Multi‐Channel Lanthanide Nanocomposites for Customized Synergistic Treatment of Orthotopic Multi‐Tumor Cases

Simultaneous photothermal ablation of multiple tumors is limited by unpredictable photo-induced apoptosis, caused by individual intratumoral differences. Here, a multi-channel lanthanide nanocomposite was used to achieve tailored synergistic treatment of multiple subcutaneous orthotopic tumors under non-uniform whole-body infrared irradiation prescription. The nanocomposite reduces intratumoral glutathione by simultaneously activating the fluorescence and photothermal channels. The fluorescence provides individual information on different tumors, allowing customized prescriptions to be made. This enables optimal induction of hyperthermia and dosage of chemo drugs, to ensure treatment efficacy, while avoiding overtherapy. With an accessional therapeutic laser system, customized synergistic treatment of subcutaneous orthotopic cancer cases with multiple tumors is possible with both high efficacy and minimized side effects

LQTS Gene LOVD Database

The Long QT Syndrome (LQTS) is a group of genetically heterogeneous disorders that predisposes young individuals to ventricular arrhythmias and sudden death. LQTS is mainly caused by mutations in genes encoding subunits of cardiac ion channels (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2). Many other genes involved in LQTS have been described recently (KCNJ2, AKAP9, ANK2, CACNA1C, SCNA4B, SNTA1, and CAV3). We created an online database (http://www.genomed.org/LOVD/introduction.html) that provides information on variants in LQTS-associated genes. As of February 2010, the database contains 1738 unique variants in 12 genes. A total of 950 variants are considered pathogenic, 265 are possible pathogenic, 131 are unknown/unclassified, and 292 have no known pathogenicity. In addition to these mutations collected from published literature, we also submitted information on gene variants, including one possible novel pathogenic mutation in the KCNH2 splice site found in ten Chinese families with documented arrhythmias. The remote user is able to search the data and is encouraged to submit new mutations into the database. The LQTS database will become a powerful tool for both researchers and clinicians. © 2010 Wiley-Liss, Inc

NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC

Fast Green FCF Attenuates Lipopolysaccharide-Induced Depressive-Like Behavior and Downregulates TLR4/Myd88/NF-κB Signal Pathway in the Mouse Hippocampus

Depression is a common neuropsychiatric disorder and new anti-depressive treatments are still in urgent demand. Fast Green FCF, a safe biocompatible color additive, has been suggested to mitigate chronic pain. However, Fast green FCF’s effect on depression is unknown. We aimed to investigate Fast green FCF’s effect on lipopolysaccharide (LPS)-induced depressive-like behavior and the underlying mechanisms. Pretreatment of Fast green FCF (100 mg/kg, i.p. daily for 7 days) alleviated depressive-like behavior in LPS-treated mice. Fast green FCF suppressed the LPS-induced microglial and astrocyte activation in the hippocampus. Fast green FCF decreased the mRNA and protein levels of Toll-like receptor 4 (TLR4) and Myeloid differentiation primary response 88 (Myd88) and suppressed the phosphorylation of nuclear factor-κB (NF-κB) in the hippocampus of LPS-treated mice. Fast green FCF also downregulated hippocampal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, but did not alter the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus of LPS-treated mice. The molecular docking simulation predicts that Fast green FCF may interact with TLR4 and interrupt the formation of the TLR4-MD2 complex. In conclusion, the anti-depressive action of Fast green FCF in LPS-treated mice may involve the suppression of neuroinflammation and the downregulation of TLR4/Myd88/NF-κB signal pathway in mouse hippocampus. Our findings indicate the potential of Fast green FCF for controlling depressive symptoms

Identification of microRNAs specific for epithelial cell adhesion molecule-positive tumor cells in hepatocellular carcinoma: HEPATOLOGY, Vol. XX, No. X, 2015

Therapies that target cancer stem cells (CSCs) hold promise in eliminating cancer burden. However, normal stem cells are likely to be targeted due to their similarities to CSCs. It is established that EpCAM is a biomarker for normal hepatic stem cells and EpCAM+AFP+ hepatocellular carcinoma (HCC) cells have enriched hepatic CSCs. We sought to determine if specific miRNAs exist in hepatic CSCs that are not expressed in normal hepatic stem cells. We performed a pair-wised comparison of the miRNA transcriptome of EpCAM+ and corresponding EpCAM− cells isolated from two primary HCC specimens, as well as from two fetal livers and three healthy adult liver donors via small RNA deep sequencing. We found that miR-150, miR-155 and miR-223 were preferentially highly expressed in EpCAM+ HCC cells, which was further validated. Their gene surrogates, identified using miRNA and mRNA profiling in a cohort of 292 HCC patients, were associated with patient prognosis. We further demonstrated that miR-155 was highly expressed in EpCAM+ HCC cells compared to corresponding EpCAM− HCC cells, fetal livers with enriched normal hepatic progenitors, and normal adult livers with enriched mature hepatocytes. Suppressing miR-155 resulted in a decreased EpCAM+ fraction in HCC cells and reduced HCC cell colony formation, migration and invasion in vitro. The reduced levels of identified miR-155 targets predicted the shortened overall survival and time to recurrence of HCC patients. Conclusion: MiR-155 was highly elevated in EpCAM+ HCC cells and might serve as a molecular target to eradicate the EpCAM+ CSC population in human HCCs

Low-Temperature, Highly Selective, Gas-Phase Oxidation of Benzyl Alcohol over Mesoporous K-Cu-TiO2 with Stable Copper(I) Oxidation State

通讯作者地址: Fan, J (通讯作者), Zhejiang Univ, Dept Chem, Key Lab Appl Chem Zhejiang Prov, Hangzhou 310027, Zhejiang Peoples R China 地址: 1. Zhejiang Univ, Dept Chem, Key Lab Appl Chem Zhejiang Prov, Hangzhou 310027, Zhejiang Peoples R China 2. Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA 电子邮件地址: [email protected], [email protected] newly developed mesoporous mixed metal oxide (K-Cu-TiO2) catalyst is capable of highly selective, gas-phase benzyl alcoholbenzaldehyde transformation at excellent yields (>99%) under surprisingly low temperatures (203 degrees C, bp of benzyl alcohol). The tow-temperature reaction conditions and integration of K and Cu(I) components into the TiO2 matrix are of vital importance for the stabilization of an active Cu(I) oxidation state and resultant stable, excellent catalytic performance.National Science Foundations of China 20873122 J0830413 National Science Foundation DMR 02-3372

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field