothermal method, which modified by Fe3+ could be used as a fluorescent probe to detect ascorbic acid (AA). MPA-CdTe QDs fluorescence probe could be used as successive sensor for metal ions and AA with "on-off-on" process. The fluorescence of QDs was quenched after adding Fe3+ to MPA-CdTe QDs. Then, the fluorescence of the Fe3+@MPA-CdTe QDs can be sensitively turned on by AA to give an "on-off-on" fluorescence response according to the oxidation-reduction between Fe3+ and AA. There was a linear relationship between fluorescence intensity quenching value and the concentration of Fe3+ in the range of 2-10 µM since Fe3+ sensitively reacted with CdTe QDs. The linear detection range for AA was 0.1-1 µM with a limit of detection of 6.6 nM. The principle is proved by fluorescence emission spectroscopy, nuclear magnetic resonance spectroscopy. The proposed method is successfully used to detect the AA in human plasma sample.

miR­590­5p inhibits tumor growth in malignant melanoma by suppressing YAP1 expression.

The microRNAs (miRNAs/miRs) involved in the carcinogenesis and progression of malignant melanoma (MM) remain unclear. In the present study, miR­590­5p was identified to be upregulated in MM cells compared with human melanocytes using a reverse transcription­quantitative polymerase chain reaction to screen established oncogenic and tumor suppressor miRNAs. miR­590­5p was demonstrated to inhibit the cell proliferation and tumor growth of MM cells in vitro and in vivo by performing Cell Counting Kit­8 and tumour xenograft assays, respectively. In addition, flowcytometry assays indicated that miR­590­5p induced cell apoptosis and cell cycle arrest at the G1 stage in MM cells. Finally, luciferase assays and western blot analysis results confirmed that the transcriptional regulator Yes­associated protein 1 (YAP1) is upregulated and inversely associated with miR­590­5p expression in MM cells, and is the direct target and functional mediator of miR­590­5p in MM. Altogether these results reveal the functional and mechanistic link between miR­590­5p and YAP1 in the progression of MM. Therefore, miR­590­5p is a potential therapeutic target in MM.

Precise theranostic nanomedicines for inhibiting vulnerable atherosclerotic plaque progression through regulation of vascular smooth muscle cell phenotype switching.

Coronary heart disease is a prevalent and fatal killer caused by vulnerable atherosclerotic plaques (VASPs). However, the precise detection and treatment of VASPs remains a difficult challenge. Here, we present the development of noninvasive human serum albumin (HSA)-based theranostic nanomedicines (NMs) for the specific diagnosis and effective therapy of VASPs. Methods: The ICG/SRT@HSA-pept NMs were formulated to contain payloads of the near-infrared (NIR) fluorescent dye indocyanine green (ICG) and the sirtuin 1 (Sirt1) activator SRT1720, and modified with a peptide moiety targeting osteopontin (OPN). The in vivo atherosclerotic mouse model was established with the high-fat diet (HFD). The in vitro vascular smooth muscle cells (VSMCs) phenotypic switching was induced using the ox-LDL stimulation. Results: Due to the overexpression of OPN in activated VSMCs and VASPs, the targeted NMs specifically accumulated within the VASPs region after intravenous injection into the atherosclerotic mice, achieving the precise detection of VASPs. In addition, in the presence of SRT1720, the NMs could activate intracellular Sirt1 and activate an antiatherogenesis effect by inhibiting the phenotypic switching of VSMCs, which is an essential contributor to the vulnerability and progression of atherosclerotic plaques. After therapeutic administration of the ICG/SRT@HSA-pept NMs for two weeks, the physiological sizes and plaque compositions of VASPs were markedly improved. Furthermore, ICG/SRT@HSA-pept NMs-treated mice presented a more favorable plaque phenotype than that was observed in free SRT1720-treated mice, suggesting the enhanced delivery of pharmaceutical agents to the atherosclerotic lesions and improved therapeutic efficacy of NMs compared with free SRT1720. Conclusions: The theranostic ICG/SRT@HSA-pept NMs showed great potential for the precise identification and targeted treatment of atherosclerotic diseases.

lncRNA-ATB functions as a competing endogenous RNA to promote YAP1 by sponging miR-590-5p in malignant melanoma.

The critical long non­coding RNAs (lncRNAs) involved in the carcinogenesis and progression of malignant melanoma (MM) have not been fully investigated. In the present study, it was identified that lncRNA activated by transforming growth factor­ß (lncRNA­ATB) was upregulated in MM tissues and cells compared with benign nevus cells and human melanocytes, via comparative lncRNA screening from Gene Expression Omnibus datasets and reverse transcription­quantitative polymerase chain reaction analysis. Furthermore, lncRNA­ATB promoted the cell proliferation, cell migration, and cell invasion of MM cells in vitro, and tumor growth in vivo. It was additionally identified that lncRNA­ATB attenuated cell cycle arrest and inhibited cellular apoptosis in MM cells. Finally, it was demonstrated that lncRNA­ATB functions as a competing endogenous RNA (ceRNA) to enhance Yes associated protein 1 expression by competitively sponging microRNA miR­590­5p in MM cells. In conclusion, the present study revealed the expression and roles of lncRNA­ATB in MM, and indicated that lncRNA­ATB functions as a ceRNA to promote MM proliferation and invasion by sponging miR­590­5p.

Peiminine serves as an adriamycin chemosensitizer in gastric cancer by modulating the EGFR/FAK pathway.

Gastric cancer (GC) is one of the most common malignancies of the digestive tract. Adriamycin (ADR) has been widely utilized in various chemotherapy regimens for treating GC, yet its long-term application may increase drug resistance resulting in treatment failure. Increasing evidence shows that bioactive natural products can be used as chemotherapeutic sensitizers that can significantly improve chemotherapy sensitivity. Peiminine (PMI) is a biologically active component extracted from Fritillaria walujewii Regel. Thus, in the present study, we aimed to investigate whether peiminine (PMI) alters the chemosensitivity of GC to adriamycin (ADR). GC cells were treated with ADR with or without PMI. MTT assay, flow cytometry and a nude mouse tumor xenograft model of SGC7901 cells were used to evaluate the chemosensitization activity of PMI combined with ADR. Western blotting was used to examine the expression of cyclin D1 and cleaved PARP. The RayBio® Human RTK phosphorylation antibody array kit was used to test the differential protein expression. Compared with the ADR group, PMI combined with ADR significantly suppressed cell proliferation and induced cell apoptosis in vitro. The growth curve and tumor weight of the tumor xenografts were significantly decreased in mice treated with the combination of PMI and ADR. However, the organs showed no obvious abnormality after treatment with PMI plus ADR. The expression of cyclin D1 was decreased and the level of cleaved PARP was increased after treatment with PMI and ADR. The expression of p-EGFR and p-FAK was downregulated in cells treated with PMI and ADR, and the validation of p-EGFR and p-FAK was in accordance with the result of the phosphorylation antibody array kit. PMI may serve as a new chemosensitizer by inhibiting the proliferation and inducing the apoptosis to enhance the chemotherapeutic drug sensitivity of ADR in GC.

IL-17 is a protection effector against the adherent-invasive Escherichia coli in murine colitis.

Inflammatory bowel disease (IBD) is caused by aberrant immune responses to the gut microbiota. Among the gut microbiota, adherent-invasive Escherichia Coli (AIEC) is thought to be the pathogen through invading the intestinal epithelial cells and causing inflammation. IL-17 secretion increase, induced by enhanced bacterial adhesion to the intestine epithelium, could on one hand protect the mucosa, but on the other hand, over amount of IL-17 initializes inflammation reactions that in turn damages the mucosa. The relationship between IL-17 and AIEC is still unclear. In this study, we tried to elucidate the function of IL-17 in AIEC-mediated colitis. Wild type (WT) and IL-17 knockout (IL-17 KO) mice were inoculated with AIEC strain E. coli LF82 and treated with dextran sodium sulphate (DSS). Histological examination of the colon was performed. Mucosa damage was assessed and scored. IL-22 and IL-17 in colon tissues were detected by ELISA, qPCR and immunohistochemistry methods. Transient AIEC colonization in IL-17 KO mice resulted in increased intestinal epithelial damage, systemic bacterial burden and mortality compared with WT controls. Moreover, IL-17 is required for the induction of IL-22 in the experimental animal models during AIEC strain E. coli LF82 colonization. These results indicate IL-17 plays a protective role in AIEC strain E. coli LF82 induced colitis by promoting IL-22 secretion.

CD4+T cell specific B7-H1 selectively inhibits proliferation of naïve T cells and Th17 differentiation in experimental autoimmune encephalomyelitis.

It is widely acknowledged that interleukin 17-producing T helper (Th17) cells are critically participant in the pathogenesis of multiple sclerosis. In the current study, we identified that the expression of CD4+T cells specific co-inhibitory molecule B7-homologue 1(B7-H1) in spleenocytes and mononuclear cells isolated from brains and spinal cord were positive correlated with Th1 and Th17 cells generation and disease severity in experimental autoimmune encephalomyelitis (EAE). Furthermore, B7-H1 transgenic mice developed milder EAE symptoms and fewer Th17 cells than B7-H1 wild type mice. We also found the proliferation of naïve CD4+CD62+T cells isolated from B7-H1 transgenic mice was inhibited. And naïve T cells isolated from B7-H1 transgenic mice produced fewer Th17 cells than WT mice in Th17-polarizing conditions, but the Th1, Th2, and inducible Treg differentiation were the similar in naïve T cells isolated from B7-H1 transgenic mice and WT mice. In conclusion, our study show CD4+T cells specific B7-H1 is a slective inhibitor in proliferation of naïve T cells, Th17 differentiation and pathogenesis of multiple sclerosis.

Protective effects of wedelolactone on dextran sodium sulfate induced murine colitis partly through inhibiting the NLRP3 inflammasome activation via AMPK signaling.

It has been reported that the ethanol extract of Wedelia chinensis attenuates murine colitis. Wedelolactone (WEL), a coumestane-type compound with many pharmacological activities, was isolated from W. chinensis. The present study aims to investigate the beneficial effects and underlying mechanisms of WEL on ulcerative colitis. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of WEL (50mg/kg) significantly attenuated pathological colonic damage and inhibited inflammatory infiltration, myeloperoxidase and alkaline phosphatase activities through MAPKs and NF-κB signaling pathways, while activating AMPK in colons treated with DSS. Further study revealed that WEL treatment dramatically inhibited NLRP3 inflammasome activation and caspase-1 phosphorylation to decrease IL-1ß release in colons treated with DSS. In addition, WEL effectively regulates the disorder of skeleton proteins in colonic epithelial cells NCM460 exposed to TNF-α and protects the intestinal barrier function by activating AMPK in vivo. In summary, the AMPK-NLRP3-IL-1ß signaling axis plays an important role in colitis following WEL treatments. These findings provide new insights into the pharmacological actions of WEL as a potential therapeutic agent for colitis.

Introgression of the crtRB1 gene into quality protein maize inbred lines using molecular markers.

Quality protein maize (QPM; Zea mays L.) has effectively enhanced levels of the amino acids, lysine, and tryptophan, over normal maize and provided balanced dietary protein for the health and development of monogastric animals and humans. However, as in normal maize, QPM varieties are low in provitamin A (ProVA), a precursor of vitamin A, which can lead to vitamin A deficiency in humans when maize is a significant part of their diet. In this study, maize inbred Hp321-1 carrying the favorable alleles crtRB1-5'TE-2 and crtRB1-3'TE-1 that can enhance levels of ProVA, was used as donor for improving ProVA in QPM inbred lines CML161 and CML171. Functional markers for identifying the favorable alleles crtRB1-5'TE-2 and crtRB1-3'TE-1 were used in foreground selection, and simple sequence repeat markers were used in background selection for the BC1F1, BC2F1, and BC2F2 generations. The background recovery rates were 77.4 and 84.5 % for CML161 and CML171 populations, respectively, in the BC1F1 generation, and 89.9 and 92.1 % in the BC2F2 generation. With foreground and background selection, the mean ProVA concentration has been improved from 1.60 µg g-1 in the parent of CML161 to 5.25 µg g-1 in its BC2F3 offspring, from 1.80 µg g-1 in the parent of CML171 to 8.14 µg g-1 in its BC2F3 offspring while maintaining similar QPM characteristics of the recurrent parents. The success from this study offers maize breeders a procedure for increasing ProVA in QPM lines, which will greatly mitigate vitamin A deficiency and protein-energy malnutrition in developing countries.

Immunosuppressive C21 steroidal glycosides from the root of Cynanchum atratum.

Six new C21 steroidal glycosides (1-6) and one dideoxysaccharide (7), named atratcynosides A-F and atratcynose A, were isolated from the 80% ethanol extract of the root of Cynanchum atratum, together with three known compounds (8-10). The structures of the new compounds were determined on the basis of extensive spectral analyses and qualitative chemical methods. All compounds were subjected to detect the immunosuppressive activities by an in vitro model of concanavalin A-induced proliferation of T-lymphocytes from mice. Compounds 1-3 showed significant immunosuppressive activities in dose-dependent manners with the IC50 values from 3.3 to 7.0 µM. Moreover, the structure-activity relationship of the steroidal glycosides on the immunosuppression was analyzed.