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| 2. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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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| 3. |
- Wu, Qi-Zhen, et al.
(författare)
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Long-term exposure to major constituents of fine particulate matter and neurodegenerative diseases : a population-based survey in the Pearl River Delta Region, China
- 2024
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 470
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions.Objectives: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases.Methods: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence.Results: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45–2.27; 1.78; 95% CI, 1.37–2.32; and 1.99; 95% CI, 1.54–2.57 for the second, third, and fourth quartiles, respectively).Conclusions: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals.Environmental implication: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.
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| 4. |
- Li, Fang-Yi, et al.
(författare)
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Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide
- 2020
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Ingår i: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 11:3, s. 826-832
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Tidskriftsartikel (refereegranskat)abstract
- The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Based on Ras isoform-specific PM microdomain localization patterns, we have developed a potent and isoform-selective peptide inhibitor, Memrasin, for detachment of K-Ras4B from the PM. Memrasin is one of the first direct inhibitors of K-Ras4B-PM interaction, and consists of a membrane l(d) region-binding sequence derived from the C-terminal region of K-Ras4B and an endosome-escape enhancing motif that can aggregate on membrane. It forms peptide-enriched domains in the l(d) region, abrogates the tethering of K-Ras4B to the PM and accordingly impairs Ras signaling activity, thereby efficiently decreasing the viability of several human lung cancer cells in a dose-responsive and K-Ras dependent manner. Memrasin provides a useful tool for exploring the biological function of K-Ras4B on or off the PM and a potential starting point for further development into anti-Ras therapeutics.
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| 5. |
- Lu, Ya-Ke, et al.
(författare)
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Reciprocal relationship between psychosocial work stress and quality of life : the role of gender and education from the longitudinal study of the Survey of Health, Ageing and Retirement in Europe
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate the reciprocal relationship between psychosocial work stress and quality of life (QoL) and to examine whether the relationship can be moderated by gender or education. Design Longitudinal, population-based study. Setting The Survey of Health, Ageing and Retirement in Europe (SHARE). Participants The study population was derived from the SHARE, and there were 2006 participants with good QoL at baseline, 1109 with high job control and 1072 with high job reward, respectively, who were followed up for 2 years to detect incidence of poor QoL, low job control and low job reward. Main outcome measures Logistic regression models were employed to explore the reciprocal relationship between psychological work stress and QoL. Stratification analyses by gender and education were performed. Results Participants with low reward (OR= 1.53, 95% CI 1.26 to 1.88) and low control (OR= 1.40, 95% CI 1.14 to 1.71) at baseline were at higher risk of poor QoL over the 2-year follow-up. The combination of low reward and low control further increased the risk (OR= 1.90, 95% CI 1.46 to 2.48). Stratified analyses revealed that these associations were more pronounced among those who had high levels of education. Further, individuals with poor QoL were at significantly higher risk of having low reward (OR= 2.14, 95% CI 1.55 to 2.96) but not low control (OR= 1.33, 95% CI0.98 to 1.79) at the 2-year follow-up, especially among those who had medium levels of education. No gender differences were found. Conclusions There is a reciprocal relationship between psychological work stress and poor QoL. Education may play an important role in the relationship.
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| 6. |
- Qiao, Ya-Mei, et al.
(författare)
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Reciprocal associations between job strain and depression : A 2-year follow-up study from the Survey of Health, Ageing and Retirement in Europe
- 2019
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Ingår i: Brain and Behavior. - : Wiley. - 2162-3279 .- 2162-3279. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: A growing number of people suffered from depression. This study examined the depression prevalence in workers across 10 European countries plus Israel and the reciprocal associations between job strain and depression.Methods: The study population consisted of 7,879 workers aged 50-63 years at baseline (2004) from the Survey of Health, Ageing, and Retirement in Europe (SHARE). Job demands (physical or psychosocial) and job control variables were derived from the Job Content Questionnaire (JCQ). Two 4-category job strains (physical and psychosocial) were obtained based on the cross-tabulation of these dichotomized demands and control variables. There were 4,284 depression-free, 3,259 high physical strain-free and 3,195 high psychosocial strain-free participants at baseline who were followed up for 2 years to detect incident depression, high physical job strain, or high psychosocial strain, respectively. The reciprocal associations between job strain and depression were analyzed by multivariate logistic regression and multivariate multilevel logistic regression adjusting for potential confounders.Results: The prevalence of depression varied from the lowest 12.5% in Germany to the highest 27.2% in France. Compared to individuals with low strain, a significantly higher risk of depression were found in individuals with high physical strain (OR = 1.39) and high psychosocial strain (OR = 1.55), after adjusting for potential confounders. Depression at baseline was not significantly associated with subsequent high job strain. Similar results were observed from multilevel models that took into consideration of the potential country-level influences.Conclusions: The prevalence of depression varies across countries in Europe. Avoiding high job strain may be an effective preventive strategy to prevent depression epidemic.
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| 7. |
- Tse, Yi-Kei, et al.
(författare)
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Morphological and functional types of tricuspid regurgitation : prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery
- 2023
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Ingår i: Clinical Research in Cardiology. - : Springer. - 1861-0684 .- 1861-0692. ; 112:10, s. 1463-1474
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Tidskriftsartikel (refereegranskat)abstract
- Background The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. Methods The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area ( RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio <= 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). Results Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental chi(2) = 6.757 and 9.094 respectively; both P < 0.05). Conclusions Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.
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| 8. |
- Yang, Zhen, et al.
(författare)
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Elevated Serum Chemokine CXC Ligand 5 Levels Are Associated with Hypercholesterolemia But Not a Worsening of Insulin Resistance in Chinese People.
- 2010
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95, s. 3926-3932
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recent study showed high chemokine CXC ligand 5 (CXCL5) is thought to be associated with insulin resistance in humans. However, evidence from large-scale populations about the relationship between serum CXCL5 level and metabolic phenotypes is scarce. Here we sought to evaluate serum CXCL5 distribution and its association with metabolic phenotypes among middle-aged and older Chinese. Research Design and Methods: We evaluated serum CXCL5 in a cross-sectional sample of 3225 Chinese aged from 50 to 88 yr in a Shanghai downtown district by ELISA. Glucose, insulin, lipid profile, inflammatory marker, and adipokine were also measured. Results: The crude mean of serum CXCL5 concentrations were 1493.31 pg/ml for men and 2059.42 pg/ml for women (P < 0.001), respectively. After multiple adjustment, the odds ratios were substantially higher for hypercholesterolemia (odds ratio 3.26, 95% confidence interval 2.36-4.51) in the highest CXCL5 quartile compared with those in the lowest quartile. These associations remained significant after further adjustment for body mass index, body fat, inflammatory marker, and adipokine. However, serum resistin CXCL5 was not associated with body mass index, percent body fat, fasting glucose, insulin levels, and homeostasis model assessment index-insulin resistance (r = 0.01, 0.01, 0.01, 0.04, and 0.03, respectively; all P > 0.05). Conclusions: Elevated circulating CXCL5 concentrations were associated with higher risk of hypercholesterolemia in middle-aged and elderly Chinese independent of obesity, inflammation, adipokines, and other risk factors but not insulin resistance.
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| 9. |
- Yang, Zhen, et al.
(författare)
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Genetic variation in the GCKR gene is associated with non-alcoholic fatty liver disease in Chinese people
- 2011
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Ingår i: Molecular Biology Reports. - : Springer Science and Business Media LLC. - 0301-4851 .- 1573-4978. ; 38:2, s. 1145-1150
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies reported that GCKR rs780094 polymorphism is associated with elevated fasting serum triglyceride levels and elevated levels of C-reactive protein (CRP). There are a ample of data on the association between circulating triglyceride, CRP concentrations and risk of non-alcoholic fatty liver (NAFLD). To determine whether the GCKR rs780094 polymorphism contributes to the development of non-alcoholic fatty liver, a case-control study was performed in 903 Chinese subjects. Among study population, 436 patients with B-mode ultrasound-proven NAFLD (318 with steatosis hepatis IA degrees, 90 with steatosis hepatis IIA degrees and 28 with steatosis hepatis IIIA degrees) and 467 controls were genotyped by using TaqMan allelic discrimination assays. We confirmed the association of GCKR rs780094 with NAFLD in Chinese people (OR = 1.607, 95% CI 1.139-2.271, P ([dom]) = 7.2 x 10(-3)). In this study, polymorphism in GCKR rs780094 was not significantly associated with the degree of fatty infiltration of the liver. In addition, the T-allele of GCKR rs780094 was significantly associated with increasing fasting triglyceride (P ([add]) = 3.8 x 10(-4)) and CRP (P ([add]) = 2.9 x 10(-4)) concentrations after adjusting for age, gender, and BMI. The association with NAFLD remained significant after adjustment for triglyceride, while adjustment for CRP abolished the association. Genetic variation in GCKR gene rs780094 polymorphism contributes to the risk of NAFLD in Chinese people. The effect of genotype on NAFLD is probably mediated through chronic low-grade systemic inflammation rather than through dislipidemia.
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