BCR-ABL Promotes PTEN Downregulation in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the t(9;22) translocation coding for the chimeric protein p210 BCR-ABL. The tumor suppressor PTEN plays a critical role in the pathogenesis of CML chronic phase, through non genomic loss of function mechanisms, such as protein down-regulation and impaired nuclear/cytoplasmic shuttling. Here we demonstrate that BCR-ABL promotes PTEN downregulation through a MEK dependent pathway. Furthermore, we describe a novel not recurrent N212D-PTEN point mutation found in the EM2 blast crisis cell line

Assessing vulnerability to psychological distress during the COVID-19 pandemic through the analysis of microblogging content

In recent years we have witnessed a growing interest in the analysis of social media data under different perspectives, since these online platforms have become the preferred tool for generating and sharing content across different users organized into virtual communities, based on their common interests, needs, and perceptions. In the current study, by considering a collection of social textual contents related to COVID-19 gathered on the Twitter microblogging platform in the period between August and December 2020, we aimed at evaluating the possible effects of some critical factors related to the pandemic on the mental well-being of the population. In particular, we aimed at investigating potential lexicon identifiers of vulnerability to psychological distress in digital social interactions with respect to distinct COVID-related scenarios, which could be “at risk” from a psychological discomfort point of view. Such scenarios have been associated with peculiar topics discussed on Twitter. For this purpose, two approaches based on a “top-down” and a “bottom-up” strategy were adopted. In the top-down approach, three potential scenarios were initially selected by medical experts, and associated with topics extracted from the Twitter dataset in a hybrid unsupervised-supervised way. On the other hand, in the bottom-up approach, three topics were extracted in a totally unsupervised way capitalizing on a Twitter dataset filtered according to the presence of keywords related to vulnerability to psychological distress, and associated with at-risk scenarios. The identification of such scenarios with both approaches made it possible to capture and analyze the potential psychological vulnerability in critical situations

Surveilling COVID-19 Emotional Contagion on Twitter by Sentiment Analysis

BACKGROUND: The fight against the COVID-19 pandemic seems to encompass a social media debate, possibly resulting in emotional contagion and the need for novel surveillance approaches. In the current study, we aimed to examine the flow and content of tweets, exploring the role of COVID-19 key events on the popular Twitter platform. METHODS: Using representative freely available data, we performed a focused, social media-based analysis to capture COVID-19 discussions on Twitter, considering sentiment and longitudinal trends between January 19 and March 3, 2020. Different populations of users were considered. Core discussions were explored measuring tweets’ sentiment, by both computing a polarity compound score with 95% Confidence Interval and using a transformer-based model, pretrained on a large corpus of COVID-19-related Tweets. Context-dependent meaning and emotion-specific features were considered. RESULTS: We gathered 3,308,476 tweets written in English. Since the first World Health Organization report (January 21), negative sentiment proportion of tweets gradually increased as expected, with amplifications following key events. Sentiment scores were increasingly negative among most active users. Tweets content and flow revealed an ongoing scenario in which the global emergency seems difficult to be emotionally managed, as shown by sentiment trajectories. CONCLUSIONS: Integrating social media like Twitter as essential surveillance tools in the management of the pandemic and its waves might actually represent a novel preventive approach to hinder emotional contagion, disseminating reliable information and nurturing trust. There is the need to monitor and sustain healthy behaviors as well as community supports also via social media-based preventive interventions

Mechanisms of p53 Functional De-Regulation: Role of the IκB-α/p53 Complex

TP53 is one of the most frequently-mutated and deleted tumor suppressors in cancer, with a dramatic correlation with dismal prognoses. In addition to genetic inactivation, the p53 protein can be functionally inactivated in cancer, through post-transductional modifications, changes in cellular compartmentalization, and interactions with other proteins. Here, we review the mechanisms of p53 functional inactivation, with a particular emphasis on the interaction between p53 and IκB-α, the NFKBIA gene product

Practical Guidance for the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia

Schizophrenia is a severe mental illness causing a high degree of disability. First-and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described

IN-VITRO REGENERATION OF CALENDULA MARITIMA GUSS. (ASTERACEAE), A THREATENED PLANT ENDEMIC TO WESTERN SICILY

Calendula maritima is a critically endangered endemic plant of Western Sicily. Besides habitat destruction, the hybridization with the contiguous congener species C. fulgida is a major threat to its conservation. For this reason, seed-based propagation and seed storage are not appropriate for conservation purposes. In the present paper we describe a rapid and prolific in vitro plant regeneration method by direct organogenesis from leaves of C. maritima. Leaf explants were cultured on solid Murashige and Skoog (MS) medium in the presence of several plant growth regulator combinations. The best shoot multiplication rate (2.5 shoots/explant) was obtained on the medium containing 4.4 µM 6-benzylaminopurine in combination with 10 µM ß-naphthoxyacetic acid. Regenerated shoots were successfully rooted on solid MS medium supplemented with several auxins and the best result was obtained with 1.0 µM indole-3-acetic acid (35% of plantlets rooted). Plantlets were thereafter established in the greenhouse (survival frequency 75%) and no phenotypic variations were observed between regenerants and the mother plant

The non-genomic loss of function of tumor suppressors: an essential role in the pathogenesis of chronic myeloid leukemia chronic phase

BACKGROUND: Chronic Myeloid Leukemia was always referred as a unique cancer due to the apparent independence from tumor suppressors’ deletions/mutations in the early stages of the disease. However, it is now well documented that even genetically wild-type tumor suppressors can be involved in tumorigenesis, when functionally inactivated. In particular, tumor suppressors’ functions can be impaired by subtle variations of protein levels, changes in cellular compartmentalization and post-transcriptional/post-translational modifications, such as phosphorylation, acetylation, ubiquitination and sumoylation. Notably, tumor suppressors inactivation offers challenging therapeutic opportunities. The reactivation of an inactive and genetically wild-type tumor suppressor could indeed promote selective apoptosis of cancer cells without affecting normal cells. MAIN BODY: Chronic Myeloid Leukemia (CML) could be considered as the paradigm for non-genomic loss of function of tumor suppressors due to the ability of BCR-ABL to directly promote functionally inactivation of several tumor suppressors. SHORT CONCLUSION: In this review we will describe new insights on the role of FoxO, PP2A, p27, BLK, PTEN and other tumor suppressors in CML pathogenesis. Finally, we will describe strategies to promote tumor suppressors reactivation in CML

Efficacy of Cannabidiol for Delta-9-Tetrahydrocannabinol-Induced Psychotic Symptoms, Schizophrenia, and Cannabis Use Disorders: A Narrative Review

Although cannabis’ major psychoactive component, ∆-9-tetrahydrocannabinol (THC), has been linked to both earlier onset and poorer outcomes of psychotic disorders, Cannabidiol (CBD) seems to have different pharmacological mechanisms and potential therapeutic properties. However, no clinical study has investigated CBD for the treatment of co-occurring psychotic and cannabis use disorders so far, even though its utility seems grounded in a plausible biological basis. The aim of this work is thus to provide an overview of available clinical studies evaluating the efficacy of CBD for psychotic symptoms induced by THC, schizophrenia, and cannabis use disorders. After searching for relevant studies in PubMed, Cochrane Library, and ClinicalTrials.gov, we included 10 clinical studies. Available evidence suggests that CBD may attenuate both psychotic-like symptoms induced by THC in healthy volunteers and positive symptoms in individuals with schizophrenia. In addition, preliminary data on the efficacy of CBD for cannabis use disorders show mixed findings. Evidence from ongoing clinical studies will provide insight into the possible role of CBD for treating psychotic and cannabis use disorders

Reciprocal Activating Interaction between Natural Killer Cells and Dendritic Cells

We analyzed the interaction between human peripheral blood natural killer (NK) cells and monocyte-derived immature dendritic cells (DC). Fresh NK cells were activated, as indicated by the induced expression of the CD69 antigen, and their cytolytic activity was strongly augmented by contact with lipopolysaccharide (LPS)-treated mature DC, or with immature DC in the presence of the maturation stimuli LPS, Mycobacterium tuberculosis or interferon (IFN)-α. Reciprocally, fresh NK cells cultured with immature DC in the presence of the maturation stimuli strongly enhanced DC maturation and interleukin (IL)-12 production. IL-2–activated NK cells directly induced maturation of DC and enhanced their ability to stimulate allogeneic naive CD4+ T cells. The effects of NK cells were cell contact dependent, although the secretion of IFN-γ and TNF also contributed to DC maturation. Within peripheral blood lymphocytes the reciprocal activating interaction with DC was restricted to NK cells, because the other lymphocyte subsets were neither induced to express CD69, nor induced to mature in contact with DC. These data demonstrated for the first time a bidirectional cross talk between NK cells and DC, in which NK cells activated by IL-2 or by mature DC induce DC maturation