Fractional flow reserve (FFR) and index of microcirculatory resistance (IMR) relationship in patients with chronic or stabilized acute coronary syndromes.

Aims: To investigate the influence of index of microcirculatory resistance (IMR) on fractional flow reserve (FFR) and adenosine-induced hyperemia (ΔPd/Pa-FFR) in patients with chronic (CCS) or stabilized acute coronary syndromes (ACS), utilizing various IMR threshold values.

Methods: Data were extracted from two ongoing Italian registries involving patients with CCS or stabilized ACS who underwent a #FullPhysiology approach [Pd/Pa, FFR, IMR, coronary flow reserve (CFR)] by bolus thermodilution technique in the left anterior descending artery. Correlations between IMR and both FFR and ΔPd/Pa-FFR were analyzed both globally and within three IMR-defined groups: Group 1 (IMR <25), Group 2 (25 ≤ IMR <40), and Group 3 (IMR ≥40).

Detailed mechanism of a DNA/RNA nucleobase substituting bridging ligand in diruthenium(II,III) and dirhodium(II,II) tetraacetato paddlewheel complexes: protonation of the leaving acetate is crucial.

Paddlewheel complexes of bimetallic scaffolds are emerging metallic agents in the bioinorganic chemistry landscape. In the most commonly employed construct, these complexes are decorated by the carboxylate moiety, prompting their possible deployment to target either protein or nucleic acid targets. In this study, density functional investigation was performed to assess viable mechanistic routes for the substitution of one acetate ligand with one chelating purine, adenine or guanine, in diruthenium and dirhodium tetraacetate paddlewheel complexes.

The impact of new onset diabetes on cardiovascular risks in orthotopic liver transplant recipients: findings from the COLT study.

Background: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT).

Clinical and functional assessment of SARS-CoV-2 sequelae among young marines - a panel study.

Background: Long-term SARS-CoV-2 adverse health outcomes are of significant concern, especially among young adults with the potential for the greatest long-term morbidity. We sought to assess and characterize these outcomes in a cohort of Marines.

Methods: We used a cohort of US Marines from a previous longitudinal, prospective observational study of acute SARS-CoV-2, most of whom were enrolled prior to infection.

A recombinant fragment antigen-binding (Fab) of trastuzumab displays low cytotoxic profile in adult human cardiomyocytes: first evidence and the key implication of FcγRIIA receptor.

Fragment crystallizable gamma receptors (FcγRs) mediate various cellular responses with significant cardiovascular implications. They contribute to the anticancer activity of trastuzumab (TRZ), a recombinant humanized monoclonal antibody that interferes with human epidermal growth factor receptor 2 (HER2), thereby blocking its physiological function in cardiac cells. This is responsible for cardiac complications that hamper TRZ clinical application.

Mechanisms in the Synthesis of S-Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study.

The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η-keto-S-η-5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J.

Inflammaging: The Next Challenge-Exploring the Role of Gut Microbiota, Environmental Factors, and Sex Differences.

The term 'inflammaging' has been coined to describe the chronic state of inflammation derived from ongoing cycles of tissue damage and the subsequent immune responses. This inflammatory status contributes to the decline of organs and physiological functions, accelerates the aging process, and increases the risk of age-related illnesses and death. During aging, the gut microbiota (GM) undergoes significant changes, including a decreased diversity of species, a decline in beneficial bacteria, and a rise in proinflammatory ones, resulting in persistent low-grade inflammation.

Non-Medical Applications of Inorganic Medicines. A Switch Based on Mechanistic Knowledge.

Metals have been used in medicine for centuries. However, it was not until much later that the effects of inorganic drugs could be rationalized from a mechanistic point of view. Today, thanks to the technologies available, this approach has been functionally developed and implemented.

Dimolybdenum (II,II) paddlewheel complexes bearing non-steroidal anti-inflammatory drug ligands: Insights into the chemico-physical profile and first biological assessment.

Multinuclear complexes are metal compounds featured by adjacent bound metal centers that can lead to unconventional reactivity. Some ML-type paddlewheel dinuclear complexes with monoanionic bridging ligands feature promising properties, including therapeutic ones. Molybdenum has been studied for the formation of multiple-bonded M compounds due to their unique scaffold, redox, and spectroscopic properties as well as for applications in several fields including catalysis and biology.

Hepatitis C Virus (HCV) Infection: Pathogenesis, Oral Manifestations, and the Role of Direct-Acting Antiviral Therapy: A Narrative Review.

Hepatitis C virus (HCV) infection is a global health concern with significant systemic implications, including a range of oral manifestations. This review aims to provide a comprehensive overview of the oral and dental pathologies related to HCV, the etiopathogenetic mechanisms linking such conditions to HCV and the impact of direct-acting antiviral (DAA) therapy. Common oral manifestations of HCV include oral lichen planus (OLP), periodontal disease, and xerostomia.

The binding of diruthenium (II,III) and dirhodium (II,II) paddlewheel complexes at DNA/RNA nucleobases: Computational evidences of an appreciable selectivity toward the AU base pairs.

Multiple medicinal strategies involve modifications of the structure of DNA or RNA, which disrupt their correct functioning. Metal complexes with medicinal effects, also known as metallodrugs, are among the agents intended specifically for the attack onto nucleosides. The diruthenium (II,III) and dirhodium (II,II) paddlewheel complexes constitute promising dual acting drugs due to their ability to release the therapeutically active bridging ligands upon their substitution by endogenous ligands.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

Background And Aims: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility.

Methods: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model.

Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.

In recent years, there has been a growing interest in the concept of the "gut-brain axis". In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of "neuroinflammation".

Clinical and Immunological Impact of Ocrelizumab Extended Interval Dosing in Multiple Sclerosis: A Single-Center, Real-World Experience.

Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs.

Diruthenium Paddlewheel Complexes Attacking Proteins: Axial versus Equatorial Coordination.

Metallodrugs are an important group of medicinal agents used for the treatment of various diseases ranging from cancers to viral, bacterial, and parasitic diseases. Their distinctive features include the availability of a metal centre, redox activity, as well as the ability to multitarget. Diruthenium paddlewheel complexes are an intensely developing group of metal scaffolds, which can securely coordinate bidentate xenobiotics and transport them to target tissues, releasing them by means of substitution reactions with biomolecular nucleophiles.

QFR for the Revascularization of Nonculprit Vessels in MI Patients: Insights From the FIRE Trial.

Background: The role of quantitative flow ratio (QFR) in the treatment of nonculprit vessels of patients with myocardial infarction (MI) is a topic of ongoing discussion.

Objectives: This study aimed to investigate the predictive capability of QFR for adverse events and its noninferiority compared to wire-based functional assessment in nonculprit vessels of MI patients.

Methods: The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial randomized 1,445 older MI patients to culprit-only (n = 725) or physiology-guided complete revascularization (n = 720).

Unveiling the mechanism of activation of the Te(IV) prodrug AS101. New chemical insights towards a better understanding of its medicinal properties.

AS101 (Ammonium trichloro (dioxoethylene-O,O') tellurate) is an important hypervalent Te-based prodrug. Recently, we started a systematic investigation on AS101 with the aim to correlate its promising biological effects as a potent immunomodulator drug with multiple medicinal applications and its specific chemical properties. To date, a substantial agreement on the rapid conversion of the initial AS101 species into the corresponding TeOCl anion does exist, and this latter species is reputed as the pharmacologically active one.

The redox-active defensive Selenoprotein T as a novel stress sensor protein playing a key role in the pathophysiology of heart failure.

Maladaptive cardiac hypertrophy contributes to the development of heart failure (HF). The oxidoreductase Selenoprotein T (SELENOT) emerged as a key regulator during rat cardiogenesis and acute cardiac protection. However, its action in chronic settings of cardiac dysfunction is not understood.

Mechanism of Action of Antitumor Au(I) N-Heterocyclic Carbene Complexes: A Computational Insight on the Targeting of TrxR Selenocysteine.

The targeting of human thioredoxin reductase is widely recognized to be crucially involved in the anticancer properties of several metallodrugs, including Au(I) complexes. In this study, the mechanism of reaction between a set of five N-heterocyclic carbene Au(I) complexes and models of the active Sec residue in human thioredoxin reductase was investigated by means of density functional theory approaches. The study was specifically addressed to the kinetics and thermodynamics of the tiled process by aiming at elucidating and explaining the differential inhibitory potency in this set of analogous Au(I) bis-carbene complexes.

Impact of pre-admission physical activity on benefits of physiology-guided complete revascularization in older patients with myocardial infarction: insights from the FIRE trial.

Aims: The present analysis from the Functional Assessment in Elderly Myocardial Infarction Patients with Multivessel Disease (FIRE) trial aims to explore the significance of pre-admission physical activity and assess whether the benefits of physiology-guided complete revascularization apply consistently to sedentary and active older patients.

Methods And Results: Patients aged 75 years or more with myocardial infarction (MI) and multivessel disease were randomized to receive physiology-guided complete revascularization or culprit-only strategy. The primary outcome was a composite of death, MI, stroke, or any revascularization within a year.