NLRP3 Inflammasomes: Dual Function in Infectious Diseases.

The Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been the most distinctive polymer protein complex. After recognizing the endogenous and exogenous danger signals, NLRP3 can cause inflammation by pyroptosis and secretion of mature, bioactive forms of IL-1ß and IL-18. The NLRP3 inflammasome is essential in the genesis and progression of infectious illnesses. Herein, we provide a comprehensive review of the NLRP3 inflammasome in infectious diseases, focusing on its two-sided effects. As an essential part of host defense with a protective impact, abnormal NLRP3 inflammasome activation, however, result in a systemic high inflammatory response, leading to subsequent damage. In addition, scientific evidence of small molecules, biologics, and phytochemicals acting on the NLRP3 inflammasome has been reviewed. We believe that the NLRP3 inflammasome helps us understand the pathological mechanism of different stages of infectious diseases and that inhibitors targeting the NLRP3 inflammasome will become a new and valuable research direction for the treatment of infectious diseases.

The case of young people who use e-cigarettes infrequently: Who is this population? What becomes of them?

BACKGROUND: Emerging data indicate that many adolescents and young adults ("youth") engage in infrequent, or occasional, e-cigarette use. However, little is known about this population as they are often subsumed into the broader "any past-30-day use" category used to define youth "current use." This study aimed to focus on infrequent e-cigarette use by youth, examining its correlates and transitional outcomes. METHODS: Participants were from a prospective cohort study of youth (aged 15-24 at baseline). Among youth who had used e-cigarettes, we classified "infrequent use" as using e-cigarettes ≤5 days in the last 30 days (n=273) and "frequent use" as using e-cigarettes ≥6 days in the last 30 days (n=278). Descriptive statistics, Markov modeling, and logistic regression were utilized. RESULTS: By the 12-month follow-up, 76.8% of those using infrequently at baseline remained in the "infrequent use" category, 6.3% reported no recent use, and 16.8% had escalated to the "frequent use" category. Among the youth using infrequently at baseline, those who did (vs. did not) escalate to frequent use by follow-up had higher baseline nicotine dependence and were more likely to have family members who used tobacco. CONCLUSIONS: Infrequent e-cigarette use is extremely common, and often fairly stable, among young people. Prevention efforts must certainly attempt to reduce escalation and attend to both individual and interpersonal factors (e.g., nicotine dependence, family use). Yet prevention efforts must additionally attend to the case of continued infrequent use, given the high prevalence of people in this category and their regular exposure to e-cigarette harms.

NLRP3 inflammasome in digestive diseases: From mechanism to therapy.

Digestive system diseases remain a formidable challenge to human health. NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most characteristic multimeric protein complex and is involved in a wide range of digestive diseases as intracellular innate immune sensors. It has emerged as a research hotspot in recent years. In this context, we provide a comprehensive review of NLRP3 inflammasome priming and activation in the pathogenesis of digestive diseases, including clinical and preclinical studies. Moreover, the scientific evidence of small-molecule chemical drugs, biologics, and phytochemicals, which acts on different steps of the NLRP3 inflammasome, is reviewed. Above all, deep interrogation of the NLRP3 inflammasome is a better insight of the pathomechanism of digestive diseases. We believe that the NLRP3 inflammasome will hold promise as a novel valuable target and research direction for treating digestive disorders.

Mechanisms of Xiaochaihu Decoction on Treating Hepatic Fibrosis Explored by Network Pharmacology.

Purpose: To explore the material basis and pharmacological mechanism of Xiaochaihu Decoction (XCHD), the classic Traditional Chinese Medicine (TCM) formula in inhibiting hepatic fibrosis (HF). Methods: The main components in XCHD were screened from the TCMSP database, ETCM database, and literature, and their potential targets were detected and predicted using the Swiss Target Prediction platform. The HF-related targets were retrieved and screened through GeneCard database and OMIM database, combined with GEO gene chips. The XCHD targets and HF targets were mapped to search common targets. The protein-protein interaction (PPI) network was acquired via the STRING11.0 database and analyzed visually using Cytoscape 3.8.0 software. The potential mechanisms of the common targets identified through GO and KEGG pathway enrichment analysis were analyzed by using Metascape database. The results were visualized through OmicShare Tools. The "XCHD compound-HF target" network was visually constructed by Cytoscape 3.8.0 software. AutoDockVina1.1.2 and PyMoL software were used to verify the molecular docking of XCHD main active compounds and HF key targets. Results: A total of 164 potential active compounds from XCHD were screened to act on 95 HF-related targets. Bioinformatics analysis revealed that quercetin, ß-sitosterol, and kaempferol may be candidate agents, which acted on multiple targets like PTGS2, HSP90AA1, and PTGS1 and regulate multiple key biological pathways like IL-17 signaling pathway, TNF signaling pathway and PI3K-Akt signaling pathway to relieve HF. Moreover, molecular docking suggested that quercetin and PTGS2 could statically bind and interact with each other through amino acid residues val-349, LEU-352, PHE-381, etc. Conclusion: This work provides a systems perspective to study the relationship between Chinese medicines and diseases. The therapeutic efficacy of XCHD on HF was the sum of multitarget and multi-approach effects from the bioactive ingredients. This study could be one of the cornerstones for further research.

The Immune Pathogenesis of Acute-On-Chronic Liver Failure and the Danger Hypothesis.

Acute-on-chronic liver failure (ACLF) is a group of clinical syndromes related to severe acute liver function impairment and multiple-organ failure caused by various acute triggering factors on the basis of chronic liver disease. Due to its severe condition, rapid progression, and high mortality, it has received increasing attention. Recent studies have shown that the pathogenesis of ACLF mainly includes direct injury and immune injury. In immune injury, cytotoxic T lymphocytes (CTLs), dendritic cells (DCs), and CD4+ T cells accumulate in the liver tissue, secrete a variety of proinflammatory cytokines and chemokines, and recruit more immune cells to the liver, resulting in immune damage to the liver tissue, massive hepatocyte necrosis, and liver failure, but the key molecules and signaling pathways remain unclear. The "danger hypothesis" holds that in addition to the need for antigens, damage-associated molecular patterns (DAMPs) also play a very important role in the occurrence of the immune response, and this hypothesis is related to the pathogenesis of ACLF. Here, the research status and development trend of ACLF, as well as the mechanism of action and research progress on various DAMPs in ACLF, are summarized to identify biomarkers that can predict the occurrence and development of diseases or the prognosis of patients at an early stage.

YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial.

INTRODUCTION: Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis. METHODS AND ANALYSIS: This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is "the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%." ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Ethics Committee of Guang'anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900021532 . Registered on February 26, 2019.

Identification of 5 Hub Genes Related to the Early Diagnosis, Tumour Stage, and Poor Outcomes of Hepatitis B Virus-Related Hepatocellular Carcinoma by Bioinformatics Analysis.

BACKGROUND: The majority of primary liver cancers in adults worldwide are hepatocellular carcinomas (HCCs, or hepatomas). Thus, a deep understanding of the underlying mechanisms for the pathogenesis and carcinogenesis of HCC at the molecular level could facilitate the development of novel early diagnostic and therapeutic treatments to improve the approaches and prognosis for HCC patients. Our study elucidates the underlying molecular mechanisms of HBV-HCC development and progression and identifies important genes related to the early diagnosis, tumour stage, and poor outcomes of HCC. METHODS: GSE55092 and GSE121248 gene expression profiling data were downloaded from the Gene Expression Omnibus (GEO) database. There were 119 HCC samples and 128 nontumour tissue samples. GEO2R was used to screen for differentially expressed genes (DEGs). Volcano plots and Venn diagrams were drawn by using the ggplot2 package in R. A heat map was generated by using Heatmapper. By using the clusterProfiler R package, KEGG and GO enrichment analyses of DEGs were conducted. Through PPI network construction using the STRING database, key hub genes were identified by cytoHubba. Finally, KM survival curves and ROC curves were generated to validate hub gene expression. RESULTS: By GO enrichment analysis, 694 DEGs were enriched in the following GO terms: organic acid catabolic process, carboxylic acid catabolic process, carboxylic acid biosynthetic process, collagen-containing extracellular matrix, blood microparticle, condensed chromosome kinetochore, arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. In the KEGG pathway enrichment analysis, DEGs were enriched in arachidonic acid epoxygenase activity, arachidonic acid monooxygenase activity, and monooxygenase activity. By PPI network construction and analysis of hub genes, we selected the top 10 genes, including CDK1, CCNB2, CDC20, BUB1, BUB1B, CCNB1, NDC80, CENPF, MAD2L1, and NUF2. By using TCGA and THPA databases, we found five genes, CDK1, CDC20, CCNB1, CENPF, and MAD2L1, that were related to the early diagnosis, tumour stage, and poor outcomes of HBV-HCC. CONCLUSIONS: Five abnormally expressed hub genes of HBV-HCC are informative for early diagnosis, tumour stage determination, and poor outcome prediction.

Calculating RF-Induced Voltages for Implanted Medical Devices in MRI Using Computational Human Models.

Despite its import as a diagnostic tool, patients with active implantable medical devices (AIMDs) are generally denied access to magnetic resonance imaging (MRI). The complexity of MRI environments stems from a multiplicity of fields and numerous scan parameters. In order to perform a risk assessment for RF-induced malfunction, manufacturers perform electromagnetic simulations using computational human models (CHMs) to calculate RF induced energy at the AIMD ports. This work explores the impact of the CHMs on the calculation of RF-induced voltages at the RF antenna port for cardiovascular implantable electronic devices (CIEDs).

Virtual Humans for Implantable Device Safety Assessment in MRI: Mitigating Magnetic Resonance Imaging Hazards for Implanted Medical Devices.

Magnetic resonance imaging (MRI) is the preferred modality for soft tissue imaging because of its nonionizing radiation and lack of contrast agent. Due to interactions between the MR system and active implantable medical devices (AIMDs), patients with implants such as pacemakers are generally denied access to MRI, which presents a detriment to that population. It has been estimated that 50-75% of patients with a cardiac device were denied access to MRI scanning and, moreover, that 17% of pacemaker patients need an MRI within 12 months of implantation [1]. In recent years, AIMD manufacturers, such as Biotronik, have assessed the conditional safety of devices in MRI.

Possible overexposure of pregnant women to emissions from a walk through metal detector.

This paper presents a systematic procedure to evaluate the induced current densities and electric fields due to walk-through metal detector (WTMD) exposure. This procedure is then used to assess the exposure of nine pregnant women models exposed to one WTMD model. First, we measured the magnetic field generated by the WTMD, then we extracted the equivalent current source to represent the WTMD emissions and finally we calculated the induced current densities and electric fields using the impedance method. The WTMD emissions and the induced fields in the pregnant women and fetus models are then compared to the ICNIRP Guidelines and the IEEE C95.6 exposure safety standard. The results prove the consistency between maximum permissible exposure (MPE) levels and basic restrictions for the ICNIRP Guidelines and IEEE C95.6. We also found that this particular WTMD complies with the ICNIRP basic restrictions for month 1-5 models, but leads to both fetus and pregnant women overexposure for month 6-9 models. The IEEE C95.6 restrictions (MPEs and basic restrictions) are not exceeded. The fetus overexposure of this particular WTMD calls for carefully conducted safety evaluations of security systems before they are deployed.