BackgroundAging, as a global demographic issue, is characterized by its rapid growth, which drives an increase in people's healthcare awareness. The emergence of wellness bases caters to this market demand. Therefore, the identification of potential areas suitable for wellness activities and the construction of wellness bases, referred to as Wellness Target Areas (WTAs), becomes a crucial first step. Currently, commonly used identification methods are mostly based on traditional statistical approaches, which are often complex, cumbersome, and subject to potential risks of subjective assumptions, affecting the reliability of WTAs identification results. Longevity level serves as a comprehensive indicator reflecting the natural and socio-economic environment of a region, making it the most indicative of the regional wellness environment status.MethodsThis study proposes using longevity level as the benchmark for WTAs identification to simplify the identification process and reduce the impact of subjective bias on the results. The study focuses on 129 county-level units in Yunnan Province. Firstly, the Geodetector (GD) is utilized to explore the complex interaction between the longevity level and the geographical environment to determine regional wellness factors. Secondly, using ArcGIS and geographical weighted regression (GWR), the study investigates the role of different wellness factors, ultimately classifying and grading the WTAs.ResultsThe longevity level in Yunnan Province exhibits a pattern of multi-point clustering, forming three major longevity regions. Factors that significantly influence longevity level include annual average precipitation, sunshine duration, PM2.5 content, per capita disposable income, density of tourist attractions, and distance from residential areas to hospitals. Based on the degree of longevity and the contribution rate of influencing factors, Yunnan Province's WTAs are classified into three levels and two types (natural and comprehensive).ConclusionOur study aims to establish a connection between longevity level and the selection of wellness bases, exploring regional wellness factors through the relationship between longevity phenomena and geographical environment, identifying potential construction areas for wellness bases (i.e., WTAs), providing new insights for the precise selection of wellness bases, effectively enhancing the scientificity of site selection, promoting population health, and contributing to the global aging process with better health.

Cremastrae Pseudobulbus Pleiones Pseudobulbus (CPPP) is derived from the dried pseudobulb of the orchid family plants Cremastra appendiculata (D.Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, or Pleione yunnanensis Rolfe, and has the properties of clearing heat, detoxification, resolving phlegm, and dispersing nodules. It is frequently used for the treatment of various malignant tumors in clinical practice, especially lung cancer. CPPP is divided into two commercial specifications in the market, Maocigu (MCG) and Bingqiuzi (BQZ). However, owing to a lack of appropriate research strategies, the active ingredients and molecular mechanisms involved have not yet been clarified. This study intended to discover the combination of effective anti-lung-cancer ingredients in CPPP and explore their potential mechanisms of action. In this study, UHPLC-MS fingerprints of MCG and BQZ were established separately. Inhibitory effects on the proliferative viability and migratory ability of A459 and H1299 cells were evaluated as pharmacodynamic indicators. GRA and BCA were used to determine spectrum–effect relationships. Next, the identification and analysis of components of drug-containing serum were performed using UHPLC-Q-Exactive Orbitrap MS. Then, the results of the two analyses were combined to jointly screen out the anti-lung-cancer candidate active monomers of CPPP, and their in vitro activities were verified. Afterward, all effective ingredient combinations of MCG (MCGC) and BQZ (BQZC) were prepared according to their contents in the original medicinal materials. Their anti-lung-cancer activities in vitro and in vivo were compared and verified. Finally, we used the human lung cancer cell line A549 and the Lewis tumor xenograft model to investigate how BQZC would influence autophagy and apoptosis processes and the mechanisms involved. Overall, 11 predominant anti-lung-cancer active ingredients from CPPP were screened. Next, MCGC and BQZC were prepared according to their contents in the original medicinal materials, respectively, and their anti-tumor effects were equivalent to those of the original materials in vitro and in vivo. We found that BQZC could inhibit lung cancer cell growth and induce protective autophagy and apoptosis in lung cancer cells by activating the AMPK–mTOR–ULK1/BMF signaling pathway. These results provide important evidence for the clinical application and deep development of CPPP against tumors.

OBJECTIVE: To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis(UC). METHODS: The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice. RESULTS: The Shuangling extract reduced the levels of seruminterleukin-1β(IL-1β), tumor necrosis factor-α(TNF-N), interleukin-6(IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways. CONCLUSION: The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.

Context: Gout is a chronic disease that imposes a huge financial and health burden on patients, which might diminish quality of life. Qin Jiao, a perennial herb found in northwestern China and Japan, is commonly used for treating various ailments.Objective: This study investigates the effects of Qin Jiao on gout and joint inflammation and elucidates its potential mechanism for gouty arthritis.Materials and methods: Study 1, a literature review was conducted using PubMed, Web of Science, and CNKI to assess the applications of Qin Jiao in arthritis treatment. Study 2 was performed to discover the component targets and gouty disease targets via TCMSP, OMIM, GeneCards and DRUGBANK, and network pharmacology analysis. Study 3, male Sprague-Dawley (SD) rats were divided into normal, model, colchicine, Qin Jiao low-dose (QJL), and Qin Jiao high-dose group (QJH), oral gavage for 40 d. Serum, synovial fluid, and synovial membrane tissue were collected to measure the expression levels of IL-1 beta, IL-6, and STAT3.Results: The research also identified potential targets and pharmacological pathways of Qin Jiao for gout treatment. In vivo study demonstrated Qin Jiao can reduce IL-1 beta levels in serum and ankle flushing fluid. ELISA analysis confirmed that Qin Jiao significantly reduces the protein expression of IL-6 and STAT3.Discussion and conclusion: Qin Jiao exerts anti-inflammatory effects on gouty arthritis by modulating the IL-6/STAT3 pathway. This study provides a biological basis for the use of Qin Jiao in treating arthritis-related diseases and offers experimental evidence for potential future drug development.

Anthracycline induced cardiotoxicity, represented by Doxorubicin (DOX), is the main side effect limiting the use of anthracyclines as effective chemotherapeutic agents. These mechanisms have not been fully elucidated. It is necessary to refine the mechanisms of DOX cardiotoxicity and to develop drugs that can counteract DOX cardiotoxicity. In previous studies, the saffron extract was reported to successfully relieve DOX cardiotoxicity, but the mechanisms are unclear. First, we quantified 3423 proteins in the hearts of DOX group rats vs. control group rats using proteomics with high-sensitivity mass spectrometry to identify key proteins and signaling pathways. Furthermore, the important role of ribosomal proteins in the mechanism of DOX cardiotoxicity was revealed by the GEO transcriptome dataset and the literature on ribosomal protein ubiquitination. Second, we analyzed the key mechanisms and targets of saffron against DOX cardiotoxicity via 4D label-free proteomics. Through validation by ELISA, we identified the proteins XIRP2, EPHX1, SORBS2, CD81, FLOT2, FLOT1, CD59, DCN, CTSD and HSPA5 as critical targets of saffron extract against DOX cardiotoxicity. These discoveries have contributed to a deeper understanding of the mechanisms of DOX cardiotoxicity, as well as to the identification of the key therapeutic targets of saffron for preventing DOX cardiotoxicity.

BackgroundAlzheimer’s disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action.ObjectiveThe present study aimed to clarify CR’s active constituents and its pharmacological mechanisms in treating AD.MethodsA D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia.ResultsThe results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR’s efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation.ConclusionThe present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.

The complexity of cancer itself and treatment makes pharmacovigilance critical in oncology. Despite rapid progress on pharmacovigilance and cancer research in the past two decades, there has been no bibliometric analysis in this field. Therefore, based on the Web of Science database, we used CiteSpace, VOS-viewer and R-bibliometrix to analyze and visualize publications, and described the development trend and research hot spots in this field. 502 publications were included. The development of pharmacovigilance and cancer research has continued to grow. The USA has the largest number of publications and citations, followed by France and UK. Vanderbilt University and Sorbonne University are the institutions that contribute the most papers, and 5 of the top 10 high-yield institutions are from France. Salem JE and Lebrun-Vignes B of Sorbonne University have published the most papers, and they have a strong cooperative relationship. Salem JE has the highest H index. Drug Safety has the largest number of publications in the field of pharmacovigilance and cancer, with a high impact factor (IF). In recent years, immune checkpoint inhibitors (ICIs) have been identified as a hot topic and will continue to be maintained. This paper can help researchers get familiar with the current situation and trend of pharmacovigilance and cancer research, and provide valuable reference for the selection of future research directions.

Gout is the most common inflammatory arthritis with an increasing prevalence and incidence across the globe. We aimed to provide a comprehensive and systematic knowledge map of gout research to determine its current status and trends over the past decade. Publications on gout research were obtained from the Web of Science Core Collection (WOSCC) database. Bibliometric R, VOSviewer, and Citespace were employed to analyze the eligible literature. A total of 5535 publications concerning gout research between 2012 and 2021 were included. Most publications and citations both numerically came from China. The strongest international cooperation belonged to the USA. The University of Auckland was the most productive institution with a leading place in research collaboration. The prime funding agency was the National Natural Science Foundation of China. Most papers were published in Clinical Rheumatology. Annals of the Rheumatic Diseases achieved the highest number of citations, H-index and IF, which showed the most excellent comprehensive strength. The individual author with the most paper authorship was Dalbeth Nicola with 241 publications and 46 H-index. Keywords and co-citation analysis discovered that pathological mechanism remains the future hotspot in gout research. It may involve gout connection with gut microbiota, NLRP3 inflammasome, xanthine oxidase, and urate-transporter ABCG2. In addition, besides metabolic diseases, the relationship between gout and heart failure may need more attention. This study clarified the current status and research frontier in gout over the past decade, which would provide valuable research references for later researchers.

Gout is a metabolic disease affected by monosodium urate (MSU) deposition, which is directly related to hyperuricemia. Recent reports on the prevalence and incidence of gout have been widely circulated worldwide. Currently, the anti-gout drugs in clinical practice are mainly small-molecule synthetic drugs, and the effectiveness and safety are limited. Reducing uric acid and inhibiting inflammation are the focused areas of drug research and development on gout. Rutin, a natural flavonoid, has been reported to alleviate inflammation in various diseases. However, whether rutin exerts protective effects on gout remains to be elucidated. This study used quails without urate oxidase as experimental animals to induce endogenous gout models through a high purine diet. We confirmed that quail in the model group developed gout symptoms at 30 days of the experiment. And the targets of uric acid metabolism, oxidative stress level, and NLRP3 inflammasome were dysregulated in quails. Rutin treatment improves gout and reduces inflammatory expression in quail. We further confirmed that rutin treatment reduced XOD activity and uric acid levels in quail. And rutin inhibited ROS production, restored oxidative stress balance, inhibited NLRP3 inflammasome activation, and exerted anti-inflammatory effects. We extracted and identified the fibroblast-like synoviocytes (FLS) for the first time. The results showed that rutin could reduce ROS production and NLRP3 inflammasome activation of FLS after uric acid stimulation. In conclusion, our findings underscore that rutin may be a gout protective agent by reducing XOD activity, inhibiting ROS production and NLRP3 inflammasome activation. Meanwhile, this study also provides an available animal model for the research drugs of gout.

Abstract Objective:This study investigated the regulatory mechanism of the NLRP3/GSDMD pathway in GA pyroptosis using network pharmacology and in vitro and in vivo experiments. Methods:In this study, network pharmacology was used to predict the mechanism of pyroptosis in Gouty arthritis, and HE, ELISA, Real-time PCR, Western blot, immunoprecipitation, and flow cytometry were used to further investigate the mechanism of NLRP3/GSDMD signal axis in GA rat model induced by MSU and THP-1 cells induced by MSU. Results:When gout arthritis pyroptosis occurred, the NOD-like receptor pathway was activated, as determined by network pharmacology. In the rat model of GA induced by MSU, the swelling degree, pathological damage, serum biochemical indices, and inflammatory factors of the joints were significantly increased, and the expressions of key pyroptosis proteins such as NLRP3, GSDMD, ASC, Caspase-1, and IL-1β were significantly increased in ankle joints, indicating the existence of a NOD-like receptor pathway mediating pyroptosis during the acute attack of GA. The results of NLRP3 and GSDMD inhibitor intervention showed that inhibitor intervention significantly inhibited the expression of pyroptosis protein. At the same time, it was found that the activation of NLRP3 inflammatory bodies was inhibited, and the expressions of GSDMD, ASC, Caspase-1 and IL-1β protein were down-regulated, but the expression of NLRP3 protein was not affected by inhibiting the activation of GSDMD and down-regulating the expression of IL-1β. The results of the cell experiment revealed that the inhibitor group prevented MSU-induced Nod-like receptor-mediated pyroptosis in THP-1. Co-precipitation results also revealed a close interaction between NLRP3 and GSDMD. Conclusion:Inhibiting the NLRP3/GSDMD signaling axis can further reduce the occurrence of pyroptosis and thus alleviate the inflammatory response in acute Gouty arthritis attacks. Through a Caspase-1-dependent mechanism, NLRP3 regulates the process of pyroptosis in the occurrence of Gouty arthritis.

Selenium (Se) is essential for the modification of human life functions and has a double-edged sword effect. However, the development of Se supplements for both medicinal and dietary is rare. Critical in vivo and in vitro correlation studies still unexplored. In this study, we developed Se-enriched chicory for the first time using chicory as a model plant. The distribution of Se and its species transformation were elucidated. In vivo and in vitro absorption correlation, safety and risk-benefit management were also focused. Results in this study showed that foliar Se application is more beneficial for cultivating Se-enriched chicory compared to root application. What is striking is SeIV converted to SeVI, SeMet, SeCys2 and SeMeCys in chicory, which is more favorable for human absorption and reduces toxicity. In gastric phase in vitro, Se from Se-enriched chicory exhibited high bioaccessibility (79.4%). The relative bioavailability of liver and kidneys as effect endpoints in vivo at high exposure to Se with 76.5%. In addition, this study first analyzed and established robust in vivo-in vitro correlations of Se in Se-enriched chicory. The prediction model for liver-gastric fluid had the best correlation (R2 = 0.853, p < 0.05). Meanwhile, graded assessment strategy revealed that the risk-benefit of Se-enriched chicory for dietary and TCM needs to be balanced separately. All evidence suggests that Se-enriched chicory could be a new candidate plant for Se supplements in the event of Se deficiency. This research will provide cases and insights into future studies and reduce the uncertainty of Se intake risk and benefit assessment from Se-enriched products.

BackgroundGout is a progressive metabolic disease closely related to hyperuricemia and urate deposition, with an increasing prevalence and incidence across the globe. Recent studies have shown that the pathological process of gout includes two stages: asymptomatic hyperuricemia and MSU crystal deposition. However, the immune response during the development of hyperuricemia to gouty arthritis is not fully elucidated.MethodsThus, an overnutrition-induced whole-course gout model was established to clarify the immune response and pathological changes in the development from hyperuricemia to gouty arthritis. The quails without urate oxidase were used as experimental animals. And we confirmed that uric acid metabolic targets were changed when quails were in the asymptomatic hyperuricemia stage. ResultsWhen the quail showed gout symptoms, the NLRP3 inflammasome was activated, and the expressions of IL-1β, TNF-α, IL-6, IL-8, and IL-18 were significantly increased. The relationship between the uric acid metabolism target and the NLRP3 inflammasome may be the critical immune response between hyperuricemia and gouty arthritis. Our data showed that, in the process of gout disease, the expression of xanthine oxidase (XOD) has been increasing, which increases the level of uric acid, disrupts the balance of oxidative stress, generates a large amount of ROS, activates the NLRP3 inflammasome, and release IL-1β. Treatment with the XOD inhibitor can reduce uric acid, restore the body’s degree of peroxidative damage and antioxidant capacity, and inhibit NLRP3 inflammasome and IL-1β. In vitro, we extracted and identified primary fibroblast-like synoviocytes (FLS) from quail for the first time. Stimulating FLS with uric acid also caused ROS release and NLRP3 inflammasome activation. However, treatment with an XOD inhibitor prevented all these responses in FLS. ConclusionOur results indicate that the immune response between the uric acid metabolism target XOD and NLRP3 inflammasomes plays a crucial role in developing hyperuricemia to gouty arthritis, and inhibition of both XOD and NLRP3 inflammasomes may be an effective treatment for avoiding the development of asymptomatic hyperuricemia to MSU crystal deposition. Meanwhile, this study also provides an advantageous animal model for pathological mechanisms and research and development drugs for gout.

Background To investigate the pharmacological mechanism of Zhizhu pill (ZZP) against gastroesophageal reflux disease (GERD), network pharmacology in combination with molecular docking was applied in this study. Methods Active compounds of ZZP and target genes related to GERD were identified through public databases. Subsequently, the obtained data were used as a basis for further network pharmacological analysis to explore the potential key active compounds, core targets, and biological processes involved in ZZP against GERD. Finally, the results predicted by network pharmacology were validated by molecular docking. Results Twenty active components of ZZP were identified to act on 59 targets related to GERD. Enrichment analysis revealed that multiple biological processes including response to oxygen levels, response to oxidative stress, and response to reactive oxygen species were involved in the GERD ZZP treatment with ZZP. ZZP had an impact on the prognosis of GERD mainly through the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and pathways in cancer. Further analysis identified the key components and core targets of ZZP against GERD, of which nobiletin, didymin, luteolin, and naringenin were key components, and PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA were the core targets. Molecular docking verified the stable bonds formed between the key components and the core targets. Conclusions The results of this study predict that the therapeutic effects of ZZP in GERD are mediated at least in part via PPARG, MMP9, JUN, TP53, PTGS2, EGFR, MAPK3, CASP3, AKT1, and VEGFA. These results may be useful in providing an experimental basis and new ideas for further research on ZZP in GERD.

Anthracyclines constitute the cornerstone of numerous chemotherapy regimens for various cancers. However, the clinical application of anthracyclines is significantly limited to their dose-dependent cardiotoxicity. A comprehensive understanding of the current status of anthracycline-induced cardiotoxicity is necessary for in-depth research and optimal clinical protocols. Bibliometric analysis is widely applied in depicting development trends and tracking frontiers of a specific field. The present study is aimed at revealing the status and trends of anthracycline-induced cardiotoxicity during the past two decades by employing bibliometric software including R-bibliometric, VOSviewer, and CiteSpace. A total of 3504 publications concerning anthracycline-induced cardiotoxicity from 2002 to 2021 were collected from the Web of Science Core Collection database. Results showed significant growth in annual yields from 90 records in 2002 to 304 papers in 2021. The United States was the most productive country with the strongest collaboration worldwide in the field. Charles University in the Czech Republic was the institution that contributed the most papers, while 7 of the top 10 productive institutions were from the United States. The United States Department of Health and Human Services and the National Institutes of Health are the two agencies that provide financial support for more than 50% of sponsored publications. The research categories of included publications mainly belong to Oncology and Cardiac Cardiovascular Systems. The Journal of Clinical Oncology had a comprehensive impact on this research field with the highest IF value and many publications. Simunek Tomas from Charles University contributed the most publications, while Lipshultz Steven E. from the State University of New York possessed the highest H-index. In addition, the future research frontiers of anthracycline-induced cardiotoxicity might include early detection, pharmacogenomics, molecular mechanism, and cardiooncology. The present bibliometric analysis may provide a valuable reference for researchers and practitioners in future research directions.

Pharmaceutical care is essential in building up the basics of public health and clinical care. A comprehensive understanding of global status in the field of pharmaceutical care is necessary for directing its research frontiers and future trends. Therefore, this study aims to make a bibliometric analysis to track the development of pharmaceutical care research worldwide during the past two decades. The publications regarding pharmaceutical care were culled from the Web of Science Core Collection (WoSCC). Countries, institutions, authors, journals, references, and keywords in this field were visually analyzed by using VOSviewer (version 1.6.17) and CiteSpace (Version 5.8.R3). As a result, 3,597 publications (3,177 articles and 420 reviews) were obtained. The annual yields grew more than three times in the past two decades, from 54 records in 2002 to 379 papers in 2021. The United States played the leading role in this research from multiple aspects, including publication (n= 1,208), citations (n= 28,759), funding agencies, and collaboration worldwide. The University of Sydney in Australia was the most contributed institution with the greatest number of publications (n= 112) in pharmaceutical care research. Hersberger KE from the University of Basel was the most productive author (n= 40). Chen TF from the University of Sydney was the author who owed the highest H-index of 19 and most citations (n= 1,501). They both significantly impacted this field. American Journal of Health System Pharmacy produced the most publications, while Pharmacotherapy had the highest IF (IF2020= 4.705) in this field. Clusters networks of co-cited references and keywords suggested that clinical pharmacy is an essential theme in pharmaceutical care. Terms of medication safety and critical care recognized by burst analysis of keywords also hint at the recent attention on clinical pharmacy. The present bibliometrics analysis may provide a comprehensive overview and valuable reference for future researchers and practitioners in the research field of pharmaceutical care.

Traditional Chinese medicine (TCM) is the key to unlock treasures of Chinese civilization. TCM and its compound play a beneficial role in medical activities to cure diseases, especially in major public health events such as novel coronavirus epidemics across the globe. The chemical composition in Chinese medicine formula is complex and diverse, but their effective substances resemble “mystery boxes”. Revealing their active ingredients and their mechanisms of action has become focal point and difficulty of research for herbalists. Although the existing research methods are numerous and constantly updated iteratively, there is remain a lack of prospective reviews. Hence, this paper provides a comprehensive account of existing new approaches and technologies based on previous studies with an in vitro to in vivo perspective. In addition, the bottlenecks of studies on Chinese medicine formula effective substances are also revealed. Especially, we look ahead to new perspectives, technologies and applications for its future development. This work reviews based on new perspectives to open horizons for the future research. Consequently, herbal compounding pharmaceutical substances study should carry on the essence of TCM while pursuing innovations in the field.

BACKGROUND Epigallocatechin gallate (EGCG) is a polyhydroxy phenolic compound extracted from tea and its antitumor effect has received widespread attention. We explored the inhibitory effect of EGCG on dimethylhydrazine (DMH)-induced colorectal cancer (CRC) using a rat model, predicted the interaction between EGCG and CRC target genes using a database, and explained the EGCG associated target pathways and mechanisms in CRC. AIM To understand the inhibitory mechanisms of EGCG on CRC cell proliferation and identify its pharmacological targets by network pharmacology analysis. METHODS DMH (40 mg/kg, s.c., twice weekly for eight weeks) was used to induce CRC in rats. After model establishment, the rats were administered with EGCG (50, 100, or 200 mg/kg, p.o., once daily for eight weeks) and killed 12 and 20 wk after the start of the experiment. Formation of aberrant crypt foci and tumor was studied by histological analysis. Using network pharmacology analysis, candidate and collective targets of EGCG and CRC were identified, and Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses were used to predict the pathways altered by EGCG. RESULTS At week 12, high-dose EGCG treatment significantly reduced the tumor formation rate, total number of tumors, cancerous and non-cancerous tumors, tumor volume, ascites formation, and aberrant crypt foci count. At week 20, all three doses of EGCG were effective. Seventy-eight collective targets of EGCG and CRC were identified, of which 28 genes were dysregulated in CRC. Kyoto Encyclopedia of Genes and Genomes and GO analyses showed that the dysregulated genes were enriched in hsa05210 (CRC), hsa04115 (p53 signaling pathway), and hsa04151 (PI3K-Akt signaling pathway), GO:0043124 (negative regulation of I-kappaB kinase/NF-kappaB signaling pathway), GO:0043409 (negative regulation of mitogen-activated protein kinase cascade), and GO:2001244 (positive regulation of intrinsic apoptotic signaling pathway) respectively. CONCLUSION EGCG inhibits the formation of DMH-induced CRC by regulating key pathways involved in tumorigenesis.

Background: High-purine diet can cause gut microbiota disorder, which is closely related to the occurrence of hyperuricemia (HUA). At the same time, the development of HUA is often accompanied by renal impairment. Chicory, a natural medicine, has a significant effect on lowering uric acid. However, whether its concrete mechanism is associated with the regulation of gut microbiota and renal damage is still unclear. Methods: Hyperuricemic quails induced by high-purine diet were used, and quails were divided into control (CON), model (MOD), and model plus high, middle, low doses of chicory. The uricosuric effect was evaluated by detecting the uric acid levels in serum and feces. Meanwhile, the morphology of intestine and kidney were observed by hematoxylin and eosin (HE) staining, and the expression of intestinal barrier junction proteins Occludin, Claudin-1 were detected by quantitative real-time polymerase chain reaction (qPCR) and western blotting. Furthermore, the latent mechanism was clarified by analyzing 16S rRNA amplicon of gut microbiota and measuring the changes of LPS/TLR4 axis inflammatory response of the kidney by western blotting and enzyme-linked immunosorbent assay (ELISA). Results: The results showed that serum uric acid levels were significantly decreased, and the feces uric acid levels were noticeably increased after the intervention of chicory. In addition, chicory could repair the damage of intestinal mucosa and improve the permeability of intestinal barrier. Moreover, the 16S rRNA sequencing analysis uncovered that chicory restored gut microbiota by increasing the probiotics flora (Bifidobacterium, Erysipelotrichaceae) and reducing the pathogenic bacteria group (Helicobacteraceae). Furthermore, it was found that chicory reduced the LPS/TLR4 axis inflammatory response by down regulating the serum LPS and TLR4/NF-κB inflammatory pathway in kidney, thus promoting the excretion of uric acid in kidney. Conclusion: Chicory intervention ameliorated HUA via modulating the imbalance of gut microbiota and suppressing LPS/TLR4 axis inflammatory reaction in quail model, which may be a promising candidate for hyperuricemia-relieving properties.

Objective To observe the effect of moxibustion on serum inflammatory factors, Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88) and nuclear factor Kappa B(NF-κB) in colon tissue of rats with diarrhea-predominant irritable bowel syndrome(IBS-D),so as to explore the mechanism of moxibustion in the treatment of IBS-D. Methods Healthy male SD rats were randomly divided into blank group, model group and moxibustion group, with 8 rats in each group. The IBS-D model was established by chronic restraint combined with gavage of Senna-leaf solution. The rats of the moxibustion group was treated with moxibustion at "Tianshu"(ST25)and "Shangjuxu"(ST37)for 30 min, once a day for 7 d. After the intervention, the rate of loose stools and the minimum threshold volume of abdominal withdrawal reflex(AWR) induced by colorectal distension were observed. The contents of serum inflammatory factors IL-1β, TNF-α and IL-6 were detected by ELISA. The pathological changes of rat colon were observed by H.E. staining. The average optical density of TLR4 and NF-κB(p65) in colon tissue was detected by immunohistochemistry. The relative expressions of TLR4, MyD88 and NF-κB(p65) mRNAs in colon tissues were detected by real-time fluorescence quantitative PCR, and the expression levels of TLR4, MyD88 and NF-κB(p65) proteins in colon tissues were detected by Western blot. Results There was a mild degree of inflammation in colon in rats of the model group. Compared with the blank group, the minimum volume threshold of AWR decreased significantly(P< 0.01), and the rate of loose stools, the contents of IL-1β, IL-6 and TNF-α in serum as well as the expressions of TLR4, MyD88, NF-κB(p65) mRNAs and protein in colon tissues were significantly increased in the model group(P<0.01). Compared with the model group, the inflammation was alleviated in colonic mucosa, the minimum volume threshold of AWR increased significantly(P<0.01), and rate of loose stools decreased significantly(P<0.01) in the moxibustion group, the contents of IL-1β, TNF-α and IL-6 in serum and the expression levels of TLR4, MyD88, NF-κB(p65) mRNAs and proteins in colon tissue decreased significantly in the moxibustion group(P<0.01). Conclusion Moxibustion ST25 and ST37 can improve diarrhea symptom and visceral hypersensitivity in IBS-D rats, which may be related with its effects in inhibiting TLR4/MyD88/NF-κB signaling pathway and reducing the expression of inflammatory factors.

Background: The production and maturation of interleukin (IL)-1β, regulated by the NF-κB and NLRP3 signaling pathways, lie at the core of gout. This study aimed to evaluate the antigout effect of Cichorium intybus L. (also known as chicory) in vivo and in vitro. Methods: A gout animal model was established with monosodium urate (MSU) crystal injections. Rats were orally administered with chicory extract or colchicine. Levels of ankle edema, inflammatory activity, and IL-1β release were observed. Several essential targets of the NF-κB and NLRP3 signaling pathways were detected. Primary macrophages were isolated to verify the antigout mechanism of chicory extract as well as chicoric acid in vitro. Results: Improvements of swelling degree, inflammatory activity, and histopathological lesion in MSU-injected ankles were observed in the treatment with chicory extract. Further, the chicory extract significantly decreased IL-1β release by suppressing the NF-κB and NLRP3 signaling pathways in gout rats. Similar to the in vivo results, IL-1β release was also inhibited by chicory extract and chicoric acid, a specific effective compound in chicory, through the NF-κB and NLRP3 signaling pathways. Conclusion: This study suggests that chicory extract and chicoric acid may be used as promising therapeutic agents against gout by inhibiting the NF-κB and NLRP3 signaling pathways.