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1.
BMC Complement Med Ther ; 21(1): 141, 2021 May 12.
Article in English | MEDLINE | ID: covidwho-1388756

ABSTRACT

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.


Subject(s)
COVID-19/drug therapy , Echinacea , Immunologic Factors/pharmacology , Monocytes/drug effects , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Gene Expression , Humans , Immunity, Innate/drug effects , Immunologic Factors/therapeutic use , Interferons/drug effects , Phytotherapy , Plant Extracts/therapeutic use
2.
Viruses ; 12(12)2020 12 01.
Article in English | MEDLINE | ID: covidwho-954243

ABSTRACT

The emergence of SARS-CoV-2 in 2019 has caused a major health and economic crisis around the globe. Gaining knowledge about its attributes and interactions with human host cells is crucial. Non-coding RNAs (ncRNAs) are involved in the host cells' innate antiviral immune response. In RNA interference, microRNAs (miRNAs) may bind to complementary sequences of the viral RNA strand, forming an miRNA-induced silencing complex, which destroys the viral RNA, thereby inhibiting viral protein expression. There are several targets for human miRNAs on SARS-CoV-2's RNA, most of which are in the 5' and 3' untranslated regions. Mutations of the viral genome causing the creation or loss of miRNA binding sites may have crucial effects on SARS-CoV-2 pathogenicity. In addition to mediating immunity, the ncRNA landscape of host cells further influences their susceptibility to virus infection, as certain miRNAs are essential in the regulation of cellular receptors that are necessary for virus invasion. Conversely, virus infection also changes the host ncRNA expression patterns, possibly augmenting conditions for viral replication and dissemination. Hence, ncRNAs typically upregulated in SARS-CoV-2 infection could be useful biomarkers for disease progression and severity. Understanding these mechanisms could provide further insight into the pathogenesis and possible treatment options against COVID-19.


Subject(s)
Coronavirus Infections/immunology , Coronavirus Infections/virology , Coronavirus/pathogenicity , RNA, Untranslated/metabolism , Animals , Antiviral Agents/metabolism , Antiviral Agents/therapeutic use , Coronavirus/genetics , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Humans , Immune Evasion/genetics , Mutation , RNA Interference , RNA, Untranslated/genetics , RNA, Untranslated/therapeutic use , RNA, Viral/genetics
3.
Ann Med Psychol (Paris) ; 178(7): 738-742, 2020 Sep.
Article in French | MEDLINE | ID: covidwho-792316

ABSTRACT

To deal with the Covid 19 pandemic, health protection measures require changes to our clinical practices. Faced up with the unprecedented nature of this situation, the liberal psychotherapist is led to rethink some aspects of the framework of his practice in order to preserve the thread of the transferential relationship. The authors develop a clinical reflection on the clinical setting in a pandemic period by exploring in particular the dynamics of telephone sessions. For telephone interviews, the question of the sound envelope is central, in particular regarding the psychic function of silence. We choose to illustrate our point with short vignettes than by relying on long-term clinical cases, more likely to represent the variety of new clinical situations encountered and the questions that accompany them. This article introduces his point by recounting the plague epidemic in ancient Greece to show the impact of the environment on humans and its collective fantasy implications. Being faced up with death, contamination, the invisible enemy brings out a palpable concern. It is indeed quite remarkable that these same reactions and concerns in front of death caused by the pandemic match whith what is related by Thucydides who survived the plague, which affected Athens during the Peloponnesian War. In another context, Winnicott highlights the place and importance of the therapeutic environment. It is both a question of adjusting the framework according to the context while maintaining certain intangible aspects representing the permanence of the link and its framework. A framework cannot exist without being kept, which is equivalent to thinking of the framework above all as an internal framework, questioning the clinician about what he values and what he makes sense in his practice. In the current context, these questions arise from the perspective of a certain flexibility, depending on the human context (child, adolescent, consultations, etc.) or external context (crisis linked to a virus, etc.) showing that it is more than never question of exercising on a case-by-case basis, taking into account changes in the environment. The initial observation during this period of confinement concerns the fact that some patients contact a therapist for the first time by telephone and wish to initiate psychotherapy (during this period) when they explain that such an initiative was not possible. despite the difficulties already encountered in the past. But there is also the opposite case: patients who have no intention of continuing the work already started during this time. Thus, faced up with the injunction of confinement, they show themselves in the psychic impossibility of following the treatment by other means such as, for example, telephone sessions. In this perspective, the silence on the phone takes on a different tone; silence reveals itself to be a source of greater anxiety than in presence: the presence of bodies, of its movements perceptible as imperceptible, of a gesture that carries or accompanies the senses, breathing, the visual context of the office and of its "decor", represent as many essential elements in the usual capacity of the frame; in the absence of these basic sensory elements, silence can be experienced as a void, or even a gap in the bond, opening Pandora's box of paranoid fantasies acting unconsciously. If silence is representative of the whole framework, it promotes in this context the partialization of the clinician's body reduced to one ear and not to a whole body. Here, it is the change of framework that mobilizes the difference, established by Mr. Klein, between the partial and total object; this circumstance neo-framework could therefore call for regressive movements, undoing the silence of its symbolic function when the bodies are present.

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