Salvatore De Rosa

Diketopiperazines produced by the Halophilic Archaeon, "Haloterrigena hispanica", activate AHL bioreporters

The generic term “quorum sensing” has been adopted to describe the bacterial cell-to-cell communication mechanism which coordinates gene expression when the population has reached a high cell density. Quorum sensing depends on the synthesis of small molecules that diffuse in and out of bacterial cells. There are few reports about this mechanism in Archaea. We report the isolation and chemical characterization of small molecules belonging to class of diketopiperazines (DKPs) in Haloterrigena hispanica, an extremely halophilic archaeon. One of the DKPs isolated, the compound cyclo-(l-prolyl–l-valine) activated N-acyl homoserine lactone (AHL) bioreporters, indicating that Archaea may have the ability to interact with AHL-producing bacteria within mixed communities.

Cacospongionolide and Scalaradial, Two Marine Sesterterpenoids as Potent Apoptosis-Inducing Factors in Human Carcinoma Cell Lines

Apoptosis, a form of programmed cell death, is a critical defence mechanism against the formation and progression of cancer and acts by eliminating potentially deleterious cells without causing such adverse effects, as inflammatory response and ensuing scar formation. Therefore, targeting apoptotic pathways becomes an intriguing strategy for the development of chemotherapeutic agents. In last decades, marine natural products, such as sesterterpenoids, have played an important role in the discovery and development of new drugs. Interestingly, many of these compounds have a strong potential as anticancer drugs by inhibiting cell proliferation and/or inducing cell death. In the present study, we investigated the effects of scalaradial and cacospongionolide, two sesterterpenoids from Cacospongia scalaris and Fasciospongia cavernosa marine sponges, on the apoptotic signalling pathway in three different human tumoral cells. Results were obtained by using DNA fragmentation, comet and viability assays, quantification of the mitochondrial transmembrane potential and Western blot. The T47D (human breast carcinoma), A431 (human epidermoid carcinoma), HeLa (human cervix carcinoma) and HCT116 (human colon carcinoma) cells were incubated for 24 h with scalaradial or cacospongionolide. Treatment of T47D cells with scalaradial or cacospongionolide for 24 h brought about a significant increase in DNA migration as well as fragmentation. Moreover, incubation of HCT116 and HeLa cells with scalaradial or cacospongionolide for 24 h caused an increased expression of pro-apoptotic proteins. Furthermore, scalaradial or cacospongionolide, added to HCT116 and HeLa cells overnight, induced a significant and concentration-dependent loss of mitochondrial transmembrane potential, an early apoptosis signalling event. These effects paralleled with those achieved with p50 and p65, NF-κB subunits, nuclear level. In conclusion, scalaradial and cacospongionolide, by determining human cancer cell apoptosis, may represent new promising compounds to inhibit cancer cell proliferation.

Further in vitro evaluation of cytotoxicity of the marine natural product derivative 4′-leucine-avarone

The cytotoxicity of 4′-leucine-avarone, amino derivative of the sponge Dysidea avara secondary metabolite avarone, was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay in vitro against seven human solid tumours for the first time. The compound tested induced dose-dependent cytotoxic response in all cancer cells showing better activity towards the lung A-549 and colon HT-29 cell lines (IC50 7.40 μM and 9.62 μM, respectively) than towards the breast adenocarcinoma ER positive MCF-7 and ER negative MDA-MB-231 cells (IC50 11.64 μM and 17.31 μM, respectively), the prostate adenocarcinoma PC-3 and epiteloid cervix carcinoma HeLa cells (IC50 14.24 μM and 15.54 μM, respectively). No toxicity was found towards the foetal lung fibroblast MRC-5 cell line at the concentrations used. According to experimental data obtained, the sesquiterpenoid quinone structure of avarone may inspire development of new drug-like substances with improved cytotoxicity on lung cancer in humans.

A new depsidone of Lobaria pulmonaria with acetylcholinesterase inhibition activity

The phytochemical investigation conducted on a foliose lichen, Lobaria pulmonaria(L.) Hoffm. (Lobariaceae), led to the isolation of a new depsidone in the form of its diacetate derivative which showed a moderate acetylcholinesterase inhibition activity (1 µg) in vitro. This is the first record of identified depsidone structure in searching for these inhibitors.

Further in vitro biological activity evaluation of amino-, thio- and ester-derivatives of avarol

Abstract The acetylcholinesterase inhibitory and/or antitumour activities of amino-, thio- and ester-derivatives of avarol selected were evaluated for the first time at in vitro conditions. Avarol-3′,4′-dithioglycol (1) and avarol-4′-(3)mercaptopropionic acid (3) were shown to be the best inhibitors of the enzyme tested (0.50u2009µg and IC50 0.05u2009mM and 0.50u2009µg and IC50 0.12u2009mM, respectively), while 4′-tryptamine-avarone (9) and avarol-3′-(3)mercaptopropionic acid (2) exhibited the highest cytotoxicity against the human breast T-47D cancer cell line (IC50 0.66u2009µg/mL and 1.25u2009µg/mL, respectively). According to experimental data obtained, the sesquiterpenoid hydroquinone structure of bioactive avarol derivatives may inspire development of new pharmacologically useful substances to be used in the treatment of Alzheimers disease and/or human breast tumour.

Cardiovascular exercise and burden of arrhythmia in patients with atrial fibrillation - A randomized controlled trial

Background Physical activity at moderate-high intensity is recommended to prevent lifestyle diseases. Patients with atrial fibrillation are at risk of a sedentary lifestyle due to fear of exercise-induced episodes of atrial fibrillation. The burden of arrhythmia can be reduced by physical exercise. The effect of exercise intensity on burden of atrial fibrillation needs to be studied further. Methods and results In a 12-week randomized controlled trial, 76 patients with paroxysmal/persistent atrial fibrillation were allocated to perform exercise at either low intensity or high intensity (50% and 80% of maximal perceived exertion, respectively). Primary outcome was burden of AF measured by daily electrocardiography-reporting during 12 weeks. Secondarily, change in maximal oxygen uptake (peak VO2) and 1-year hospitalization was compared between low and high intensity exercise. Sixty-three patients completed the follow-up. In the intention-to-treat analysis, we found no statistical difference in burden of atrial fibrillation between low and high intensity exercise (incidence rate ratio 0.742, 95% CI 0.29–1.91, P = 0.538). No serious adverse events were reported and there was no difference in hospitalization between the two exercise groups. Both exercise groups improved significantly in peak VO2 (low intensity: 3.62 mL O2/kg/min, SD 3.77; high intensity: 2.87 mL O2/kg/min, SD 4.98), with no statistical difference between-groups (mean difference: 0.76 mL O2/kg/min, 95% CI -3.22–1.7). Conclusions High intensity physical exercise was not superior to low intensity physical exercise in reducing burden of atrial fibrillation. HI exercise was well tolerated; no evidence of an increased risk was found for HI compared to LI exercise. Larger studies are required to further prove our findings. Trial registration ClinicalTrials.gov NCT01817998

Chemical Composition and Biological Activities of the Black Sea Algae Polysiphonia denudata (Dillw.) Kutz. and Polysiphonia denudata f. fragilis (Sperk) Woronich

Abstract The two investigated algae had almost identical sterol composition, but there were significant differences in the com position of the polar components and especially in the composition of the volatiles. P. denudata f. fragilis extracts possessed a stronger biological activity (antibacterial, antifungal and toxicity against Artemia salina). Despite the minute morphological differences between the two algae, we recommend P. denudata f. fragilis to be regarded as P. denudata subsp. fragilis.

320-row CT renal perfusion imaging in patients with aortic dissection: A preliminary study

Objective To investigate the clinical value of renal perfusion imaging in patients with aortic dissection (AD) using 320-row computed tomography (CT), and to determine the relationship between renal CT perfusion imaging and various factors of aortic dissection. Methods Forty-three patients with AD who underwent 320-row CT renal perfusion before operation were prospectively enrolled in this study. Diagnosis of AD was confirmed by transthoracic echocardiography. Blood flow (BF) of bilateral renal perfusion was measured and analyzed. CT perfusion imaging signs of AD in relation to the type of AD, number of entry tears and the false lumen thrombus were observed and compared. Results The BF values of patients with type A AD were significantly lower than those of patients with type B AD (P = 0.004). No significant difference was found in the BF between different numbers of intimal tears (P = 0.288), but BF values were significantly higher in cases with a false lumen without thrombus and renal arteries arising from the true lumen than in those with thrombus (P = 0.036). The BF values measured between the true lumen, false lumen and overriding groups were different (P = 0.02), with the true lumen group having the highest. Also, the difference in BF values between true lumen and false lumen groups was statistically significant (P = 0.016), while no statistical significance was found in the other two groups (P > 0.05). The larger the size of intimal entry tears, the greater the BF values (P = 0.044). Conclusions This study shows a direct correlation between renal CT perfusion changes and AD, with the size, number of intimal tears, different types of AD, different renal artery origins and false lumen thrombosis, significantly affecting the perfusion values.

Marine Sponge Sesterpenoids as Potent Apoptosis-Inducing Factors in Human Carcinoma Cell Lines

Cancer is a leading cause of death in industrialized countries. Although mortality rates have declined in recent years owing to earlier detection and more options in treatment, most cancers remain incurable. Mutations and epigenetic alterations of cancer genes promote the malignant transformation of cancer progenitor cells by disrupting key processes involved in normal growth control and tissue homeostasis. In addition, tumor development and progression are also dependent on the microenvironment surrounding the malignant cell. Conventional chemotherapy for cancer utilizes cytotoxic agents that elicit their therapeutic effect partly through apoptosis induction. Moreover, overexpression of anti-apoptotic proteins in cancer cells can inhibit programmed cell death and engender chemoresistance. Therefore, chemotherapeutic interventions fail to determine complete health in patients . Conversely, drugs developed more recently, known as ‘targeted therapy’, may show less unwanted toxicity, although they are generally cytostatic. Thus, there is an urgent need to develop new effective drugs. Natural products play a dominant role in the discovery of lead compounds for the development of drugs to treat human diseases. Terpenoids are by far the largest class of natural products. Within this class of compounds, the sesterterpenes form a rare group of isoprenoids, which occur in widely differing source. Particularly, marine organisms have provided a large number of sesterterpenoids , possessing novel carbon skeleton and a wide variety of biological activities. It has been largely reported that the anti-inflammatory activity is the most relevant among the biological activities observed for marine sesterterpenoids. Herein, we describe the link between chronic inflammation and cancer, and the more significant biologically active sesterterpenoids from marine organisms, grouped in a biogenetic sequence. Moreover, natural products that do not contain 25 carbon atoms but are obviously sesterterpene derivatives are also included. The high potential for some of these products suggested that they could be developed as drugs for the treatment of inflammation and cancer-related inflammation.

RETRACTED ARTICLE: Further in vitro biological activity evaluation of amino-, thio- and ester-derivatives of avarol

Abstract The acetylcholinesterase inhibitory and/or antitumour activities of amino-, thio- and ester-derivatives of avarol selected were evaluated for the first time at in vitro conditions. Avarol-3′,4′-dithioglycol (1) and avarol-4′-(3)mercaptopropionic acid (3) were shown to be the best inhibitors of the enzyme tested (0.50u2009µg and IC50 0.05u2009mM and 0.50u2009µg and IC50 0.12u2009mM, respectively), while 4′-tryptamine-avarone (9) and avarol-3′-(3)mercaptopropionic acid (2) exhibited the highest cytotoxicity against the human breast T-47D cancer cell line (IC50 0.66u2009µg/mL and 1.25u2009µg/mL, respectively). According to experimental data obtained, the sesquiterpenoid hydroquinone structure of bioactive avarol derivatives may inspire development of new pharmacologically useful substances to be used in the treatment of Alzheimers disease and/or human breast tumour.