Luteolin (3', 4', 5,7-tetrahydroxyflavone) has been identified as commonly present in plants. Plants with a high luteolin content have been used ethnopharmacologically to treat inflammation-related symptoms. Both isolated luteolin and extracts from luteolin-rich plants have been studied using various models and exhibited anti-inflammatory activity.This paper uses recent research findings with a broad range of study models to describe the anti-inflammatory activity of luteolin, particularly its mechanisms at the molecular level; provide guidance for future research; and evaluate the feasibility of developing luteolin into an anti-inflammatory drug.We summarize reports about the anti-inflammatory activity of luteolin published since 2009, which we found in MEDLINE/PubMed, Scopus, Web of Knowledge, and Google Scholar. To acquire broad information, we extended our search to online FDA documents.Luteolin is a flavonoid commonly found in medicinal plants and has strong anti-inflammatory activity in vitro and in vivo. Some of its derivatives, such as luteolin-7-O-glucoside, have also shown anti-inflammatory activity. The action mechanism of luteolin varies, but Src in the nuclear factor (NF)-κB pathway, MAPK in the activator protein (AP)- 1 pathway, and SOCS3 in the signal transducer and activator of transcription 3 (STAT3) pathway are its major target transcription factors. A clinical trial with a formulation containing luteolin showed excellent therapeutic effect against inflammation-associated diseases.In silico, in vitro, in vivo, and clinical studies strongly suggest that the major pharmacological mechanism of luteolin is its anti-inflammatory activity, which derives from its regulation of transcription factors such as STAT3, NF-κB, and AP-1. Much work remains to ensure the safety, quality, and efficacy of luteolin before it can be used to treat inflammation-related diseases in humans.Copyright © 2018 Elsevier B.V. All rights reserved.

When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here, we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both prolongevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting toward substrates involved in longevity assurance. Copyright © 2014 Elsevier Inc. All rights reserved.

Medicinal mushroom Phellinus linteus ("Sanghuang" in Chinese, ) is a famous fungus which is widely used in China, Korea, and other Asian countries. As a traditional Chinese medicine with a 2000-year long history, medicinal applications of Phellinus linteus mainly include treating hemorrhage, hemostasis and diseases related to female menstruation according to Chinese clinical empirical practice. A number of studies reported Phellinus linteus possessed good therapeutic effects on various ailments including tumor, diabetes, inflammation, obesity, etc. The present paper comprehensively reviewed the traditional uses, fermentation, constituent and pharmacology of Phellinus linteus based on scientific literature as well as critical analysis of the research. This review aimed to provide latest information and new foundations and directions for further investigations on Phellinus linteus. All available information about Phellinus linteus was supplied by library database and electronic search (CNKI, Google Scholar, ScienceDirect, Web of Science, PubMed, etc.). Some local and ancient books as well as brilliant scholars were also important information resources. Improvement of fermentation techniques promoted the production of Phellinus linteus. Studies of constituents showed the main chemical composition of Phellinus linteus included polysaccharides, flavones, triterpenes, aromatic acids, amino acids, etc. and polysaccharides were found to account for the largest proportion. Pharmacological researches revealed Phellinus linteus possessed a variety of biological activities including anti-cancer, immuno-regulation, anti-diabetes, anti-oxidation and anti-inflammation. Based on these summarized information, this review was presented to provide helpful references and beneficial directions for future studies of Phellinus linteus. Copyright © 2016 Elsevier B.V. All rights reserved.

() is a medicinal fungus that is widely used in East Asia for the adjuvant treatment of cancer. To elucidate the antitumor effective substances and mechanism of, we designed an approach incorporating cytotoxicity screening, phytochemical analysis, network pharmacology construction, and cellular and molecular experiments. The dichloromethane extract of (DCMPI) was identified as the active portion in HT-29 cells. Nineteen constituents were identified, and 5 were quantified by UPLC-ESI-Q/TOF-MS. Eight ingredients were obtained in the network pharmacology study. In total, 473 putative targets associated with DCMPI and 350 putative targets related to colon cancer were derived from online databases and target prediction tools. Protein-protein interaction networks of drug and disease putative targets were constructed, and 84 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to reactive oxygen species (ROS) metabolic processes and intrinsic apoptotic pathways. Then, a cellular experiment was used to validate the drug-target mechanisms predicted by the system pharmacology analysis. Experimental results showed that DCMPI increased intracellular ROS levels and induced HT-29 cell apoptosis. Molecular biology experiments indicated that DCMPI not only increased Bax and Bad protein expression and promoted PARP and caspase-3/9 cleavage but also down-regulated Bcl-2 and Bcl-xl protein levels to induce apoptosis in HT-29 cells. In conclusion, our study provides knowledge on the chemical composition and antitumor mechanism of, which may be exploited as a promising therapeutic option for colon cancer.

Signal transducer and activator of transcription protein 3 (STAT3) is a latent cytosolic transcription factor that is widely recognized as being a master regulator of the cellular functions that lead to the cancer phenotype. Constitutively activated STAT3 protein activity is routinely observed in human cancers, promoting uncontrolled cell proliferation and suppressing apoptosis. Until relatively recently, inhibition of STAT3 transcriptional activity was achieved indirectly via suppression of upstream kinase activators and extracellular cytokine and (or) growth factor stimuli. However, activated STAT3 forms transcriptionally functional STAT3-STAT3 dimers, providing a valid juncture for targeted downstream molecular inhibition. STAT3's prominent role in cancer has seen a decade of innovative and novel approaches to targeting constitutively active STAT3 protein-protein complexes. This mini-review outlines the progress made towards identifying molecular agents capable of silencing aberrant STAT3 signalling through the disruption of STAT3 complexation events.

The identification of JAK2/MPL mutations in patients with myeloproliferative neoplasms (MPN) has led to the clinical development of JAK kinase inhibitors, including ruxolitinib. Ruxolitinib reduces splenomegaly and systemic symptoms in myelofibrosis and improves overall survival; however, the mechanism by which JAK inhibitors achieve efficacy has not been delineated. Patients with MPN present with increased levels of circulating proinflammatory cytokines, which are mitigated by JAK inhibitor therapy. We sought to elucidate mechanisms by which JAK inhibitors attenuate cytokine-mediated pathophysiology. Single-cell profiling demonstrated that hematopoietic cells from myelofibrosis models and patient samples aberrantly secrete inflammatory cytokines. Pan-hematopoietic Stat3 deletion reduced disease severity and attenuated cytokine secretion, with similar efficacy as observed with ruxolitinib therapy. In contrast, Stat3 deletion restricted to MPN cells did not reduce disease severity or cytokine production. Consistent with these observations, we found that malignant and nonmalignant cells aberrantly secrete cytokines and JAK inhibition reduces cytokine production from both populations.Our results demonstrate that JAK-STAT3-mediated cytokine production from malignant and nonmalignant cells contributes to MPN pathogenesis and that JAK inhibition in both populations is required for therapeutic efficacy. These findings provide novel insight into the mechanisms by which JAK kinase inhibition achieves therapeutic efficacy in MPNs.©2015 American Association for Cancer Research.

Substantial progress has been made in the field of "omics" research (e.g., Genomics, Transcriptomics, Proteomics, and Metabolomics), leading to a vast amount of biological data. In order to represent large biological data sets in an easily interpretable manner, this information is frequently visualized as graphs, i.e., a set of nodes and edges. Nodes are representations of biological molecules and edges connect the nodes depicting some kind of relationship. Obviously, there is a high demand for computer-based assistance for both visualization and analysis of biological data, which are often heterogeneous and retrieved from different sources. This chapter focuses on software tools that assist in visual exploration and analysis of biological networks. Global requirements for such programs are discussed. Utilization of visualization software is exemplified using the widely used Cytoscape tool. Additional information about the use of Cytoscape is provided in the Notes section. Furthermore, special features of alternative software tools are highlighted in order to assist researchers in the choice of an adequate program for their specific requirements.

Reactive oxygen species (ROS) have been shown to cause DNA damage, protein denaturation, loss of antioxidative enzyme activity, and lipid peroxidation. Thus, ROS are associated with tissue damage and are considered to be prime contributing factors in inflammation, diabetes, aging, and cancer. In this study, we investigated whether or not hispidin protects pancreatic MIN6N β-cells from oxidative stress caused by hydrogen peroxide. Treatment of MIN6N β-cells with 0.5 mM hydrogen peroxide for 4 hours caused significant loss of cell viability and an increase in the number of apoptotic cells. However, pretreatment of MIN6N β-cells with hispidin for 24 hours reduced loss of cell viability and decreased the number of apoptotic cells. In addition, 70 μM hispidin significantly scavenged intracellular ROS and inhibited apoptosis and caspase-3 induced by hydrogen peroxide. Furthermore, the generation of thiobarbituric acid-reactive substances was inhibited in the presence of hispidin in a dose-dependent manner. Also, 70 μM hispidin significantly increased insulin secretion in hydrogen peroxide-treated MIN6N β-cells. These results suggest that hispidin may be effective for protecting MIN6N β-cells from ROS toxicity in diabetes.

The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.Copyright 2004 Wiley Periodicals, Inc.

Rheumatoid arthritis (RA) is a chronic autoimmune mediated joint disease with severe complications affecting 1% of the population worldwide. Although the exact mechanism underlying the aggravation of RA remains unknown, its occurrence can lead to joint degradation and functional disability. Recent evidences have shown that the aberrant expression of microRNAs (miRNAs) play a prominent role in the furtherance of RA. Over the last decade, various intensive studies have validated different microRNAs to be good candidates for diagnostic purposes and for monitoring the disease progression in various inflammatory diseases. A deeper understanding of the molecular mechanism through which miRNAs amplify the production of inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), pro-inflammatory mediators, growth factors and MMPs will act as potential therapeutic targets. More importantly, several studies have briefly reported the crucial role of TLR dependent MAPK signaling pathway, which mediates the pathological features of RA. In this review, we summarize the recent findings and provide a detailed report of the molecular mechanism of microRNA along with the role of TLR/MAPK signaling pathway in RA. However, the major aim of this review is to correlate the aberrantly expressed microRNAs in TLR/MAPK pathway with various well reported bioactive compounds that can modulate these signaling pathways in rheumatoid arthritis. Targeting miRNA expression using specific bioactive compounds might be a potent and an effective target in RA treatment by suppressing the TLR/MAPK pathway.Copyright © 2017 Elsevier B.V. All rights reserved.

MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. At least three MAPK families have been characterized: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. The above effects are fulfilled by regulation of cell cycle engine and other cell proliferation related proteins. In this paper we discussed their functions and cooperation with other signal pathways in regulation of cell proliferation.

Platycodin-D (PD) is an effective triterpene saponin extracted from the root of Platycodon grandiflorum which has been used clinically to treat pulmonary diseases in traditional Chinese medicine. Recently, it has been reported that PD has anti-tumor effects in various cancer models through the induction of apoptosis. However, whether PD induces autophagy in both cell lines and its molecular mechanisms have not been elucidated. Here, our present study confirmed that PD induced autophagy in both NCI-H460 and A549 cells via up-regulating the expression levels of Atg-3, Atg-7 and Beclin-1. Meanwhile, PD contributed to the up-regulation of LC3-II at both protein and mRNA levels. Further detection of the PI3K/Akt/mTOR signaling pathway compared to LY294002 (PI3K kinase inhibitor), RAP (mTOR kinase inhibitor) and insulin (an activator of PI3K/Akt/mTOR signaling pathway) showed that PD induced autophagy through inhibiting the pathway at p-Akt (Ser473), p-p70S6K (Thr389) and p-4EBP1 (Thr37/46) in both cell lines. Moreover, the examination of MAPK signaling pathway showed that PD treatment increased the phosphorylation of JNK and p38 MAPK, while decreased the phosphorylation of Erk1/2 in both cell lines. Additionally, the effects assessed with a panel of pharmacologic inhibitors, including U0126 (Erk1/2 kinase inhibitor), SP600125 (JNK kinase inhibitor) and SB203580 (p38 MAPK kinase inhibitor) suggested that the activation of JNK and p38 MAPK participated in PD-induced autophagy. Taken together, these findings suggested that PD induced autophagy in NCI-H460 and A549 cells through inhibiting PI3K/Akt/mTOR signaling pathway and activating JNK and p38 MAPK signaling pathways. Therefore, PD may be an alternative compound for NSCLC therapy.

用H₂₂荷瘤小鼠对6种“桑黄”类真菌的水提取物进行了抗肿瘤活性研究。结果表明,除鲍姆木层孔菌水提取物低剂量组外,粗毛纤孔菌、椭圆嗜蓝孢孔菌、山野木层孔菌的水提取物高、低剂量组以及火木层孔菌、鲍姆木孔菌、瓦尼木层孔菌的水提取物高剂量组均具有显著抑瘤作用,抑瘤率均大于40%,其中;椭圆嗜蓝孢孔菌水提取物高剂量组（1 000 mg/kg）的抑瘤效果最佳。与阳性组和生理盐水组相比,粗毛纤孔菌高剂量组小鼠的胸腺指数均有极显著性差异（P<0.01）,其余各组小鼠胸腺指数无显著性差异。6种“桑黄”类真菌水提取物均对提高小鼠肿瘤细胞中Bax的表达起到了促进作用;对Bcl-2的表达起到了抑制作用。