Ferritin nanovehicle for targeted delivery of cytochrome C to cancer cells

In this work, we have exploited the unique properties of a chimeric archaeal-human ferritin to encapsulate, deliver and release cytochrome c and induce apoptosis in a myeloid leukemia cell line. The chimeric protein combines the versatility in 24-meric assembly and cargo incorporation capability of Archaeglobus fulgidus ferritin with specific binding of human H ferritin to CD71, the “heavy duty” carrier responsible for transferrin-iron uptake. Delivery of ferritin-encapsulated cytochrome C to the Acute Promyelocytic Leukemia (APL) NB4 cell line, highly resistant to transfection by conventional methods, was successfully achieved in vitro. The effective liberation of cytochrome C within the cytosolic environment, demonstrated by double fluorescent labelling, induced apoptosis in the cancer cells

Internalizing and externalizing symptoms among unaccompanied refugee and Italian adolescents

This study investigated the prevalence of emotional and behavioral symptoms in unaccompanied refugee adolescents living in Italy; an area which remains under-researched despite the relatively high number of asylum seekers registered in Italy compared to other industrialized countries. The Child Behavior Checklist (CBCL) for 6–18 year-olds was completed by a social worker or parent for each of the 120 participating adolescents; sixty male unaccompanied refugee adolescents and sixty male native Italian adolescents. The paper presents findings that illustrate high levels of emotional and behavioral problems in unaccompanied refugee youth living in Italy. On all components of the CBCL, unaccompanied refugee adolescents were found to present with significantly more problems, as reported by social workers, compared to the Italian group of adolescents. In the light of these results, the importance of interventions and culturally sensitive therapeutic programs for refugee youth is discussed

The buffering role of paternal parenting stress in the relationship between maternal parenting stress and children's problematic behaviour

The present study aimed at exploring the relationship between parenting stress and children's problematic behaviour in the families of 99 children aged 8–11 years. Parenting stress was assessed by parents, using the Parenting Stress Index, and children's problematic behaviour was assessed by teachers, using the Strengths and Difficulties Questionnaire. A moderation regression analysis showed a conditioning effect of paternal parenting stress in the relationship between maternal parenting stress and children's problematic behaviour. In the presence of high levels of paternal parenting stress, the relationship between maternal parenting stress and children's problematic behaviour was significant and strong (p =.01). When paternal parenting stress levels were low, the relationship between maternal parenting stress and children's problematic behaviour was not significant (p =.49). The results underlined that paternal parenting stress may buffer the relationship between maternal parenting stress and children's problematic behaviour. Clinical implications are discussed

Parents and children during the COVID-19 lockdown: the influence of parenting distress and parenting self-efficacy on children’s emotional well-being

On March 10, 2020, Italy went into lockdown due to the Coronavirus Disease-19 (COVID-19) pandemic. The World Health Organization highlighted how the lockdown had negative consequences on psychological well-being, especially for children. The present study aimed to investigate parental correlates of children’s emotion regulation during the COVID-19 lockdown. Within the Social Cognitive Theory framework, a path model in which parenting self-efficacy and parental regulatory emotional self-efficacy mediated the relationship between parents’ psychological distress and both children’s emotional regulation, and children’s lability/negativity, was investigated. A total of 277 parents of children aged from 6 to 13 years completed an online survey that assessed their psychological distress, regulatory emotional self-efficacy, and parenting self-efficacy. Parents reported also children’s emotional regulation and lability/negativity. A structural equation model (SEM) using MPLUS 8.3 was tested. Results showed that the hypothesized model exhibited excellent fit, chi-square (83) = 140.40, p < 0.01, RMSEA = 0.05, CFI = 0.97, TLI = 0.96, SRMR = 0.04. The influences of parents’ psychological distress and parents’ regulatory emotional self-efficacy on children’s emotional regulation and lability/negativity were mediated by parenting self-efficacy. The mediation model was invariant across children’s biological sex and age, and geographical residence area (high risk vs. low risk for COVID-19). Results suggested how parents’ beliefs to be competent in managing parental tasks might be a protective factor for their children’s emotional well-being. Implications for intervention programs are discussed

Exploring the use of dimethyl fumarate as microglia modulator for neurodegenerative diseases treatment

The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression

A novel strategy for molecular interfaces optimization: the case of ferritin-transferrin receptor interaction

Protein-protein interactions regulate almost all cellular functions and rely on a fine tune of surface amino acids properties involved on both molecular partners. The disruption of a molecular association can be caused even by a single residue mutation, often leading to a pathological modification of a biochemical pathway. Therefore the evaluation of the effects of amino acid substitutions on binding, and the ad hoc design of protein-protein interfaces, is one of the biggest challenges in computational biology. Here, we present a novel strategy for computational mutation and optimization of protein-protein interfaces. Modeling the interaction surface properties using the Zernike polynomials, we describe the shape and electrostatics of binding sites with an ordered set of descriptors, making possible the evaluation of complementarity between interacting surfaces. With a Monte Carlo approach, we obtain protein mutants with controlled molecular complementarities. Applying this strategy to the relevant case of the interaction between Ferritin and Transferrin Receptor, we obtain a set of Ferritin mutants with increased or decreased complementarity. The extensive molecular dynamics validation of the method results confirms its efficacy, showing that this strategy represents a very promising approach in designing correct molecular interfaces

Cervicoscopy and Microcolposcopy in the Evaluation of Squamo Columnar Junction and Cervical Canal in LSIL Patients with Inadequate or Negative Colposcopy

OBJECTIVE: The present study evaluated indications’ validity of cervicoscopic and microcolposcopic examination in LSIL patients with unsatisfactory or negative colposcopy. MATHERIAL AND METHODS: In the cervico-vaginal pathology unit of the “San Giovanni Calibita Fatebenefratelli” University of Rome “Tor Vergata”, 119 patients with a positive cervical cytology (LSIL), were submitted to the exam for the following two indications: 1) unsatisfactory colposcopy 37 (31.1%); 2) negative colposcopy 82 (68.9%). RESULTS: Cervicoscopy allowed the SCJ visualization in 115 (9.6%) patients. In 4 patients 3.4%, the SCJ visualization was not possible due to cervical stenosis. Cervicoscopy without staining, revealed endocervical squamous columnar junction in 33 (28.7%) patients. The blue dye in panoramic view detected endocervical SCJ in 41 (35.7%), out of 115 patients (>5 mm in 34 (29.6%) patients and >10 mm in 7 (6.1%)). CONCLUSIONS: Cervicoscopic examination revealed 7.8% of CIN2-3 in LSIL patients with inadequate or negative colposcopy. In patients with negative colposcopy the percentage of undiagnosed lesions inside the cervical canal was very low. The blue dye added sensitivity to the exam

Negative parental responses to coming out and family functioning in a sample of lesbian and gay young adults

Parental responses to youths' coming out (CO) are crucial to the subsequent adjustment of children and family. The present study investigated the negative parental reaction to the disclosure of same-sex attraction and the differences between maternal and paternal responses, as reported by their homosexual daughters and sons. Participants' perceptions of their parents' reactions (evaluated through the Perceived Parental Reactions Scale, PPRS), age at coming out, gender, parental political orientation, and religiosity involvement, the family functioning (assessed through the Family Adaptability and Cohesion Evaluation Scales, FACES IV), were assessed in 164 Italian gay and lesbian young adults. Pearson correlation coefficients were calculated to assess the relation between family functioning and parental reaction to CO. The paired sample t-test was used to compare mothers and fathers' scores on the PPRS. Hierarchical multiple regression was conducted to analyze the relevance of each variable. No differences were found between mothers and fathers in their reaction to the disclosure. The analysis showed that a negative reaction to coming out was predicted by parents' right-wing political conservatism, strong religious beliefs, and higher scores in the scales Rigid and Enmeshed. Findings confirm that a negative parental reaction is the result of poor family resources to face a stressful situation and a strong belief in traditional values. These results have important implications in both clinical and social fields

Adolescent Development and the Parent–Adolescent Relationship in Diverse Family Forms Created by Assisted Reproduction

Assisted reproduction techniques (ARTs) are employed by single individuals and couples who are not otherwise able to conceive spontaneously. While the use of ARTs is increasing, research is lacking on the attempts made by adolescent offspring conceived via ARTs to integrate their ART conception into their identity and negotiate a connection with, and autonomy from, their parents. The present article reviews studies investigating adolescent development and the parent–adolescent relationship in diverse family forms created by ARTs (mainly heterosexual and lesbian parent families), and discusses the results in light of attachment, identity development, and emotional distance regulation theories. Overall, the results indicate that the psychological adjustment of adolescents conceived via ARTs is not undermined by the manner of their conception, and that they enjoy positive relationships with their parents with no difference from those enjoyed by spontaneously conceived adolescents. However, it remains unknown whether the development of a reproductive identity in adolescence is likely to influence adolescents’ interest in searching for or contacting their donors, surrogates, and/or donor siblings. The results suggest the relevance of considering the parent–adolescent relationship, disclosure, and identity formation issues when planning psychological counseling and support interventions with ART parents and their adolescent offspring, and emphasize the need to further investigate these aspects in diverse ART families, including single-, gay-, bisexual-, and trans*-parent families