Interoception Sensitivity and Autonomic Regulation During Social Interaction in Schizophrenia

Introduction The awareness of one's body constitutes a basic experience of Self which modulates the individual engagement in social interactions. Indeed, Interoception Sensitivity (IS), an index of individual ability to represent one's own internal body states, is implicated in the autonomic regulation in interpersonal context. Schizophrenia deficits in Self-experience and awareness, which frequently entail anomalies in self-other relationship, capture the ever-growing attention of researchers. Nevertheless, IS and autonomic regulation of schizophrenic patients in social context are completely new and not yet investigated aspects of Schizophrenia. Aim To investigate whether Schizophrenia could be associated with lower IS and with a dysfunctional autonomic regulation during social interaction. Methods 24 chronic schizophrenia patients, and a matched group of healthy controls, performed a Social and a Non-social task while respiratory sinus arrhythmia (an index of autonomic regulation) was measured. In the Social task participants viewed an experimenter performing a caress-like movement at different distances from their hand. In the Non-social task a metal stick was moved at the same distances from the participants' hand. As measure of IS, a cardiac Mental Tacking Task was performed. Results Comparing to controls, Schizophrenia patients presented lower IS, absence of relation between IS and autonomic regulation, and an anomalous autonomic regulation in social and non-social contexts. Conclusions Deficits in Self-experience, associated with Schizophrenia, could be extended to patients' sensitivity to internal bodily signals. Moreover, the observed altered autonomic regulation will be part of interpersonal interaction deficit frequently associated to Schizophrenia

Interoception and Positive Symptoms in Schizophrenia

The present study focuses on the multifaceted concept of self-disturbance in schizophrenia, adding knowledge about a not yet investigated aspect, which is the interoceptive accuracy. Starting from the assumption that interoceptive accuracy requires an intact sense of self, which otherwise was proved to be altered in schizophrenia, the aim of the present study was to explore interoceptive accuracy in a group of schizophrenia patients, compared to healthy controls. Furthermore, the possible association between interoceptive accuracy and patients' positive and negative symptomatology was assessed. To pursue these goals, a group of 23 schizophrenia patients and a group of 23 healthy controls performed a heartbeat perception task. Patients' symptomatology was assessed by means of the Positive and Negative Syndrome Scale (PANSS). Results demonstrated significantly lower interoceptive accuracy in schizophrenia patients compared to healthy controls. This difference was not accounted for participants' age, BMI, anxiety levels, and heart rate. Furthermore, patients' illness severity, attention and pharmacological treatment did not influence their interoceptive accuracy levels. Interestingly, a strong positive relation between interoceptive accuracy and positive symptoms severity, especially Grandiosity, was found. The present results demonstrate for the first time that interoceptive accuracy is altered in schizophrenia. Furthermore, they prove a specific association between interoceptive accuracy and positive symptomatology, suggesting that the symptom Grandiosity might be protective against an altered basic sense of self in patients characterized by higher sensibility to their inner bodily sensations

Extracellular Vesicles and Epidermal Growth Factor Receptor Activation: Interplay of Drivers in Cancer Progression

Extracellular vesicles (EVs) are of great interest to study the cellular mechanisms of cancer development and to diagnose and monitor cancer progression. EVs are a highly heterogeneous population of cell derived particles, which include microvesicles (MVs) and exosomes (EXOs). EVs deliver intercellular messages transferring proteins, lipids, nucleic acids, and metabolites with implications for tumour progression, invasiveness, and metastasis. Epidermal Growth Factor Receptor (EGFR) is a major driver of cancer. Tumour cells with activated EGFR could produce EVs disseminating EGFR itself or its ligands. This review provides an overview of EVs (mainly EXOs and MVs) and their cargo, with a subsequent focus on their production and effects related to EGFR activation. In particular, in vitro studies performed in EGFR-dependent solid tumours and/or cell cultures will be explored, thus shedding light on the interplay between EGFR and EVs production in promoting cancer progression, metastases, and resistance to therapies. Finally, an overview of liquid biopsy approaches involving EGFR and EVs in the blood/plasma of EGFR-dependent tumour patients will also be discussed to evaluate their possible application as candidate biomarkers

Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation

: Little is known about the signaling network responsible for the organization of the perinuclear actin cap, a recently identified structure holding unique roles in the regulation of nuclear shape and cell directionality. In cancer cells expressing a constitutively active MET, we show a rearrangement of the actin cap filaments, which crash into perinuclear patches associated with spherical nuclei, meandering cell motility and inactivation of the mechano-transducer YAP1. MET ablation is sufficient to reactivate YAP1 and restore the cap, leading to enhanced directionality and flattened nuclei. Consistently, the introduction of a hyperactive MET in normal epithelial cells, enhances nuclear height and alters the cap organization, as also confirmed by TEM analysis. Finally, the constitutively active YAP1 mutant YAP5SA is able to overcome the effects of oncogenic MET. Overall, our work describes a signaling axis empowering MET-mediated YAP1 dampening and actin cap misalignment, with implications for nuclear shape and cell motility

The autocrine loop of ALK receptor and ALKAL2 ligand is an actionable target in consensus molecular subtype 1 colon cancer

In the last years, several efforts have been made to classify colorectal cancer (CRC) into well-defined molecular subgroups, representing the intrinsic inter-patient heterogeneity, known as Consensus Molecular Subtypes (CMSs)

The role of glial cells in mental illness: a systematic review on astroglia and microglia as potential players in schizophrenia and its cognitive and emotional aspects

Schizophrenia is a complex and severe mental disorder that affects approximately 1% of the global population. It is characterized by a wide range of symptoms, including delusions, hallucinations, disorganized speech and behavior, and cognitive impairment. Recent research has suggested that the immune system dysregulation may play a significant role in the pathogenesis of schizophrenia, and glial cells, such as astroglia and microglia known to be involved in neuroinflammation and immune regulation, have emerged as potential players in this process. The aim of this systematic review is to summarize the glial hallmarks of schizophrenia, choosing as cellular candidate the astroglia and microglia, and focusing also on disease-associated psychological (cognitive and emotional) changes. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched PubMed, Scopus, and Web of Science for articles that investigated the differences in astroglia and microglia in patients with schizophrenia, published in the last 5 years. The present systematic review indicates that changes in the density, morphology, and functioning of astroglia and microglia may be involved in the development of schizophrenia. The glial alterations may contribute to the pathogenesis of schizophrenia by dysregulating neurotransmission and immune responses, worsening cognitive capabilities. The complex interplay of astroglial and microglial activation, genetic/epigenetic variations, and cognitive assessments underscores the intricate relationship between biological mechanisms, symptomatology, and cognitive functioning in schizophrenia

Cancer omics strategies for personalized treatments

The Consensus Molecular Subtypes (CMSs) classification stratifies colorectal cancer (CRC) into four well-defined molecular subgroups, providing incredible support to personalized medicine. Indeed, the huge inter-patient heterogeneity observed in CRC makes it difficult to define a therapeutic strategy from which every patient can benefit. Unfortunately, so far really few targetable biomarkers are known in the CRC setting, leading to an urgent need for new targeted therapies. Here we performed a bioinformatic meta-analysis over a cohort of 1700 CMS-stratified CRC patients, identifying a negative correlation between high levels of anaplastic lymphoma kinase (ALK) expression and relapse-free survival, exclusively in the CMS1 subtype. No correlation with ALK expression was pointed out in the other three subgroups. The association of ALK with CMS1 led to generate the hypothesis that ALK pharmacological inhibition may elicit therapeutic potential in this subgroup. Thus, we tested ALK inhibitors and an ALK-directed ADC on several CRC in vitro models, stratified according to the CMS classification as well as on CRC patient-derived organoids and mice. ALK interception strongly inhibited CMS1-cells, organoids, and tumor proliferation and was responsible for the dampening of ALK activation along with the downstream. Mechanistically, we found that CMS1 cells display several mRNA copies of both ALK and ALKAL2 ligand, suggesting a role for ALK abundance in the differential response to its inhibition. Collectively, these findings support the hypothesis that ALK may represent an attractive target for CMS1 colorectal cancer therapy

Changes in biodeterioration patterns of mural paintings: Multi-temporal mapping for a preventive conservation strategy in the Crypt of the Original Sin (Matera, Italy)

Multi-temporal investigation of biodeterioration patterns (BPs)in cultural heritage sites is crucial for the development of effective management plans. Here, microscopy and biomolecular methods were employed to analyze the BPs, which took place in the Crypt of the Original Sin (Italy)over a wide temporal scale, i.e., from 2001 to 2017. Before restoration interventions, performed in 2002–2003, a variety of BPs was observed, including green patinas (Chlorophyceae), brown-black patinas (Cyanobacteria), rosy discolorations (Actinobacteria)and some colonization by lichens, mosses and ferns. Restoration included biocide treatments as well as structural interventions causing environmental modifications of the site. To interpret the ecological relationships between environmental factors and temporal changes, we combined the analysis of ecological information on the various BPs with the results of a multivariate statistical analysis. Using BPs as bioindicators, humidity maps of the plasters were generated and water infiltration paths reconstructed. Several years after biocide application, a significant reduction of BPs was observed, together with limited colonization by dematiaceous and meristematic fungi. Our observations demonstrate the usefulness of combining structural and environmental interventions for an effective restoration strategy; these interventions reduced the moisture levels of the walls, consequently reducing biological colonization. Moreover, our findings suggest that monitoring BPs during time can be of guidance in the long-term maintenance of cultural heritage, and provide an evidence-based model for preventive interventions and biocide treatments

A putative role for interleukin 1 pathway in resistance to EGFR blockade

Cetuximab (CX) is a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), which is commonly utilized to treat patients with metastatic colorectal cancer (mCRC). Unfortunately, clinicians often observe a residual disease, with a population of cells surviving the treatment and eventually enabling CX resistance. Our previous studies, performed with a cohort of 150 CRC xenopatients, associated poor response to CX with increased abundance of a set of inflammatory cytokines, including IL1A, B and IL8. Stemming from these observations, our working hypothesis assumes that, resistance to CX is acquired, in a subset of CRC patients, through cell plasticity and consequent rewiring of signalling networks, which confer to tumors dependency on the IL1 pathway. In order to assess the effect of IL1 activity, we employed a colon cancer model unresponsive to cetuximab, as previously characterized in our laboratory. To inhibit activation of the IL1 pathway we used anakinra, an IL1-receptor antagonist and parthenolide, which modulates the activity of NF-kB, the transcription factor involved in the feed-forward loop of inflammation mediators. Furthermore, we employed a recombinant decoy (IL1R-Fc), namely a soluble protein combining the human immunoglobulin Fc portion linked to the extracellular region of IL1-receptor, with the ability to sequester IL1 directly from the medium. We generated stable clones of CXresistant cells expressing IL1R-Fc. Our preliminary results show that inhibition of IL1R leads to a proliferation decrease of colorectal cancer cells. These findings support the hypothesis of a compensatory activation of the IL1-receptor pathway in cetuximab-resistant CRC cells. Hence, modulating IL1 signalling might represent a new therapeutic strategy suitable for patients who acquired refractoriness to monoclonal antibody therapy