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2022 ◽  
Vol 14 (1) ◽  
pp. 216-229
En-Si Ma ◽  
Zheng-Xin Wang ◽  
Meng-Qi Zhu ◽  
Jing Zhao

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 165
Laura R. Rodríguez ◽  
Tamara Lapeña-Luzón ◽  
Noelia Benetó ◽  
Vicent Beltran-Beltran ◽  
Federico V. Pallardó ◽  

Calcium (Ca2+) is a versatile secondary messenger involved in the regulation of a plethora of different signaling pathways for cell maintenance. Specifically, intracellular Ca2+ homeostasis is mainly regulated by the endoplasmic reticulum and the mitochondria, whose Ca2+ exchange is mediated by appositions, termed endoplasmic reticulum–mitochondria-associated membranes (MAMs), formed by proteins resident in both compartments. These tethers are essential to manage the mitochondrial Ca2+ influx that regulates the mitochondrial function of bioenergetics, mitochondrial dynamics, cell death, and oxidative stress. However, alterations of these pathways lead to the development of multiple human diseases, including neurological disorders, such as amyotrophic lateral sclerosis, Friedreich’s ataxia, and Charcot–Marie–Tooth. A common hallmark in these disorders is mitochondrial dysfunction, associated with abnormal mitochondrial Ca2+ handling that contributes to neurodegeneration. In this work, we highlight the importance of Ca2+ signaling in mitochondria and how the mechanism of communication in MAMs is pivotal for mitochondrial maintenance and cell homeostasis. Lately, we outstand potential targets located in MAMs by addressing different therapeutic strategies focused on restoring mitochondrial Ca2+ uptake as an emergent approach for neurological diseases.

2022 ◽  
Vol 20 ◽  
Andrea Miuli ◽  
Giacomo d'Andrea ◽  
Mauro Pettorruso ◽  
Gianluca Mancusi ◽  
Alessio Mosca ◽  

Abstract: Cocaine Use Disorder (CUD) is one of the diseases with the greatest social and health impact, due to the high cost of rehabilitation management and the high risk of dangerous behavior and relapse. This pathology frequently leads to unsuccessful attempts to interrupt the consumption, resulting in relapses and a vicious circle binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation (craving). The alternation of these phases in addictions was well illustrated by Koob and colleagues in the so-called “addictive cycle”, which nowadays represents a landmark in the addiction field. Recently, there has been an increased interest in the international literature for biomarkers able to explain the several phases of addiction, and one of the most studied biomarkers is undoubtedly Brain-derived Neurotrophic Factor (BDNF). In this perspective article, we discuss the potential role of BDNF as biomarker of the CUD phases described in the “Addictive Cycle”, speculating about the close relationship between BDNF fluctuations and the clinical course of CUD. Furthermore, we discuss BDNF potential role as “staging” biomarker, able to predict disease worsening. Finding valuable biomarkers of CUD severity and disease stage could shift clinicians' attention from the perspective of behavioral symptomatic treatment to a novel brain-based approach, allowing more effective and targeted therapeutic strategies to be developed, thus determining major benefits for CUD patients.

Thomas CT Michaels ◽  
Alexander John Dear ◽  
Samuel Cohen ◽  
Michele Vendruscolo ◽  
Tuomas P. J. Knowles

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 141
Camille Esneau ◽  
Alexandra Cate Duff ◽  
Nathan W. Bartlett

Rhinoviruses (RVs) have been reported as one of the main viral causes for severe respiratory illnesses that may require hospitalization, competing with the burden of other respiratory viruses such as influenza and RSV in terms of severity, economic cost, and resource utilization. With three species and 169 subtypes, RV presents the greatest diversity within the Enterovirus genus, and despite the efforts of the research community to identify clinically relevant subtypes to target therapeutic strategies, the role of species and subtype in the clinical outcomes of RV infection remains unclear. This review aims to collect and organize data relevant to RV illness in order to find patterns and links with species and/or subtype, with a specific focus on species and subtype diversity in clinical studies typing of respiratory samples.

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 381
Xin Wang ◽  
Jihye Lee ◽  
Changqing Xie

Cancer stem cells (CSCs) are a subset of the tumor population that play critical roles in tumorigenicity, metastasis, and relapse. A key feature of CSCs is their resistance to numerous therapeutic strategies which include chemotherapy, radiation, and immune checkpoint inhibitors. In recent years, there is a growing body of literature that suggests a link between CSC maintenance and autophagy, a mechanism to recycle intracellular components during moments of environmental stress, especially since CSCs thrive in a tumor microenvironment that is plagued with hypoxia, acidosis, and lack of nutrients. Autophagy activation has been shown to aid in the upkeep of a stemness state along with bolstering resistance to cancer treatment. However, recent studies have also suggested that autophagy is a double-edged sword with anti-tumorigenic properties under certain circumstances. This review summarizes and integrates what has been published in the literature in terms of what role autophagy plays in stemness maintenance of CSCs and suggests that there is a more complex interplay between autophagy and apoptosis which involves multiple pathways of regulation. Future cancer therapy strategies are needed to eradicate this resistant subset of the cell population through autophagy regulation.

2022 ◽  
Vol 12 (1) ◽  
Joan Calvet ◽  
Antoni Berenguer-Llergo ◽  
Marina Gay ◽  
Marta Massanella ◽  
Pere Domingo ◽  

AbstractCOVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20–3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17–4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

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