Michal Becker-Cohen  Ari Zimran  Tama Dinur  Maayan Tiomkin  Claudia Cozma  Arndt Rolfs  David Arkadir  Elena Shulman  Orly Manor  Ora Paltiel  Gilad Yahalom  Daniela Berg  Shoshana Revel-Vilk 《International journal of molecular sciences》2022,23(20)

Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40–75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40–74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7–33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14–32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2–26.4%), smell assessment (12.4%, 95% CI 6.6–20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7–19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0–43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD.  相似文献   

    

Olimpia Daniela Frent  Laura Gratiela Vicas  Narcis Duteanu  Claudia Mona Morgovan  Tunde Jurca  Annamaria Pallag  Mariana Eugenia Muresan  Sanda Monica Filip  Roxana-Liana Lucaciu  Eleonora Marian 《International journal of molecular sciences》2022,23(20)

From the multitude of materials currently available on the market that can be used in the development of microparticles, sodium alginate has become one of the most studied natural anionic polymers that can be included in controlled-release pharmaceutical systems alongside other polymers due to its low cost, low toxicity, biocompatibility, biodegradability and gelatinous die-forming capacity in the presence of Ca²⁺ ions. In this review, we have shown that through coacervation, the particulate systems for the dispensing of drugs consisting of natural polymers are nontoxic, allowing the repeated administration of medicinal substances and the protection of better the medicinal substances from degradation, which can increase the capture capacity of the drug and extend its release from the pharmaceutical form.  相似文献   

    

Claudia La Corte  Nicol Baranzini  Annalisa Grimaldi  Maria Giovanna Parisi 《International journal of molecular sciences》2022,23(12)

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Chiara Cipollina  Andreina Bruno  Salvatore Fasola  Marta Cristaldi  Bernardo Patella  Rosalinda Inguanta  Antonio Vilasi  Giuseppe Aiello  Stefania La Grutta  Claudia Torino  Elisabetta Pace 《International journal of molecular sciences》2022,23(3)

Exposure of the airways epithelium to environmental insults, including cigarette smoke, results in increased oxidative stress due to unbalance between oxidants and antioxidants in favor of oxidants. Oxidative stress is a feature of inflammation and promotes the progression of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). Increased oxidative stress leads to exhaustion of antioxidant defenses, alterations in autophagy/mitophagy and cell survival regulatory mechanisms, thus promoting cell senescence. All these events are amplified by the increase of inflammation driven by oxidative stress. Several models of bronchial epithelial cells are used to study the molecular mechanisms and the cellular functions altered by cigarette smoke extract (CSE) exposure, and to test the efficacy of molecules with antioxidant properties. This review offers a comprehensive synthesis of human in-vitro and ex-vivo studies published from 2011 to 2021 describing the molecular and cellular mechanisms evoked by CSE exposure in bronchial epithelial cells, the most used experimental models and the mechanisms of action of cellular antioxidants systems as well as natural and synthetic antioxidant compounds.  相似文献   

    

Ilaria Laudadio  Alex Bastianelli  Valerio Fulci  Claudia Carissimi  Eleonora Colantoni  Francesca Palone  Roberta Vitali  Elisa Lorefice  Salvatore Cucchiara  Anna Negroni  Laura Stronati 《International journal of molecular sciences》2022,23(18)

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Nicola Mitwasi  Claudia Arndt  Liliana R. Loureiro  Alexandra Kegler  Frederick Fasslrinner  Nicole Berndt  Ralf Bergmann  Vaclav Ho&#x;ej&#x;í  Claudia Rssig  Michael Bachmann  Anja Feldmann 《International journal of molecular sciences》2022,23(9)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.  相似文献   

    

Claudia Mihaela Ninciuleanu  Raluca Ianchi&#x;  Elvira Alexandrescu  C&#x;t&#x;lin Ionu Mih&#x;escu  Sabina Burlacu  Bogdan Tric&#x;  Cristina Lavinia Nistor  Silviu Preda  Cristina Scomoroscenco  C&#x;t&#x;lina Gîfu  Cristian Petcu  Mircea Teodorescu 《International journal of molecular sciences》2022,23(18)

The present work aims to show how the main properties of poly(methacrylic acid) (PMAA) hydrogels can be engineered by means of several silicon-based fillers (Laponite XLS/XLG, montmorillonite (Mt), pyrogenic silica (PS)) employed at 10 wt% concentration based on MAA. Various techniques (FT-IR, XRD, TGA, SEM, TEM, DLS, rheological measurements, UV-VIS) were used to comparatively study the effect of these fillers, in correlation with their characteristics, upon the structure and swelling, viscoelastic, and water decontamination properties of (nano)composite hydrogels. The experiments demonstrated that the nanocomposite hydrogel morphology was dictated by the way the filler particles dispersed in water. The equilibrium swelling degree (SDe) depended on both the pH of the environment and the filler nature. At pH 1.2, a slight crosslinking effect of the fillers was evidenced, increasing in the order Mt < Laponite < PS. At pH > pKa_MAA (pH 5.4; 7.4; 9.5), the Laponite/Mt-containing hydrogels displayed a higher SDe as compared to the neat one, while at pH 7.4/9.5 the PS-filled hydrogels surprisingly displayed the highest SDe. Rheological measurements on as-prepared hydrogels showed that the filler addition improved the mechanical properties. After equilibrium swelling at pH 5.4, G’ and G” depended on the filler, the Laponite-reinforced hydrogels proving to be the strongest. The (nano)composite hydrogels synthesized displayed filler-dependent absorption properties of two cationic dyes used as model water pollutants, Laponite XLS-reinforced hydrogel demonstrating both the highest absorption rate and absorption capacity. Besides wastewater purification, the (nano)composite hydrogels described here may also find applications in the pharmaceutical field as devices for the controlled release of drugs.  相似文献   

    

Diego La Mendola  Maria Letizia Trincavelli  Claudia Martini 《International journal of molecular sciences》2022,23(18)

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Luis Felipe Quiroz-Iturra  Kevin Simpson  Daniela Arias  Cristbal Silva  Christian Gonzlez-Calquin  Leticia Amaza  Michael Handford  Claudia Stange 《International journal of molecular sciences》2022,23(20)

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Claudia Riccardi  Federica D&#x;Aria  Dominga Fasano  Filomena Anna Digilio  Maria Rosaria Carillo  Jussara Amato  Laura De Rosa  Simona Paladino  Mariarosa Anna Beatrice Melone  Daniela Montesarchio  Concetta Giancola 《International journal of molecular sciences》2022,23(20)

Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.  相似文献