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.     

Comparison of 2 blind approaches to the paravertebral brachial plexus regional block in canine cadavers

The paravertebral brachial plexus block (PVB) provides thoracic limb analgesia. The objective was to describe a blind craniocaudal (CC) approach to the PVB and compare its accuracy, time, and difficulty of performance with a blind dorsoventral (DV) approach. The operator was initially trained by experienced clinicians to perform both approaches on 5 cadavers. Next, a CC or DV approach to the PVB was performed on both thoracic limbs of 20 cadavers (20 for each approach). Methylene blue dye was equally divided into 4 aliquots to stain the ventral branches of the sixth to eighth cervical and first thoracic spinal nerves. Successfully stained (stain ≥ 1 cm) spinal nerves were counted. The time to perform each approach was recorded and ease of performance was scored using a numerical scale (1 “easy” to 4 “difficult”). The phrenic nerve was checked for stain. A Wilcoxon signed-rank test was used to compare approaches. The data are presented as median (interquartile range; minimum to maximum range). The number of stained nerves with the CC approach 3 (1; 2 to 4), was higher than the DV approach 2 (2; 0 to 4) (P = 0.002). The time (in seconds) to perform the CC approach 125 (79; 70 to 194), was not different from the DV approach 142 (54; 101 to 232) (P = 0.084). The CC approach 2 (2; 1 to 4) was easier to perform than the DV approach 3 (1; 2 to 4) (P = 0.024). No phrenic nerve staining was observed with either approach. The CC approach is an alternative to the DV approach for performing the PVB in dogs.     

Mussel Shells,a Valuable Calcium Resource for the Pharmaceutical Industry

(1) Background: The mussel (Mytilus edulis, Mytilus galloprovincialis) is the most widespread lamellibranch mollusk, being fished on all coasts of the European seas. Mussels are also widely grown in Japan, China, and Spain, especially for food purposes. This paper shows an original technique for mussel shell processing for preparation of calcium salts, such as calcium levulinate. This process involves synthesis of calcium levulinate by treatment of Mytilus galloprovincialis shells with levulinic acid. The advantage of mussel shell utilization results in more straightforward qualitative composition. Thus, the weight of the mineral component lies with calcium carbonate, which can be used for extraction of pharmaceutical preparations. (2) Methods: Shell powder was first deproteinized by calcination, then the mineral part was treated with levulinic acid. The problem of shells generally resulting from the industrialization of marine molluscs creates enough shortcomings, if one only mentions storage and handling. One of the solutions proposed by us is the capitalization of calcium from shells in the pharmaceutical industry. (3) Results: The toxicity of calcium levulinate synthesized from the mussel shells was evaluated by the method known in the scientific literature as the Constantinescu phytobiological method (using wheat kernels, Triticum vulgare Mill). Acute toxicity of calcium levulinate was evaluated; the experiments showed the low toxicity of calcium levulinate. (4) Conclusion: The experimental results highlighted calcium as the predominant element in the composition of mussel shells, which strengthens the argument of capitalizing the shells as an important natural source of calcium.     

RESPONSE OF WHEAT COMPOSITE CROSS POPULATIONS TO DISEASE AND CLIMATE VARIATION OVER 13 GENERATIONS

• Agronomic performance of wheat populations comparable to modern cultivars.• Performance of populations depends on parental cultivar selection.• Agronomic advantage of populations under particular environmental stresses.• Heterogeneous populations better suited to low-input conditions.Since the F₅ (2005), three winter wheat composite cross populations (CCPs) based on germplasm specifically suitable for low-input conditions were subjected to natural selection under organic and conventional management. In the F₆, each CCP was divided into two parallel populations (12 CCPs in total) and maintained continuously until 2018. Commonly used modern cultivars with different disease susceptibilities were grown alongside to assess the agronomic performance of the CCPs. The organically managed CCPs were comparable in yield and foliar disease resistance to two continuously used reference cultivars, Achat and Capo. In contrast, under conventional management the cv. Capo outyielded the CCPs (Achat was not tested), highlighting the importance of parental cultivar choice for specific management systems. The CCPs were found to be moderately resistant to brown rust and even to the newly emerged stripe rust races prevalent in Europe since 2011. Differences between the CCPs were mainly due to parental genetic background and were significant in the first five generations, but were no longer so in the last five generations. In addition, these differences tended to vary depending on the experimental year and the environmental stresses present. In conclusion, the CCPs despite being derived from older cultivars are able to compete with more recently released reference cultivars under organic farming practices and represent a dynamic germplasm resource.     

Effect of three diets on the gametogenic development and fatty acid profile of Paracentrotus lividus (Lamarck, 1816) gonads

In this study, the effects of three diets were investigated to enhance Paracentrotus lividus production for commercial purposes. P. lividus were fed ad libitum for 80 days with: diet A—fresh Codium tomentosum Stackhouse, 1797; diet B—formulated using a jellified mix of macroalgae and vegetables, including C. tomentosum (20%), Coralina sp. Linnaeus, 1758 (17%), cabbage Brassica oleracea var. capitata Linnaeus, 1753 (30%), carrot Daucus carota Linnaeus, 1753 (30%) and agar (3%) as a gelling agent. Diet C consisted of maize Zea mays Linnaeus, 1753 (56%) and New Zealand spinach Tetragonia tetragonoides (Pallas, 1781) Kuntze, 1891 (44%). Their effects on the gonadal and somatic growths, gonadosomatic index (GI) and gametogenesis were evaluated, as well as on the total lipid content and fatty acid composition of sea urchin's gonads. Diet A provided high values of eicosapentaenoic acid (EPA). Gonads of sea urchins fed with diet A were found mostly in growth and maturation stages of gametogenesis and showed the lowest lipid content. Sea urchins fed with diet B presented their gonads in the reabsorption stage and had the highest values of omega‐3 polyunsaturated fatty acids (PUFAs). Sea urchins fed with diet C were in the early stages of gametogenesis and had the highest values of lipid content, plus omega‐6 PUFAs. Once as an ingredient in a balanced mix with vegetables, C. tomentosum can be a key factor to the development of new promising high‐quality and low‐cost feed for P. lividus roe enhancement.     

Effect of dietary carbohydrate-to-lipid ratios on growth, lipid deposition and metabolic hepatic enzymes in juvenile Senegalese sole (Solea senegalensis, Kaup)

A study was undertaken to determine the effect of various dietary carbohydrate‐to‐lipid ratios on growth performance, whole‐body composition and tissue lipid content in Senegalese sole (Solea senegalensis) juveniles. Data on the dietary regulation of key hepatic enzymes of the lipogenic and glycolytic pathways (glucose‐6‐phosphate dehydrogenase, G6PD; malic enzyme, ME; fatty acid synthetase, FAS; pyruvate kinase, PK and glucokinase, GK) were also generated. Four isonitrogenous (crude protein: 52% dry matter (DM)) diets were formulated to contain one of two lipid levels (11% and 21% DM). Within each dietary lipid level, the nature of the carbohydrate fraction (raw or extruded peas) was varied. Triplicate groups of 54 sole (initial body weight: 23.6±1.2 g) were grown in recirculated seawater over 67 days. Fish were fed using automated feeders. At the end of the study, whole‐body, liver, viscera and muscle samples were withdrawn for analyses. During the experimental period, the mean fish weight about doubled in all treatments. No significant differences were found in growth performance (ranging from 1.1% to 1.4% body weight day^?1) among dietary treatments. High‐fat diets increased whole‐body fat content. Similarly, daily fat gain ranged from 0.54 to 0.78 g kg^?1 day^?1 and highest values were found in fish fed high‐lipid diets. Dietary treatments also affected tissue lipid content (liver, viscera and muscle), with highest values in fish fed high‐fat diets. The nature of dietary carbohydrates had little influence on performance criteria, but affected tissue lipid deposition. The activities of G6PD, ME and FAS were depressed by elevated levels of dietary lipid, confirming the inhibitory effect of dietary fats on lipid biosynthesis. At both dietary lipid levels, ME and FAS activities were little affected by dietary carbohydrate. Activities of PK and GK were not affected by the starch level of the diets. In Senegalese sole juveniles, the lipogenic pathway is more susceptible to modulation by dietary means (particularly through lipid intake) than the glycolytic pathway.