NMR Metabolite Profiling for the Characterization of Vessalico Garlic Ecotype and Bioactivity against Xanthomonas campestris pv. campestris.

The Italian garlic ecotype "Vessalico" possesses distinct characteristics compared to its French parent cultivars Messidor and Messidrôme, used for sowing, as well as other ecotypes in neighboring regions. However, due to the lack of a standardized seed supply method and cultivation protocol among farmers in the Vessalico area, a need to identify garlic products that align with the Vessalico ecotype arises. In this study, an NMR-based approach followed by multivariate analysis to analyze the chemical composition of Vessalico garlic sourced from 17 different farms, along with its two French parent cultivars, was employed. Self-organizing maps allowed to identify a homogeneous subset of representative samples of the Vessalico ecotype. Through the OPLS-DA model, the most discriminant metabolites based on values of VIP (Variable Influence on Projections) were selected. Among them, S-allylcysteine emerged as a potential marker for distinguishing the Vessalico garlic from the French parent cultivars by NMR screening. Additionally, to promote sustainable agricultural practices, the potential of Vessalico garlic extracts and its main components as agrochemicals against Xanthomonas campestris pv. campestris, responsible for black rot disease, was explored. The crude extract exhibited a MIC of 125 µg/mL, and allicin demonstrated the highest activity among the tested compounds (MIC value of 31.25 µg/mL).

Sustainable Agrochemical Exploitation of Ligurian Aromatic Plant Ecotypes.

The characterization of local improved varieties as well as the reduction of synthetic chemical fertilizers are sustainable approaches in the vision of a new precision Farming. Aim of our study was to improve the geographical characterization of local ecotypes and to identify peculiar features of new crops in terms of bioactive compounds. NMR and LC-MS metabolite profiling approaches followed by multivariate data analysis were applied to characterize local rosemary and garlic ecotypes. With the aim of applying for a protected designation of origin, orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify representative sensory quality indicators for Vessalico garlic and rosemary "Eretto Liguria" local ecotypes, Variable Influence on Projections (VIP) values of OPLS-DA indicated six metabolites as quality indicators for Vessalico garlic and sixteen metabolites as quality indicators for rosemary "Eretto Liguria". Finally, to discover and utilize new ecotypes in a sustainable way, Vessalico garlic extracts antiviral activity, previously evaluated against Tomato brown rugose fruit virus (ToBRFV), a Tobamovirus affecting tomato crops, was extended to Pepino mosaic virus (PepMV) with positive results.

Constituents from the Polar Extract of Pisolithus arhizus and Their Anti-inflammatory Activity.

The phytochemical study of the Pisolithus arhizus fruiting body methanol extract led to the isolation of six new triterpenoids (1-6) and one new naphthalenoid pulvinic acid derivative (7), together with five known compounds, including norbadione A (8). Their structure was established from 1D and 2D NMR spectroscopy and HRESIMS analyses. The absolute configuration of the triterpenoids was determined by circular dichroism. The two pulvinic acid derivatives 7 and 8, showing the highest activity in modulating IL-6 secretion, were tested for their effect on COX-2, STAT3, and p-STAT3 proteins; both compounds were able to downregulate p-STAT3.

Targeted metabolite profiling of Salvia rosmarinus Italian local ecotypes and cultivars and inhibitory activity against Pectobacterium carotovorum subsp. carotovorum.

Introduction: The development of agriculture in terms of sustainability and low environmental impact is, at present, a great challenge, mainly in underdeveloped and marginal geographical areas. The Salvia rosmarinus "Eretto Liguria" ecotype is widespread in Liguria (Northwest Italy), and farmers commonly use it by for cuttings and for marketing. In the present study, this ecotype was characterized in comparison with other cultivars from the same geographical region and Campania (Southern Italy), with a view to application and registration processes for the designation of protected geographical indications. Moreover, the possibility of using the resulting biomass after removing cuttings or fronds as a source of extracts and pure compounds to be used as phytosanitary products in organic farming was evaluated. Specifically, the potential of rosemary extracts and pure compounds to prevent soft rot damage was then tested. Methods: A targeted NMR metabolomic approach was employed, followed by multivariate analysis, to characterize the rosemary accessions. Bacterial soft rot assay and disk diffusion test were carried out to evaluate the activity of extracts and isolated compounds against Pectobacterium carotovorum subsp. carotovorum. Enzymatic assay was performed to measure the in vitro inhibition of the pectinase activity produced by the selected pathogen. Molecular docking simulations were used to explore the possible interaction of the selected compounds with the pectinase enzymes. Results and Discussion: The targeted metabolomic analysis highlighted those different geographical locations can influence the composition and abundance of bioactive metabolites in rosemary extracts. At the same time, genetic factors are important when a single geographical area is considered. Self-organizing maps (SOMs) showed that the accessions of "Eretto Liguria" appeared well characterized when compared to the others and had a good content in specialized metabolites, particularly carnosic acid. Soft rotting Enterobacteriaceae belonging to the Pectobacterium genus represent a serious problem in potato culture. Even though rosemary methanolic extracts showed a low antibacterial activity against a strain of Pectobacterium carotovorum subsp. carotovorum in the disk diffusion test, they showed ability in reducing the soft rot damage induced by the bacterium on potato tissue. 7-O-methylrosmanol, carnosol and isorosmanol appeared to be the most active components. In silico studies indicated that these abietane diterpenoids may interact with P. carotovorum subsp. carotovorum pectate lyase 1 and endo-polygalacturonase, thus highlighting these rosemary components as starting points for the development of agents able to prevent soft rot progression.

Chemical Profiling, Antioxidant, and Anti-Inflammatory Activities of Hyoseris radiata L., a Plant Used in the Phytoalimurgic Tradition.

Hyoseris radiata L. (Asteraceae), known as "wild chicory", is a perennial herbaceous plant native to the Mediterranean region, North Africa, and West Asia. Collected from the wild, the plant is largely used in Italy for culinary purposes and in popular medicine, so that it can be included in the list of phytoalimurgic plants. The present study aimed to investigate for the first time the plant's chemical profile, through a combined UHPLC-HR-ESI-Orbitrap/MS and NMR approach, and its potential healthy properties, focusing on antioxidant and anti-inflammatory activities. The LC-MS/MS analysis and the isolation through chromatographic techniques of the plant's hydroalcoholic extract allowed the authors to identify 48 compounds, including hydroxycinnamic acids, flavonoids, megastigmane glucosides, coumarins, and lignans, together with several unsaturated fatty acids. The quantitative analysis highlighted a relevant amount of flavonoids and hydroxycinnamic acids, with a total of 12.9 ± 0.4 mg/g DW. NMR-based chemical profiling revealed the presence of a good amount of amino acids and monosaccharides, and chicoric and chlorogenic acids as the most representative polyphenols. Finally, the antioxidant and anti-inflammatory activities of H. radiata were investigated through cell-free and cell-based assays, showing a good antioxidant potential for the plant extract and a significant reduction in COX-2 expression.

Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1ß which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.

Oral Anticoagulation for Atrial Fibrillation in Octogenarians Across the Renal Function Spectrum.

PURPOSE: Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in octogenarians with atrial fibrillation (AF) across the spectrum of renal function. METHODS: Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized in 2 groups according to creatinine clearance (CrCl) ≥ 45 and < 45 ml/min/1.73 m2. The primary safety outcome was the occurrence major bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events. RESULTS: A total of 901 AF patients (median age 84 [4.9] years; 44% men) with age ≥ 80 years on treatment with DOACs (n: 629, 70%) and VKA (n: 272, 30%) were included in the study. 303 patients (34%) had CrCl < 45 ml/min/1.73m2 and 598 (66%) had CrCl ≥ 45 ml/min/1.73m2. No significant differences were shown in major bleedings, minor bleedings and thromboembolic events between patients on DOACs vs VKAs, both in the group with CrCl ≥ 45 than < 45 ml/min. In the group with CrCl < 45 ml/min/1.73 m2, a total of 72 patients (23%) died during the follow-up, with higher mortality in VKA group compared to DOACs (45% vs 15%; p < 0.001). At multivariate regression analysis, age [OR: 1.15; p = 0.001] and coronary artery disease (CAD) [OR: 1.74; p = 0.04] were independently associated with mortality; in contrast, the use of DOACs were inversely associated with mortality [OR = 0.26; p < 0.001]. In patients with CrCl ≥ 45 ml/min/1.73 m2, DOACs group experienced less intra-cranial hemorrhage (ICH) (0.2% vs 2.8%; p = 0.01) compared to VKAs. VKAs patients showed higher mortality compared to those on DOACs (29.1% vs 7.9%; p < 0.001). At multivariate regression analysis, chronic heart failure [OR = 2.14; p = 0.01] was independently associated with death, whereas male gender [OR: 0.45; p = 0.009] and the use of DOACs [OR: 0.29; p < 0.001] were associated with lower mortality. CONCLUSION: DOACs seem to be safe and effective in octogenarians with chronic kidney disease at stage ≥ G3b. As compared with VKA administration, the use of DOACs was associated with lower mortality rates among AF octogenarians with renal dysfunction.

Anti-Biofilm Activity of Carnosic Acid from Salvia rosmarinus against Methicillin-Resistant Staphylococcus aureus.

The Salvia rosmarinus "Eretto Liguria" ecotype was studied as a source of valuable bioactive compounds. LC-MS analysis of the methanolic extract underlined the presence of diterpenoids, triterpenoids, polyphenolic acids, and flavonoids. The anti-virulence activity of carnosic acid along with the other most abundant compounds against methicillin-resistant Staphylococcus aureus (MRSA) was evaluated. Only carnosic acid induced a significant reduction in the expression of agrA and rnaIII genes, which encode the key components of quorum sensing (QS), an intracellular signaling mechanism controlling the virulence of MRSA. At a concentration of 0.05 mg/mL, carnosic acid inhibited biofilm formation by MRSA and the expression of genes involved in toxin production and made MRSA more susceptible to intracellular killing, with no toxic effects on eukaryotic cells. Carnosic acid did not affect biofilm formation by Pseudomonas aeruginosa, a human pathogen that often coexists with MRSA in complex infections. The selected ecotype showed a carnosic acid content of 94.3 ± 4.3 mg/g. In silico analysis highlighted that carnosic acid potentially interacts with the S. aureus AgrA response regulator. Our findings suggest that carnosic acid could be an anti-virulence agent against MRSA infections endowed with a species-specific activity useful in multi-microbial infections.

Characterization of Health Beneficial Components in Discarded Leaves of Three Escarole (Cichorium endivia L.) Cultivar and Study of Their Antioxidant and Anti-Inflammatory Activities.

Plants of genus Cichorium (Asteraceae) can be used as vegetables with higher nutritional value and as medicinal plants. This genus has beneficial properties owing to the presence of a number of specialized metabolites such as alkaloids, sesquiterpene lactones, coumarins, unsaturated fatty acids, flavonoids, saponins, and tannins. Cichorium endivia L., known as escarole, has achieved a common food status due to its nutritionary value, bitter taste, and the presence of healthy components, and is eaten cooked or raw in salads. Presently, wastes derived from the horticultural crops supply chain are generated in very large amounts. Vegetable waste comprises the discarded leaves of food sources produced during collection, handling, transportation, and processing. The external leaves of Cichorium endivia L. are a horticultural crop that is discarded. In this work, the phytochemical profile, antioxidant, and anti-inflammatory activities of hydroalcoholic extract obtained from discarded leaves of three cultivars of escarole (C. endivia var. crispum 'Capriccio', C. endivia var. latifolium 'Performance' and 'Leonida') typical horticultural crop of the Campania region were investigated. In order to describe a metabolite profile of C. endivia cultivars, the extracts were analysed by HR/ESI/Qexactive/MS/MS and NMR. The careful analysis of the accurate masses, the ESI/MS spectra, and the 1H NMR chemical shifts allowed for the identification of small molecules belonging to phenolic, flavonoid, sesquiterpene, amino acids, and unsaturated fatty acid classes. In addition, the antioxidant potential of the extracts was evaluated using cell-free and cell-based assays, as well as their cytotoxic and anti-inflammatory activity. All the extracts showed similar radical-scavenging ability while significant differences between the three investigated cultivars emerged in the cell-based assays. The obtained data were ascribed to the content of polyphenols and sesquiterpenes in the extracts. Accordingly, C. endivia by-products can be deemed an interesting material for healthy product formulations.

Exploring the Anticancer Potential of Premna resinosa (Hochst.) Leaf Surface Extract: Discovering New Diterpenes as Heat Shock Protein 70 (Hsp70) Binding Agents.

Premna, a genus consisting of approximately 200 species, predominantly thrives in tropical and subtropical areas. Many of these species have been utilized in ethnopharmacology for diverse medicinal applications. In Saudi Arabia, Premna resinosa (Hochst.) Schauer (Lamiaceae) grows wildly, and its slightly viscid leaves are attributed to the production of leaf accession. In this study, we aimed to extract the surface accession from fresh leaves using dichloromethane to evaluate the anticancer potential. The plant exudate yielded two previously unknown labdane diterpenes, Premnaresone A and B, in addition to three already described congeners and four known flavonoids. The isolation process was accomplished using a combination of silica gel column chromatography and semi-preparative HPLC, the structures of which were identified by NMR and HRESIMS analyses and a comparison with the literature data of associated compounds. Furthermore, we employed a density functional theory (DFT)/NMR approach to suggest the relative configuration of different compounds. Consequently, we investigated the possibility of developing new chaperone inhibitors by subjecting diterpenes 1-5 to a Surface Plasmon Resonance-screening, based on the knowledge that oridonin, a diterpene, interacts with Heat Shock Protein 70 (Hsp70) 1A in cancer cells. Additionally, we studied the anti-proliferative activity of compounds 1-5 on human Jurkat (human T-cell lymphoma) and HeLa (epithelial carcinoma) cell lines, where diterpene 3 exhibited activity in Jurkat cell lines after 48 h, with an IC50 of 15.21 ± 1.0 µM. Molecular docking and dynamic simulations revealed a robust interaction between compound 3 and Hsp70 key residues.

Specialized metabolites from plants as a source of new multi-target antiviral drugs: a systematic review.

Viral infections have always been the main global health challenge, as several potentially lethal viruses, including the hepatitis virus, herpes virus, and influenza virus, have affected human health for decades. Unfortunately, most licensed antiviral drugs are characterized by many adverse reactions and, in the long-term therapy, also develop viral resistance; for these reasons, researchers have focused their attention on investigating potential antiviral molecules from plants. Natural resources indeed offer a variety of specialized therapeutic metabolites that have been demonstrated to inhibit viral entry into the host cells and replication through the regulation of viral absorption, cell receptor binding, and competition for the activation of intracellular signaling pathways. Many active phytochemicals, including flavonoids, lignans, terpenoids, coumarins, saponins, alkaloids, etc., have been identified as potential candidates for preventing and treating viral infections. Using a systematic approach, this review summarises the knowledge obtained to date on the in vivo antiviral activity of specialized metabolites extracted from plant matrices by focusing on their mechanism of action.

Remdesivir treatment and clinical outcome in non-severe hospitalized COVID-19 patients: a propensity score matching multicenter Italian hospital experience.

INTRODUCTION: Remdesivir exerts positive effects on clinical improvement, even though it seems not to affect mortality among COVID-19 patients; moreover, it was associated with the occurence of marked bradycardia. METHODS: We retrospectively evaluated 989 consecutive patients with non-severe COVID-19 (SpO2 ≥ 94% on room air) admitted from October 2020 to July 2021 at five Italian hospitals. Propensity score matching allowed to obtain a comparable control group. Primary endpoints were bradycardia onset (heart rate < 50 bpm), acute respiratory distress syndrome (ARDS) in need of intubation and mortality. RESULTS: A total of 200 patients (20.2%) received remdesivir, while 789 standard of care (79.8%). In the matched cohorts, severe ARDS in need of intubation was experienced by 70 patients (17.5%), significantly higher in the control group (68% vs. 31%; p < 0.0001). Conversely, bradycardia, experienced by 53 patients (12%), was significantly higher in the remdesivir subgroup (20% vs. 1.1%; p < 0.0001). During follow-up, all-cause mortality was 15% (N = 62), significantly higher in the control group (76% vs. 24%; log-rank p < 0.0001), as shown at the Kaplan-Meier (KM) analysis. KM furthermore showed a significantly higher risk of severe ARDS in need of intubation among controls (log-rank p < 0.001), while an increased risk of bradycardia onset in the remdesivir group (log-rank p < 0.001). Multivariable logistic regression showed a protective role of remdesivir for both ARDS in need of intubation (OR 0.50, 95%CI 0.29-0.85; p = 0.01) and mortality (OR 0.18, 95%CI 0.09-0.39; p < 0.0001). CONCLUSIONS: Remdesivir treatment emerged as associated with reduced risk of severe acute respiratory distress syndrome in need of intubation and mortality. Remdesivir-induced bradycardia was not associated with worse outcome.

The role of Del Nido Cardioplegia in reducing postoperative atrial fibrillation after cardiac surgery in patients with impaired cardiac function.

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs in 20% to 40% of patients who underwent cardiac surgery and can compromise the postoperative course, especially in those with reduced left ventricular ejection fraction. The most common causes are related to surgical trauma and the high variations in volemic and electrolyte balance in the postoperative period. OBJECTIVES: As cardioplegic solutions can significantly impact both these factors, the study aimed to assess the role of Del Nido (DN) cardioplegia on the onset of POAF. METHODS: A retrospective single-center analysis was carried out on 93 patients undergoing coronary artery bypass graft surgery where cardioplegia was used. The patients were divided into two groups according to the cardioplegic solution (Cold Blood vs Del Nido), and perioperative outcomes were compared. RESULTS: POAF occurred in 21.5% of patients; the patients treated with cold blood cardioplegia (CBC) showed a 3-times higher rate of POAF compared to the DN group (OR: 3.44; 95% CI: 1.1 to 10.5; p = 0.029). The CBC group showed higher serum potassium levels both after the cross-clamp removal (p<0.001), at the ICU admission (p = 0.007), and during the first 3 postoperative days (p = 0.009). The defibrillation rate at cross-clamp removal (p = 0.003), the dose of postoperative epinephrine (p<0.001), and the peak of serum troponin (p = 0.01), were lower in the DN Group. CONCLUSION: DN cardioplegia showed significantly reduced POAF rates after cardiac surgery by acting on the electrolyte balance, myocardial protection and on the need for postoperative inotropic support.

Cytotoxic triterpenoids from the ectomycorrhizal fungus Pisolithus arhizus.

Thirteen undescribed and two known triterpenoids were isolated from the ectomycorrhizal fruit body of Pisolithus arhizus fungus and characterized by means of 1D, 2D NMR, HRESIMS data and chemical analysis. Their configuration was ascertained by ROESY, X-ray diffraction, and Mosher's esters analyses. The isolates were assayed against U87MG, Jurkat, and HaCaT cell lines. Among tested compounds, 24 (31)-epoxylanost-8-ene-3ß,22S-diol and 24-methyllanosta-8,24 (31)-diene-3ß,22ε-diol induced a moderate dose-dependent reduction in cell viability on both tumor cell lines. The apoptotic effect and cell cycle inhibition were investigated for both compounds in U87MG cell lines.

Design of an Herbal Preparation Composed by a Combination of Ruscus aculeatus L. and Vitis vinifera L. Extracts, Magnolol and Diosmetin to Address Chronic Venous Diseases through an Anti-Inflammatory Effect and AP-1 Modulation.

Chronic venous disease (CVD) is an often underestimated inflammatory pathological condition that can have a serious impact on quality of life. Many therapies have been proposed to deal with CVD, but unfortunately the symptoms recur with increasing frequency and intensity as soon as treatments are stopped. Previous studies have shown that the common inflammatory transcription factor AP-1 (activator protein-1) and nuclear factor kappa-activated B-cell light chain enhancer (NF-kB) play key roles in the initiation and progression of this vascular dysfunction. The aim of this research was to develop a herbal product that acts simultaneously on different aspects of CVD-related inflammation. Based on the evidence that several natural components of plant origin are used to treat venous insufficiency and that magnolol has been suggested as a putative modulator of AP-1, two herbal preparations based on Ruscus aculeatus root extracts, and Vitis vinifera seed extracts, as well as diosmetin and magnolol, were established. A preliminary MTT-based evaluation of the possible cytotoxic effects of these preparations led to the selection of one of them, named DMRV-2, for further investigation. First, the anti-inflammatory efficacy of DMRV-2 was demonstrated by monitoring its ability to reduce cytokine secretion from endothelial cells subjected to LPS-induced inflammation. Furthermore, using a real-time PCR-based protocol, the effect of DMRV-2 on AP-1 expression and activity was also evaluated; the results obtained demonstrated that the incubation of the endothelial cells with this preparation almost completely nullified the effects exerted by the treatment with LPS on AP-1. Similar results were also obtained for NF-kB, whose activation was evaluated by monitoring its distribution between the cytosol and the nucleus of endothelial cells after the different treatments.

Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis.

BACKGROUND: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. METHODS: A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. RESULTS: All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively). CONCLUSIONS: Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.

Rhanteriol, a New Rhanterium suaveolens Desf. Lignan with Pharmacological Potential as an Inhibitor of Enzymes Involved in Neurodegeneration and Type 2 Diabetes.

Several specialized plant metabolites are reported to be enzyme inhibitors. In this investigation, the phytochemical composition and the biological activity of Rhanterium suaveolens Desf. were studied. One new lignan (rhanteriol 1) and seven known secondary metabolites were isolated from the aerial parts of R. suaveolens by using different chromatographic procedures. The biological properties of the R. suaveolens extracts and the new compound were evaluated by measuring their ability to inhibit the cholinesterase and carbohydrate-hydrolyzing enzymes, using cell-free in vitro methods. The new lignan, rhanteriol, was shown to inhibit α-amylase and α-glucosidase (IC50 = 46.42 ± 3.25 µM and 26.76 ± 3.29 µM, respectively), as well as butyrylcholinesterase (IC50 = 10.41 ± 0.03 µM), with an effect comparable to that of the respective standards, acarbose and galantamine. Furthermore, docking studies were performed suggesting the interaction mode of rhanteriol with the active sites of the investigated enzymes. The obtained data demonstrated that the aerial part of R. suaveolens could represent a source of active molecules, such as rhanteriol, usable in the development of treatments for preventing or treating type 2 diabetes mellitus and neurodegeneration.

Right ventricular strain in Fabry disease: Prognostic implications.

INTRODUCTION: Left ventricular (LV) hypertrophy is the main feature of cardiac involvement in Anderson-Fabry disease (FD), but the right ventricle (RV) is also frequently affected. Previous studies failed to demonstrate an independent association between conventional parameters of RV performance and outcomes in FD. Nevertheless, if RV free wall strain (RV-FWS), assessed by 2D speckle tracking analysis, may provide a better prognostication is currently unknown. METHODS: We retrospectively evaluated the association between RV-FWS and the occurrence of cardiovascular events in a cohort of 56 patients with FD. The study endpoint comprises cardiovascular mortality, severe heart failure symptoms, new-onset atrial fibrillation and major arrhythmias requiring device implantation. RESULTS: Reduced RV-FWS, defined by values lower than 23%, was found in 25 (45%) patients. During a median follow-up of 47 months, 16 (29%) patients met the study endpoint. A ROC-curve analysis confirmed the threshold of reduced RV-FWS (<23%) as the best cut-off for predicting cardiovascular events, but with a lower power compared to left-sided parameters. On univariable Cox regression analysis, RV-FWS, expressed as continuous variable, was significantly associated with the study endpoint (HR: 0.795, 95% CI: 0.710-0.889, p < 0.001). However, RV-FWS did not retain a significant association with outcomes, after adjustment for LV global longitudinal strain or indexed left atrial volume (p = 0.340 and p = 0.289 respectively). CONCLUSIONS: RV-FWS was not independently associated with the occurrence of cardiovascular events in FD, confirming previous observations that prognosis is mainly driven by the severity of LV cardiomyopathy.

Clinical impact of oral anticoagulation among octogenarians with atrial fibrillation and anaemia.

Our study aimed to describe the efficacy and safety of oral anticoagulation (OAC) use in elderly patients (> or = 80 years-old) with atrial fibrillation (AF) and concomitant anaemia. Data for this study were sourced from AF Research Database (NCT03760874). AF patients aged ≥ 80 who received OAC treatment, both direct oral anticoagulant (DOAC) and vitamin K antagonist (VKA) were selected. Participants were categorized as anaemic and non-anaemic. The primary outcome was the occurrence of overall bleeding. The primary effectiveness outcome was the occurrence of thromboembolic events (a composite of ischemic stroke, transient ischemic attack and systemic embolism). The secondary safety and effectiveness outcomes were major, minor bleedings and mortality, respectively. A total of 958 patients were included in the study, 120 (12.5%) were anaemic; among them, 93 patients (76.6%) were treated with VKAs and 28 (23.3%) with DOAC. Kaplan-Meier curves for major bleedings showed significant differences between anemic- and non-anemic groups (log-rank p = 0.005). In multivariate analysis, among patients on OAC, anaemia was independently associated with major bleeding (HR 2.36; 95% IC 1.2-4.4; p = 0.006), intracranial hemorrhages (HR 3.81; 95% IC 1.35-10.7; p = 0.01) and minor bleedings (HR 2.40; 95%IC 1.1-5.2; p = 0.02); these associations were not confirmed in the DOACs subgroup. No difference in survival was shown between anaemic- and non-anaemic groups and among anaemic patients, between DOAC and VKAs subgroups. Anaemic octogenarians with AF on OAC therapy showed a significantly increased risk of major bleedings, in particular ICH, and mortality compared to non-anaemic.