Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures.

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation - hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

Intrarelationships between suboptimal health status and anxiety symptoms: A network analysis.

BACKGROUND: Suboptimal health status is a global public health concern of worldwide academic interest, which is an intermediate health status between health and illness. The purpose of the survey is to investigate the relationship between anxiety statuses and suboptimal health status and to identify the central symptoms and bridge symptoms. METHODS: This study recruited 26,010 participants aged <60 from a cross-sectional study in China in 2022. General Anxiety Disorder-7 (GAD-7) and suboptimal health status short form (SHSQ-9) were used to quantify the levels of anxiety and suboptimal health symptoms, respectively. The network analysis method by the R program was used to judge the central and bridge symptoms. The Network Comparison Test (NCT) was used to investigate the network differences by gender, place of residence, and age in the population. RESULTS: In this survey, the prevalence of anxiety symptoms, SHS, and comorbidities was 50.7 %, 54.8 %, and 38.5 %, respectively. "Decreased responsiveness", "Shortness of breath", "Uncontrollable worry" were the nodes with the highest expected influence. "Irritable", "Exhausted" were the two symptom nodes with the highest expected bridge influence in the network. There were significant differences in network structure among different subgroup networks. LIMITATIONS: Unable to study the causal relationship and dynamic changes among variables. Anxiety and sub-health were self-rated and may be limited by memory bias. CONCLUSIONS: Interventions targeting central symptoms and bridge nodes may be expected to improve suboptimal health status and anxiety in Chinese residents. Researchers can build symptom networks for different populations to capture symptom relationships.

The Emerging Landscape for Combating Resistance Associated with Energy-Based Therapies via Nanomedicine.

Cancer represents a serious disease with significant implications for public health, imposing substantial economic burden and negative societal consequences. Compared to conventional cancer treatments, such as surgery and chemotherapy, energy-based therapies (ET) based on athermal and thermal ablation provide distinct advantages, including minimally invasive procedures and rapid postoperative recovery. Nevertheless, due to the complex pathophysiology of many solid tumors, the therapeutic effectiveness of ET is often limited. Nanotechnology offers unique opportunities by enabling facile material designs, tunable physicochemical properties, and excellent biocompatibility, thereby further augmenting the outcomes of ET. Numerous nanomaterials have demonstrated the ability to overcome intrinsic therapeutic resistance associated with ET, leading to improved antitumor responses. This comprehensive review systematically summarizes the underlying mechanisms of ET-associated resistance (ETR) and highlights representative applications of nanoplatforms used to mitigate ETR. Overall, this review emphasizes the recent advances in the field and presents a detailed account of novel nanomaterial designs in combating ETR, along with efforts aimed at facilitating their clinical translation.

Mechanism of Sophorae Flavescentis Radix (Kushen) in treating NSCLC: Insights from miRNA-mRNA network analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae Flavescentis Radix (Kushen) is the primary herb component of Compound Kushen Injection (CKI), an approved clinical treatment for tumors. Despite CKI's widespread use, the underlying mechanisms of Kushen regarding microRNA-target and pathway remain unclear in non-small cell lung cancer (NSCLC). AIM OF THE STUDY: This study aimed to elucidate the crucial miRNAs-targets and pathways responsible for the Kushen's impact on NSCLC. MATERIALS AND METHODS: CCK8, colony formation, and apoptosis assays were performed to assess the effects of Kushen on NSCLC cells. Subsequently, we treated the A549 cell line with varying concentrations of Kushen to obtain mRNA and miRNA expression profiles. A DE (differentially expressed) miRNAs-DEGs network was then constructed to identify the critical miRNA-mRNA interaction influenced by Kushen. Furthermore, we performed clinical significance and prognosis analyses of hub genes to narrow down key genes and their corresponding miRNAs. Finally, the effects of Kushen on critical miRNA-mRNA interaction and related pathway were verified by in vitro and in vivo experiments. RESULTS: In this study, we initially demonstrated that Kushen significantly inhibited cell proliferation, suppressed colony formation, and induced apoptosis in the A549 cells, PC9 cells, and the A549 zebrafish xenograft model. Through expression profile analysis, a DE miRs-DEGs network was constructed with 16 DE miRs and 68 DEGs. Through the network analysis and expression validation, we found Kushen could significantly down-regulate miR-183-5p expression and up-regulate EGR1 expression. Additionally, Kushen affected the PTEN/Akt pathway, increasing PTEN expression and decreasing pAkt expression. Finally, matrine, the essential active compound of Kushen, also inhibited cell growth, induced apoptosis, and regulated miR-183-5p/EGR1 and PTEN/AKT pathway. CONCLUSIONS: Altogether, these findings supported the critical role of miR-183-5p/EGR1 and the PTEN/AKT pathway in the beneficial effects of Kushen on NSCLC, highlighting the therapeutic potential of Kushen in NSCLC treatment.

Effects of Natural Products on Enzymes Involved in Ferroptosis: Regulation and Implications.

Ferroptosis is a form of regulated cell death that is characterized by the accumulation of iron-dependent lipid peroxides. The regulation of ferroptosis involves both non-enzymatic reactions and enzymatic mechanisms. Natural products have demonstrated potential effects on various enzymes, including GPX4, HO-1, NQO1, NOX4, GCLC, and GCLM, which are mainly involved in glutathione metabolic pathway or oxidative stress regulation, and ACSL3 and ACSL4, which mainly participate in lipid metabolism, thereby influencing the regulation of ferroptosis. In this review, we have provided a comprehensive overview of the existing literature pertaining to the effects of natural products on enzymes involved in ferroptosis and discussed their potential implications for the prevention and treatment of ferroptosis-related diseases. We also highlight the potential challenge that the majority of research has concentrated on investigating the impact of natural products on the expression of enzymes involving ferroptosis while limited attention is given to the regulation of enzyme activity. This observation underscores the considerable potential and scope for exploring the influence of natural products on enzyme activity.

Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

Cinnamomi ramulus inhibits cancer cells growth by inducing G2/M arrest.

Introduction: Cinnamomi ramulus (CR) is one of the most widely used traditional Chinese medicine (TCM) with anti-cancer effects. Analyzing transcriptomic responses of different human cell lines to TCM treatment is a promising approach to understand the unbiased mechanism of TCM. Methods: This study treated ten cancer cell lines with different CR concentrations, followed by mRNA sequencing. Differential expression (DE) analysis and gene set enrichment analysis (GSEA) were utilized to analyze transcriptomic data. Finally, the in silico screening results were verified by in vitro experiments. Results: Both DE and GSEA analysis suggested the Cell cycle pathway was the most perturbated pathway by CR across these cell lines. By analyzing the clinical significance and prognosis of G2/M related genes (PLK1, CDK1, CCNB1, and CCNB2) in various cancer tissues, we found that they were up-regulated in most cancer types, and their down-regulation showed better overall survival rates in cancer patients. Finally, in vitro experiments validation on A549, Hep G2, and HeLa cells suggested that CR can inhibit cell growth by suppressing the PLK1/CDK1/ Cyclin B axis. Discussion: This is the first study to apply transcriptomic analysis to investigate the cancer cell growth inhibition of CR on various human cancer cell lines. The core effect of CR on ten cancer cell lines is to induce G2/M arrest by inhibiting the PLK1/CDK1/Cyclin B axis.

Metal Nanoparticles as Novel Agents for Lung Cancer Diagnosis and Therapy.

Lung cancer is one of the most common malignancies worldwide and contributes to most cancer-related morbidity and mortality cases. During the past decades, the rapid development of nanotechnology has provided opportunities and challenges for lung cancer diagnosis and therapeutics. As one of the most extensively studied nanostructures, metal nanoparticles obtain higher satisfaction in biomedical applications associated with lung cancer. Metal nanoparticles have enhanced almost all major imaging strategies and proved great potential as sensor for detecting cancer-specific biomarkers. Moreover, metal nanoparticles could also improve therapeutic efficiency via better drug delivery, improved radiotherapy, enhanced gene silencing, and facilitated photo-driven treatment. Herein, the recently advanced metal nanoparticles applied in lung cancer therapy and diagnosis are summarized. Future perspective on the direction of metal-based nanomedicine is also discussed. Stimulating more research interests to promote the development of metal nanoparticles in lung cancer is devoted.

STING as an emerging therapeutic target for drug discovery: Perspectives from the global patent landscape.

BACKGROUND: The STimulator of INterferon Genes (STING) plays an essential role in the innate immune system by inducing the expression of type I interferons (IFNs) and inflammatory cytokines upon sensing cytosolic DNA. Although modulating STING has shown promise as a potential treatment for cancers and inflammatory and autoimmune diseases in substantial pre-clinical studies, current preliminary clinical results of STING agonists have demonstrated limited anti-tumor efficacy. Currently, there is ongoing R&D targeting STING and focusing on the delivery of next-generation therapeutics. Whereas no comprehensive analysis on the STING patent landscape has been conducted to fill the gap between basic research progress and drug development and commercialization. AIM OF REVIEW: This study summarized the current agents in the clinical stage and global patenting profiles to help identify the current status, development trends, and emerging technologies of the nascent field of STING modulation. KEY SCIENTIFIC CONCEPTS OF REVIEW: Rapidly increasing R&D efforts and outcomes targeting STING were indicated by the recently increasing number and pharmacologic classes of drug candidates in clinic as well as in emergent technological patenting activities. Despite the overall fragmental ownership of patents, several pioneers that have advanced the clinical evaluation of novel STING agonists have established the basis of STING-relevant inventions through their influential patents in the field. These patents also facilitated progress on novel STING modulators, relevant delivery systems, pharmaceutical compositions, and combination strategies with the potential for further enhancing therapeutic outcomes by targeting STING.

Fatigue and Recovery of Muscles for Pulling Tasks.

Manual materials handling (MMH) contributes to musculoskeletal disorders (MSDs) in the workplace. The development and recovery of muscle fatigue are essential in work/rest arrangements for MMH tasks. A pulling experiment, including a muscle fatigue test and a muscle fatigue recovery test, was conducted. In the muscle fatigue test, the participant performed a pulling task on a treadmill with a walking velocity of 1 km/h until they could no longer do so. The load was either 30 or 45 kg. The maximum endurance time (MET) was recorded. The pull strength (PS) of the participant both before and after the pulling task was measured. The subjective ratings of muscle fatigue after the pulling task were recorded. In the muscle fatigue recovery test, the participant took a rest after performing the pulling task. The participants reported their subjective ratings of muscle fatigue on the CR-10 scale after taking a rest for a time period t, where t = 1, 2,…, 6 min. The PS of the participant was then measured again. It was found that the load significantly affected the MET for pulling tasks. The load was insignificant to the decrease of the PS, but was significant to the decrease rate (PS decrease per min) of the PS. The PS decrease rate for the 45 kg condition (30.8 ± 16.5 N/min) was significantly higher (p < 0.05) than that of the 30 kg condition (15.4 ± 5.5 N/min). The recovery time significantly affected the PS and CR-10. Two MET models were established to explore the development of muscle fatigue in pulling tasks. A PS model was constructed to describe the recovery of muscle force. A CR-10 model was proposed to show the subjective ratings of recovery. These models are beneficial for determining the work/rest allowance for pulling tasks.

What, Where, When and How of COVID-19 Patents Landscape: A Bibliometrics Review.

Two years after COVID-19 came into being, many technologies have been developed to bring highly promising bedside methods to help fight this epidemic disease. However, owing to viral mutation, how far the promise can be realized remains unclear. Patents might act as an additional source of information for informing research and policy and anticipating important future technology developments. A comprehensive study of 3741 COVID-19-related patents (3,543 patent families) worldwide was conducted using the Derwent Innovation database. Descriptive statistics and social network analysis were used in the patent landscape. The number of COVID-19 applications, especially those related to treatment and prevention, continued to rise, accompanied by increases in governmental and academic patent assignees. Although China dominated COVID-19 technologies, this position is worth discussing, especially in terms of the outstanding role of India and the US in the assignee collaboration network as well as the outstanding invention portfolio in Italy. Intellectual property barriers and racist treatment were reduced, as reflected by individual partnerships, transparent commercial licensing and diversified portfolios. Critical technological issues are personalized immunity, traditional Chinese medicine, epidemic prediction, artificial intelligence tools, and nucleic acid detection. Notable challenges include balancing commercial competition and humanitarian interests. The results provide a significant reference for decision-making by researchers, clinicians, policymakers, and investors with an interest in COVID-19 control.

The Changing Global Landscape in the Development of Artemisinin-Based Treatments: A Clinical Trial Perspective.

Artemisinin and its derivatives (ARTs), due to their potent antimalarial activities, are widely used as frontline antimalarials across the world. Although the large-scale deployment of ARTs has significantly contributed to a substantial decline in malaria deaths, the global malaria burden is still high. New antimalarial treatments need to be developed to manage the growing artemisinin resistance. Understanding the status of ART development is crucial for developing strategies for new alternatives and identifying opportunities to develop ART-based treatments. This study sampled ART clinical trials from the past two decades to gain an overview of the global ART-development landscape. A total of 768 trials were collected to analyze the disease focuses, activity trends, development status, geographic distribution, and combination treatment profiles of ART trials. The findings highlighted the constant focus of ARTs on malaria, the evolving combination research focus, the distinctions between ART development preferences across global regions, the urgent demands for treatments for artemisinin-resistant malaria, and the unavoidable need to consider ART combinations in the development of new antimalarials.

A network pharmacology-based study on the quality control markers of antithrombotic herbs: Using Salvia miltiorrhiza - Ligusticum chuanxiong as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (Danshen, DS), the dried root and rhizome of Salvia miltiorrhiza Bunge and Ligusticum chuanxiong (Chuanxiong, CX), the dried rhizomes of Ligusticum striatum DC are effective in invigorating blood circulation and eliminating stasis which is highly related with cardiovascular disease (CVD). AIM OF STUDY: The identification of activity-based chemical markers is very important, but the complex mechanism of "multi-component, multi-target, and multi-effect" within traditional Chinese medicine (TCM) poses a great challenge to this work. In this study, we combined network pharmacological prediction with experimental validation of the DS and CX to explore an effective method for discovering quality control (QC) of antithrombotic herbs by clarifying the intermediate layer "module/cluster" between the whole complex system and a single component. MATERIALS AND METHODS: Based on structural similarity analysis of compound and the thrombosis network published before, we firstly modularized two layers called chemical cluster (CC) network and functional module (FM) network respectively and linked them into one bilayer modularized compound target (BMCT) network. "Two-step" calculation was applied on identifying the significant compounds as the potential QC markers from CC. The in vitro inhibitory activity of selected QC marker compounds on thrombin was evaluated to partially verify their pharmacological activities. HPLC was used to determine contents. RESULTS: According to the network-based analysis, nine compounds with great importance in the BMCT network were identified as QC markers of DS-CX, including tanshinone I, tanshinone IIA, cryptotanshinone, salvianolic acid B, ferulic acid, salvianolic acid A, rosmarinic acid, chlorogenic acid, and coniferyl ferulate. Enzyme inhibitory test partially verified the activity of tanshinone I and tanshinone IIA. Chemical profiling indicated that the nine marker compounds are the main components in the herbal pair. CONCLUSIONS: This study identified activity-based QC markers of DS-CX herbal pair and provided a new methodology that can be used in the QC of other herbs, herbal pairs, or formulas.

Modeling and Validation of Fatigue and Recovery of Muscles for Manual Demolition Tasks.

Manual demolition tasks are heavy, physically demanding tasks that could cause muscle fatigue accumulation and lead to work-related musculoskeletal disorders (WMSDs). Fatigue and recovery models of muscles are essential in understanding the accumulation and the reduction in muscle fatigue for forceful exertion tasks. This study aims to explore the onset of muscle fatigue under different work/rest arrangements during manual demolition tasks and the offset of fatigue over time after the tasks were performed. An experiment, including a muscle fatigue test and a muscle fatigue recovery test, was performed. Seventeen male adults without experience in demolition hammer operation were recruited as human participants. Two demolition hammers (large and small) were adopted. The push force was either 20 or 40 N. The posture mimicked that of a demolition task on a wall. In the muscle fatigue test, the muscle strength (MS) before and after the demolition task, maximum endurance time (MET), and the Borg category-ratio-10 (CR-10) ratings of perceived exertion after the demolition task were measured. In the muscle fatigue recovery test, MS and CR-10 at times 1, 2, 3, 4, 5, and 6 min were recorded. Statistical analyses were performed to explore the influence of push force and the weight of the tool on MS, MET, and CR-10. Both muscle fatigue models and muscle fatigue recovery models were established and validated. The results showed that push force affected MET significantly (p < 0.05). The weight of the tool was significant (p < 0.05) only on the CR-10 rating after the first pull. During the muscle fatigue recovery test, the MS increase and the CR-10 decrease were both significant (p < 0.05) after one or more breaks. Models of MET and MS prediction were established to assess muscle fatigue recovery, respectively. The absolute (AD) and relative (RD) deviations of the MET model were 1.83 (±1.94) min and 34.80 (±31.48)%, respectively. The AD and RD of the MS model were 1.39 (±0.81) N and 1.9 (±1.2)%, respectively. These models are capable of predicting the progress and recovery of muscle fatigue, respectively, and may be adopted in work/rest arrangements for novice workers performing demolition tasks.

Enzyme Activity of Natural Products on Cytochrome P450.

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions.

MicroRNAs (miRNAs) are noncoding RNAs with 18-26 nucleotides; they pair with target mRNAs to regulate gene expression and produce significant changes in various physiological and pathological processes. In recent years, the interaction between miRNAs and their target genes has become one of the mainstream directions for drug development. As a large-scale biological database that mainly provides miRNA-target interactions (MTIs) verified by biological experiments, miRTarBase has undergone five revisions and enhancements. The database has accumulated >2 200 449 verified MTIs from 13 389 manually curated articles and CLIP-seq data. An optimized scoring system is adopted to enhance this update's critical recognition of MTI-related articles and corresponding disease information. In addition, single-nucleotide polymorphisms and disease-related variants related to the binding efficiency of miRNA and target were characterized in miRNAs and gene 3' untranslated regions. miRNA expression profiles across extracellular vesicles, blood and different tissues, including exosomal miRNAs and tissue-specific miRNAs, were integrated to explore miRNA functions and biomarkers. For the user interface, we have classified attributes, including RNA expression, specific interaction, protein expression and biological function, for various validation experiments related to the role of miRNA. We also used seed sequence information to evaluate the binding sites of miRNA. In summary, these enhancements render miRTarBase as one of the most research-amicable MTI databases that contain comprehensive and experimentally verified annotations. The newly updated version of miRTarBase is now available at https://miRTarBase.cuhk.edu.cn/.

Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.

Molecular evidence of herbal formula: a network-based analysis of Si-Wu decoction.

INTRODUCTION: Emerging network pharmacology (NP) combines phytochemical information with bioinformatics tools allowing herbal formulae to be illustrated holistically in the context of phytochemical basis and therapeutic mechanisms. OBJECTIVE: This study attempted to explore the holistic molecular evidence of herbal formula Si-Wu decoction (SWD) by using the method of NP. MATERIAL AND METHOD: Databases of traditional medicines combined with PubChem, SciFinder, SEA, STRING, and KEGG were employed to gather information for establishing the "compound similarity" (CS) network and the "target-(pathway)-target" (TPT) network. Gephi software was applied to visualise the networks, with further module-based and node-based network topological analysis. Moreover, the approved drugs and shortest path analysis were used to validate the TPT network. RESULTS: The CS network presented the phytochemical profile of SWD, including the major compound groups of iridoid glycosides, glycosides, phthalide lactones, phenylpropanoids, and monoterpenoids. Furthermore, the topological analysis of TPT network depicted the holistic property of SWD in interpretable neuroendocrine immunomodulation (NIM) perspective, and the node degree analysis indicated a closer connection of SWD with endocrine or metabolism system. Moreover, by combing the analysis of the CS network and TPT network, potential active ingredients could be primarily identified. CONCLUSION: The phytochemical profile and molecular target profile, which might pave the way for an understanding of SWD in modern science and provide a reference for relevant quality research and evaluation, were demonstrated by network analysis. Moreover, the methods could be further applied to discover the phytochemical or biomolecular evidence with distinct advantages in dealing with the tremendous separated information.

MethHC 2.0: information repository of DNA methylation and gene expression in human cancer.

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.