Designing antimicrobial peptides using deep learning and molecular dynamic simulations.

With the emergence of multidrug-resistant bacteria, antimicrobial peptides (AMPs) offer promising options for replacing traditional antibiotics to treat bacterial infections, but discovering and designing AMPs using traditional methods is a time-consuming and costly process. Deep learning has been applied to the de novo design of AMPs and address AMP classification with high efficiency. In this study, several natural language processing models were combined to design and identify AMPs, i.e. sequence generative adversarial nets, bidirectional encoder representations from transformers and multilayer perceptron. Then, six candidate AMPs were screened by AlphaFold2 structure prediction and molecular dynamic simulations. These peptides show low homology with known AMPs and belong to a novel class of AMPs. After initial bioactivity testing, one of the peptides, A-222, showed inhibition against gram-positive and gram-negative bacteria. The structural analysis of this novel peptide A-222 obtained by nuclear magnetic resonance confirmed the presence of an alpha-helix, which was consistent with the results predicted by AlphaFold2. We then performed a structure-activity relationship study to design a new series of peptide analogs and found that the activities of these analogs could be increased by 4-8-fold against Stenotrophomonas maltophilia WH 006 and Pseudomonas aeruginosa PAO1. Overall, deep learning shows great potential in accelerating the discovery of novel AMPs and holds promise as an important tool for developing novel AMPs.

GATA3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in breast cancer.

BACKGROUND: Inadequate DNA damage repair promotes aberrant differentiation of mammary epithelial cells. Mammary luminal cell fate is mainly determined by a few transcription factors including GATA3. We previously reported that GATA3 functions downstream of BRCA1 to suppress aberrant differentiation in breast cancer. How GATA3 impacts DNA damage repair preventing aberrant cell differentiation in breast cancer remains elusive. We previously demonstrated that loss of p18, a cell cycle inhibitor, in mice induces luminal-type mammary tumors, whereas depletion of either Brca1 or Gata3 in p18 null mice leads to basal-like breast cancers (BLBCs) with activation of epithelial-mesenchymal transition (EMT). We took advantage of these mutant mice to examine the role of Gata3 as well as the interaction of Gata3 and Brca1 in DNA damage repair in mammary tumorigenesis. RESULTS: Depletion of Gata3, like that of Brca1, promoted DNA damage accumulation in breast cancer cells in vitro and in basal-like breast cancers in vivo. Reconstitution of Gata3 improved DNA damage repair in Brca1-deficient mammary tumorigenesis. Overexpression of GATA3 promoted homologous recombination (HR)-mediated DNA damage repair and restored HR efficiency of BRCA1-deficient cells. Depletion of Gata3 sensitized tumor cells to PARP inhibitor (PARPi), and reconstitution of Gata3 enhanced resistance of Brca1-deficient tumor cells to PARP inhibitor. CONCLUSIONS: These results demonstrate that Gata3 functions downstream of BRCA1 to promote DNA damage repair and suppress dedifferentiation in mammary tumorigenesis and progression. Our findings suggest that PARP inhibitors are effective for the treatment of GATA3-deficient BLBCs.

Electrical feedback system for enhancing the RF power of photodetector.

In this paper, we propose a system for enhancing the RF output power of the photodetector, especially the power of fundamental tune and second-order harmonic, by feeding back part of the RF signal through an electrical feedback circuit. As a result of bias modulation and opto-electric mixing, the RF output power can be effectively enhanced. The structure of uni-traveling carrier photodetector (UTC-PD) is employed in this work. With the RF enhancement system, the power of fundamental tune and second-order harmonic improve by 6.4 dB and 9.9 dB respectively, under the condition of 26 dBm input optical power, 3 V bias voltage, and 14 GHz input optical signal. Further, it was observed that third-order harmonic appeared under the influence of this system.

Cerebral Palsy Heterogeneity: Clinical Characteristics and Diagnostic Significance from a Large-Sample Analysis.

INTRODUCTION: Cerebral palsy (CP) is a nonprogressive movement disorder resulting from a prenatal or perinatal brain injury that benefits from early diagnosis and intervention. The timing of early CP diagnosis remains controversial, necessitating analysis of clinical features in a substantial cohort. METHODS: We retrospectively reviewed medical records from a university hospital, focusing on children aged ≥24 months or followed up for ≥24 months and adhering to the International Classification of Diseases-10 for diagnosis and subtyping. RESULTS: Among the 2012 confirmed CP cases, 68.84% were male and 51.44% had spastic diplegia. Based on the Gross Motor Function Classification System (GMFCS), 62.38% were in levels I and II and 19.88% were in levels IV and V. Hemiplegic and diplegic subtypes predominantly fell into levels I and II, while quadriplegic and mixed types were mainly levels IV and V. White matter injuries appeared in 46.58% of cranial MRI findings, while maldevelopment was rare (7.05%). Intellectual disability co-occurred in 43.44% of the CP cases, with hemiplegia having the lowest co-occurrence (20.28%, 58/286) and mixed types having the highest co-occurrence (73.85%, 48/65). Additionally, 51.67% (697/1,349) of the children with CP aged ≥48 months had comorbidities. CONCLUSIONS: This study underscores white matter injury as the primary CP pathology and identifies intellectual disability as a common comorbidity. Although CP can be identified in infants under 1 year old, precision in diagnosis improves with development. These insights inform early detection and tailored interventions, emphasizing their crucial role in CP management.

RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.

The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1-H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial-temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability.

Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA.

Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of RTT105 causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA double-stranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or break-induced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes high-fidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPA-interacting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism.

Global research trends in tongue cancer from 2000 to 2022: bibliometric and visualized analysis.

OBJECTIVES: This study conducts a systematic bibliometric analysis of tongue cancer publications to identify key topics, hotspots, and research distribution. METHODS: We analyzed tongue cancer publications in the Web of Science core collection database, assessing their quantity and quality. We investigated contributors, including countries, affiliations, journals, authors, and categories, within collaborative networks. Additionally, we synthesized key research findings using various analytical techniques, such as alluvial flow, burstness analysis, cluster analysis, co-occurrence network of associations, and network layer overlay. RESULTS: From 2000 to 2022, this bibliometric study covers 2205 articles and reviews across 617 journals, involving 72 countries, 2233 institutions, and 11,266 authors. It shows consistent growth, particularly in 2016. Key contributors include China (499 publications), Karolinska Institute (84 publications), Oral Oncology (144 publications), and Tuula Salo (47 publications). Other notable contributors are the USA (16,747 citations), the National Cancer Institute (NCI) (2597 citations), and the Memorial Sloan-Kettering Cancer Center (MSK) (2231 citations). Additionally, there are significant teams led by Tuula Salo and Dalianis. We have identified six primary clusters: #0 apoptosis, #1 depth of invasion, #2 radiotherapy, #3 hpv, #4 tongue cancer, #5 oral cancer. The top ten highly cited documents primarily pertain to epidemiology, prognostic indicators in early-stage oral tongue cancer, and HPV. Additionally, we observed 16 reference clusters, with depth of invasion (#3), young patients (#4), and tumor budding (#6) gaining prominence since 2012, indicating sustained research interests. CONCLUSIONS: This analysis emphasizes the increasing scholarly interest in tongue cancer research. The bibliometric evaluation highlights pivotal recent research themes such as HPV, depth of invasion, tumor budding, and surgical margins. CLINICAL RELEVANCE: The bibliometric analysis highlights the key topics and studies which have shaped the understanding and management of tongue cancer.

Correlation between lesion location and dysphagia characteristics in post-stroke patients.

OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.

Biotic resistance to fish invasions in southern China: Evidence from biomass, habitat, and fertility limitation.

Understanding the mechanisms underlying the invasion success or failure of alien species can help to predict future invasions and cope with the invaders. The biotic resistance hypothesis posits that diverse communities are more resistant to invasion. While many studies have examined this hypothesis, the majority of them have focused on the relationship between alien and native species richness in plant communities, and results have often been inconsistent. In southern China, many rivers have been invaded by alien fish species, providing an opportunity to test the resistance of native fish communities to alien fish invasions. Using survey data for 60,155 freshwater fish collected from five main rivers of southern China for 3 years, we assessed the relationships between native fish richness and the richness and biomass of alien fishes at river and reach spatial scales, respectively. Based on two manipulative experiments, we further examined the impact of native fish richness on habitat selection and the reproductive ability of an exotic model species Coptodon zillii. We found no apparent relationship between alien and native fish richness, whereas the biomass of alien fish significantly decreased with increasing native fish richness. In experiments, C. zillii preferred to invade those habitats that had low native fish richness, given evenly distributed food resources; reproduction of C. zillii was strongly depressed by a native carnivorous fish Channa maculata. Together, our results indicate that native fish diversity can continue to provide biotic resistance to alien fish species in terms of limiting their growth, habitat selection, and reproduction when these aliens have successfully invaded southern China. We thus advocate for fish biodiversity conservation, especially for key species, to mitigate against the population development and ecological impact of alien fish species.

METTL3-m6A-Rubicon axis inhibits autophagy in nonalcoholic fatty liver disease.

N6-methyladenosine (m6A) mRNA modification plays critical roles in various biological events and is involved in multiple complex diseases. However, the role of m6A modification in autophagy in nonalcoholic fatty liver disease (NAFLD) remains largely unknown. Here, we report that m6A modification was increased in livers of NAFLD mouse models and in free fatty acid (FFA)-treated hepatocytes, and the abnormal m6A modification was attributed to the upregulation of methyltransferase like 3 (METTL3) induced by lipotoxicity. Knockdown of METTL3 promoted hepatic autophagic flux and clearance of lipid droplets (LDs), while overexpression of METTL3 inhibited these processes. Mechanistically, METTL3 directly bound to Rubicon mRNA and mediated the m6A modification, while YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), as a partner of METTL3, interacted with the m6A-marked Rubicon mRNA and promoted its stability. Subsequently, RUBICON inhibited autophagosome-lysosome fusion and further blocked clearance of LDs. Taken together, our results showed a critical role of METTL3 and YTHDF1 in regulating lipid metabolism via the autophagy pathway and provided a novel insight into m6A mRNA methylation in NAFLD.

Simulation and design of a high-speed and high-power modified uni-traveling carrier photodiode based on the electric field distribution in the depletion region.

A modified uni-traveling carrier photodiode with an electric field control layer is proposed to achieve high-speed and high-power performance at a lower bias voltage. By inserting the 10 nm p-type InGaAs electric field control layer between the intrinsic absorption layer and space layer, the electric field distribution in the depleted absorption layer and depleted non-absorption layer can be changed. It is beneficial for reducing power consumption and heat generation, meanwhile suppressing the space-charge effect. Compared with the original structure without the electric field control layer, the 3 dB bandwidth of the 20 µm diameter novel structure, to the best of our knowledge, is improved by 27.1% to 37.5 GHz with a reverse bias of 2 V, and the RF output power reaches 23.9 dBm at 30 GHz. In addition, under 8 V bias voltage, the bandwidth reaches 47.3 GHz.

Novel Cuproptosis-Related Gene Signature for Precise Identification of High-Risk Populations in Low-Grade Gliomas.

Background: Patients with low-grade glioma (LGG) have wildly varying average lifespans. However, no effective way exists for identifying LGG patients at high risk. Cuproptosis is a recently described form of cell death associated with the abnormal aggregation of lipid acylated proteins. Few investigations have been conducted on cuproptosis-associated genes and LGG thus far. The purpose of this research is to establish a predictive model for cuproptosis-related genes in order to recognise LGG populations at high risk. Methods: We analyzed 926 LGGs from 2 public datasets, all of which were RNA sequencing datasets. On the basis of immune scores, the LGG population was split into different risk categories with X-tile. LASSO and Cox regressions were employed to filter cuproptosis-associated genes and construct prediction models. The accuracy of the predictive models was measured by using TCGA internal validation set and the CGGA external validation set. In addition, LGG immune cell infiltration was viewed using CIBERSORT and ssGSEA algorithms and correlation analysis was done with cuproptosis-related genes. Finally, immune escape capacity in LGG low- and high-risk groups was evaluated using the TIDE method. Results: The prediction model constructed by four cuproptosis-related genes was used to identify high-risk populations in LGG. It performed well in training and all validation sets (AUC values: 0.915, 0.894, and 0.774). Meanwhile, we found that FDX1 and ATP7A in the four cuproptosis-related genes were positively correlated with immune response, while GCSH and ATP7B were opposite. In addition, the high immune score group had a lower TIDE score, indicating that their immune escape capacity was weak. Conclusion: High-risk individuals in LGG can be reliably identified by the model based on cuproptosis-related genes. Furthermore, cuproptosis is closely related to tumor immune microenvironment, which gives a novel approach to treating LGG.

Molecular genotyping of Candida albicans isolated from different sites may trace the etiological infection routes: Observation in China.

BACKGROUND: Invasive candidiasis is a growing concern worldwide, especially in immunocompromised patients, including ICU patients. OBJECTIVES: As Candida albicans is the leading cause of candidaemia, it is important to investigate the evolution of C. albicans in patients with candidaemia. METHODS: We analysed 238 strains of C. albicans isolated from different body sites. Antifungal susceptibility testing, CAI loci genotyping and multilocus sequence typing (MLST) of all isolates were performed. The relationships among the total isolates that differed in sequence at only one of the seven housekeeping gene loci were analysed using eBURST. RESULTS: Multilocus sequence typing analysis in 238 isolates by combining seven housekeeping alleles revealed 175 diploid sequence types, in which 84 were newly identified. eBURST analysis for these data recognised 19 clonal complexes (CCs) and 79 singletons. Besides, seventy-three CAI genotypes were identified. Blood isolates showed maximum genotypes (49), and the dominant genotypes were CAI 17-21 and CAI 21-21. Oral isolates possessed 25 CAI genotypes, and the dominant genotypes were CAI 17-21 and CAI 21-21 as well. Since isolates with CAI allele numbers <30 showed easier transmission, CAI 17-21 and CAI 21-21 were the most frequently transmitted. Finally, the CAI genotypes were classified into six groups. CONCLUSIONS: This work revealed the oral and blood strains isolated from the patients with candidaemia in ICU shared the identical dominant CAI genotypes. Our data expanded the C. albicans MLST database and helped with understanding the evolution and spread of invasive candidiasis.

Log Sequence Anomaly Detection Method Based on Contrastive Adversarial Training and Dual Feature Extraction.

The log messages generated in the system reflect the state of the system at all times. The realization of autonomous detection of abnormalities in log messages can help operators find abnormalities in time and provide a basis for analyzing the causes of abnormalities. First, this paper proposes a log sequence anomaly detection method based on contrastive adversarial training and dual feature extraction. This method uses BERT (Bidirectional Encoder Representations from Transformers) and VAE (Variational Auto-Encoder) to extract the semantic features and statistical features of the log sequence, respectively, and the dual features are combined to perform anomaly detection on the log sequence, with a novel contrastive adversarial training method also used to train the model. In addition, this paper introduces the method of obtaining statistical features of log sequence and the method of combining semantic features with statistical features. Furthermore, the specific process of contrastive adversarial training is described. Finally, an experimental comparison is carried out, and the experimental results show that the method in this paper is better than the contrasted log sequence anomaly detection method.

Melanin Concentrating Hormone Signaling Deficits in Schizophrenia: Association With Memory and Social Impairments and Abnormal Sensorimotor Gating.

BACKGROUND: Evidence from anatomical, pharmacological, and genetic studies supports a role for the neuropeptide melanin concentrating hormone system in modulating emotional and cognitive functions. Genome-wide association studies revealed a potential association between the melanin concentrating hormone receptor (MCHR1) gene locus and schizophrenia, and the largest genome-wide association study conducted to date shows a credible genome-wide association. METHODS: We analyzed MCHR1 and pro-melanin concentrating hormone RNA-Seq expression in the prefrontal cortex in schizophrenia patients and healthy controls. Disruptions in the melanin concentrating hormone system were modeled in the mouse brain by germline deletion of MCHR1 and by conditional ablation of melanin concentrating hormone expressing neurons using a Cre-inducible diphtheria toxin system. RESULTS: MCHR1 expression is decreased in the prefrontal cortex of schizophrenia samples (false discovery rate (FDR) P < .05, CommonMind and PsychEncode combined datasets, n = 901) while pro-melanin concentrating hormone is below the detection threshold. MCHR1 expression decreased with aging (P = 6.6E-57) in human dorsolateral prefrontal cortex. The deletion of MCHR1 was found to lead to behavioral abnormalities mimicking schizophrenia-like phenotypes: hyperactivity, increased stereotypic and repetitive behavior, social impairment, impaired sensorimotor gating, and disrupted cognitive functions. Conditional ablation of pro-melanin concentrating hormone neurons increased repetitive behavior and produced a deficit in sensorimotor gating. CONCLUSIONS: Our study indicates that early disruption of the melanin concentrating hormone system interferes with neurodevelopmental processes, which may contribute to the pathogenesis of schizophrenia. Further neurobiological research on the developmental timing and circuits that are affected by melanin concentrating hormone may lead to a therapeutic target for early prevention of schizophrenia.

Bre1-dependent H2B ubiquitination promotes homologous recombination by stimulating histone eviction at DNA breaks.

Repair of DNA double-strand breaks (DSBs) requires eviction of the histones around DNA breaks to allow the loading of numerous repair and checkpoint proteins. However, the mechanism and regulation of this process remain poorly understood. Here, we show that histone H2B ubiquitination (uH2B) promotes histone eviction at DSBs independent of resection or ATP-dependent chromatin remodelers. Cells lacking uH2B or its E3 ubiquitin ligase Bre1 exhibit hyper-resection due to the loss of H3K79 methylation that recruits Rad9, a known negative regulator of resection. Unexpectedly, despite excessive single-strand DNA being produced, bre1Δ cells show defective RPA and Rad51 recruitment and impaired repair by homologous recombination and response to DNA damage. The HR defect in bre1Δ cells correlates with impaired histone loss at DSBs and can be largely rescued by depletion of CAF-1, a histone chaperone depositing histones H3-H4. Overexpression of Rad51 stimulates histone eviction and partially suppresses the recombination defects of bre1Δ mutant. Thus, we propose that Bre1 mediated-uH2B promotes DSB repair through facilitating histone eviction and subsequent loading of repair proteins.

Promoting axon regeneration in the adult CNS by modulation of the melanopsin/GPCR signaling.

Cell-type-specific G protein-coupled receptor (GPCR) signaling regulates distinct neuronal responses to various stimuli and is essential for axon guidance and targeting during development. However, its function in axonal regeneration in the mature CNS remains elusive. We found that subtypes of intrinsically photosensitive retinal ganglion cells (ipRGCs) in mice maintained high mammalian target of rapamycin (mTOR) levels after axotomy and that the light-sensitive GPCR melanopsin mediated this sustained expression. Melanopsin overexpression in the RGCs stimulated axonal regeneration after optic nerve crush by up-regulating mTOR complex 1 (mTORC1). The extent of the regeneration was comparable to that observed after phosphatase and tensin homolog (Pten) knockdown. Both the axon regeneration and mTOR activity that were enhanced by melanopsin required light stimulation and Gq/11 signaling. Specifically, activating Gq in RGCs elevated mTOR activation and promoted axonal regeneration. Melanopsin overexpression in RGCs enhanced the amplitude and duration of their light response, and silencing them with Kir2.1 significantly suppressed the increased mTOR signaling and axon regeneration that were induced by melanopsin. Thus, our results provide a strategy to promote axon regeneration after CNS injury by modulating neuronal activity through GPCR signaling.

[Virtual screening for components in Chicory combined with CNT2 target based on molecular docking].

To virtual screen the compound of Chicory combined with the concentrative nucleoside transporter 2 (CNT2) in molecular docking technology.The homology model of hCNT2 was produced, and then the Vina software was employed to virtual screen the Chicory compound combined with CNT2. Compared with 7,8,3'-trihydroxyflavone, a CNT2 inhibitors, 23 score higher chicory compounds were hit.Meanwhile, the ten top compounds have been revealed that play important role in decrease the uric level. The bioactivity to CNT2 needs to be investigatedin experiment. CNT2 may be a potential target of chicory, which decreases the absorption of purine nucleoside in intestinal tract.

Relationship between High-Performance Liquid Chromatography Fingerprints and Uric Acid-Lowering Activities of Cichorium intybus L.

This study aimed to explore the spectrum-effect relationships between high-performance liquid chromatography fingerprints and the uric acid-lowering activities of chicory. Chemical fingerprints of chicory samples from ten different sources were determined by high-performance liquid chromatography, and then investigated by similarity analysis and hierarchical clustering analysis. Pharmacodynamics experiments were conducted in animals to obtain the uric acid-lowering activity information of each chicory sample. The spectrum-effect relationships between chemical fingerprints and the uric acid-lowering activities of chicory were established by canonical correlation analysis. The structures of potential effective peaks were identified by liquid chromatography with tandem mass spectrometry. The results showed that a close correlation existed between the spectrum and effect of chicory. Aesculin, chlorogenic acid, chicoric acid, isochlorogenic acid A/B/C and 13,14-seco-stigma5(6),14(15)-diene-3α-ol might be the main effective constituents. This work provides a general model of the combination of high-performance liquid chromatography and uric acid-lowering activities to study the spectrum-effect relationships of chicory, which can be used to discover the principle components responsible for the bioactivity.

[Molecular docking analysis of xanthine oxidase inhibition by constituents of cichory].

Human xanthine oxidase is considered to be a target for therapy of hyperuricemia. Cichorium intybus is a Chinese plant medicine which widely used in Xinjiang against various diseases. In order to screen the inhibitors of xanthine oxidase from C. intybus and to explore main pharmacological actions of cichory a compound collection of C. intybus was built via consulting related references about chemical research on cichory. The three-dimensional crystal structure of xanthine oxidase (PDB code: 1N5X) from Protein Data Bank was downloaded.. Autodock 4.2 was employed to screen the inhibitors of xanthine oxidase from cichory 70 compounds were found to possess quite low binding free energy comparing with TEI (febuxostat). C. intybus contains constituents possessing potential inhibitive activity against xanthine oxidase. It can explain the main pharmacological actions of cichory which can significantly lower the level of serum uric acid.