Showing papers by "Francesco Salvatore published in 2020"

Secondary Metabolites Produced by Macrophomina phaseolina Isolated from Eucalyptus globulus

Abstract: In the course of investigations on the role of secondary metabolites in plant-microbe interactions, the production of secondary metabolites by Macrophomina phaseolina isolates from Eucalyptus globulus, was studied. This fungus is responsible for several plant diseases which affect crop productivity and industry. Although secondary metabolites may play a role in disease development, there are very few reports on M. phaseolina metabolomics and, as far as we know, isolates from eucalypts have not been investigated for secondary metabolites production. In the present paper, metabolites typical of fungi, from the family Botryosphaeriaceae, were identified for the first time as products of M. phaseolina. Furthermore, the isolate under examination was grown in the presence and absence of host stem tissue, and metabolite profiles were compared. Five products are reported for the first time in this species and azelaic acid was exclusively produced in the presence of eucalypt stem. Finally, phytotoxicity and cytotoxicity tests of culture filtrates and crude organic extracts were also performed. Key Contribution: Lipophilic metabolites produced by M. phaseolina might play a role in the plant-fungus interactions responsible for serious diseases of E. globulus.

Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy

Abstract: Mesoporous silicon microparticles (MSMPs) can incorporate drug-carrying nanoparticles (NPs) into their pores An NP-loaded MSMP is a multistage vector (MSV) that forms a Matryoshka-like structure that protects the therapeutic cargo from degradation and prevents its dilution in the circulation during delivery to tumor cells We developed an MSV constituted by 1 µm discoidal MSMPs embedded with PEGylated liposomes containing oxaliplatin (oxa) which is a therapeutic agent for colorectal cancer (CRC) To obtain extra-small liposomes able to fit the 60 nm pores of MSMP, we tested several liposomal formulations, and identified two optimal compositions, with a prevalence of the rigid lipid 1,2-distearoyl-sn-glycero-3-phosphocholine and of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] To improve the MSV assembly, we optimized the liposome-loading inside the MSMP and achieved a five-fold increase of the payload using an innovative lyophilization approach This procedure also increased the load and limited dimensional changes of the liposomes released from the MSV in vitro Lastly, we found that the cytotoxic efficacy of oxa-loaded liposomes and-oxa-liposome-MSV in CRC cell culture was similar to that of free oxa This study increases knowledge about extra-small liposomes and their loading into porous materials and provides useful hints about alternative strategies for designing drug-encapsulating NPs

Genotype-Phenotype Correlation: A Triple DNA Mutational Event in a Boy Entering Sport Conveys an Additional Pathogenicity Risk.

Abstract: The purpose of this paper is to present a clinical and laboratory study of a family, in which a 12-year-old boy was examined to assess his health status before starting competitive sports. A variety of clinical and instrumental tests were used to evaluate the status of the heart and its functions. Using Sanger sequencing (SS), we sequenced six related genes to verify suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) hypothesized at the cardiac assessment and, subsequently, by a next-generation sequencing (NGS)-based multi-gene panel for more paramount genetic risk of sudden cardiac death (SCD) assessment. SS revealed two variants in the PKP2 gene, one was inherited from the father and the other from the mother. The analysis on a large panel of genes (n = 138), putatively associated with sudden cardiac death, revealed, in the proband, a third variant in a different gene (DES) that encodes the protein desmin. Our results indicate that: i) NGS revealed a mutational event in a gene not conventionally screened as a first-line test in the presence of clinical suspicion of the arrhythmic disease; ii) a plurality of variants in different genes in the same subject (the proband) may increase the risk of heart disease; iii) in silico analysis with various methodological software and bioinformatic prediction tools indicates that the cumulative effects of the three variants in the same subject constitute an additional risk factor. This case report indicates that more pathogenic variants or likely pathogenic variants can contribute to the clinical phenotype of an individual, thereby contributing to the diagnosis and prognosis of inherited heart diseases.

Bivalent Metal-Chelating Properties of Harzianic Acid Produced by Trichoderma pleuroticola Associated to the Gastropod Melarhaphe neritoides.

Abstract: Harzianic acid is a secondary metabolite of Trichoderma, structurally belonging to the dienyltetramic acid subgroup of the tetramic acids. Biological activities of harzianic acid are of great interest for its antimicrobial and plant growth-promoting activities, which might be related to its chelating properties. In the present work harzianic acid, isolated from cultures of a strain of Trichoderma pleuroticola associated to the gastropod Melarhaphe neritoides, was studied as a complexant agent of a number of biologically relevant transition metals (i.e., Zn2+, Fe2+, Cu2+, and Mn2+), using UV-VIS, potentiometry, MS and NMR techniques. Our findings show the coordination capacity of harzianic acid toward the above cations through the formation of neutral or charged complexes in a variable ratio depending on the metal and pH conditions.

The shift of the paradigm between ageing and diseases.

Abstract: In the area of the Medical Sciences, the chronological age has always been, and still is, an indicator by which we try to understand the health status of an individual. However, besides considering people born with an already expressed disease, each human genome has sequence alterations called predisposing mutations; carriers of such genetic alterations have an increased risk of contracting diseases during their life. In addition, the exposome, i.e. the totality of environmental noxae ("hits") to which our body is exposed throughout life (through ingestion, breathing, body surface hits, and psychosociological stress agents, etc.) contributes to increase gradually but inexorably the frailty of an organism, and this process is usually referred to as "physiological ageing". This position paper proposes that we invert our visual angle and view the passage-of-time not as the cause of diseases, but consider the genome alterations present at birth and the noxae received during our life as the real major causes of ageing. The Biomedical Sciences are now increasingly unraveling the etiopathogenesis of most chronic degenerative diseases; thus, it will be possible to monitor and treat those that most contribute to the increased frailty of each person, which is now referred to with the misnomer "physiological ageing". These concepts are not banal; indeed, they imply that we must try to avoid the causes of alterations that result later in chronic degenerative diseases. Thus, we should shift our attention from the cure to the prevention of alterations/diseases also to improve both the length and quality of our life. Moreover, this approach involves real personalized or individualized medicine, thus conferring a more direct benefit to each of us by finalizing either the cure or the monitoring of diseases.

Identification of the Main Metabolites of a Marine-Derived Strain of Penicillium brevicompactum Using LC and GC MS Techniques.

Abstract: Marine-derived fungi are an important source of many valuable compounds with original structures and diverse physico-chemical properties. In this work, the metabolomic profile of a strain of Penicillium brevicompactum, recovered from a snakelocks sea anemone (Anemonia sulcata), was investigated through the parallel application of LC-ESI-HRMS, GC-MS, and NMR. Our strategy allowed the identification of mycophenolic acid, brevianamide A, and several compounds belonging to the thiosilvatins. Among the latter, five products are reported for the first time in this species. The main product of this series, cis-bis(methylthio)silvatin, was also tested for antiproliferative activity on both cancer and non-tumoral colon cell lines.

Effect of γ-Aminobutyric Acid (GABA) on the Metabolome of Two Strains of Lasiodiplodia theobromae Isolated from Grapevine.

Abstract: The effect of γ-aminobutyric acid (GABA) on the metabolome of two strains of Lasiodiplodia theobromae isolated from grapevine that hold a different degree of virulence to the host plant (LA-SOL3 (more virulent), LA-SV1 (less virulent)) was investigated. The culture filtrates and crude extracts from the two strains grown in the presence and absence of 10 mM of GABA were tested for phytotoxicity on tomato plant cuttings and leaves, respectively. Considering the opportunistic nature of this fungus for humans, crude extracts were also tested for cytotoxicity on mammalian cell lines. We found that culture filtrates and crude extracts have a decreased toxicity in the presence of GABA. Metabolomic analysis, conducted on both strains at both growth conditions, revealed the production of several compounds, such as indole-3-carboxylic acid (ICA, which is the main compound produced by L. theobromae), 3-indolecarboxyaldehyde, (3R,4S)-botryodiplodin, (R)-mellein. Finally, data demonstrate that GABA both induces a decrease in the amount of ICA, and a diversification of the metabolites produced by L. theobromae.

Fatty Acids from Ganoderma lucidum Spores: Extraction, Identification and Quantification

Abstract: Ganoderma lucidum is a rich and promising source of bioactive compounds capable of positively influencing the human health. For this reason, G. lucidum is the target of vigorous investigational activities, focusing on the extraction of substances with potential biomedical applications, as well as on the improvement of analytical methodologies for their screening. In the present study, three different extraction processes (i.e., extraction with n-hexane, in Soxhlet apparatus with n-hexane and reflux with chloroform) were employed to evaluate the lipid content of G. lucidum spores. The experimental data from the produced extracts were compared with ones from the commercial liquid extract obtained with supercritical CO2 extraction of G. lucidum spores. To achieve this goal, the gas chromatography-mass spectrometry (GC-MS) methodology was optimized for an accurate and reliable identification and quantification of fatty acids in triglycerides of G. lucidum spores. Significant amounts of oleic and palmitic acids were found in the examined extracts. In particular, our findings show that economical and convenient extraction procedures, which are simple, low cost and no need for expensive tools, allow to produce extracts with a lipid composition similar to the one obtained with hard strategies of extraction.

Adapted recreational football small-sided games improve cardiac capacity, body composition and muscular fitness in patients with type 2 diabetes.

Abstract: BACKGROUND The usefulness of adapted small-sided games (SSGs) in improving cardiac function in subjects with T2DM is still debated. Here we evaluated the effects of 18 weeks indoor muscular activation training (6 weeks; IMA) followed by adapted SSGs football training (12 weeks) on cardiac function, muscular fitness, body composition and adiponectin expression in sedentary T2DM volunteers. METHODS Six T2DM patients underwent IMA protocol of 6 weeks, twice a week followed by 12 weeks SSGs (5-a-side, once a week) training. Glucose, lipid profile and serum homocysteine concentration, body composition (BC), bone mineral density (DEXA), were determined at baseline and after 18 weeks (IMA+SSGs). VO 2max and muscular fitness were recorded at baseline and after IMA (6 weeks) and SSGs (12 weeks), respectively. RESULTS No significant differences were found for VO 2max and muscular fitness after 6weeks of IMA. After 18 weeks (6 weeks IMA + 12 weeks SSGs) of training, significant improvements were found in the following parameters: work capacity, VO 2peak , Ventilation (VE peak ), breathing reserve consumption and oxygen uptake efficiency slope (P<0.05); leg fitness (P<0.05), BC (P<0.05), vertebral column T-score (P<0.01) and adiponectin (total and high-molecular-weight; P<0.05). Compared to baseline, a reduction in serum homocysteine occurred after 18 weeks of training (P<0.05). CONCLUSIONS We evidenced that weekly adapted SSGs friendly football matches for 12 weeks improve cardiorespiratory capacity and the expression of independent markers associated with cardiovascular risk in T2DM patients, suggesting an overall reduced CVD-risk in these patients. These preliminary data encourage us to test the efficacy of this type of exercise in a larger population.