Abstract
Conformational diseases, such as Alzheimer, Parkinson and Huntington diseases, are part of a common class of neurological disorders characterized by the aggregation and progressive ...accumulation of proteins bearing aberrant conformations. Huntington disease (HD) has autosomal dominant inheritance and is caused by mutations leading to an abnormal expansion in the polyglutamine (polyQ) tract of the huntingtin (HTT) protein, leading to the formation of HTT inclusion bodies in neurons of affected patients. Interestingly, recent experimental evidence is challenging the conventional view by which the disease pathogenesis is solely a consequence of the intracellular accumulation of mutant protein aggregates. These studies reveal that transcellular transfer of mutated huntingtin protein is able to seed oligomers involving even the wild-type (WT) forms of the protein. To date, there is still no successful strategy to treat HD. Here, we describe a novel functional role for the HSPB1-p62/SQSTM1 complex, which acts as a cargo loading platform, allowing the unconventional secretion of mutant HTT by extracellular vesicles. HSPB1 interacts preferentially with polyQ-expanded HTT compared with the WT protein and affects its aggregation. Furthermore, HSPB1 levels correlate with the rate of mutant HTT secretion, which is controlled by the activity of the PI3K/AKT/mTOR signalling pathway. Finally, we show that these HTT-containing vesicular structures are biologically active and able to be internalized by recipient cells, therefore providing an additional mechanism to explain the prion-like spreading properties of mutant HTT. These findings might also have implications for the turn-over of other disease-associated, aggregation-prone proteins.
Graphical Abstract
Graphical Abstract
Vitiligo is a chronic acquired pigmentary skin disorder characterized by well-defined asymptomatic white macule as a result of loss of functional melanocytes in the epidermis. The psychological ...burden experienced by patients is of great interest and consequently research of the best medical approach is constantly developing. This review focuses on surgical approach and the combination of surgery and phototherapy. In addition, reflectance confocal microscopy (RCM) could be useful to discriminate between stable or active vitiligo and to evaluate efficacy of therapy.
We searched PubMed with the following keywords: (vitiligoTitle/Abstract) AND therapyTitle/Abstract) AND surgeryTitle/Abstract) AND phototherapyTitle/Abstract) AND reflectance confocal microscopyTitle/Abstract).
To date, surgery is an effective therapeutic approach in stable vitiligo. Phototherapy, which is the most effective medical option, can improve the results obtained with surgery if performed in combination. Preliminary data show that RCM help physician in evaluating stability of vitiligo and is also useful to monitor clinical response.
Vitiligo is a psychosocially debilitating disease requiring a multidisciplinary approach. Even if a standard management could not be stated, combination of surgery and phototherapy in stable vitiligo could lead to great improvement than monotherapy. RCM is a modern tool which should be used in order to perform surgery and phototherapy properly and to subsequently evaluate efficacy on a microscopic level.
Corrigendum: Sunshine on ‘Zebra People’ Cortelazzi, C.; De Felici Del Giudice, M.B.; Pierobon, E. ...
Journal of the European Academy of Dermatology and Venereology,
February 2022, 2022-Feb, 2022-02-00, 20220201, Letnik:
36, Številka:
2
Journal Article
Sunshine on ‘Zebra People’ Cortelazzi, C.; De Felici Del Giudice, M.B.; Pierobon, E. ...
Journal of the European Academy of Dermatology and Venereology,
20/May , Letnik:
35, Številka:
5
Journal Article
Recenzirano
Byline: C. Cortelazzi, M.B. De Felici Del Giudice, E. Pierobon, G. Pellacani, S. Di Nuzzo
Objectives
The aim of this study was to demonstrate in a prospective multicentre study that Barbed Reposition Pharyngoplasty (BRP) procedure is safe and effective in management of obstructive sleep ...apnoea/hypopnea syndrome (OSAHS) patients.
Design
Prospective study.
Setting
Multicentre study.
Participants
Patients suffering from obstructive sleep apnoea.
Main outcomes measures
Values of postoperative apnoea‐hypopnea index (AHI), oxygen desaturation index (ODI), epworth sleepiness scale (ESS).
Results
111 Barbed Reposition Pharyngoplasty procedures standing alone or as a part of multilevel surgery for OSAHS, performed between January and September 2016, were analysed in 15 different centres. The average hospitalisation period was 2.5 ± 0.5 days. The mean patient age was 46.3 ± 10.5 years. The average body mass index at the time of the procedure was 27.9 ± 3.2, and the majority of the patients were men (83%). The mean preoperative and postoperative apnoea/hypopnea index was 33.4 ± 19.5 and 13.5 ± 10.3, respectively (P < .001). The mean preoperative and postoperative ESS score was 10.2 ± 4.5 and 6.1 ± 3.6, respectively (P < .001). The mean preoperative and postoperative ODI were 29.6 ± 20.7 and 12.7 ± 10.8, respectively (P < .001).
Conclusions
Patients undergoing BRP standing alone or as part of a multilevel approach for the treatment of OSAHS have a reasonable expectation for success with minimal morbidity.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite progress in surgical and medical neuro-oncology, prognosis for GBM patients remains dismal. It has been demonstrated ...that the modest benefit of conventional therapies is due to the presence of glioblastoma stem cells (GSCs) that cause tumor relapse and chemoresistance. Thus, the identification of specific ligands for GSCs could be fundamental for GBM improvement in survival.
Here, using a cell-SELEX approach on human primary GSCs, we generated RNA aptamers –namely, a 40L sequence and A40s, a truncated form– that bind GSCs.
The aptamers were selective for human GSCs, they were able to inhibit stemness, cell growth and migration, and strongly reduced tumor proliferation in vivo. Moreover, 40L and A40s were rapidly internalized upon target binding and, therefore, may serve as selective vehicles for therapeutics. Furthermore, A40s is able to cross the blood brain barrier (BBB). Using several approaches, we have identified the aptamer target in the Ephrin type-A receptor 2 (EphA2) which is overexpressed in GSCs compared to differentiated cells.
Given the role of GSCs in GBM recurrence and therapy resistance, 40L and A40s represent innovative therapeutic and diagnostic tool for GBM.
Gerolama Condorelli.
Federico II, Naples.
All authors have declared no conflicts of interest.
Abstract Background and aims The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of ...human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006. Methods and results Claimed effects, OVs and the related MMs were collected from EFSA Guidance documents and applications for authorization of health claims under Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed effect was sufficiently defined and was considered beneficial by EFSA. The collection, collation and critical analysis of the relevant scientific literature consisted in the definition of the keywords, the PubMed search strategies and the creation of databases of references. The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context of the specific claimed effects. Conclusions The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims, as well as to the stakeholders for the proper design of human intervention studies aimed to substantiate such health claims.
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