Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells

CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.

NEI 2022 Abstracts

The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.

Bioactive compounds in Layacha brown rice (Oryza sativa L.) improve immune responses in mice via activation of transcription factor Nrf2

Dysregulated or weak immunity is caused by ageing, chemo-radiotherapy, COVID-19, infections, steroids, pollutants and toxins. Bioactive foods are required for boosting immunity. In the present study, nine rice (Oryza sativa L.) varieties were selected from the repository of 23,250 Indian germplasm accessions. The immunomodulatory effects of these rice varieties were assessed in vitro and in vivo. Layacha-rice-methanolic-extract (Larimex) significantly enhanced innate (>20%) and adaptive (>10%) immune responses evinced from higher bacterial phagocytosis by macrophages, increased mitogen-induced T-cell proliferation (11%) and scavenged reactive oxygen species (ROS) (70–80%). Larimex activated transcription factor Nrf2 and its downstream genes Nqo1, Ho1 and Txnrd1 in immune cells. Larimex significantly improved immune responses (>20%) only in cells from wild type but not Nrf2 knock-out mice indicating its causal role in boosting immunity. Untargeted metabolomics of Layacha rice showed preponderance of metabolic pathways and bioactive compounds, which activate Nrf2 in mammalian cells. Layacha rice can be a suitable food for boosting immunity.

SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis.

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.

A Literature Review on the Antiviral Mechanism of Luteolin

Background: Viral infections pose some of the most serious human health concerns worldwide. The infections caused by several viruses, including coronavirus, hepatitis virus, and human immunodeficiency virus, are difficult to treat. Method(s): This review details the findings of a literature search performed on the antiviral properties of luteolin. The keywords engaged in the search are "virus" along with "luteolin." Results: Luteolin possesses antiviral properties, which is the basis for the current review. It is an important natural flavonoid with numerous important biological properties, including anti-inflammatory, immune regulatory, and antitumor effects, and is found in vegetables, fruits, and several medicinal plants. Recent studies have revealed that many traditional Chinese medicines that contain luteolin inhibit the replication of coronaviruses. Conclusion(s): Luteolin effectively inhibits the replication of coronavirus, influenza virus, enterovirus, rotavirus, herpes virus, and respiratory syncytial virus, among others. In particular, it prevents viral infection by improving the body's nonspecific immunity and antioxidation capacity and inhibiting many pathways related to virus infection and replication, such as MAPK, PI3K-AKT, TLR4/8, NF-kappaB, Nrf-2/hemeoxygenase-1, and others. It also regulates the expression of some receptors and factors, including hepatocyte nuclear factor 4alpha, p53, NLRP3, TNF-alpha, and interleukins, thereby interfering with the replication of viruses in cells. Luteolin also promotes the repair of damaged cells induced by proinflammatory factors by regulating the expression of inflammatory molecules. The overall effect of these processes is the reduction in viral replication and, consequently, the viral load. This review summarizes the antiviral effect of luteolin and the mechanism underlying this property.Copyright © The Author(s) 2023.

CO-SPROUT: A PILOT DOUBLE-BLINDED RANDOMISED CONTROL TRIAL of BROCCOLI SPROUT for PREGNANT WOMEN with COVID-19: STUDY PROTOCOL

Background: COVID-19 is caused by SARS-CoV-2 and has is responsible for over 619 million infections and over 6.5 million deaths globally since identification in 2019. Infection during pregnancy is associated with increased adversity including increased risks of admission to intensive care, increased ventilatory support, preeclampsia, preterm birth and maternal death. Vaccination remains the best protection against severe disease. The majority of trials for novel or repurposed COVID-19 therapies including mRNA vaccinations have excluded pregnant or lactating women despite being an at-risk population. Broccoli sprout extract contains a naturally occurring phytonutrient sulforaphane which upregulates the Nrf2 transcription factor resulting in expression of antioxidant proteins, anti-inflammatory effects and has demonstrated anti-viral effects in-vitro . Severe COVID-19 results in excessive cytokine production resulting in a proinflammatory state with significant oxidative stress and multi-organ dysfunction with evidence of placental abnormalities in almost half of infected mothers. Method(s): CO-Sprout is a pilot, double blinded, placebo controlled randomised trial that is recruiting pregnant women ( n = 60) between 20 and 36 weeks completed gestation with COVID-19 diagnosed within 5 days. Participants are randomised to either broccoli sprout capsules (containing 21 mg sulforaphane) or identical placebo (microcrystalline cellulose) twice daily for 14 days. The primary outcome will be duration (days) of COVID-19 related symptoms and other exploratory outcomes including unplanned hospital admissions, birth outcomes, inflammatory markers, microbiome and placental changes. Patients are recruited through maternity departments at Monash Health and Jessie McPherson Private Hospital. Result(s): Trial in progress. Conclusion(s): Trial results to be published after trial completion.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

The possibilities of using the effects of ozone therapy in neurology

OBJECTIVES: The beneficial effects of ozone therapy consist mainly of the promotion of blood circulation: peripheral and central ischemia, immunomodulatory effect, energy boost, regenerative and reparative properties, and correction of chronic oxidative stress. Ozone therapy increases interest in new neuroprotective strategies that may represent therapeutic targets for minimizing the effects of oxidative stress. METHOD(S): The overview examines the latest literature in neurological pathologies treated with ozone therapy as well as our own experience with ozone therapy. The effectiveness of treatments is connected to the ability of ozone therapy to reactivate the antioxidant system to address oxidative stress for chronic neurodegenerative diseases, strokes, and other pathologies. Application options include large and small autohemotherapy, intramuscular application, intra-articular, intradiscal, paravertebral and epidural, non-invasive rectal, transdermal, mucosal, or ozonated oils and ointments. The combination of different types of ozone therapy stimulates the benefits of the effects of ozone. RESULT(S): Clinical studies on O2-O3 therapy have been shown to be efficient in the treatment of neurological degenerative disorders, multiple sclerosis, cardiovascular, peripheral vascular, orthopedic, gastrointestinal and genitourinary pathologies, fibromyalgia, skin diseases/wound healing, diabetes/ulcers, infectious diseases, and lung diseases, including the pandemic disease caused by the COVID-19 coronavirus. CONCLUSION(S): Ozone therapy is a relatively fast administration of ozone gas. When the correct dose is administered, no side effects occur. Further clinical and experimental studies will be needed to determine the optimal administration schedule and to evaluate the combination of ozone therapy with other therapies to increase the effectiveness of treatment.Copyright © 2021 Neuroendocrinology Letters.

NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children.

Respiratory diseases caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV) are frequent causes of the hospitalization of children; nonetheless, RSV is responsible for the most severe and life-threatening illnesses. Viral infection triggers an inflammatory response, activating interferon (IFN)-mediated responses, including IFN-stimulated genes (ISG) expression with antiviral and immunomodulatory activities. In parallel, the reactive oxygen species (ROS) production activates nuclear factor erythroid 2-related factor 2 (NRF2), whose antioxidant activity can reduce inflammation by interacting with the NF-kB pathway and the IFN response. To clarify how the interplay of IFN and NRF2 may impact on clinical severity, we enrolled children hospitalized for bronchiolitis and pneumonia, and measured gene expression of type-I and III IFNs, of several ISGs, of NRF2 and antioxidant-related genes, i.e., glucose-6-phosphate dehydrogenase (G6PD), heme oxygenase 1 (HO1), and NAD(P)H dehydrogenase [Quinone] 1 (NQO1) in RSV- (RSV-A N = 33 and RSV-B N = 30) and HRV (N = 22)-positive respiratory samples. NRF2 and HO1 expression is significantly elevated in children with HRV infection compared to RSV (p = 0.012 and p = 0.007, respectively), whereas ISG15 and ISG56 expression is higher in RSV-infected children (p = 0.016 and p = 0.049, respectively). Children admitted to a pediatric intensive care unit (PICU) had reduced NRF2 expression (p = 0.002). These data suggest, for the first time, that lower activation of the NRF2 antioxidant response in RSV-infected infants may contribute to bronchiolitis severity.

Functional Role of Natural Antioxidants in Controlling Oxidative Stress Associated with SARS-CoV-2 Infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pathogenic coronavirus that emerged in late 2019, resulting in coronavirus disease (COVID-19). COVID-19 can be potentially fatal among a certain group of patients. Older age and underlying medical illness are the major risk factors for COVID-19-related fatal respiratory dysfunction. The reason for the pathogenicity of COVID-19 in the older age group remains unclear. Factors, such as coagulopathy, cytokine storm, metabolic disrup-tion, and impaired T cell function, may worsen the symptoms of the disease. Recent literature has indicat-ed that viral infections are particularly associated with a high degree of oxidative stress and an imbalance of antioxidant response. Although pharmacological management has taken its place in reducing the severity of COVID-19, the antioxidants can serve as an adjunct therapy to protect an individual from oxidative damage triggered by SARS-CoV-2 infection. In general, antioxidant enzymes counteract free radicals and prevent their formation. The exact functional role of antioxidant supplements in reducing disease symptoms of SARS-CoV-2 infection remains mostly unknown. In this review, the functional role of natural antioxidants in SARS-CoV-2 infection management is discussed in brief.Copyright © 2022 Bentham Science Publishers.

Impact of the NRF2 activator, stabilised synthetic sulforaphane, on systemic inflammation in COVID19: results from the STAR-COVID19 trial

Introduction: Dysregulated immune responses are implicated in the pathogenesis of severe COVID19 and may be modulated by the transcription factor Nrf2. Hypothesis: Treatment with stabilised, synthetic sulforaphane (S-SFN)-an Nrf2 inducer-improves clinical status in hospitalised patients with suspected COVID19 pneumonia by curbing the inflammatory response. Method(s): Double-blind RCT of S-SFN (300mg, once daily, 14 days;EudraCT 2020-003486-19) in patients hospitalised with confirmed or suspected COVID19, in Dundee, UK. The primary outcome was the 7 point WHO Clinical Status scale at day 15. Blood samples were taken on days 1, 8 and 15 for measurement of 45 serum cytokines using the Olink Target48 panel. Key neutrophil functions were assessed including migration, phagocytosis and bacterial killing. Result(s): 133 participants were randomized (placebo n=68, S-SFN n=65) from Nov 2020 to May 2021. S-SFN treatment did not improve clinical status at day 15 (adjusted OR 0.87 95%CI 0.41-1.83). In serum, Nrf2 target TGFalpha was significantly increased at day 15 in those receiving S-SFN treatment compared with placebo (p=0.004;linear mixed effects model). Other targets implicated in cytokine storm, including IL6, IL1beta and TNFalpha, were unchanged. Patients receiving Tocilizumab (n=20) were excluded from exploratory analyses due to a strong impact upon IL6 levels, leading to significant increases at day 8 across the study population (p=0.015). S-SFN treatment did not significantly affect neutrophil function. Conclusion(s): S-SFN treatment modulated select Nrf2 targets but did not modulate key cytokines. Further analyses to delineate drug activity are ongoing.

Differentially expressed FOXO1, NFE2L2 and NFKB1 mRNAs are associated with differentially regulated corona- and influenza viral receptor genes and Toll-like receptor pathway genes in human bronchial epithelial cells under hyperbaric oxygen exposure

As hyperbaric oxygen (HBO) has been shown to mitigate the COVID-19 symptoms, we were interested in studying whether HBO exposure affects expression of viral entry genes and innate immune genes in the air-liquid interface (ALI)-cultured human bronchial epithelial cells (HBECs) derived from normal individuals (NHBECs) and age-matched COPD patients (DHBECs), which were cultured under normoxia or daily exposure of 40-min hyperbaric oxygen (HBO) with 100% O2 at 2.5 ATA for 28 days in total. We found for the first time that HBO exposure differentially regulated mucociliary differentiation of HBECs by respectively decreasing and increasing expression of CGRP, MUC5AC, FOXJ1, NOTCH3 and HEYL in NHBECs and DHBECs, and respectively decreased and increased FOXO1 expression whereas increased and decreased NFE2L2 and NFKB1 expression in NHBECs and DHBECs, in association with respectively decreased and increased expression the SARS-CoV-2 entry genes ACE2 and 2 TMPRSS2 and the tight junction protein genes TJP1 and TJP2, and in association with respectively increased and decreased expression of the cell growth and inflammatory transcription factors SRF, c-FOS and TP63, as well as the TLR pathway genes TLR3, AKT1, IL-1B, IL-5, IL-6, IL-33, IRAK4 and NFKBIA in NHBECs and DHBECs. (Figure Presented).

Stabilised, synthetic sulforaphane in hospitalized patients with suspected COVID-19 pneumonia: a double-blind, placebo-controlled RCT

Introduction: The transcription factor Nrf2 downregulates key inflammatory cytokines in COVID-19 (IL-6, IL-1b, COX-2 and TNF-a). We investigated the efficacy of S-SFN (stabilised sulforaphane, activator of Nrf2) to improve clinical outcomes in patients hospitalized with suspected COVID-19. Method(s): Randomized, double-blind, placebo-controlled trial, patients hospitalised with suspected or confirmed COVID-19, radiological pneumonia and a CURB65 score of >= 1 were randomized 1:1 to once-daily S-SFN 300mg or placebo for 14 days. The primary outcome was the 7-point WHO Clinical Status (CS) scale at day 15. Key secondary outcomes included time to clinical improvement, national early warning score (NEWS), oxygen and ventilation use, and mortality. Result(s): The trial was terminated due to futility after 133 patients had been enrolled (S-SFN, n=65 and placebo, n=68). 103 had PCR confirmed COVID-19 infection. S-SFN treatment was not associated with improved CS at day 15 (OR 0.87 95%CI (0.41-1.83, p=0.712). There was no difference in time to clinical improvement (HR 1.02 (0.70- 1.49)). S-SFN was not associated with a reduced length of hospital stay (6.2days vs 7.4days (S-SFN)). There were 26 deaths during the 29-day follow-up, 11 (16.2%) and 15 (23.1%) patients died in the placebo and S-SFN treated groups respectively (HR 1.45 (0.67-3.16)). There were no differences between treatment groups with respect to oxygen or ventilation free days. Adverse events were reported in 44.1% of placebo treated and 64.6% of S-SFN treated patients. Conclusion(s): S-SFN treatment did not improve day 15 clinical status in hospitalized patients with suspected or confirmed COVID-19 infection.

SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection.

Several viruses have been shown to modulate the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2), the master regulator of redox homeostasis. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, also seems to disrupt the balance between oxidants and antioxidants, which likely contributes to lung damage. Using in vitro and in vivo models of infection, we investigated how SARS-CoV-2 modulates the transcription factor NRF2 and its dependent genes, as well as the role of NRF2 during SARS-CoV-2 infection. We found that SARS-CoV-2 infection downregulates NRF2 protein levels and NRF2-dependent gene expression in human airway epithelial cells and in lungs of BALB/c mice. Reductions in cellular levels of NRF2 seem to be independent of proteasomal degradation and the interferon/promyelocytic leukemia (IFN/PML) pathway. Furthermore, lack of the Nrf2 gene in SARS-CoV-2-infected mice exacerbates clinical disease, increases lung inflammation, and is associated with a trend toward increased lung viral titers, indicating that NRF2 has a protective role during this viral infection. In summary, our results suggest that SARS-CoV-2 infection alters the cellular redox balance by downregulating NRF2 and its dependent genes, which exacerbates lung inflammation and disease, therefore, suggesting that the activation of NRF2 could be explored as therapeutic approach during SARS-CoV-2 infection. IMPORTANCE The antioxidant defense system plays a major function in protecting the organism against oxidative damage caused by free radicals. COVID-19 patients often present with biochemical characteristics of uncontrolled pro-oxidative responses in the respiratory tract. We show herein that SARS-CoV-2 variants, including Omicron, are potent inhibitors of cellular and lung nuclear factor erythroid 2-related factor 2 (NRF2), the master transcription factor that controls the expression of antioxidant and cytoprotective enzymes. Moreover, we show that mice lacking the Nrf2 gene show increased clinical signs of disease and lung pathology when infected with a mouse-adapted strain of SARS-CoV-2. Overall, this study provides a mechanistic explanation for the observed unbalanced pro-oxidative response in SARS-CoV-2 infections and suggests that therapeutic strategies for COVID-19 may consider the use of pharmacologic agents that are known to boost the expression levels of cellular NRF2.

Does atmospheric dimethyldiselenide play a role in reducing COVID-19 mortality?

Environmental selenium (Se) distribution in the US is uneven, yet US residents appear to have a relatively narrow range of serum Se concentrations, according to the NHANES III survey data; this is probably due to the modern food-distribution system. In the US, Se concentration in alfalfa leaves has been used as a proxy for regional Se exposure (low, medium or high, corresponding to ≤ 0.05, 0.06-0.10 and ≥ 0.11 ppm respectively). Se in plants, soil, water, and bacteria can be transformed into volatile dimethyldiselenide, which can be inhaled and excreted via the lung. Hence, pulmonary Se exposure may be different in states with different atmospheric Se levels. We found a significantly higher death rate from COVID-19 in low-Se states than in medium-Se or high-Se states, though the case densities of these states were not significantly different. Because inhaled dimethyldiselenide is a potent inducer of nuclear-factor erythroid 2 p45-related factor 2 (Nrf2), exposure to higher atmospheric dimethyldiselenide may increase Nrf2-dependent antioxidant defences, reducing the activation of NFκB by SARS-CoV-2 in the lung, thereby decreasing cytokine activation and COVID-19 severity. Atmospheric dimethyldiselenide may thereby play a role in COVID-19 mortality, although the extent of its involvement is unclear. Synopsis Loss of pulmonary dimethydiselenide via exhalation may help explain a significantly higher death rate from COVID-19 in states with low environmental (atmospheric) Se concentrations.

Transcription factor Nrf2 as a potential therapeutic target for COVID-19.

The coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2). Critically ill patients with SARS-COV-2 infection frequently exhibit signs of high oxidative stress and systemic inflammation, which accounts for most of the mortality. Antiviral strategies to inhibit the pathogenic consequences of COVID-19 are urgently required. The nuclear factor erythroid 2-related transcription factor (Nrf2) is a transcription factor that is involved in antioxidant and anti-inflammatory defense in several tissues and cells. This review tries to present an overview of the role of Nrf2 in the treatment of COVID-19.

Is Nuclear Factor Erythroid 2-Related Factor 2 a Target for the Intervention of Cytokine Storms?

The term "cytokine storm" describes an acute pathophysiologic state of the immune system characterized by a burst of cytokine release, systemic inflammatory response, and multiple organ failure, which are crucial determinants of many disease outcomes. In light of the complexity of cytokine storms, specific strategies are needed to prevent and alleviate their occurrence and deterioration. Nuclear factor erythroid 2-related factor 2 (NRF2) is a CNC-basic region-leucine zipper protein that serves as a master transcription factor in maintaining cellular redox homeostasis by orchestrating the expression of many antioxidant and phase II detoxification enzymes. Given that inflammatory response is intertwined with oxidative stress, it is reasonable to assume that NRF2 activation limits inflammation and thus cytokine storms. As NRF2 can mitigate inflammation at many levels, it has emerged as a potential target to prevent and treat cytokine storms. In this review, we summarized the cytokine storms caused by different etiologies and the rationale of interventions, focusing mainly on NRF2 as a potential therapeutic target.

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives.

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.