Marine Anticancer Agents: An Overview with a Particular Focus on Their Chemical Classes

The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.     

Selection,characterization and genetic analysis of laboratory mutants of <Emphasis Type="Italic">Botryotinia fuckeliana</Emphasis> (<Emphasis Type="Italic">Botrytis cinerea</Emphasis>) resistant to the fungicide boscalid

Resistance to the fungicide boscalid in laboratory mutants of Botryotinia fuckeliana (Botrytis cinerea) was investigated. The baseline sensitivity to boscalid was evaluated in terms of colony growth (EC₅₀ = 0.3–3 μg ml⁻¹; MIC = 10–30 μg ml⁻¹) and conidial germination (EC₅₀ = 0.03–0.1 μg ml⁻¹; MIC = 1–3 μg ml⁻¹) tests. Mutants were selected in vitro from wild-type strains of the fungus on a fungicide-amended medium containing acetate as a carbon source. Mutants showed two different levels of resistance to boscalid, distinguishable through the conidial germination tests: low (EC₅₀ ∼ 0.3 μg ml⁻¹, ranging from 0.03 to 1 μg ml⁻¹; MIC > 100 μg ml⁻¹) and high (EC₅₀ > 100 μg ml⁻¹) resistance. Analysis of meiotic progeny from crosses between resistant mutants and sensitive reference strains showed that resistant phenotypes were due to mutations in single major gene(s) inherited in a Mendelian fashion, and linked with both the Daf1 and Mbc1 genes, responsible for resistance to dicarboximide and benzimidazole fungicides, respectively. Gene sequence analysis of the four sub-units of the boscalid-target protein, the succinate dehydrogenase enzyme, revealed that single or double point mutations in the highly conserved regions of the iron-sulphur protein (Ip) gene were associated with resistance. Mutations resulted in proline to leucine or phenylalanine replacements at position 225 (P225L or P225F) in high resistant mutants, and in a histidine to tyrosine replacement at position 272 (H272Y) in low resistant mutants. Sequences of the flavoprotein and the two transmembrane sub-units of succinate dehydrogenase were never affected.     

Daily variations of serum lipids in Ovis aries under different lighting and feeding conditions

The aim of this study was to discriminate the impact of lighting and feeding conditions on the regulation of lipid metabolism in Ovis aries. Six clinically healthy female Comisana ewes, not pregnant and not lactating were kept under different environmental conditions: 12:12 light-dark (LD) cycle, constant darkness and fasting. Blood samples were collected at the end of each period of treatment every 4 h for a 24-h period. Blood concentration of triglycerides, total cholesterol and non-esterified fatty acid showed robust daily rhythmicity in ewes maintained under 12:12 LD cycle and fed ad libitum. Conversely, either constant darkness or fasting had a deep impact on all lipid parameters investigated. Our results suggest that lighting and feeding conditions have an impact on daily variations in lipid metabolism in ewes.     

The influence of gamete co-incubation length on the in vitro fertility and sex ratio of bovine bulls with different penetration speed

The objectives of this work were to evaluate whether the sperm penetration speed is correlated to the in vitro fertility and whether adapting the gamete co-incubation length to the kinetics of the bull improves in vitro fertility and affects the sex ratio. In vitro matured oocytes were co-incubated with spermatozoa from four different bulls (A-D). At various post-insemination (p.i.) times (4, 8, 12, 16 and 20 h), samples of oocytes were fixed and stained with DAPI for nuclei examination, while the remaining ones were transferred into culture to evaluate embryo development. The blastocysts produced were sexed by PCR. Two bulls (A and B) had faster kinetics than the others (C and D), as shown by the higher penetration rates recorded at 4 h p.i. (43%, 30%, 11% and 6%, respectively for bulls A, B, C and D; p<0.01). The differences in the kinetics among bulls did not reflect their in vitro fertility. The incidence of polyspermy was higher for faster penetrating bulls (36%, 24%, 16% and 4%, respectively for bulls A, B, C and D; p<0.01) and at longer co-incubation times (0%, 16%, 19%, 30% and 34%, respectively at 4, 8, 12, 16 and 20 h p.i.; p<0.01). The fertilizing ability of individual bulls may be improved by adapting the co-incubation length to their penetration speed. A sperm-oocyte co-incubation length of 8 h ensured the greatest blastocyst yields for the two faster penetrating bulls. On the contrary, 16 h co-incubation was required to increase (p<0.01) cleavage rate of the two slower bulls. Bulls with a faster kinetics did not alter the embryo sex ratio towards males. The female/male (F/M) ratios recorded were 2.1, 1.4, 1.2, 1.3 and 1.6, respectively at 4, 8, 12, 16 and 20 h p.i.     

Meat quality and intramuscular fatty acid composition of Catria Horse

In order to extend scientific knowledge on autochthonous Italian equine meat, the physical–chemical parameters of Catria Horse Longissimus thoracis (LT) muscle and its nutritional characteristics have been investigated. Ten steaks of Catria foal raised at pasture and fattened indoors for 2 months were dissected, and LT muscle was analyzed for chemical composition, total iron, drip loss, colorimetric characteristics, intramuscular fat, fatty acid profile and nutritional indexes. Steak dissection showed that LT muscle accounted for 36.78% and fat accounted for 9.19% of weight of steak. Regarding chemical composition, protein and fat content was 20.31% and 2.83%, respectively. Total iron content (1.95 mg/100 g) was lower than data reported in the literature. Color parameters showed a luminous and intense red hue muscle. The sum of unsaturated fatty acid composition (50.3%) was higher than the sum of saturated fatty acids (46.64 %). The fatty acid profile and nutritional values of Catria Horse meat could be modified adopting extensive rearing systems and grazing. The data suggests that further investigation on the composition of Catria Horse meat should be carried out to valorize this autochthonous breed, reared in sustainable livestock systems, and its meat in local short‐chain systems.     

Closed cycle subirrigation with low concentration nutrient solution can be used for soilless tomato production in saline conditions

Closed cycle soilless techniques can be adopted to minimize water and fertilizer losses in greenhouse cultivation. There is a general lack of information regarding the soilless cultivation of vegetables with closed cycle subirrigation techniques, specifically when using saline water. In this study, a trough bench subirrigation system (SUB), with two fertilizer concentrations (“100%”, containing 9.8 mol m⁻³ N-NO₃, 1.6 mol m⁻³ P-H₂PO₄, 8.7 mol m⁻³ K⁺, 2.8 mol m⁻³ Ca⁺, 1.8 mol m⁻³ Mg⁺, 4 mol m⁻³ S-SO₄, and “70%”, containing 70% of the macronutrient concentration) in the nutrient solution (NS), was compared with open cycle drip-irrigation (DRIP with “100%” NS). For all the three treatments, NS was prepared using rain water (0.05 dS m⁻¹) and adding NaCl (1 g L⁻¹), in order to simulate moderate saline irrigation water. The effect of the treatments on tomato (Solanum lycopersicum L.) plant growth, yield, fruit quality, water use efficiency (WUE) and fertilizer consumption was evaluated. Substrate and recirculating NS composition were also studied. Subirrigation, regardless of NS concentration, reduced plant height (by 30 cm), leaf area (by 1411 cm²), total fresh and dry weight (by 429 and 48.5 g plant⁻¹, respectively) but not dry matter percentage of the whole plant, with respect to DRIP. Yield was reduced when plants were subirrigated with the higher concentrated NS, but no differences with open cycle DRIP were recorded when the lower NS concentration was used in SUB. Fruit quality was not affected by irrigation system or NS concentration. The higher WUE was obtained with subirrigation. NaCl accumulated similarly over the crop cycle in recirculating NS of both SUB treatments and in growing substrates of all the three treatments. Higher salt concentration was found in subirrigated substrates, in particular in the upper part of the substrate profile. Fertilizers accumulated in the subirrigated substrates when the higher NS concentration was used, but not when the NS concentration was reduced by 30%. The results of this study indicate that tomato can be grown successfully in a closed cycle subirrigation system, using saline water, by reducing the fertilizer NS concentration normally used with traditional open cycle systems.