Biological Effect of Licochalcone C on the Regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO Signaling Pathways in H9c2 Cells in Response to LPS Stimulation

Polyphenols compounds are a group molecules present in many plants. They have antioxidant properties and can also be helpful in the management of sepsis. Licochalcone C (LicoC), a constituent of Glycyrrhiza glabra, has various biological and pharmacological properties. In saying this, the effect of LicoC on the inflammatory response that characterizes septic myocardial dysfunction is poorly understood. The aim of this study was to determine whether LicoC exhibits anti-inflammatory properties on H9c2 cells that are stimulated with lipopolysaccharide. Our results have shown that LicoC treatment represses nuclear factor-κB (NF-κB) translocation and several downstream molecules, such as inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, LicoC has upregulated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signaling pathway. Finally, 2-(4-Morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), a specific PI3K inhibitor, blocked the protective effects of LicoC. These findings indicate that LicoC plays a pivotal role in cardiac dysfunction in sepsis-induced inflammation.The Italian Ministry for University and Research is acknowledged for financial support

Hydroxytyrosol Reduces Foam Cell Formation and Endothelial Inflammation Regulating the PPARγ/LXRα/ABCA1 Pathway.

Cholesterol accumulation in macrophages leads to the formation of foam cells and increases the risk of developing atherosclerosis. We have verified whether hydroxytyrosol (HT), a phenolic compound with anti-inflammatory and antioxidant properties, can reduce the cholesterol build up in THP-1 macrophage-derived foam cells. We have also investigated the potential mechanisms. Oil Red O staining and high-performance liquid chromatography (HPLC) assays were utilized to detect cellular lipid accumulation and cholesterol content, respectively, in THP-1 macrophages foam cells treated with HT. The impact of HT on cholesterol metabolism-related molecules (SR-A1, CD36, LOX-1, ABCA1, ABCG1, PPARγ and LRX-α) in foam cells was assessed using real-time PCR (RT-qPCR) and Western blot analyses. Finally, the effect of HT on the adhesion of THP-1 monocytes to human vascular endothelial cells (HUVEC) was analyzed to study endothelial activation. We found that HT activates the PPARγ/LXRα pathway to upregulate ABCA1 expression, reducing cholesterol accumulation in foam cells. Moreover, HT significantly inhibited monocyte adhesion and reduced the levels of adhesion factors (ICAM-1 and VCAM-1) and pro-inflammatory factors (IL-6 and TNF-α) in LPS-induced endothelial cells. Taken together, our findings suggest that HT, with its ability to interfere with the import and export of cholesterol, could represent a new therapeutic strategy for the treatment of atherosclerotic disease

The effect of pharmacological treatment on ADMA in patients with heart failure.

Asymmetric dimethylarginine (ADMA) plays a crucial role in the arginine-nitric oxide (NO) pathway. NO plays an important role in controlling vascular tone and regulates the contractile properties of cardiac myocytes. The purpose of this study was to investigate the effect of pharmacological treatment on asymmetrical dimethylarginine (ADMA) plasma levels in patients with acute congestive heart failure (HF). Patients with symptomatic acute congestive HF (NYHA Class III-IV) and impaired left ventricular (LV) function (ejection fraction less than 40 percent) were included in the study. ADMA and SDMA concentrations were assessed before and after pharmacological treatment in 18 critically ill patients on the intensive care unit by high performance liquid chromatography. All patients received a complete pharmacological treatment (diuretics, digoxin, ACE-inhibitors or angiotensin receptor blockers, and nitroglicerin) for the treatment of acute congestive HF. ADMA plasma levels of critically ill patients were significantly higher after pharmacological treatment respect baseline values (pre-treatment). In critically ill patients with acute congestive HF acute renal impairment function and the modulation of NOS determine plasma ADMA/SDMA levels after therapy

Astaxanthin Treatment Reduced Oxidative Induced Pro-Inflammatory Cytokines Secretion in U937: SHP-1 as a Novel Biological Target

It has been suggested that oxidative stress activates various intracellular signaling pathways leading to secretion of a variety of pro-inflammatory cytokines and chemokines. SHP-1 is a protein tyrosine phosphatase (PTP) which acts as a negative regulator of immune cytokine signaling. However, intracellular hydrogen peroxide (H2O2), generated endogenously upon stimulation and exogenously from environmental oxidants, has been known to be involved in the process of intracellular signaling through inhibiting various PTPs, including SHP-1. In this study, we investigated the potential role of astaxanthin, an antioxidant marine carotenoid, in re-establishing SHP-1 negative regulation on pro-inflammatory cytokines secretion in U-937 cell line stimulated with oxidative stimulus. ELISA measurement suggested that ASTA treatment (10 µM) reduced pro-inflammatory cytokines secretion (IL-1β, IL-6 and TNF-α) induced through H2O2, (100 µM). Furthermore, this property is elicited by restoration of basal SHP-1 protein expression level and reduced NF-κB (p65) nuclear expression, as showed by western blotting experiments

Loss of Bone Mineral Density Associated with Age in Male Rats Fed on Sunflower Oil Is Avoided by Virgin Olive Oil Intake or Coenzyme Q Supplementation

The role of dietary fat unsaturation and the supplementation of coenzyme Q have been evaluated in relation to bone health. Male Wistar rats were maintained for 6 or 24 months on two diets varying in the fat source, namely virgin olive oil, rich in monounsaturated fatty acids, or sunflower oil, rich in n-6 polyunsaturated fatty acids. Both dietary fats were supplemented or not with coenzyme Q10 (CoQ10). Bone mineral density (BMD) was evaluated in the femur. Serum levels of osteocalcin, osteopontin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), adrenocorticotropin (ACTH) and parathyroid hormone (PTH), as well as urinary F2-isoprostanes were measured. Aged animals fed on virgin olive oil showed higher BMD than those fed on sunflower oil. In addition, CoQ10 prevented the age-related decline in BMD in animals fed on sunflower oil. Urinary F2-isoprostanes analysis showed that sunflower oil led to the highest oxidative status in old animals, which was avoided by supplementation with CoQ10. In conclusion, lifelong feeding on virgin olive oil or the supplementation of sunflower oil on CoQ10 prevented, at least in part mediated by a low oxidative stress status, the age-related decrease in BMD found in sunflower oil fed animals.This work was supported by the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832)

Marine Carotenoids and Cardiovascular Risk Markers

Marine carotenoids are important bioactive compounds with physiological activities related to prevention of degenerative diseases found principally in plants, with potential antioxidant biological properties deriving from their chemical structure and interaction with biological membranes. They are substances with very special and remarkable properties that no other groups of substances possess and that form the basis of their many, varied functions and actions in all kinds of living organisms. The potential beneficial effects of marine carotenoids have been studied particularly in astaxanthin and fucoxanthin as they are the major marine carotenoids. Both these two carotenoids show strong antioxidant activity attributed to quenching singlet oxygen and scavenging free radicals. The potential role of these carotenoids as dietary anti-oxidants has been suggested to be one of the main mechanisms for their preventive effects against cancer and inflammatory diseases. The aim of this short review is to examine the published studies concerning the use of the two marine carotenoids, astaxanthin and fucoxanthin, in the prevention of cardiovascular diseases

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The Biological Effects of Ivabradine in Cardiovascular Disease

A large number of studies in healthy and asymptomatic subjects, as well as patients with already established cardiovascular disease (CAD) have demonstrated that heart rate (HR) is a very important and major independent cardiovascular risk factor for prognosis. Lowering heart rate reduces cardiac work, thereby diminishing myocardial oxygen demand. Several experimental studies in animals, including dogs and pigs, have clarified the beneficial effects of ivabradine associated with HR lowering. Ivabradine is a selective inhibitor of the hyperpolarisation activated cyclic-nucleotide-gated funny current (If) involved in pacemaker generation and responsiveness of the sino-atrial node (SAN), which result in HR reduction with no other apparent direct cardiovascular effects. Several studies show that ivabradine substantially and significantly reduces major risks associated with heart failure when added to guideline-based and evidence-based treatment. However the biological effect of ivabradine have yet to be studied. This effects can appear directly on myocardium or on a systemic level improving endothelial function and modulating immune cell migration. Indeed ivabradine is an ‘open-channel’ blocker of human hyperpolarization-activated cyclic nucleotide gated channels of type-4 (hHCN4), and a ‘closed-channel’ blocker of mouse HCN1 channels in a dose-dependent manner. At endothelial level ivabradine decreased monocyte chemotactin protein-1 mRNA expression and exerted a potent anti-oxidative effect through reduction of vascular NADPH oxidase activity. Finally, on an immune level, ivabradine inhibits the chemokine-induced migration of CD4-positive lymphocytes. In this review, we discuss the biological effects of ivabradine and highlight its effects on CAD

BASI MOLECOLARI E CELLULARI DELLA VITA

Prefazione La biologia è … un campo dalle possibilità illimitate, dal quale ci dobbiamo attendere le più sorprendenti delucidazioni; non possiamo quindi indovinare quali risposte essa potrà dare … ai problemi che le abbiamo posto. Forse queste risposte saranno tali da far crollare tutto l’artificioso edificio delle nostre ipotesi. (Sigmund Freud) La Biologia ha compiuto passi da gigante nel tempo intercorso tra la predizione di Freud e i nostri giorni. Nonostante ciò, il suo insegnamento a livello universitario, relativamente a molti corsi di laurea nei quali non costituisce materia fondante, vive un momento di grande incertezza. Infatti, le riforme degli ordinamenti con la suddivisione dei corsi di laurea in triennali e specialistici prima e magistrali poi, e l’introduzione dei corsi di laurea professionalizzanti hanno costretto molte facoltà a rivedere profondamente e radicalmente le loro offerte formative. Nella maggior parte dei casi, è proposto un numero eccessivo di insegnamenti da impartire in poche ore e con contenuti disciplinari ancora non ben definiti, con l’idea che la laurea triennale debba avere la capacità di preparare gli studenti ad affacciarsi al mondo del lavoro. L’organizzazione degli insegnamenti in moduli integrati, cioè insiemi di attività caratterizzati da una certa coerenza, pur essendo guidata dall’obiettivo condivisibile di impartire una preparazione di ampio respiro, ha rappresentato una fonte di problemi nell’identificazione dei programmi didattici relativi a ogni disciplina. Ciò richiede ancora, in molti casi, un’azione sensibilizzata alla selezione degli argomenti da trattare in ogni modulo e all’integrazione con le discipline affini. In questo contesto e in quanto impegnati in attività didattica in questi corsi, abbiamo sentito la necessità di tarare accuratamente l’insegnamento della Biologia, che copre un insieme enorme di argomenti, per adattarlo alle nuove esigenze. “Basi molecolari e cellulari della vita” è frutto di uno sforzo critico che ha permesso di rivedere i contenuti fondamentali della Biologia, indirizzandoli in modo specifico alla formazione di base delle figure destinate ad operare in molti casi in un ambiente clinico e al diretto contatto con i pazienti. Nella sua struttura, il volume è adatto a coprire la preparazione per le professioni sanitarie, quali ad es. quelle infermieristiche e riabilitative, le professioni tecnico-sanitarie, le professioni sanitarie tecniche della prevenzione, ma è stato formulato anche con l’obiettivo di soddisfare le esigenze degli studenti dei corsi di laurea triennale in scienze motorie. Gli argomenti trattati guidano gli studenti, indipendentemente dalla preparazione acquisita con gli studi secondari, alla comprensione degli indispensabili argomenti di base della struttura e delle funzioni delle macromolecole, della logica costruttiva delle strutture biologiche e dei diversi livelli di organizzazione della materia vivente. Sono poi trattate la struttura e l’organizzazione funzionale delle cellule procarioti, con le caratteristiche dei domini Archea e Bacteria, e di quelle eucarioti, fino ai virus, responsabili di diverse malattie nelle piante negli animali e nell’uomo. Particolare risalto è dato ovviamente alla biologia della cellula eucariote, con una panoramica essenziale dei principi unitari che ne assicurano il bilancio energetico, e dei meccanismi alla base dell’espressione dell’informazione genetica. Sono quindi descritti i sistemi di membrana, le interazioni delle cellule con l’ambiente che le circonda, il ciclo cellulare e le divisioni delle cellule somatiche e germinali, la riproduzione sessuata e asessuata con cenni dei processi cellulari che guidano lo sviluppo iniziale dell’embrione di mammifero e umano, ed è dato particolare rilievo agli aspetti strutturali e fisiologici delle cellule muscolari striate e lisce e dell’apparato muscolare scheletrico/cardiaco. Sono infine trattati gli argomenti della genetica, con la struttura dei genomi procarioti ed eucarioti, la trasmissione, le mutazioni e l’evoluzione dell’informazione genetica, compresi i meccanismi, più recentemente identificati, delle modificazioni epigenetiche. Il testo così strutturato, sintetico ma esauriente, potrà soddisfare le esigenze di un’ampia fascia di studenti indipendentemente dal corso di studio prescelto. Con questo volume, tutti gli studenti saranno in grado di comprendere i principi biologici di base e il linguaggio appropriato, entrambi necessari allo studio dei corsi successivi, ma anche di identificare le aree di interesse, selezionare le fonti di informazione scientifica e interpretarne i dati, costruendosi un bagaglio culturale necessario sia alla formazione limitata al corso di laurea triennale, che all’eventuale proseguimento degli studi in corsi di laurea magistrale o di formazione post-laurea. Ringraziamo sentitamente il Dott. Piccin per la fiducia e l’incoraggiamento profusi nella realizzazione del manuale; la Sig.ra Barbara Cariali e il Sig. Marco Marzola per aver dato veste grafica al volume. Saremo inoltre molto grati a tutti coloro che vogliano segnalarci ogni errore, inesattezza o svista che, nonostante i nostri sforzi, il manuale possa contenere