Marine Cyclic Peptides: Antimicrobial Activity and Synthetic Strategies

Oceans are a rich source of structurally unique bioactive compounds from the perspective of potential therapeutic agents. Marine peptides are a particularly interesting group of secondary metabolites because of their chemistry and wide range of biological activities. Among them, cyclic peptides exhibit a broad spectrum of antimicrobial activities, including against bacteria, protozoa, fungi, and viruses. Moreover, there are several examples of marine cyclic peptides revealing interesting antimicrobial activities against numerous drug-resistant bacteria and fungi, making these compounds a very promising resource in the search for novel antimicrobial agents to revert multidrug-resistance. This review summarizes 174 marine cyclic peptides with antibacterial, antifungal, antiparasitic, or antiviral properties. These natural products were categorized according to their sources—sponges, mollusks, crustaceans, crabs, marine bacteria, and fungi—and chemical structure—cyclic peptides and depsipeptides. The antimicrobial activities, including against drug-resistant microorganisms, unusual structural characteristics, and hits more advanced in (pre)clinical studies, are highlighted. Nocathiacins I–III (91–93), unnarmicins A (114) and C (115), sclerotides A (160) and B (161), and plitidepsin (174) can be highlighted considering not only their high antimicrobial potency in vitro, but also for their promising in vivo results. Marine cyclic peptides are also interesting models for molecular modifications and/or total synthesis to obtain more potent compounds, with improved properties and in higher quantity. Solid-phase Fmoc- and Boc-protection chemistry is the major synthetic strategy to obtain marine cyclic peptides with antimicrobial properties, and key examples are presented guiding microbiologist and medicinal chemists to the discovery of new antimicrobial drug candidates from marine sources.     

Short-term changes in nitrogen availability, gas fluxes (CO2, NO, N2O) and microbial biomass after tillage during pasture re-establishment in Rondônia, Brazil

Anthropogenic conversion of primary forest to pasture for cattle production is still frequent in the Amazon Basin. Practices adopted by ranchers to restore productivity to degraded pasture have the potential to alter soil N availability and N gas losses from soils. We examined short-term (35 days) effects of tillage prior to pasture re-establishment on soil N availability, CO₂, NO and N₂O fluxes and microbial biomass C and N under degraded pasture at Nova Vida ranch, Rondônia, Brazilian Amazon. We collected soil samples and measured gas fluxes in tilled and control (non tilled pasture) 12 times at equally spaced intervals during October 2001 to quantify the effect of tillage. Maximum soil NH₄⁺ and NO₃⁻ pools were 13.2 and 6.3 kg N ha⁻¹ respectively after tillage compared to 0.24 and 6.3 kg N ha⁻¹ in the control. Carbon dioxide flux ranged from 118 to 181 mg C–CO₂ m² h⁻¹ in the control (non-tilled) and from 110 to 235 mg C–CO₂ m² h⁻¹ when tilled. Microbial biomass C varied from 365 to 461 μg g⁻¹ in the control and from 248 to 535 μg g⁻¹ when tilled. The values for N₂O fluxes ranged from 1.22 to 96.9 μg N m⁻² h⁻¹ in the tilled plots with a maximum 3 days after the second tilling. Variability in NO flux in the control and when tilled was consistent with previous measures of NO emissions from pasture at Nova Vida. When tilled, the NO/N₂O ratio remained <1 after the first tilling suggesting that denitrification dominated N cycling. The effects of tilling on microbial parameters were less clear, except for a decrease in qCO₂ and an increase in microbial biomass C/N immediately after tilling. Our results suggest that restoration of degraded pastures with tillage will lead to less C matter, at least initially. Further long-term research is needed.     

Blueberry Residue Encapsulation by Ionotropic Gelation

In the processing of fruits such as blueberry (Vaccinium sp), that has high levels of phenolic acid, the food industry produces tons of organic waste that causes harm to the environment. Encapsulation is a technique used to take advantage of these wastes. Several methods are used to encapsulate substances, among them ionotropic gelation proves to be a simple, precise, efficient and economical method for obtaining particles with encapsulated bioactives. In this manner, the aim of this study was to test sodium alginate as wall material to encapsulate blueberry residue by ionotropic gelation. The microbeads were characterized by scanning electron microscopy (SEM), x-ray diffraction (XRD), total phenolic compounds, antioxidant capacity and in vitro dissolution. The results showed that the microbeads had surface invagination; retention of 67.01% of the phenolic compounds after encapsulation and 68.2%, phenolic release 120 min after in vitro dissolution. The results suggest that the tested matrix was suitable for encapsulation. The produced microbeads are promising for applications in food products, once the phenolic compounds present in the blueberry residues were maintained after encapsulation.     

Spasmolytic Effect of Caulerpine Involves Blockade of Ca2+ Influx on Guinea Pig Ileum

In this work, we investigated the spasmolytic effect of caulerpine, a bisindole alkaloid isolated from marine algae of the Caulerpa genus, on guinea pig ileum. Our findings indicated that caulerpine inhibited phasic contractions induced by carbachol (IC₅₀ = 7.0 ± 1.9 × 10⁻⁵ M), histamine (IC₅₀ = 1.3 ± 0.3 × 10⁻⁴ M) and serotonin (IC₅₀ = 8.0 ± 1.4 × 10⁻⁵ M) in a non-selective manner. Furthermore, caulerpine concentration-dependently inhibited serotonin-induced cumulative contractions (pD′₂ = 4.48 ± 0.08), shifting the curves to the right with E_max reduction and slope of 2.44 ± 0.21, suggesting a noncompetitive antagonism pseudo-irreversible. The alkaloid also relaxed the ileum pre-contracted by KCl (EC₅₀ = 9.0 ± 0.9 × 10⁻⁵ M) and carbachol (EC₅₀ = 4.6 ± 0.7 × 10⁻⁵ M) in a concentration-dependent manner. This effect was probably due to inhibition of Ca²⁺ influx through voltage-gated calcium channels (Ca_V), since caulerpine slightly inhibited the CaCl₂-induced contractions in depolarizing medium without Ca²⁺, shifting the curves to the right and with E_max reduction. According to these results, the spasmolytic effect of caulerpine on guinea pig ileum seems to involve inhibition of Ca²⁺ influx through Ca_V. However, other mechanisms are not discarded.     

Mid-infrared absorption properties of green wood

There is a lack of quantitative data on the penetration depth and the amount of energy absorbed by green wood under infrared (IR) radiation. This lack of knowledge is a potential barrier to the development of IR heating as an alternative to soaking as a means of warming logs prior to peeling in the manufacture of plywood. Experimental measurements of normal hemispherical spectral reflectance and transmittance over the range 550–5,500 cm^?1 wavenumbers on four wood species, beech, birch, Douglas-fir and spruce have brought new knowledge on mid-infrared absorption properties of green wood and removed some uncertainties. For instance, it is not possible to deliver energy deeper than up to 0.3 mm below the wood surface because 70–90 % of all incident IR radiation on the wood surface is absorbed in this layer. Some wood features, such as surface quality, the presence of knots and of free water in wood (the latter two having a more significant effect) influence the amount of energy absorbed. These results illustrate that IR radiation can heat the surface layers, but then heat penetrates deeper into the inside layers of wood by conduction.     

Soil organic carbon fractions and humic substances are affected by land uses of Caatinga forest in Brazil

Caatinga is a Brazilian dry ecosystem that occupies around 1 million km² and is one of the largest tropical dry forests of the world. About 46% of the area that was originally covered has been deforested. Land use can cause pronounced reduction in soil carbon stocks that play a major role in the global carbon cycle. The objective of this study was to improve our understanding of the effect of land use on oxidizable carbon fractions, total carbon stocks and humic substances in different layers of soil in a Brazilian semi-arid region. We analyzed soils from tropical dry forest (TDF), forest succession with Anadenanthera falcata (ANA), with Tabebuia alba (TAB), secondary scrubby regeneration (SCR), and non-irrigated maize (MS). Forests showed larger fractions of more labile carbon, except for TDF. The most recalcitrant fraction of carbon stock, humin fraction stock, with the different land use decreased by 38–53% compared to TDF. Oxidizable carbon fractions, carbon stocks, and humic fraction stocks were able to differentiate the successional land uses and agricultural cover from TDF, mainly in the 0–5?cm layer. Our results show that changes in land use, especially with ANA forest succession, showed a larger labile carbon fraction, indicating easy decomposition and loss. Our results provide an alternative tool for the management of deforested areas in tropical dry caatinga ecosystems. This would contribute to the conservation of dry forest systems and could serve as guideline for sustainable management of agriculturally impacted caatinga areas.     

Production,chemical composition,and fatty acid profile of milk from buffaloes fed with cupuaçu (Theobroma grandiflorum) cake and murumuru (Astrocaryum murumuru) cake in the Eastern Amazon

The objective was to evaluate the effect of concentrate supplementation using by-products of the Amazonian industry on milk production, milk composition, and milk fatty acid profile of dairy buffaloes. Twelve lactating buffaloes (544.5 ± 35.6 kg, 6.4 ± 2.2 years old, 59 ± 6 days in milk) were allotted in a pasture of Mombaça grass and managed under rotational grazing (4 days occupancy/28 days rest). A 3 × 3 Latin square was adopted, and each animal alternately received three supplementary treatments based on corn bran + soybean meal or cupuaçu cake or murumuru cake for 21 days per treatment. Murumuru cake increased the levels of lauric acid and myristic acid in the milk (p < 0.05). Murumuru cake reduced the unsaturated fatty acid contents in the milk compared with animals fed control diet or cupuaçu cake (24.27% vs. 25.24% vs. 25.08%). The n-6/n-3 ratio was 2.6, 1.97, and 2.0 in the control, cupuaçu, and murumuru groups, respectively. Based on this parameter, cakes made from cupuaçu as well as murumuru could be considered to be adequate for inclusion in dairy water buffalo feed. However, the murumuru cake addition requires some caution because its use induces the secretion of higher levels of lauric and myristic fatty acids that are related to human cardiovascular disease.     

Kisspeptin,c‐Fos and CRFR Type 2 Co‐expression in the Hypothalamus after Insulin‐Induced Hypoglycaemia

Normal reproductive function is dependent upon availability of glucose and insulin‐induced hypoglycaemia is a metabolic stressor known to disrupt the ovine oestrous cycle. We have recently shown that IIH has the ability to delay the LH surge of intact ewes. In the present study, we examined brain tissue to determine: (i) which hypothalamic regions are activated with respect to IIH and (ii) the effect of IIH on kisspeptin cell activation and CRFR type 2 immunoreactivity, all of which may be involved in disruptive mechanisms. Follicular phases were synchronized with progesterone vaginal pessaries and at 28 h after progesterone withdrawal (PW), animals received saline (n = 6) or insulin (4 IU/kg; n = 5) and were subsequently killed at 31 h after PW (i.e., 3 h after insulin administration). Peripheral hormone concentrations were evaluated, and hypothalamic sections were immunostained for either kisspeptin and c‐Fos (a marker of neuronal activation) or CRFR type 2. Within 3 h of treatment, cortisol concentrations had increased whereas plasma oestradiol concentrations decreased in peripheral plasma (p < 0.05 for both). In the arcuate nucleus (ARC), insulin‐treated ewes had an increased expression of c‐Fos. Furthermore, the percentage of kisspeptin cells co‐expressing c‐Fos increased in the ARC (from 11 to 51%; p < 0.05), but there was no change in the medial pre‐optic area (mPOA; 14 vs 19%). CRFR type 2 expression in the lower part of the ARC and the median eminence was not altered by insulin treatment. Thus, disruption of the LH surge after IIH in the follicular phase is not associated with decreased kisspeptin cell activation or an increase in CRFR type 2 in the ARC but may involve other cell types located in the ARC nucleus which are activated in response to IIH.     

Canine fetal echocardiography: correlations for the analysis of cardiac dimensions

The aim of this study was to develop regression models for correlation of canine fetal heart development with body size to characterize normal development or suggest cardiac anomalies. Twenty clinically healthy pregnant bitches, either brachycephalic and non-brachycephalic, were examined ultrasonographically. Transabdominal fetal echocardiography was conducted every 4 days from the beginning of cardiac chambers differentiation until parturition. Ten cardiac parameters were measured: length, width and diameter of the heart; heart area; left and right ventricular dimensions; left and right atrial dimensions; and aortic and pulmonary artery diameter. Femoral length, biparietal diameter and abdominal cross-sectional area were also recorded. Regression equations were developed for each parameter of fetal body size, and linear and logarithmic models were compared. The model with the highest correlation coefficient was chosen to produce equations to calculate relative dimensions based on the correlations. Only the left-ventricular chamber differed between the two racial groups. Biparietal diameter was the independent parameter that produced the highest correlation coefficient for the most fetal cardiac dimensions, although good correlations were also observed using femoral length and abdominal cross-sectional area. Heart width and heart diameter were used as surrogates of cardiac development, as these measurements showed the best statistical correlation. Quantitative evaluation of fetal cardiac structures can be used to monitor normal and abnormal cardiac development.