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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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- 2019
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Journal article (peer-reviewed)
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- Kato, Norihiro, et al.
(author)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Journal article (peer-reviewed)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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- Wang, Chao-Jie, et al.
(author)
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Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer
- 2009
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In: Disease Markers. - 0278-0240 .- 1875-8630. ; 26:1, s. 27-34
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Journal article (peer-reviewed)abstract
- We are just beginning to understand how microRNAs (miRNAs) are involved in tumor-related processes in humans. Applying real-time RT-PCR, we investigated the miR-31, miR-143 and miR-145 expression in 98 primary CRC specimens, along with the corresponding normal mucosa specimens, and analyze the relationship of their expression with clinicopathological features. Our results showed the miR-31 expression was up-regulated in CRC compared to normal mucosa (p = 0.001). Furthermore, miR-31 expression was positively related to advanced TNM stage (p = 0.026) and deeper invasion of tumors (p = 0.024). MiR-145 was down-regulated in both colon (p = 0.001) and rectal (p = 0.012) cancer. MiR-143 was only down-regulated in colon cancer (p = 0.023) but not in rectal cancer (p = 0.351). There was no relationship of miR-143 and miR-145 expression with other clinicopathological features (p > 0.05), except that the miR-145 expression was related to cancer site (p = 0.03). In conclusion, the miR-31 overexpression may be involved in the development and progression of CRC. The miR-143 and miR-145 may play a certain role in the development of colon and/or rectal cancers but not in progression of the disease.
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| 9. |
- Xie, Xu-Qin, et al.
(author)
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miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
- 2020
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In: MOLECULAR THERAPY-ONCOLYTICS. - : CELL PRESS. - 2372-7705. ; 17, s. 320-331
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Journal article (peer-reviewed)abstract
- Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU] +leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC.
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| 10. |
- Yang, Liu, et al.
(author)
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Prenatal and postnatal early life exposure to greenness and particulate matter of different size fractions in relation to childhood rhinitis : A multi-center study in China
- 2024
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In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 938
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Journal article (peer-reviewed)abstract
- The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0–1 year old) and the second (1–2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0–40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.
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