Smartphone and social network addiction in early adolescents: The role of self-regulatory self-efficacy in a pilot school-based intervention.

BACKGROUND: Youths' online problematic behaviors, such as smartphone or social network sites (SNS) addiction, gained increasing attention nowadays, due to their impact on concurrent and later adjustment, such as emotional and/or behavioral problems, academic impairments, or relational issues. AIMS: This study aims to evaluate the effectiveness of a pilot school-based intervention to contrast online addictive behaviors while fostering adolescents' self-regulative abilities. MATERIALS & METHODS: The intervention started in January 2022 in an Italian junior high school located in Rome, and consisted of four meetings with students. A total sample of 462 15-year-old adolescents (Mage = 15.2; SD = 0.50; 41% females; Ncontrol = 214; Nintervention = 248) was considered. Within the latent difference score framework, we examined short-term changes from the pre-to-the-postintervention levels of SNS and smartphone addiction, and self-regulatory self-efficacy (SRSE) beliefs as a possible booster of the intervention's effectiveness. RESULTS: Results showed a significant decrease in both online addictions (SNS and smartphone addiction), controlling for age, gender, sexual orientation, and socioeconomic status, because of the short-term efficacy of the project. The buffering effect of SRSE beliefs was further supported. CONCLUSION: These findings emphasized the usefulness of promoting youths' self-regulative beliefs to contrast problematic tendencies, according to a Positive Youth Development perspective which focused on resources rather than only on the prevention of negative outcomes for youths' adjustment.

Parental Happiness Socialization and Youth Adjustment in Italy and Azerbaijan in the COVID-19 Pandemic Era.

This study aims to cross-culturally identify the parental socialization strategies in response to a child's happiness and their associations with youth academic and socio-emotional adjustment, controlling for the impact of the COVID-19 pandemic. Participants were a convenient sample of Italian (N = 606, 81.9% mothers) and Azerbaijanis (N = 227, 61.4% mothers) parents of youths (Mage = 12.89, SD = 4.06; 51% girls). Parents filled out an online survey to assess their socialization strategies in response to their children's happiness, their children's negative emotion regulation and dysregulation, academic performance, and prosocial behavior. Exploratory factorial analysis showed the presence of two factors that enclosed supportive and unsupportive parental socialization strategies. A multiple-group path analysis model showed that similarly across countries, supportive parental strategies were positively related to youths' prosocial behavior and that unsupportive parental strategies were positively related to youths' negative emotion dysregulation, and negatively related to youths' academic performance and negative emotion regulation. Those results emerged controlling for parents' and adolescents' gender and age, parents' educational level, social desirability, and Covid-related problems. This study advances cross-cultural knowledge about the impact of the strategies that parents use to socialize their children's happiness in the unique context of the COVID-19 pandemic.

Signaling Induced by Chronic Viral Hepatitis: Dependence and Consequences.

Chronic viral hepatitis is a main cause of liver disease and hepatocellular carcinoma. There are striking similarities in the pathological impact of hepatitis B, C, and D, although these diseases are caused by very different viruses. Paired with the conventional study of protein-host interactions, the rapid technological development of -omics and bioinformatics has allowed highlighting the important role of signaling networks in viral pathogenesis. In this review, we provide an integrated look on the three major viruses associated with chronic viral hepatitis in patients, summarizing similarities and differences in virus-induced cellular signaling relevant to the viral life cycles and liver disease progression.

Negative Parenting, Adolescents' Emotion Regulation, Self-Efficacy in Emotion Regulation, and Psychological Adjustment.

This study examines associations between parents' rejection and control, adolescents' self-efficacy in their regulation of negative emotions, and maladjustment. Path analyses were employed to test (a) whether adolescents' dysregulation and self-efficacy regarding anger/sadness regulation mediate the relationship between parental rejection/control and adolescent maladjustment; (b) whether adolescent adjustment mediates the association between parental rejection/control and dysregulation and self-efficacy regarding anger/sadness regulation. Participants included 103 Italian adolescents (Time 1: M age = 15.57; 53% male), their mothers (n = 103), and their fathers (n = 79). Follow up data were assessed one year later (Time 2). At Time 1, adolescent reports of the frequency of mothers' and fathers' rejection and control were examined. At Time 2, adolescent-reports of their beliefs about self-efficacy in regulating anger and sadness, as well as anger and sadness dysregulation, were assessed by two methods: questionnaire and mobile ecological momentary assessment. At Time 2, mothers', fathers', and adolescents' reports of adolescents' aggressive behaviors and depressive problems were also assessed. Maternal rejection was associated with higher one year later aggressive problems, which in turn were associated with higher dysregulation of sadness, and lower self-efficacy in dealing with both anger and sadness. In addition, maternal rejection was associated with higher depressive symptoms one year later, which in turn were associated with lower self-efficacy in dealing with sadness and higher dysregulation of both anger and sadness. Finally, maternal control was associated with higher depressive symptoms, whereas paternal control was associated with lower depressive symptoms.

Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development.

Despite breakthroughs in antiviral therapies, chronic viral hepatitis B and C are still the major causes of liver fibrosis and hepatocellular carcinoma (HCC). Importantly, even in patients with controlled infection or viral cure, the cancer risk cannot be fully eliminated, highlighting a persisting oncogenic pressure imposed by epigenetic imprinting and advanced liver disease. Reliable and minimally invasive biomarkers for early fibrosis and for residual HCC risk in HCV-cured patients are urgently needed. Chronic infection with HBV and/or HCV dysregulates oncogenic and profibrogenic signaling within the host, also displayed in the secretion of soluble factors to the blood. The study of virus-dysregulated signaling pathways may, therefore, contribute to the identification of reliable minimally invasive biomarkers for the detection of patients at early-stage liver disease potentially complementing existing noninvasive methods in clinics. With a focus on virus-induced signaling events, this review provides an overview of candidate blood biomarkers for liver disease and HCC risk associated with chronic viral hepatitis and epigenetic viral footprints.

GOLT1B Activation in Hepatitis C Virus-Infected Hepatocytes Links ER Trafficking and Viral Replication.

Chronic hepatitis C carries a high risk of development of hepatocellular carcinoma (HCC), triggered by both direct and indirect effects of the virus. We examined cell-autonomous alterations in gene expression profiles associated with hepatitis C viral presence. Highly sensitive single molecule fluorescent in situ hybridization applied to frozen tissue sections of a hepatitis C patient allowed the delineation of clusters of infected hepatocytes. Laser microdissection followed by RNAseq analysis of hepatitis C virus (HCV)-positive and -negative regions from the tumoral and non-tumoral tissues from the same patient revealed HCV-related deregulation of expression of genes in the tumor and in the non-tumoral tissue. However, there was little overlap between both gene sets. Our interest in alterations that increase the probability of tumorigenesis prompted the examination of genes whose expression was increased by the virus in the non-transformed cells and whose level remained high in the tumor. This strategy led to the identification of a novel HCV target gene: GOLT1B, which encodes a protein involved in ER-Golgi trafficking. We further show that GOLT1B expression is induced during the unfolded protein response, that its presence is essential for efficient viral replication, and that its expression is correlated with poor outcome in HCC.

Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis.

Hepatitis C virus (HCV) is a major cause of liver disease including metabolic disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCV induces and promotes liver disease progression by perturbing a range of survival, proliferative, and metabolic pathways within the proinflammatory cellular microenvironment. The recent breakthrough in antiviral therapy using direct-acting antivirals (DAAs) can cure >90% of HCV patients. However, viral cure cannot fully eliminate the HCC risk, especially in patients with advanced liver disease or comorbidities. HCV induces an epigenetic viral footprint that promotes a pro-oncogenic hepatic signature, which persists after DAA cure. In this review, we summarize the main signaling pathways deregulated by HCV infection, with potential impact on liver pathogenesis. HCV-induced persistent signaling patterns may serve as biomarkers for the stratification of HCV-cured patients at high risk of developing HCC. Moreover, these signaling pathways are potential targets for novel chemopreventive strategies.

Combined Analysis of Metabolomes, Proteomes, and Transcriptomes of Hepatitis C Virus-Infected Cells and Liver to Identify Pathways Associated With Disease Development.

BACKGROUND & AIMS: The mechanisms of hepatitis C virus (HCV) infection, liver disease progression, and hepatocarcinogenesis are only partially understood. We performed genomic, proteomic, and metabolomic analyses of HCV-infected cells and chimeric mice to learn more about these processes. METHODS: Huh7.5.1dif (hepatocyte-like cells) were infected with culture-derived HCV and used in RNA sequencing, proteomic, metabolomic, and integrative genomic analyses. uPA/SCID (urokinase-type plasminogen activator/severe combined immunodeficiency) mice were injected with serum from HCV-infected patients; 8 weeks later, liver tissues were collected and analyzed by RNA sequencing and proteomics. Using differential expression, gene set enrichment analyses, and protein interaction mapping, we identified pathways that changed in response to HCV infection. We validated our findings in studies of liver tissues from 216 patients with HCV infection and early-stage cirrhosis and paired biopsy specimens from 99 patients with hepatocellular carcinoma, including 17 patients with histologic features of steatohepatitis. Cirrhotic liver tissues from patients with HCV infection were classified into 2 groups based on relative peroxisome function; outcomes assessed included Child-Pugh class, development of hepatocellular carcinoma, survival, and steatohepatitis. Hepatocellular carcinomas were classified according to steatohepatitis; the outcome was relative peroxisomal function. RESULTS: We quantified 21,950 messenger RNAs (mRNAs) and 8297 proteins in HCV-infected cells. Upon HCV infection of hepatocyte-like cells and chimeric mice, we observed significant changes in levels of mRNAs and proteins involved in metabolism and hepatocarcinogenesis. HCV infection of hepatocyte-like cells significantly increased levels of the mRNAs, but not proteins, that regulate the innate immune response; we believe this was due to the inhibition of translation in these cells. HCV infection of hepatocyte-like cells increased glucose consumption and metabolism and the STAT3 signaling pathway and reduced peroxisome function. Peroxisomes mediate ß-oxidation of very long-chain fatty acids; we found intracellular accumulation of very long-chain fatty acids in HCV-infected cells, which is also observed in patients with fatty liver disease. Cells in livers from HCV-infected mice had significant reductions in levels of the mRNAs and proteins associated with peroxisome function, indicating perturbation of peroxisomes. We found that defects in peroxisome function were associated with outcomes and features of HCV-associated cirrhosis, fatty liver disease, and hepatocellular carcinoma in patients. CONCLUSIONS: We performed combined transcriptome, proteome, and metabolome analyses of liver tissues from HCV-infected hepatocyte-like cells and HCV-infected mice. We found that HCV infection increases glucose metabolism and the STAT3 signaling pathway and thereby reduces peroxisome function; alterations in the expression levels of peroxisome genes were associated with outcomes of patients with liver diseases. These findings provide insights into liver disease pathogenesis and might be used to identify new therapeutic targets.

Oncogenic Signaling Induced by HCV Infection.

The liver is frequently exposed to toxins, metabolites, and oxidative stress, which can challenge organ function and genomic stability. Liver regeneration is therefore a highly regulated process involving several sequential signaling events. It is thus not surprising that individual oncogenic mutations in hepatocytes do not necessarily lead to cancer and that the genetic profiles of hepatocellular carcinomas (HCCs) are highly heterogeneous. Long-term infection with hepatitis C virus (HCV) creates an oncogenic environment by a combination of viral protein expression, persistent liver inflammation, oxidative stress, and chronically deregulated signaling events that cumulate as a tipping point for genetic stability. Although novel direct-acting antivirals (DAA)-based treatments efficiently eradicate HCV, the associated HCC risk cannot be fully eliminated by viral cure in patients with advanced liver disease. This suggests that HCV may persistently deregulate signaling pathways beyond viral cure and thereby continue to perturb cancer-relevant gene function. In this review, we summarize the current knowledge about oncogenic signaling pathways derailed by chronic HCV infection. This will not only help to understand the mechanisms of hepatocarcinogenesis but will also highlight potential chemopreventive strategies to help patients with a high-risk profile of developing HCC.

Reverse screening on indicaxanthin from Opuntia ficus-indica as natural chemoactive and chemopreventive agent.

Indicaxanthin is a bioactive and bioavailable betalain pigment extracted from Opuntia ficus indica fruits. Indicaxanthin has pharmacokinetic proprieties, rarely found in other phytochemicals, and it has been demonstrated that it provides a broad-spectrum of pharmaceutical activity, exerting anti-proliferative, anti-inflammatory, and neuromodulator effects. The discovery of the Indicaxanthin physiological targets plays an important role in understanding the biochemical mechanism. In this study, combined reverse pharmacophore mapping, reverse docking, and text-based database search identified Inositol Trisphosphate 3-Kinase (ITP3K-A), Glutamate carboxypeptidase II (GCPII), Leukotriene-A4 hydrolase (LTA4H), Phosphoserine phosphatase (HPSP), Phosphodiesterase 4D (PDE4D), AMPA receptor (GluA3 and GluA2 subunits) and Kainate receptor (GluK1 isoform) as potential targets for Indicaxanthin. These targets are implicated in neuromodulation, and inflammatory regulation, normally expressed mostly in the CNS, and expressed (or overexpressed) in cancer tissues (i.e. breast, thyroid, and prostate cancer cells). Moreover, this study provides qualitative and quantitative information about dynamic interactions of Indicaxanthin at the binding site of target proteins, through molecular dynamics simulations and MM-GBSA.

The role of p21 Waf1/Cip1 in large airway epithelium in smokers with and without COPD.

Airway epithelium alterations, including squamous cell metaplasia, characterize smokers with and without chronic obstructive pulmonary disease (COPD). The p21 regulates cell apoptosis and differentiation and its role in COPD is largely unknown. Molecules regulating apoptosis (cytoplasmic p21, caspase-3), cell cycle (nuclear p21), proliferation (Ki67/PCNA), and metaplasia (survivin) in central airways from smokers (S), smokers-COPD (s-COPD) and non-smokers (Controls) were studied. The role of cigarette smoke extracts (CSE) in p21, survivin, apoptosis (caspase-3 and annexin-V binding) and proliferation was assessed in a bronchial epithelial cell line (16HBE). Immunohistochemistry, image analysis in surgical samples and flow-cytometry and carboxyfluorescein succinimidyl ester proliferative assay in 16HBE with/without CSE were applied. Cytoplasmic and nuclear p21, survivin, and Ki67 expression significantly increased in large airway epithelium in S and in s-COPD in comparison to Controls. Caspase-3 was similar in all the studied groups. p21 correlated with epithelial metaplasia, PCNA, and Ki67 expression. CSE increased cytoplasmic p21 and survivin expression but not apoptosis and inhibited the cell proliferation in 16HBE. In large airway epithelium of smokers with and without COPD, the cytoplasmic p21 inhibits cell apoptosis, promotes cell proliferation and correlates with squamous cell metaplasia thus representing a potential pre-oncogenic hallmark.