Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.

Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks.

circRNAs as Epigenetic Regulators of Integrity in Blood-Brain Barrier Architecture: Mechanisms and Therapeutic Strategies in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease leading to progressive demyelination and neuronal loss, with extensive neurological symptoms. As one of the most widespread neurodegenerative disorders, with an age onset of about 30 years, it turns out to be a socio-health and economic issue, thus necessitating therapeutic interventions currently unavailable. Loss of integrity in the blood-brain barrier (BBB) is one of the distinct MS hallmarks.

Epigenetic role of LINE-1 methylation and key genes in pregnancy maintenance.

Spontaneous abortion is a pregnancy complication characterized by complex and multifactorial etiology. About 5% of childbearing women are globally affected by early pregnancy loss (EPL) and most of them experience recurrence (RPL). Epigenetic mechanisms and controlled inflammation are crucial for pregnancy maintenance and genetic predispositions may increase the risk affecting the maternal-fetal crosstalk.

Anti-Inflammatory and Cortical Responses after Transcranial Direct Current Stimulation in Disorders of Consciousness: An Exploratory Study.

Disorders of consciousness (DoC) due to severe traumatic brain injury (TBI) are associated with severe disability and an alteration of cortical activation, angiogenesis, and inflammation, which are crucial elements for behavioural recovery. This exploratory study aimed to evaluate anti-inflammatory and cortical responses after transcranial direct current stimulation (tDCS) in traumatic prolonged disorders of consciousness. Ten minimally conscious state (MCS) patients underwent ten sessions of anodal tDCS (five sessions/week, two weeks, 40 min/session) on the primary motor cortex bilaterally.

Semen Cryopreservation to Expand Male Fertility in Cancer Patients: Intracase Evaluation of Semen Quality.

To preserve male fertility after diagnosis of any kind of cancer, a prompt assessment of the semen quality and an appropriate semen cryopreservation must be performed before radio-chemotherapy starts. The present work aims to evaluate the semen parameters at diagnosis of different cancer patients before cryopreservation and after thawing. Testicular tumors and lymphomas are among the most common cancers in younger patients, and while chemotherapy significantly increases patients' survival, it can epigenetically alter the semen fluid, resulting in temporary or permanent infertility.

LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).

Background: Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity.

Results: We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene.

miRNAs Epigenetic Tuning of Wall Remodeling in the Early Phase after Myocardial Infarction: A Novel Epidrug Approach.

Myocardial infarction (MI) is one of the leading causes of death in Western countries. An early diagnosis decreases subsequent severe complications such as wall remodeling or heart failure and improves treatments and interventions. Novel therapeutic targets have been recognized and, together with the development of direct and indirect epidrugs, the role of non-coding RNAs (ncRNAs) yields great expectancy.

Integrative toxicogenomics: Advancing precision medicine and toxicology through artificial intelligence and OMICs technology.

More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards personalized treatment. Additionally, the promotion of non-animal testing has fueled the computational toxicogenomics as a pivotal part of the next-gen risk assessment paradigm. Artificial Intelligence (AI) has the potential to provid new ways analyzing the patient data and making predictions about treatment outcomes or toxicity.

Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides.

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective.

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of , , , , , and genes.

Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types. We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations. A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up ( = 0.

The circular RNA landscape in multiple sclerosis: Disease-specific associated variants and exon methylation shape circular RNA expression profile.

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). Despite several efforts, the mechanisms regulating circRNAs expression are still largely unknown and the circRNA profile and regulation in MS-relevant cell models has not been completely investigated. In this work, we aimed at exploring the global landscape of circRNA expression in MS patients, also evaluating a possible correlation with their genetic and epigenetic background.

Micropatterned Neurovascular Interface to Mimic the Blood-Brain Barrier's Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model.

A hybrid blood-brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet-outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded.

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics).

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection.

TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake.

TNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation.

Sustainable Agriculture through Multidisciplinary Seed Nanopriming: Prospects of Opportunities and Challenges.

The global community decided in 2015 to improve people's lives by 2030 by setting 17 global goals for sustainable development. The second goal of this community was to end hunger. Plant seeds are an essential input in agriculture; however, during their developmental stages, seeds can be negatively affected by environmental stresses, which can adversely affect seed vigor, seedling establishment, and crop production.

Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors.

In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies. The purpose of the current study was to investigate the ability of ibrutinib plus the MDM2-inhibitor nutlin-3 to counteract the tumor microenvironment protective effect.

-Segregation of c.1171C>T Stop Codon (p.R391*) in Gene and c.1691G>A Transition (p.R506Q) in Gene and Selected GWAS Multilocus Approach in Inherited Thrombophilia.

Inherited thrombophilia (e.g., venous thromboembolism, VTE) is due to rare loss-of-function mutations in anticoagulant factors genes (i.

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting behavior and communication, presenting with extremely different clinical phenotypes and features. ASD etiology is composite and multifaceted with several causes and risk factors responsible for different individual disease pathophysiological processes and clinical phenotypes. From a genetic and epigenetic side, several candidate genes have been reported as potentially linked to ASD, which can be detected in about 10-25% of patients.

Baseline and overtime variations of soluble adhesion molecule plasma concentrations are associated with mobility recovery after rehabilitation in multiple sclerosis patients.

Rehabilitative exercise outcomes and plasma concentrations of soluble adhesion molecules (sEndoglin, sE-Selectin, sL-Selectin, sICAM-1, sNCAM, sNCAM-1, sVCAM-1, sPECAM-1, sVAP-1) were evaluated in 60 severely disabled progressive multiple sclerosis (MS) patients at 4-time points. Changes of sE-Selectin, sL-Selectin, and sPECAM-1 concentrations were observed over time, and their variations were significantly correlated with rehabilitative outcome variations. Baseline sVAP-1 concentrations were able to predict functional mobility recovery.

Rehabilitation Improves Mitochondrial Energetics in Progressive Multiple Sclerosis: The Significant Role of Robot-Assisted Gait Training and of the Personalized Intensity.

Abnormal levels of pyruvate and lactate were reported in multiple sclerosis (MS). We studied the response of markers of mitochondrial function to rehabilitation in relation to type, intensity and endurance performance in severely disabled MS patients. Forty-six progressive MS patients were randomized to receive 12 walking sessions of robot-assisted gait training (RAGT, = 23) or conventional overground therapy (CT, = 23).

Genetic Hypothesis and Pharmacogenetics Side of Renin-Angiotensin-System in COVID-19.

The importance of host genetics and demography in coronavirus disease 2019 (COVID-19) is a crucial aspect of infection, prognosis and associated case fatality rate. Individual genetic landscapes can contribute to understand Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) burden and can give information on how to fight virus spreading and the associated severe acute respiratory distress syndrome (ARDS). The spread and pathogenicity of the virus have become pandemic on specific geographic areas and ethnicities.

TRAIL treatment prevents renal morphological changes and TGF-β-induced mesenchymal transition associated with diabetic nephropathy.

Background: TNF-related apoptosis-inducing ligand (TRAIL) has attracted attention not only as an anti-cancer agent, but also as a potential treatment for diabetes. Animal studies have shown that TRAIL delivery ameliorated glucose control in type 1 and type 2 diabetes. It is currently unknown whether TRAIL positive effects are maintained in more severe forms of type 2 diabetes, and whether they include renoprotection.

Functional recovery in multiple sclerosis patients undergoing rehabilitation programs is associated with plasma levels of hemostasis inhibitors.

Background: Increasing evidence for contribution of hemostasis components in multiple sclerosis (MS) has been reported. Hemostasis protein inhibitors display key regulatory roles, extending to regulation of innate immune response and inflammation, and promotion of blood-brain barrier integrity. Whereas the effects on hemostasis of exercise and rehabilitation strategies have been extensively investigated, relationships between MS rehabilitation strategies and hemostasis have not been previously reported.