Comparative evaluation of rhFGF18 and rhGDF11 treatment in a transient ischemia stroke model.

Background: Pharmacological treatments for ischemic stroke remain limited to thrombolysis, which is associated with increased risk of potentially fatal hemorrhage. Treatments with Recombinant Human Fibroblast Growth Factor 18 (rhFGF18) and Growth and Differentiation Factor 11 (rhGDF11) appear promising based on different preclinical models. The goal of this study was to compare the effects of rhFGF18 and rhGDF11 directly on survival, behavioral deficits, and histological fingerprint of cerebral ischemia in the Wistar rat middle cerebral artery occlusion (MCAO) model of stroke. Methods: Ischemia-reperfusion injury was induced using a 2-hour transient MCAO. Animals were administered rhFGF18 (infusion), rhGDF11 (multi-injection), or Phosphate Buffered Saline (PBS) vehicle control and followed for 42 days. Motor-Cognitive deficits were evaluated using the Morris Water Maze at Days 0 (pre-MCAO), 7, 21, and 42. Histopathological assessments were performed on Days 21 and 42. Results: Day 7 post-ischemia water maze performance times increased 38.3%, 2.1%, and 23.1% for PBS, rhFGF18, and rhGDF11-treated groups, respectively. Fraction of neurons with abnormal morphology (chromatolysis, pyknotic nuclei, somal degeneration) decreased in all groups toward Day 42 and was lowest for rhFGF18. AChE-positive fiber density and activity increased over time in the rhFGF18 group, remained unchanged in the rhGDF11 treatment arm, and declined in the PBS control. Metabolic increases were greatest in rhGDF11 treated animals, with both rhFGF18 and rhGDF11 achieving improvements over PBS, as evidenced by increased succinate dehydrogenase and lactate dehydrogenase activity. Finally, rhFGF18 treatment exhibited a trend for reduced mortality relative to PBS (5.6%, 95% CI [27.3%, 0.1% ] vs. 22.2%, 95% CI [47.6%, 6.4% ]). Conclusions: rhFGF18 treatment appears promising in improving survival and promoting motor-cognitive recovery following cerebral ischemia-reperfusion injury.

Modern Approaches to Lower Lipoprotein(a) Concentrations and Consequences for Cardiovascular Diseases.

Lipoprotein(a) (Lp(a)) is a low density lipoprotein particle that is associated with poor cardiovascular prognosis due to pro-atherogenic, pro-thrombotic, pro-inflammatory and pro-oxidative properties. Traditional lipid-lowering therapy does not provide a sufficient Lp(a) reduction. For PCSK9 inhibitors a small reduction of Lp(a) levels could be shown, which was associated with a reduction in cardiovascular events, independently of the effect on LDL cholesterol. Another option is inclisiran, for which no outcome data are available yet. Lipoprotein apheresis acutely and in the long run decreases Lp(a) levels and effectively improves cardiovascular prognosis in high-risk patients who cannot be satisfactorily treated with drugs. New drugs inhibiting the synthesis of apolipoprotein(a) (an antisense oligonucleotide (Pelacarsen) and two siRNA drugs) are studied. Unlike LDL-cholesterol, for Lp(a) no target value has been defined up to now. This overview presents data of modern capabilities of cardiovascular risk reduction by lowering Lp(a) level.

Growth, aboveground biomass, and nutrient concentration of young Scots pine and lodgepole pine in oil shale post-mining landscapes in Estonia.

The investigation was carried out in 8-year-old Scots pine (Pinus sylvestris L.) and lodgepole pine (Pinus contorta var. latifolia Engelm.) plantations on post-mining area, Northeast Estonia. The aim of the study was to assess the suitability of lodgepole pine for restoration of degraded lands by comparing the growth, biomass, and nutrient concentration of studied species. The height growth of trees was greater in the Scots pine stand, but the tree aboveground biomass was slightly larger in the lodgepole pine stand. The aboveground biomass allocation to the compartments did not differ significantly between species. The vertical distribution of compartments showed that 43.2% of the Scots pine needles were located in the middle layer of the crown, while 58.5% of the lodgepole pine needles were in the lowest layer of the crown. The largest share of the shoots and stem of both species was allocated to the lowest layer of the crown. For both species, the highest NPK concentrations were found in the needles and the lowest in the stems. On the basis of the present study results, it can be concluded that the early growth of Scots pine and lodgepole pine on oil shale post-mining landscapes is similar.

Short-term responses of soil chemistry, needle macronutrients and tree growth to clinker dust and fertiliser in a stand of Scots pine.

Waste management of clinker dust by spreading it on forest soil was studied in a 25-year-old Scots pine stand on acidic sandy soil. Clinker dust (0.5 kg m⁻²), fertiliser (N, P, K, Mg, 0.05 kg m⁻²; N 190 kg ha⁻¹) and untreated soil were applied on 120-m² plots in four replicates. The fertiliser was included to confirm the nutrient limitation in the stand. Clinker dust increased the soil pH by 1.2 units relative to the pH of 4.6 in the untreated soil by the second year. Soil K and Mg concentrations were larger in the dust and fertiliser treatments. Nutrient diagnostics indicated that needles of untreated trees were deficient in N and K. Fertiliser treatment indicated that the growth of trees was limited by N, since the fertiliser tended to increase needle K, N, N/P, needle dry mass and diameters of stem and shoots. By an auxiliary dataset, no effects of the dust and fertiliser on possible excess of the micronutrient Mn were observed. Clinker dust increased needle K concentration, but due to the N limitation, there was no increase in the growth of stems, branches, shoots and needles. It was concluded that in plots of 120 m² application of clinker dust at a rate of 0.5 kg m⁻² was safe for the 21-year-old Scots pine stand in this trial on an acid nutrient-poor sandy soil during 4 years after the treatment.

A comparison of the growth of Scots pine (Pinus sylvestris L.) in a reclaimed oil shale post-mining area and in a Calluna site in Estonia.

The growth of Scots pine and its suitability for afforestation of post-mining landscapes in Northeast Estonia were assessed in comparative analytical studies by using morphological parameters and mineral nutrition characteristics. The growth and nutrient uptake of Scots pine growing on post-mining substrate were compared with the characteristics of pines of the same age (22-23 years) in a Calluna forest site type predominant in North Estonia in similar climatic zone. Results of the analyses of soil upper layers showed that the concentration of N and P in soil did not differ between the opencast spoil and Calluna site, but significantly higher pH of soil and concentrations of K, Ca, and Mg were found in mine spoil. The concentrations of K and Mg in needles were significantly higher in the post-mining area, but the concentrations of N, P, and Ca did not differ significantly. Comparison of the needle nutrient concentration with the standard for optimum concentrations revealed P deficit in the post-mining area and P and K deficit in the Calluna site. Scots pine formed longer and thinner needles and shoots in the post-mining substrate than in the Calluna site. It was assumed that in the post-mining area the growth of pines is predominantly dependent on K and Ca concentrations in their tissues as the biomass of needles was strongly correlated with the K/Ca ratio, whereas the biomass in the Calluna site was correlated with the N/P ratio. The height and diameter of trees were significantly larger in the post-mining area.