TCMSSD: A comprehensive database focused on syndrome standardization.

BACKGROUD: Quantitative and standardized research on syndrome differentiation has always been at the forefront of modernizing Traditional Chinese Medicine (TCM) theory. However, the majority of existing databases primarily concentrate on the network pharmacology of herbal prescriptions, and there are limited databases specifically dedicated to TCM syndrome differentiation. PURPOSE: In response to this gap, we have developed the Traditional Chinese Medical Syndrome Standardization Database (TCMSSD, http://tcmssd.ratcm.cn). METHODS: TCMSSD is a comprehensive database that gathers data from various sources, including TCM literature such as TCM Syndrome Studies (Zhong Yi Zheng Hou Xue) and TCM Internal Medicine (Zhong Yi Nei Ke Xue) and various public databases such as TCMID and ETCM. In our study, we employ a deep learning approach to construct the knowledge graph and utilize the BM25 algorithm for syndrome prediction. RESULTS: The TCMSSD integrates the essence of TCM with the modern medical system, providing a comprehensive collection of information related to TCM. It includes 624 syndromes, 133,518 prescriptions, 8,073 diseases (including 1,843 TCM-specific diseases), 8,259 Chinese herbal medicines, 43,413 ingredients, 17,602 targets, and 8,182 drugs. By analyzing input data and comparing it with the patterns and characteristics recorded in the database, the syndrome prediction tool generates predictions based on established correlations and patterns. CONCLUSION: The TCMSSD fills the gap in existing databases by providing a comprehensive resource for quantitative and standardized research on TCM syndrome differentiation and laid the foundation for research on the biological basis of syndromes.

Evaluation of Clinical Efficacy of Acupuncture and Moxibustion for Asthma: Systematic Review and Meta-Analysis.

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

Application of Biotechniques for In Vitro Virus and Viroid Elimination in Pome Fruit Crops.

Sustainable production of pome fruit crops is dependent upon having virus-free planting materials. The production and distribution of plants derived from virus- and viroid-negative sources is necessary not only to control pome fruit viral diseases but also for sustainable breeding activities, as well as the safe movement of plant materials across borders. With variable success rates, different in vitro-based techniques, including shoot tip culture, micrografting, thermotherapy, chemotherapy, and shoot tip cryotherapy, have been employed to eliminate viruses from pome fruits. Higher pathogen eradication efficiencies have been achieved by combining two or more of these techniques. An accurate diagnosis that confirms complete viral elimination is crucial for developing effective management strategies. In recent years, considerable efforts have resulted in new reliable and efficient virus detection methods. This comprehensive review documents the development and recent advances in biotechnological methods that produce healthy pome fruit plants. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis.

OBJECTIVE: This study aimed to elucidate the multitarget mechanism of the Mori Ramulus - Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA). METHODS: The targets of the herb pair and RA were predicted from databases and screened through cross-analysis. The core targets were obtained using protein-protein interaction (PPI) network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, animal experiments were conducted to validate the anti-RA effect and mechanism of this herb pair. RESULTS: This approach successfully identified 9 active compounds of MT that interacted with 6 core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1ß). Pathway and functional enrichment analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The consistency of interactions between active components and targets in these pathways was confirmed through molecular docking. Moreover, the potential therapeutic effect of MT was verified in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted genes and pathways. CONCLUSION: The present work suggests that the therapeutic effect of MT herb pair on RA may be attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.

Glutamine enhances sucrose taste through a gut microbiota-gut-brain axis in Drosophila.

AIMS: Amino acids (AAs) are known to play important roles in various physiological functions. However, their effect on sweet taste perception remains largely unknown. MAIN METHODS: We used Drosophila to evaluate the effect of each AA on sucrose taste perception. Individual AA was supplemented into diets and male flies were fed on these diets for 6 days. The proboscis extension response (PER) assay was applied to assess the sucrose taste sensitivity of treated flies. We further utilized the RNA-seq and germ-free (GF) flies to reveal the underlying mechanisms of sucrose taste sensitization induced by glutamine (Gln). KEY FINDINGS: We found that supplementation of Gln into diets significantly enhances sucrose taste sensitivity. This sucrose taste sensitization is dependent on gut microbiota and requires a specific gut bacterium Acetobacter tropicalis (A. tropicalis). We further found that CNMamide (CNMa) in the gut and CNMa receptor (CNMaR) in dopaminergic neurons are required for increased sucrose taste sensitivity by Gln diet. Finally, we demonstrated that a gut microbiota-gut-brain axis is required for Gln-induced sucrose taste sensitization. SIGNIFICANCE: These findings can advance understanding of the complex interplay between host physiology, dietary factors, and gut microbiota.

Natural compounds as obesity pharmacotherapies.

Obesity has become a serious global public health problem, affecting over 988 million people worldwide. Nevertheless, current pharmacotherapies have proven inadequate. Natural compounds have garnered significant attention due to their potential antiobesity effects. Over the past three decades, ca. 50 natural compounds have been evaluated for the preventive and/or therapeutic effects on obesity in animals and humans. However, variations in the antiobesity efficacies among these natural compounds have been substantial, owing to differences in experimental designs, including variations in animal models, dosages, treatment durations, and administration methods. The feasibility of employing these natural compounds as pharmacotherapies for obesity remained uncertain. In this review, we systematically summarized the antiobesity efficacy and mechanisms of action of each natural compound in animal models. This comprehensive review furnishes valuable insights for the development of antiobesity medications based on natural compounds.

Comprehensive analysis of JAZ family members in Ginkgo biloba reveals the regulatory role of the GbCOI1/GbJAZs/GbMYC2 module in ginkgolide biosynthesis.

Ginkgo biloba L., an ancient relict plant known as a 'living fossil', has a high medicinal and nutritional value in its kernels and leaves. Ginkgolides are unique diterpene lactone compounds in G. biloba, with favorable therapeutic effects on cardiovascular and cerebrovascular diseases. Thus, it is essential to study the biosynthesis and regulatory mechanism of ginkgolide, which will contribute to quality improvement and medication requirements. In this study, the regulatory roles of the JAZ gene family and GbCOI1/GbJAZs/GbMYC2 module in ginkgolide biosynthesis were explored based on genome and methyl jasmonate-induced transcriptome. Firstly, 18 JAZ proteins were identified from G. biloba, and the gene characteristics and expansion patterns along with evolutionary relationships of these GbJAZs were analyzed systematically. Expression patterns analysis indicated that most GbJAZs expressed highly in the fibrous root and were induced significantly by methyl jasmonate. Mechanistically, yeast two-hybrid assays suggested that GbJAZ3/11 interacted with both GbMYC2 and GbCOI1, and several GbJAZ proteins could form homodimers or heterodimers between the GbJAZ family. Moreover, GbMYC2 is directly bound to the G-box element in the promoter of GbLPS, to regulate the biosynthesis of ginkgolide. Collectively, these results systematically characterized the JAZ gene family in G. biloba and demonstrated that the GbCOI1/GbJAZs/GbMYC2 module could regulate ginkgolides biosynthesis, which provides a novel insight for studying the mechanism of JA regulating ginkgolide biosynthesis.

[Distribution, hazard evaluation, and control measures of allergenic airborne pollen]. / è‡´æ•æ€§æ°”ä¼ èŠ±ç²‰çš„åˆ†å¸ƒã€å±å®³è¯„ä»·åŠé˜²æ²»æŽªæ–½.

Allergenic airborne pollen can induce hay fever such as rhinitis and asthma. Many studies have been conducted on the allergenic pollution caused by airborne pollen. We synthesized available studies to summarize the temporal and spatial distributions of airborne pollen and influencing meteorological factors. We further summarized and discussed the hazards of airborne pollen sensitization on human health and evaluation indicators for classifying hazard levels. We described the research progress of prevention and control measures of airborne pollen induced pollution from the perspectives of source control, route monitoring, and prevention of susceptible population. Considering the limitations of current studies, we proposed some research directions on allergenic airborne pollen. The types of allergenic plants needed to be clearly identified and allergentic potential should be quantitatively identified. The methods of pollen collection and concentration monitoring needed to be improved and standardized. This review could provide a scientific guidance for the study on preventing and treating pollen allergies as well as optimizing urban green space planning.

Traditional Chinese Medicine Shi-Bi-Man regulates lactic acid metabolism and drives hair follicle stem cell activation to promote hair regeneration.

BACKGROUND: As a supplement for promoting hair health, Shi-Bi-Man (SBM) is a prescription comprising various traditional Chinese medicines. Though SBM has been reported to promote hair regeneration, its molecular mechanism remains unclear. Cynomolgus monkeys (Macaca fascicularis) are non-human primates with a gene expression profile similar to that of humans. The purpose of this research is to evaluate the effect of SBM on promoting hair regeneration in cynomolgus monkeys and to reveal the underlying mechanism. METHODS: The effect of SBM on hair regeneration was observed by skin administration on 6 cynomolgus monkeys with artificial back shaving. The molecular mechanism of SBM was studied using single-cell RNA sequencing (scRNA-seq) in combination with quantitative polymerase chain reaction (qPCR) detection for gene transcription level, and immunofluorescence staining verification for protein level. RESULTS: SBM significantly induced hair regeneration in cynomolgus monkeys, increased hair follicle number and facilitated hair follicle development. ScRNA-seq revealed an increase in the number of hair follicle stem cells (HFSCs) with a higher activation state, as evidenced by the higher expression of activation marker LDHA related to metabolism and the proliferation marker MKI67. Immunofluorescence analysis at the protein level and qPCR at the mRNA level confirmed the sequencing data. Cellchat analysis revealed an enrichment of ligand-receptor pairs involved in intercellular communication in Laminin-related pathways. CONCLUSION: SBM significantly promotes hair regeneration in cynomolgus monkeys. Mechanically, SBM can up-regulate LDHA-mediated lactic acid metabolism and drive HFSC activation, which in turn promotes the proliferation and differentiation of HFSCs.

Plasma 25-Hydroxyvitamin D Levels and Survival in Stage III Colon Cancer: Findings from CALGB/SWOG 80702 (Alliance).

PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association. EXPERIMENTAL DESIGN: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2). RESULTS: Vitamin D deficiency [25(OH)D <12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank<0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51-0.92) for DFS, 0.57 (0.40-0.80) for OS, and 0.71 (0.52-0.98) for TTR. A U-shaped dose-response pattern was observed for DFS and OS (both Pnonlinearity<0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events. CONCLUSIONS: Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.

[Component identification and analysis in vivo of Sanhan Huashi formula].

Sanhan Huashi formula(SHF) is the intermediate of a newly approved traditional Chinese medicine(TCM) Sanhan Huashi Granules for the treatment of COVID-19 infection. The chemical composition of SHF is complex since it contains 20 single herbal medicines. In this study, UHPLC-Orbitrap Exploris 240 was used to identify the chemical components in SHF and in rat plasma, lung and feces after oral administration of SHF, and heat map was plotted for characterizing the distribution of the chemical components. Chromatographic separation was conducted on a Waters ACQUITY UPLC BEH C_(18)(2.1 mm×100 mm, 1.7 µm) using 0.1% formic acid(A)-acetonitrile(B) as mobile phases in a gradient elution. Electrospray ionization(ESI) source was used to acquire data in positive and negative mode. By reference to quasi-molecular ions and MS/MS fragment ions and in combination with MS spectra of reference substances and compound information in literature reports, 80 components were identified in SHF, including 14 flavonoids, 13 coumarins, 5 lignans, 12 amino-compounds, 6 terpenes and 30 other compounds; 40 chemical components were identified in rat plasma, 27 in lung and 56 in feces. Component identification and characterization of SHF in vitro and in vivo lay foundations for disclosure of its pharmacodynamic substances and elucidation of the scientific connotation.

Experimental validation for mechanisms of Qizhiweitong particles against Chronic Non-atrophic gastritis based on metabolomics and network pharmacology.

Qizhiweitong particles (QZWT), a classic Chinese herbal prescription derived from the Sinisan decoction in Shang Han Za Bing Lun, has definitive clinical efficacy in treating Chronic Non-atrophic Gastritis (CNG) in China. However, its mechanism of action at the metabolic level remains unclear. The aim of this study was to explore the mechanisms of QZWT against CNG based on non-targeted metabolomics combined with network pharmacology and experimentally validated by enzyme linked immunosorbent assays (ELISA). First, CNG model rats were established by free drinking ammonia water combined with starvation and satiety disorder for 12 weeks. Taking gastric tissue as the object, ultra-high performance liquid chromatography tandem mass spectrometry based metabolomics and network pharmacology were conducted to identify the key compounds, core targets and pathways that mediate the effects of QZWT against CNG. Furthermore, the targets from network pharmacology and the metabolites from metabolomics were jointly analyzed to select crucial metabolism pathways by MetaScape. Finally, the key metabolic enzymes and metabolites were experimentally validated by ELISA. The results indicated that there were 29 differential metabolites were identified and considered to be metabolic biomarkers of QZWT in the treatment of CNG. Among them, 8 of the differential metabolites showed a significant reduction in the content of QZWT groups. Arachidonic acid (AA) metabolic and glycerophospholipid (GP) metabolic are the most crucial metabolic pathways for QZWT to treat CNG. QZWT regulated AA and GP metabolism by synergetic reducing the level of AA, Phospholipid acid and Lysophosphatidic acid and inhibiting the enzyme activity of prostaglandin endoperoxide synthase 1 and prostaglandin endoperoxide synthase 2. And a compound-reaction-enzyme-gene network of mechanism for QZWT against CNG was established. In conclusion, this study reveals the complicated mechanisms of QZWT against CNG. Our work presents a novel strategy to identify the potential mechanisms of pharmacological effects derived from a compound prescription of TCM.

[Herbal-moxa plaster for diarrhea type irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between herbal-moxa plaster and moxa-box moxibustion for diarrhea type irritable bowel syndrome (IBS-D) of spleen and kidney yang deficiency. METHODS: Eighty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a herbal-moxa plaster group and a moxa-box moxibustion group, 40 cases in each group. The patients in the two groups were treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 24+), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Yinlingquan (SP 9), and Taixi (KI 3), etc. In addition, the patients in the herbal-moxa plaster group were treated with herbal-moxa plaster (Wenyang Fuzheng ointment, composed of prepared monkshood, prepared evodia rutaecarpa, dried ginger, cinnamon, etc.) at Shenque (CV 8), Guanyuan (CV 4), Zhongwan (CV 12) and bilateral Tianshu (ST 25), Shenshu (BL 23) and Shangjuxu (ST 37); the patients in the moxa-box moxibustion group were treated with moxa-box moxibustion at the same acupoints as the herbal-moxa plaster group. The acupuncture-moxibustion treatment was provided once every other day for 4 weeks (14 treatments). Before and after treatment, the scores of clinical symptom of TCM, irritable bowel syndrome (IBS) symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) were compared between the two groups, and the clinical efficacy was evaluated. RESULTS: Compared with those before treatment, each item scores and total scores of clinical symptom of TCM, and IBS-SSS scores in the two groups were reduced after treatment (P<0.05). The abdominal bloating score, stool frequency score and total score of clinical symptom of TCM as well as IBS-SSS score in the herbal-moxa plaster group were lower than those in the moxa-box moxibustion group (P<0.05). Compared with those before treatment, the IBS-QOL scores in the two groups were increased after treatment (P<0.05), and the IBS-QOL score in the herbal-moxa plaster group was higher than that in the moxa-box moxibustion group (P<0.05). The total effective rate was 92.5% (37/40) in the herbal-moxa plaster group, which was higher than 85.0% (34/40) in the moxa-box moxibustion group (P<0.05). CONCLUSION: On the basis of conventional acupuncture treatment, herbal-moxa plaster could effectively improve the clinical symptoms and quality of life in IBS-D patients of spleen and kidney yang deficiency, and its efficacy is superior to that of moxa-box moxibustion.

Toxic effects of Tripterygium glycoside tablets on the reproductive system of male rats by metabolomics, cytotoxicity, and molecular docking.

BACKGROUND: Tripterygium glycoside tablets (TGT) is the most common preparation from Tripterygium wilfordii Hook F, which is widely used in clinical for treating rheumatoid arthritis (RA) and other autoimmune diseases. However, its serious reproductive toxicity limits its application. PURPOSE: This study aimed to elucidate the toxic effects of TGT on the reproductive system of male RA rats and its potential toxic components and mechanism. METHODS: Collagen-induced arthritis (CIA) rat model was established, and TGT suspension was given at low, medium, and high doses. Gonadal index, pathological changes, and the number of spermatogenic cells were used to evaluate the toxic effects of TGT on the reproductive system. Non-targeted metabolomics of testicular tissue was conducted by UHPLC-QTOF/MS. Combined with network toxicology, the key targets of TGT-induced reproductive toxicity were screened and RT-qPCR was used to validation. In vitro toxicity of 19 components of TGT was evaluated using TM3 and TM4 cell lines. Molecular docking was used to predict the interaction between toxic components and key targets. RESULTS: TGT reduced testicular and epididymis weight. Pathology analysis showed a lot of deformed and atrophic spermatogenic tubules. The number of spermatogenic cells decreased significantly (P<0.0001). A total of 58 different metabolites including platelet-activating factor (PAF), lysophosphatidylcholine (Lyso PC), phosphatidylinositol (PI), glutathione (GSH), and adenosine monophosphate (AMP) were identified by testicular metabolomics. Glycerophospholipid metabolism, ether lipid metabolism, and glutathione metabolism were key pathways responsible for the reproductive toxicity of TGT. Ten key reproductive toxicity targets were screened by network toxicology. The cytotoxicity test showed that triptolide, triptonide, celastrol, and demethylzeylasteral could significantly reduce the viability of TM3 and TM4 cells. Alkaloids had no apparent toxic effects. Molecular docking showed that the four toxic components had a good affinity with 10 key targets. All binding energies were less than -7 kcal/mol. The RT-qPCR results showed the Cyp19a1 level was significantly up-regulated. Pik3ca and Pik3cg levels were significantly down-regulated. CONCLUSION: Through testicular metabolomics, we found that TGT may cause reproductive toxicity through CYP19A1, PIK3CA, and PIK3CG three target, which was preliminarily revealed. This study laid the foundation for elucidating the toxicity mechanism of TGT and evaluating its safety and quality.

An integrated strategy combining network toxicology and feature-based molecular networking for exploring hepatotoxic constituents and mechanism of Epimedii Folium-induced hepatotoxicity in vitro.

Epimedii Folium (EF), a commonly used herbal medicine to treat osteoporosis, has caused serious concern due to potential hepatotoxicity. Until now, its intrinsic hepatotoxic mechanism and hepatotoxic ingredients remain unclear. Here, a novel high-throughput approach was designed to investigate the intrinsic hepatotoxic of EF. High-content screen imaging (HCS) and biochemical tests were first performed to obtain the cytotoxicity parameter matrix of 17 batch EF samples. EF-treated alpha mouse liver 12 (AML12) cells showed increased reactive oxygen species (ROS), reduced glutathione (GSH) and mitochondrial membrane potential (MMP), and apoptosis and cholestasis were further observed. Network toxicology predicted that EF-triggered hepatotoxiciy was involved in transcription factor (TF) activity. The FXR expression, screened by a TF PCR array, exhibited down-regulation following EF extract administration. Moreover, EF inhibited bile acid (BA) metabolism pathway in an FXR-dependent manner. Pearson correlation between the cytotoxicity parameter matrix and quantification feature table obtained from UHPLC-QTOF data of EF suggested 7 prenylated flavonoids possessed potent hepatotoxicities and their cytotoxicity order was further summarized. The transcriptional repression effects of them on FXR were also verified. Collectively, our findings indicate that FXR is probably responsible for EF-induced hepatotoxicity and prenylated flavonoids may be a major class of hepatotoxic constituents in EF.

Nutritional geometry framework of sucrose taste in Drosophila.

Dietary protein (P) and carbohydrate (C) have a major impact on the sweet taste sensation. However, it remains unclear whether the balance of P and C influences the sweet taste sensitivity. Here, we use the nutritional geometry framework (NGF) to address the interaction of protein and carbohydrates on sweet taste using Drosophila as a model. Our results reveal that high-protein, low-carbohydrate (HPLC) diets sensitize to sweet taste and low-protein, high-carbohydrate (LPHC) diets desensitize sweet taste in both male and female flies. We further investigate the underlying mechanisms of the effects of two diets on sweet taste using RNA sequencing. When compared to the LPHC diet, the mRNA expression of genes involved in the metabolism of glycine, serine, and threonine is significantly upregulated in the HPLC diet group, suggesting these amino acids may mediate sweet taste perception. We further find that sweet sensitization occurs in flies fed with the LPHC diet supplemented with serine and threonine. Our study demonstrates that sucrose taste sensitivity is affected by the balance of dietary protein and carbohydrates possibly through changes in serine and threonine.

An integrated strategy to explore the wine-processed mechanism of Corni Fructus on chronic renal failure based on metabolomics, network analysis and bioinformatics approaches.

OBJECTIVES: Corni Fructus is one of the most famous traditional Chinese medicines (TCMs) for the treatment of various chronic kidney diseases. Wine-processed Corni Fructus (WCF) is the main processed form of Crude Corni Fructus (CCF). In this study, potential mechanisms of action of CCF and WCF on chronic renal failure (CRF) model were developed to explore wine-processed mechanism of Corni Fructus. METHODS: An integrated strategy combining metabolomics, network analysis and bioinformatics analysis has been established to investigate the therapeutic mechanisms of WCF and CCF in rats with CRF. KEY FINDINGS: The histopathological results showed that both WCF and CCF improved kidney injury and dysfunction of CRF rats, but WCF was more effective than CCF. Metabolic pathway analysis indicated that 24 metabolites and 5 major disturbed pathways associated with CCF, while WCF regulated 27 metabolites and 2 metabolic pathways. Bioinformatic analysis and network analysis revealed that 8 genes and 7 genes were regulated by CCF and WCF on CRF rats, respectively. The quantitative real-time polymerase chain reaction experiments verified the regulatory ability of CCF and WCF on the expression of 4 genes. CONCLUSIONS: An integrated strategy combined metabolomics, network analysis and bioinformatics was established to provide valuable holistic insight to explore the processing mechanism of TCMs.

Revealing active components and action mechanism of Fritillariae Bulbus against non-small cell lung cancer through spectrum-effect relationship and proteomics.

BACKGROUND: Fritillariae Bulbus (FB) is widely used as a traditional medicine for the treatment of lung meridian diseases. It has been proved that FB has good anti-non-small cell lung cancer (NSCLC) activity. However, the active components and potential mechanism are still not clear. PURPOSE: To reveal the bioactive components of FB against NSCLC and potential mechanism through spectrum-effect relationship and proteomics. METHOD: First, the FB extract was chemically profiled by UHPLC-QTOF-MS and the inhibitory effect of FB extract on A549 cell viability was evaluated by Cell Counting Kit-8 assay. Second, orthogonal-partial least squares-regression analysis was applied to screen potential active compounds through correlating the chemical profile with corresponding inhibitory effect. Third, the anti-NSCLC activities of potential active components were further investigated in terms of cell proliferation, cell cycle and cell apoptosis in vitro and tumor growth in vivo. Finally, proteomics was utilized to reveal the underlying anti-NSCLC mechanism. RESULTS: Six potential active components including verticine, verticinone, zhebeirine, ebeiedinone, yibeissine and peimisine were screened out by spectrum-effect relationship. Among them, zhebeirine showed higher inhibitory effect on A549 cell viability with IC50 value of 36.93 µM and dosage-dependent inhibition of A549 xenograft tumor growth in nude mice. Proteomics and western blotting assays indicated that zhebeirine could arrest cell cycle by down-regulating the expressions of CDK1, CDK2, Cyclin A2, Cyclin B2 and inhibiting the phosphorylation of p53. Moreover, the proteins participating in p53 signaling pathway including PCNA, 14-3-3σ, CHEK1 were significantly decreased, which suggested that zhebeirine affected cell cycle progression through p53 signaling pathway. CONCLUSION: This study not only provides scientific evidence to support the clinical application of FB against NSCLC, but also demonstrates that zhebeirine is a promising anti-NSCLC lead compound deserving further studies.

Integrative strategy for quality control of Radix Bupleuri based on non-targeted metabolomic profiling and molecular networking.

Quality control of Radix Bupleuri (RB) can be challenging due to the complexity of origin, the similar morphological characteristics, and the diversity of the multiple components. In this study, an integrated strategy for extensive identification of metabolites in plants based on multiple data processing methods was proposed to distinguish four commercially available RB species. First, the pre-processed mass spectrometry data was uploaded to Global Natural Products Social Molecular Networking (GNPS) for spectral library search and molecular network analysis, which can effectively differentiate isomers and reduce molecular redundancy. Second, the possible cleavage mode was summarized from the characteristic MS/MS fragment ions of saikoside standard, and then the possible structure of saikoside in the sample was deduced according to the cleavage patterns. Third, collected all kinds of RB components reported in the literature and matched the information in the samples to obtain more comprehensive information about metabolites. Finally, chemical markers were found employing chemometrics. This strategy not only increases the variety and number of identified components, but also improves the accuracy of the data. Based on this strategy, a total of 132 components were identified from different species of RB, and 14 chemical constituents were considered to be potential chemical markers to distinguish four kinds of RB. Among them, saikogenin a, hydroxy-saikosaponin a, hydroxy-saikosaponin d, and rutinum were of great significance for identification. The method proposed in this study not only successfully identified and distinguished four species of RB, but also laid a good theoretical foundation for regulating the RB market. This strategy provides promising perspectives in the accurate analysis of the ingredients of traditional Chinese medicine.