Fentanyl: New Wave, New Age, New Addiction?

This paper aims to take over the rampant phenomenon of the illicit use/abuse for volutary purposes of fentanyl. This synthetic drug is normally used as a potent anaesthetic and analgesic molecule. Unfortunately, in recent decades, this substance has conquered and seduced millions of people in the 'westernised' world, claiming numerous victims, especially young people.

Research in Defense Mechanisms: What Do We Stand?

More than a century is passed since Freud conceived the concept of defense mechanisms. In this article, we retrace the historical evolution of the construct and offer a narrative review of current clinical and empirical literature on its relevance in clinical psychology. Conceptual contributions and empirical findings on the relationship between defenses and personality, as well as between defensive styles and psychopathology (e.

TERRA G-quadruplex stabilization behind the anti-multiple myeloma activity: Novel insights about resveratrol pleiotropic effects.

Resveratrol (RSV) is a nutraceutical compound belonging to the nonflavonoid polyphenol family, whose antioxidants, anti-inflammatory, and antitumoral properties have been widely investigated. The ability of RSV to provide beneficial effects for neurological, cardiovascular, and cancer disorders rekindled the interest to explore the molecular mechanisms behind its pleiotropic effects, which are due to the modulation of coding and noncoding genes involved in many key biological pathways. With a computational approach, including docking studies and thermodynamics calculations followed by 200-ns-long molecular dynamics and a clustering analysis, we hypothesized the stabilizing binding between RSV and G4 structures of telomeric repeat-containing RNA (TERRA), which is a tumor-suppressive long noncoding RNAs (lncRNA) involved in the regulation of telomere maintenance.

UMG1/CD3ε-bispecific T-cell engager redirects T-cell cytotoxicity against diffuse large B-cell lymphoma.

UMG1 is a unique epitope of CD43, not expressed by normal cells and tissues of haematopoietic and non-haematopoietic origin, except thymocytes and a minority (<5%) of peripheral blood T lymphocytes. By immunohistochemistry analysis of tissue microarray and pathology slides, we found high UMG1 expression in 20%-24% of diffuse large B-cell lymphomas (DLBCLs), including highly aggressive BCL2 and CD20 cases. UMG1 membrane expression was also found in DLBCL bone marrow-infiltrating cells and established cell lines.

Adolescents and the Consequences of COVID-19.

In the pandemic period due to the strong restrictions made necessary to deal with the spread of the Sars COVID-19 Virus, adolescents were the subjects who, most of all, suffered from isolation and lack of sociality, due to social distancing. It was necessary to change their habits, their lifestyles, the way they live social relationships and relate to others. Furthermore, those of them who were facing health difficulties at the time were faced with the impossibility of the services to guarantee safety conditions, so that in most cases many medical, psychiatric and psychological activities were suspended, with hospitalizations postponed to a date to be defined, appointments canceled with a high risk of losing contact with the patient.

Eating Disorders and Psychiatric Comorbidity.

Psychiatric comorbidity is present in more than 70% of people with an Eating Disorders (ED), before or during the acute state of illness or in the long-term course. These comorbidities include personality disorders (>53%), anxiety disorders (>50%), mood disorders (>40%) and substance abuse (>10%). This work aims to analyse the different treatments available for patients affected by eating disorders and other psychiatric comorbidity.

Gender Dysphoria and DNA.

Gender dysphoria (GD) describes individuals for whom the native sex and expressed gender are not coincident and most of them self-identify as transgender women or men. It has been shown that genetic factors play an important role in GD and the presence of specific genetic variants in candidate genes could be correlated. On the other hand, twins studies have estimated its heritability.

Victim Blaming: Being a Victim Twice. Comparison of Emotional and Socio-Cultural Aspects.

World Health Organization Director-General Margaret Chan said that violence against women is a global structural issue. It is a health problem of epidemic dimensions, the analysis of 141 researches carried out in 81 countries shows that 35% of women suffer some form of violence during their lifetime. These data were presented in the largest study ever done on the physical and sexual abuse suffered by women in all regions of the planet.

Hit identification of novel small molecules interfering with MALAT1 triplex by a structure-based virtual screening.

Nowadays, RNA is an attractive target for the design of new small molecules with different pharmacological activities. Among several RNA molecules, long noncoding RNAs (lncRNAs) are extensively reported to be involved in cancer pathogenesis. In particular, the overexpression of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) plays an important role in the development of multiple myeloma (MM).

A Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) for ovarian cancer.

Background: Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC).

Methods: pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence.

The First-In-Class Anti-AXL×CD3ε Pronectin™-Based Bispecific T-Cell Engager Is Active in Preclinical Models of Human Soft Tissue and Bone Sarcomas.

Sarcomas are heterogeneous malignancies with limited therapeutic options and a poor prognosis. We developed an innovative immunotherapeutic agent, a first-in-class Pronectin™-based Bispecific T-Cell Engager (pAXL×CD3ε), for the targeting of AXL, a TAM family tyrosine kinase receptor highly expressed in sarcomas. AXL expression was first analyzed by flow cytometry, qRT-PCR, and Western blot on a panel of sarcoma cell lines.

TERRA G-quadruplex stabilization as a new therapeutic strategy for multiple myeloma.

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability, and telomere dysfunction is an important cause of acquired genomic alterations. Telomeric repeat-containing RNA (TERRA) transcripts are long non-coding RNAs involved in telomere stability through the interaction with shelterin complex. Dysregulation of TERRAs has been reported across several cancer types.

Exploiting DNA Ligase III addiction of multiple myeloma by flavonoid Rhamnetin.

Background: DNA ligases are crucial for DNA repair and cell replication since they catalyze the final steps in which DNA breaks are joined. DNA Ligase III (LIG3) exerts a pivotal role in Alternative-Non-Homologous End Joining Repair (Alt-NHEJ), an error-prone DNA repair pathway often up-regulated in genomically unstable cancer, such as Multiple Myeloma (MM). Based on the three-dimensional (3D) LIG3 structure, we performed a computational screening to identify LIG3-targeting natural compounds as potential candidates to counteract Alt-NHEJ activity in MM.

Eating and Nutrition Disorders: Intra and Post-Lockdown Pandemic Emergencies.

Eating Disorders (ED), currently specified as Eating and Nutrition Disorders (DAN), have impacted their morbidity since the last years of the last century, afflicting large segments of the population, predominantly youth, in the westernized "hemisphere." In addition, the COVID-19 pandemic has impacted and negatively influenced eating behaviors in both the general population and DAN sufferers. In agreement with many authors, distancing and social isolation have produced eating disconducts or aggravated symptoms in patients undergoing treatment.

Genetics As a Key to Understand Mood Disorders.

Mood disorders are mental health class that health professionals use to broadly describe all types of depression and bipolar disorders. Heritability of both bipolar and depressive disorder is in the range of 50%, which means that genes alone are not sufficient to explain all the cases of mood disorders, but they confer a substantial risk which is combined with environmental stressors to determine the final illness. In the recent years, a number of studies considered the idea to develop a strategic plan to employ the tools of genetics to advance the understanding, treatment, and outcomes for mood disorders.

Violence Against Women: An Ever-Increasing Emergency. Path of Escape from Violence.

Violence against women is a complex phenomenon that poses many difficulties. The greatest obstacles, however, are those that women themselves encounter, often with children, who choose to get out of the situation or relationship of violence they experience. Material, economic, housing, psychological difficulties; in this difficult path to escape from violence, women need support and support, needs to which I respond to the Anti-violence Centers (CAV) that have been operating in the various territories for years.

Eating Disorders: The Role of the Family in Development and Maintenance of Children's Problems in the Pandemic Period.

Introduction: According to data released by the Ministry of Health in 2021 in Italy about three million young people suffer from eating disorders with onset before the age of 13 and the number tends to be increasing. This work aims to understand if and to what extent the areas of family functioning are related to the way of eating of adolescents in the period of restriction due to COVID-19. In particular, which dimensions of family functioning can be correlated with dysfunctional eating habits.

The New Microtubule-Targeting Agent SIX2G Induces Immunogenic Cell Death in Multiple Myeloma.

Microtubule-targeting agents (MTAs) are effective drugs for cancer treatment. A novel diaryl [1,2]oxazole class of compounds binding the colchicine site was synthesized as cis-restricted-combretastatin-A-4-analogue and then chemically modified to have improved solubility and a wider therapeutic index as compared to vinca alkaloids and taxanes. On these bases, a new class of tricyclic compounds, containing the [1,2]oxazole ring and an isoindole moiety, has been synthetized, among which SIX2G emerged as improved MTA.

A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited.

Chromene Derivatives as Selective TERRA G-Quadruplex RNA Binders with Antiproliferative Properties.

In mammalian cells, telomerase transcribes telomeres in large G-rich non-coding RNA, known as telomeric repeat-containing RNA (TERRA), which folds into noncanonical nucleic acid secondary structures called G-quadruplexes (G4s). Since TERRA G4 has been shown to be involved in telomere length and translation regulation, it could provide valuable insight into fundamental biological processes, such as cancer growth, and TERRA G4 binders could represent an innovative strategy for cancer treatment. In this work, the three best candidates identified in our previous virtual screening campaign on bimolecular DNA/RNA G4s were investigated on the monomolecular Tel DNA and TERRA G4s by means of molecular modelling simulations and in vitro and in cell analysis.

Oleil Hydroxytyrosol (HTOL) Exerts Anti-Myeloma Activity by Antagonizing Key Survival Pathways in Malignant Plasma Cells.

Polyphenols from olive oil are endowed with several biological activities. Chemical modifications have been recently applied to these compounds to improve their therapeutic activity in different pathological settings, including cancer. Herein, we describe the in vitro effects on multiple myeloma (MM) cells of oleil hydroxytyrosol (HTOL), a synthetic fatty ester of natural hydroxytyrosol with oleic acid.

An Epidepic in the Pandemic: The Most Difficult Challenge for Young Adolescents.

The pandemic due to COVID-19 has had a huge psychological impact on individuals all over the world, in particular the international literature is noting an increase in pathologies among children and adolescents adolescenti (Pappa et al. 2020, Keles et al. 2020, Pigaiani et al.