| 1. |
|
|
| 2. |
- Klionsky, Daniel J., et al.
(author)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- 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. 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 vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most 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 field 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. 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. 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.
|
|
| 3. |
-
- 2019
-
Journal article (peer-reviewed)
|
|
| 4. |
- Korinek, Michal, et al.
(author)
-
Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP
- 2017
-
In: Frontiers in Pharmacology. - : FRONTIERS MEDIA SA. - 1663-9812. ; 8
-
Journal article (peer-reviewed)abstract
- Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z, 13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E, 12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R *-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14-3.73 mu M) and elastase release (IC50 1.26-4.57 mu M) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187-and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E, 12Z-octadecadienoic acid, IC50 92.4 and 49.7 mu M, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.
|
|
| 5. |
- Wang, Anqi, et al.
(author)
-
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
-
Journal article (peer-reviewed)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
|
|
| 6. |
- Wu, Ya-ting, et al.
(author)
-
Selective and simultaneous determination of trace bisphenol A and tebuconazole in vegetable and juice samples by membrane-based molecularly imprinted solid-phase extraction and HPLC
- 2014
-
In: Food Chemistry. - : Elsevier BV. - 1873-7072 .- 0308-8146. ; 164, s. 527-535
-
Journal article (peer-reviewed)abstract
- Nanofibrous molecularly imprinted membranes (nano-MIMs) with multi-analyte selectivity were prepared by encapsulating two types of molecularly imprinted polymer nanoparticles (MIP-NPs) into electrospun polyvinyl alcohol nanofibers. The obtained nano-MIMs maintained high molecular selectivity offered by each of the MIP-NPs. Nano-MIM embedding BPA-imprinted nanoparticles and TBZ-imprinted nanoparticles together showed the highest binding selectivity for acid bisphenol A (BPA) and basic tebuconazole (TBZ). This nano-MIM was used as affinity material of membrane-based molecularly imprinted solid-phase extraction (m-MISPE) to extract trace BPA and TBZ in vegetables and juices simultaneously. The recoveries of BPA and TBZ from different samples were higher than 70.33% with RSDs lower than 9.57%. m-MISPE gave better HPLC separation efficiencies and higher recoveries than conventional SPE based on C18/SCX. Multi-analyte selective m-MISPE combined with HPLC realized selective and simultaneous determination of several trace analytes with opposite charges/polarities in different food samples. (C) 2014 Elsevier Ltd. All rights reserved.
|
|
