| 1. |
- 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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| 2. |
- Razavi-Shearer, Devin M., et al.
(författare)
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Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories
- 2024
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Ingår i: JOURNAL OF HEPATOLOGY. - 0168-8278 .- 1600-0641. ; 80:2, s. 232-242
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened.
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| 3. |
- Percetti, M., et al.
(författare)
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TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study
- 2022
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 37:9, s. 1938-1943
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Tidskriftsartikel (refereegranskat)abstract
- Background Parkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK. Objectives The aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK-related autosomal dominant progressive external ophthalmoplegia (TWNK-adPEO). Methods Genomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK-adPEO patients with parkinsonism were retrospectively analyzed. Results Six of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK-adPEO patients, 5 (28%) had parkinsonism. Conclusions We show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. (c) 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.
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| 4. |
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| 5. |
- Contessotto, P., et al.
(författare)
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Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model
- 2023
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI. Thus, we develop an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. Upon histological and functional investigation to validate the proposed model and comparison with STEMI full ligation model, RNA-seq and proteomics show the distinctive features of post-NSTEMI tissue remodelling. Transcriptome and proteome-derived pathway analyses at acute (7 days) and late (28 days) post-NSTEMI pinpoint specific alterations in cardiac post-ischaemic extracellular matrix. Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions show distinctive patterns of complex galactosylated and sialylated N-glycans in cellular membranes and extracellular matrix. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on developing targeted pharmacological solutions to contrast adverse fibrotic remodelling. The study of the pathophysiology and possible interventions for non-ST-segment elevation myocardial infarction is hindered by the lack of a reproducible pre-clinical model. Here, authors develop an ovine model to reproduce post-ischemic remodeling in non-ST myocardial infarction and reveal distinct complex sugar moieties in cellular membranes and extracellular matrix patterns in infarcted tissue.
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| 6. |
- Solan, M., et al.
(författare)
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Towards a greater understanding of pattern, scale and process in marine benthic systems: a picture is worth a thousand worms
- 2003
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Ingår i: Journal of Experimental Marine Biology and Ecology. - 0022-0981. ; 285, s. 313-338
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Tidskriftsartikel (refereegranskat)abstract
- Historically, advances in our knowledge of benthic community structure and functioning have necessarily relied upon destructive sampling devices (grabs, cores, anchor dredges, etc.) that lose valuable contextual information in the process of sampling. In the last 40 years, instrumentation capable of measuring dynamic events and/or processes within and immediately above the seafloor has been developed that facilitates the collection of ecological information. Of these, both acoustic and optical imaging devices have played a significant role in revealing much about the physiology and behaviour of, and interactions between benthic species, and the sedimentary habitat in which they reside. While a number of reviews have separately considered the methodological and technical aspects of imaging technologies, the collective contribution that imaging has made to benthic ecology has received less attention. In this short review, we attempt to highlight key instances over the last 40 years where either acoustic or optical-based imaging techniques have provided new ecological insights and information about fine-grained sedimentary environments. In so doing, we focus on the ecological advances that have formed the precursor to current research efforts and introduce some of the latest revelations from appropriate and emerging imaging applications. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 7. |
- Sakellariou, P., et al.
(författare)
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Chronic L-menthol-induced browning of white adipose tissue hypothesis: A putative therapeutic regime for combating obesity and improving metabolic health
- 2016
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Ingår i: Medical Hypotheses. - : Elsevier BV. - 0306-9877. ; 93, s. 21-26
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Obesity constitutes a serious global health concern reaching pandemic prevalence rates. The existence of functional brown adipose tissue (BAT) in adult humans has provoked intense research interest in the role of this metabolically active tissue in whole-body energy balance and body weight regulation. A number of environmental, physiological, pathological, and pharmacological stimuli have been proposed to induce BAT-mediated thermogenesis and functional thermogenic BAT-like activity in white adipose tissue (WAT), opening new avenues for therapeutic strategies based on enhancing the number of beige adipocytes in WAT. Hypothesis: Recent evidence support a role of L-menthol cooling, mediated by TRPM8 receptor, on UCP1-dependent thermogenesis and BAT-like activity in classical WAT depots along with the recruitment of BAT at specific anatomical sites. L-Menthol-induced BAT thermogenesis has been suggested to occur by a beta-adrenergic-independent mechanism, avoiding potential side-effects due to extensive beta-adrenergic stimulation mediated by available beta receptor agonists. L-Menthol has been also linked to the activation of the cold-gated ion channel TRPA1. However, its role in L-menthol-induced UCP1-dependent thermogenic activity in BAT and WAT remains undetermined. White adipose tissue plasticity has important clinical implications for obesity prevention and/or treatment because higher levels of UCP1-dependent thermogenesis can lead to enhanced energy expenditure at a considerable extent. We hypothesize that chronic dietary L-menthol treatment could induce TRPM8- and TRPA1-dependent WAT adaptations, resembling BAT-like activity, and overall improve whole-body metabolic health in obese and overweight individuals. Conclusions: The putative impact of chronic L-menthol dietary treatment on the stimulation of BAT-like activity in classical WAT depots in humans remains unknown. A detailed experimental design has been proposed to investigate the hypothesized L-menthol-induced browning of WAT. If our hypothesis was to be confirmed, TRPM8/TRPA1-induced metabolic adaptations of WAT to BAT-like activity could provide a promising novel therapeutic approach for increasing energy expenditure, regulating body weight, and preventing obesity and its related co-morbidities in humans. (C) 2016 Elsevier Ltd. All rights reserved.
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| 8. |
- Schnitzbauer, Andreas A, et al.
(författare)
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A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.
- 2010
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.
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