ABSTRACT
Post-COVID-19 syndrome was defined as a persistent and protracted illness, which follows acute COVID-19 infection. This condition continues for more than 12 weeks and cannot be attributed to other clinical situations. Researchers and clinicians are allied in unraveling the molecular pathogenetic mechanisms and the clinical development of this unexpected SARS-CoV-2 infectious evolution. Anosmia, dysgeusia, fatigue, dyspnea, and 'brain fog' are common symptoms observed in the Post-COVID-19 syndrome, depicting a multiorgan involvement associated with injuries involving mainly cardiovascular, pulmonary, musculoskeletal, and neuropsychiatric systems. This commentary analyzes the state of the art of Post-COVID-19 interdisciplinary studies, confirming that we are facing a truly intricate biomedicine story.
Subject(s)
COVID-19/complications , COVID-19/diagnosis , COVID-19/metabolism , Humans , SARS-CoV-2/isolation & purification , Post-Acute COVID-19 SyndromeABSTRACT
Social anhedonia, or the diminished capacity to experience pleasure and reward from social affiliation, is a major symptom of different psychiatric disorders, including some forms of infantile autism and schizophrenia spectrum disorders. The brain opioid hypothesis of social attachment is a promising model for achieving insights into how neurobiological and developmental factors contribute to the regulation of social reward. In this study, genetic knocking-out and naltrexone (NTRX) treatment during the first 4 days of life were used to disrupt opioid neurotransmission in mouse pups and their attachment relationships with the mother. Both permanent (genetic) and transient (pharmacological) manipulations of opioid neurotransmission exerted long-term effects on social affiliation. When juveniles, both µ-opioid receptor knockout mice and NTRX-treated pups showed reduced interest in peers and no preference for socially rewarding environment. These results demonstrate that sociability in juvenile mice is highly dependent on the establishment during infancy of a positive affective relationship with their mothers and that opioid neurotransmission has a major role in the regulation of social hedonic capacity. If the validity of this animal model will be confirmed by future research, translational studies focusing on the interaction between early experience and opioid neurotransmission could provide useful insights for identifying endophenotypes of human psychiatric disorders associated with social anhedonia.
Subject(s)
Anhedonia/physiology , Behavior, Animal/physiology , Disease Models, Animal , Naltrexone/adverse effects , Object Attachment , Reactive Attachment Disorder/chemically induced , Receptors, Opioid, mu/genetics , Synaptic Transmission/genetics , Analysis of Variance , Anhedonia/drug effects , Animals , Behavior, Animal/drug effects , Mice , Mice, Knockout , Reactive Attachment Disorder/genetics , Receptors, Opioid, mu/drug effects , Receptors, Opioid, mu/physiology , Synaptic Transmission/drug effects , Synaptic Transmission/physiologyABSTRACT
X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis proteins family that selectively binds and inhibits caspase-3, -7 and -9. As such, XIAP is an extremely potent suppressor of apoptosis and an attractive target for cancer treatment. Che-1 is an antiapoptotic agent involved in the control of gene transcription and cell proliferation. Recently, we showed that the checkpoint kinases ATM/ATR and checkpoint kinase 2 physically and functionally interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce transcription of p53, and Che-1 depletion strongly sensitizes tumor cells to anticancer drugs. Here we show that Che-1 activates XIAP expression in response to DNA damage. This effect is mediated by Che-1 phosphorylation and requires NF-kappaB. Notably, we found that XIAP expression is necessary for antiapoptotic activity of Che-1 and that in vivo downregulation of Che-1 by small interference RNA strongly enhanced the cytotoxicity of anticancer drugs.
Subject(s)
Apoptosis Regulatory Proteins/physiology , Apoptosis , DNA Damage , Repressor Proteins/physiology , Transcription Factors/physiology , X-Linked Inhibitor of Apoptosis Protein/biosynthesis , Animals , Apoptosis Regulatory Proteins/antagonists & inhibitors , Apoptosis Regulatory Proteins/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm , Humans , Male , Mice , Mice, Nude , NF-kappa B/metabolism , NIH 3T3 Cells , RNA Interference , Repressor Proteins/antagonists & inhibitors , Repressor Proteins/genetics , Transcription Factors/antagonists & inhibitors , Transcription Factors/genetics , Transcriptional Activation , Up-Regulation , X-Linked Inhibitor of Apoptosis Protein/geneticsABSTRACT
Raji cells, a CR2-positive Burkitt lymphoma cell line, incubated in normal human serum, activate C3 and fix C3-derived fragments. The presence of these molecules on the cell surface does not affect subsequent Epstein-Barr virus (EBV) binding but it prevents superinfection. On the other hand, EBV superinfection is enhanced if Raji cells were incubated with heat-inactivated serum whose C3 fragments may bind only through receptor-binding sites. These results indicate that the region on cell surface offering the covalent site to C3 fragments would be essential for EBV superinfection. Incubation of Raji cells for 1 min with EBV results in the phosphorylation of CR2 and of a high-molecular-weight protein followed by their dephosphorylation, completed already after 20 min. This finding ascribes to EBV a prompt action through its receptor, different from that of other compounds causing a prolonged CR2 phosphorylation. Our data suggest that at least two binding sites are required for EBV superinfection of Raji cells or that specific patterns of CR2 phosphorylation may modulate Raji superinfection by EBV.
