Proteotoxic stress-induced apoptosis in cancer cells: understanding the susceptibility and enhancing the potency

Leiomyosarcoma (LMS) is aggressive cancer with few therapeutic options. LMS cells are more sensitive to proteotoxic stress compared to normal smooth muscle cells. We used small compound 2c to induce proteotoxic stress and compare the transcriptomic adaptations of immortalized human uterine smooth muscle cells (HUtSMC) and LMS cells SK-UT-1. We found that the expression of the heat shock proteins (HSPs) gene family is upregulated with higher efficiency in normal cells. In contrast, the upregulation of BH3-only proteins is higher in LMS cells. HSF1, the master regulator of HSP transcription, is sequestered into transcriptionally incompetent nuclear foci only in LMS cells, which explains the lower HSP upregulation. We also found that several compounds can enhance the cell death response to proteotoxic stress. Specifically, when low doses were used, an inhibitor of salt-inducible kinases (SIKs) and the inhibitor of IRE1 alpha, a key element of the unfolded protein response (UPR), support proteotoxic-induced cell death with strength in LMS cells and without effects on the survival of normal cells. Overall, our data provide an explanation for the higher susceptibility of LMS cells to proteotoxic stress and suggest a potential option for co-treatment strategies

Psychiatric and neuropsychological issues in Marfan syndrome: A critical review of the literature

The cooccurrence of Marfan syndrome and psychiatric disorders has been reported for many years. Furthermore, neuropsychological deficits have been shown to be associated with Marfan syndrome. The aim of the present article is to summarize findings from the sparse studies and case reports available. The results hold clinical and therapeutic implications and suggest that psychological and neuropsychological domains in Marfan syndrome patients should be carefully assessed. In particular, some patients may require specific rehabilitation programs. On this basis, a multidisciplinary approach to Marfan syndrome treatment seems mandatory

Conduct disorders and psychopathy in children and adolescents: Aetiology, clinical presentation and treatment strategies of callous-unemotional traits

Conduct Disorder (CD) is a psychiatric diagnosis characterized by a repetitive and persistent pattern of behaviour in which the basic rights of others and major age-appropriate social norms or rules are violated. Callous Unemotional (CU) traits are a meaningful specifier in subtyping CD for more severe antisocial and aggressive behaviours in adult psychopathology; they represent the affective dimension of adult psychopathy, but they can be also detected in childhood and adolescence. The CU traits include lack of empathy, sense of guilt and shallow emotion, and their characterization in youth can improve our diagnostic, prognostic and therapeutic abilities. A strong genetic liability, in interaction with parenting and relevant environmental factors, can lead to elevated levels of CU traits in children. We pointed out that CU traits can be detected in early childhood, may remain stable along the adolescence, but a decrease following intensive and specialized treatment is possible. We here provide a narrative review of the available evidences on CU traits in three main domains: aetiology (encompassing genetic liability and environmental risk factors), presentation (early signs and longitudinal trajectories) and treatments

Emotional symptoms and their related factors in adolescents during the acute phase of Covid-19 outbreak in South Italy

Several studies have shown that during COVID-19 pandemic outbreak, emotional symptoms increased in the general population. Less is known about youths

Differences in Metabolic Factors Between Antipsychotic-Induced Weight Gain and Non-pharmacological Obesity in Youths

Background: Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs. Objectives: The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients. Methods: Nineteen non-diabetic youth (mean age 159 months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n = 19, mean age 147 months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system. Results: C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin were significantly higher in the antipsychotic-induced weight gain group, whereas visfatin was significantly higher in the untreated obese patients. When age, sex, pubertal status, and body mass index were controlled, C-peptide, glucose-dependent insulinotropic polypeptide, and visfatin remained significant, whereas adipsin fell slightly below the threshold of statistical significance. No other statistically significant difference emerged. Conclusions: Antipsychotic-induced weight gain and untreated obesity showed some similarities, confirming that levels of some hormones, such as leptin and ghrelin, are related to body mass index rather than to antipsychotic exposure. Some differences were also noted; for example, the antipsychotic-induced weight gain group displayed higher C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin, which may reflect β-cell stress and may suggest susceptibility to insulin resistance and lower visfatin, possibly indicating a lower inflammatory status