Search Results (13)

This study aimed to evaluate the hepatoprotective effects of nettle (Urtica dioica L.) leaf water extracts on oxygen consumption in the fatty acid oxidation (FAO) pathway using an in vitro fatty liver HepG2 cell model and employing an oxygraphy approach. It also examined the impact of these extracts on HepG2 cell lipid accumulation and viability under oxidative stress. The extracts were obtained via maceration with preservatives or by sonication with/without preservatives. Their chemical composition, including polyphenols, vitamins, and minerals, was analyzed. Bioactivity was confirmed through antioxidant and antiglycation in vitro assays. The extracts contained minerals, water-soluble vitamins, and polyphenols, primarily phenolic acids and rutin. Sonication increased the polyphenol yield, advanced glycation end-product (AGE) inhibition, and total antioxidant capacity compared to maceration. The added preservatives enhanced DPPH scavenging, while SOD-mimicking effects were comparable across extraction methods. In the liver steatosis model, the nettle extracts improved HepG2 cell viability under oxidative stress, reduced lipid accumulation, and enhanced mitochondrial oxygen consumption in the FAO pathway at mitochondria complex I. These findings demonstrate the impact of nettle leaf water extracts on oxygen flux in different oxidative phosphorylation states of the FAO pathway and deepen the understanding of nettle’s protective role in hepatic steatosis. The obtained results confirm the hepatoprotective effects of nettles through multiple mechanisms, primarily involving antioxidant activity, modulation of lipid accumulation, and mitochondrial protection. Full article

Fungal communities can be used as indicators of various environmental processes in forest ecosystems. The diversity of these communities is linked to aboveground plants and soil properties. We assessed fungal diversity at four Norway spruce sampling sites that were growing on fertile mineral soils (Oxalidosa) in northwestern Latvia. Three sites were managed—a three-year-old clear-cut and fifty- and eighty-five-year-old stands; one site was unmanaged—a naturally regenerated site after wind damage in 1969. For metabarcoding, we used a fungal internal transcribed spacer (ITS2) and high throughput sequencing with the Ion Torrent platform. Our results showed high operational taxonomic unit richness in the samples, with notable variation in community composition between individual plots both within and among sites, with the highest being in managed, middle-aged stands and the lowest in unmanaged. Significant differences in the diversity of soil fungal communities were not detected between the sites. Redundancy analysis indicated that pH, soil organic matter, organic carbon, and nitrogen were the most important soil variables that explained the variation in fungal communities. The unmanaged stand differed notably by community composition. This study highlights the importance of monitoring forest soil environmental parameters and fungal communities to gain a more comprehensive assessment of forestry management regimes. Full article

Background and Objectives. Neurogenesis is an integral process in post-stroke recovery, involving the recruitment of proliferating neuroblasts from neurogenic niches of the mammal brain. However, the role of neurogenesis in the long-term restoration following ischemic stroke is fragmented. Post-stroke motor dysfunction includes challenges in the proper, coordinated use of hands and is present in roughly two-thirds of human patients. In this study, we investigated chronic behavioral and biochemical alterations after transient cerebral ischemia in adult male mice. Materials and Methods: Twelve-week-old C57BL/6N male mice were used, and fMCAo lasting 60 min was induced. At multiple timepoints after fMCAo induction, a single pellet reaching task was performed. Six months after the procedure, we immunohistochemically determined the number of proliferating neuroblasts (BrdU and DCX-positive) and the number of differentiated astrocytes (GFAP-positive) in both brain hemispheres. Results: The reaching ability of fMCAo mice was impaired from one month to six months after the induction of ischemia. Neuroblast proliferation was increased in the ipsilateral SVZ, whereas GFAP+ cell count was elevated in the hippocampal DG of both hemispheres of the fMCAo group mice. Conclusions: Our current report demonstrates the long-term effects of transient cerebral ischemia on mice functional parameters and neurogenesis progression. Our data demonstrate that transient cerebral ischemia promotes a long-lasting regenerative response in the ipsilateral brain hemisphere, specifically in the neurogenic SVZ and DG regions. Full article

Cerebral ischemia/reperfusion (I/R) refers to a secondary brain injury that results in mitochondrial dysfunction of variable extent, leading to neuronal cell damage. The impact of this process has mainly been studied in the short term, from the early hours up to one week after blood flow reperfusion, and in the ischemic hemisphere only. The focus of this study was to assess the long-term impacts of I/R on mitochondrial functionality using high-resolution fluorespirometry to evaluate state-dependent activities in both ischemic (ipsilateral) and non-ischemic (contralateral) hemispheres of male mice 60, 90, 120, and 180 days after I/R caused by 60-min-long filament-induced middle cerebral artery occlusion (fMCAo). Our results indicate that in cortical tissues, succinate-supported oxygen flux (Complex I&II OXPHOS state) and H₂O₂ production (Complex II LEAK state) were significantly decreased in the fMCAo (stroke) group ipsilateral hemisphere compared to measurements in the contralateral hemisphere 60 and 90 days after stroke. In hippocampal tissues, during the Complex I&II ET state, mitochondrial respiration was generally lower in the ipsilateral compared to the contralateral hemisphere 90 days following stroke. An aging-dependent impact on mitochondria oxygen consumption following I/R injury was observed 180 days after surgery, wherein Complex I&II activities were lowest in both hemispheres. The obtained results highlight the importance of long-term studies in the field of ischemic stroke, particularly when evaluating mitochondrial bioenergetics in specific brain regions within and between separately affected cerebral hemispheres. Full article

Background and Objectives: Dissecting the complex pathological cascade of an ischemic stroke in preclinical models is highly warranted to understand the course of this disease in humans. Neurogenesis and angiogenesis are integral for post-stroke recovery, yet it is not clear how these processes are altered months after an ischemic stroke. In this study, we investigated the changes that take place subacutely after focal cerebral ischemia in experimental adult male mice. Materials and Methods: Male 12-week-old C57BL/6 mice underwent a 60 min long fMCAo or sham surgery. Two months after the procedure, we examined the immunohistochemistry to assess the changes in neuroblast (DCX) and differentiated neuron (NeuN) numbers, as well as the density of the pro-angiogenic factor VEGF. Results: We found decreased neuroblast numbers in both brain hemispheres of the fMCAo mice: by more than 85% in the dentate gyrus and by more than 70% in the subventricular zone. No neuroblasts were found in the contralateral hemisphere of the fMCAO mice or the sham controls, but a small population was detected in the ipsilateral ischemic core of the fMCAo mice. Intriguingly, the number of differentiated neurons in the ipsilateral ischemic core was lower by 20% compared to the contralateral hemisphere. VEGF expression was diminished in both brain hemispheres of the fMCAo mice. Conclusions: Our current report shows that focal cerebral ischemia induces changes in neuroblast numbers and the pro-angiogenic factor VEGF in both cerebral hemispheres 2 months after an fMCAo in mice. Our data show that focal cerebral ischemia induces a long-term regenerative response in both brain hemispheres. Full article

Callosotomy is an invasive method that is used to study the role of interhemispheric functional connectivity in the brain. This surgical approach is technically demanding to perform in small laboratory animals, such as rodents, due to several methodological challenges. To date, there exist two main approaches for transecting the corpus callosum (CC) in rodents: trephine hole(s) or unilateral craniotomy, which cause damage to the cerebral cortex or the injury of large vessels, and may lead to intracranial hemorrhage and animal death. This study presents an improved surgical approach for complete corpus callosotomy in mice using an interhemispheric approach combined with bilateral and extended craniotomy across the midline. This study demonstrated that bilateral and extended craniotomy provided the visual space required for hemisphere and sinus retraction, thus keeping large blood vessels and surrounding brain structures intact under the surgical microscope using standardized surgical instruments. We also emphasized the importance of good post-operative care leading to an increase in overall animal survival following experimentation. This optimized surgical approach avoids extracallosal tissue and medium- to large-sized cerebral blood vessel damage in mice, which can provide higher study reproducibility/validity among animals when revealing the role of the CC in various neurological pathologies. Full article

Alzheimer’s disease (AD) is the most common cause of dementia. Fingolimod has previously shown beneficial effects in different animal models of AD. However, it has shown contradictory effects when it has been applied at early disease stages. Our objective was to evaluate fingolimod in two different treatment paradigms. To address this aim, we treated male and female APP-transgenic mice for 50 days, starting either before plaque deposition at 50 days of age (early) or at 125 days of age (late). To evaluate the effects, we investigated the neuroinflammatory and glial markers, the Aβ load, and the concentration of the brain-derived neurotrophic factor (BDNF). We found a reduced Aβ load only in male animals in the late treatment paradigm. These animals also showed reduced microglia activation and reduced IL-1β. No other treatment group showed any difference in comparison to the controls. On the other hand, we detected a linear correlation between BDNF and the brain Aβ concentrations. The fingolimod treatment has shown beneficial effects in AD models, but the outcome depends on the neuroinflammatory state at the start of the treatment. Thus, according to our data, a fingolimod treatment would be effective after the onset of the first AD symptoms, mainly affecting the neuroinflammatory reaction to the ongoing Aβ deposition. Full article

The annual shoot elongation could be described by a non-linear growth model to characterize differences in its dynamics among spruce genotypes, the effect of each shoot elongation phase on the total shoot length, and the genetic differences for a particular growth phase. The terminal shoot length was measured in two open-pollinated progeny trials of Norway spruce on average once per week during the ninth growing season. For the analysis, 10% of families with the longest annual increment (shoot) and 10% with the shortest were selected for each trial. The Gompertz model was fitted to individual tree data, and the mean values of its coefficients for each group of families were obtained. Family significantly (p < 0.001) affected total shoot length and all growth rhythm parameters, with similar trends reported in both studied sites. Heritability of Gompertz model coefficients in most cases exceeded that of the tree height. The superior10% of families started shoot elongation slightly but non-significantly earlier (all p > 0.05) than the other groups of families and had more intense shoot elongation (mm per day) during the entire growing season. A strong negative relation was found between the slope coefficient of the cumulative shoot elongation lines and the total height increment. The group of families with the longest increment had flatter relative shoot elongation lines, indicating relatively more evenly distributed growth within the growing season. In contrast, families with the shortest increment tended to accumulate a higher proportion of height increment during the active growth phase and reduced relative growth intensity more rapidly. The 10% of families with the largest annual increment showed superior characteristics in all shoot elongation phases, resulting in 30–40% longer shoots compared to the 10% of families with the smallest annual increment. The significant differences in Gompertz model coefficients indicate that genotypes with favorable growth patterns might be selected. Full article

Wood ash recycling can be a reasonable method for energy producers to decrease waste problems. Using wood ash as a fertilizer or liming material could improve soil macro and micronutrient content in peat soils. Therefore, the effect of wood ash on Norway spruce (Picea abies (L.) Karst) and Scots pine (Pinus sylvestris L.) juvenile growth and nutrient content in the soil after spreading wood ash in medium to high doses before and after planting seedlings was investigated in peat forests in the Eastern part of Latvia. The aim of the study was to evaluate the effect of high doses of wood ash on soil properties and the growth of planted Norway spruce and Scots pine seedlings up to 10 years after experiment establishment. Wood ash was applied a year before planting seedlings in doses of 5 and 10 t ha⁻¹ and right after planting in concentrations of 5, 10, 15, and 20 t ha⁻¹. Changes in macronutrient content (i.e., phosphorus [P], and potassium [K]) and tree height and diameter at breast height were measured at one and 10 years after establishing the experiment. Fertilization one year prior to planting the seedlings exhibited a positive response on tree height and diameter growth compared to fertilization after the seedlings were planted. Soil samples from fertilized plots one year after establishment contained more P and K in the soil than the control plots. Wood ash application of the highest doses did not reach the overdose limit, as the tree growth (height and diameter at breast height) results of fertilized plots were similar to those of the control fields; therefore, no significant negative effect on tree growth was discovered. Full article

The needles of conifer trees are one of the richest sources of natural polyprenols. Polyprenol homologs from Abies sibirica L. lipophilic 80% purified extract were analyzed and quantified. In total, 10 peaks (Prenol-11 to Prenol-20) were observed in the ultra-high-performance liquid chromatography–diode array detector (UHPLC-DAD) chromatogram of Siberian fir with the most abundant compound being Prenol-15 (relative amount 37.23 + 0.56% of the total polyprenol yield). Abies sibirica L. polyprenol solubility and incorporation efficiency into liposomes were studied in various commercially available lecithin mixtures (Phosal IP40, Phosal 75SA, and Lipoid P45). The resulting multilamellar polyprenol liposomes were morphologically characterized by Light and Transmission Electron Microscopy, and the liposome size was discovered to be polymodal with the main peak at 1360 nm (90% of the volume). As polyprenols are fully soluble only in lipids, a liposomal formulation based upon co-solubilization and a modified ethanol injection method of polyprenols into the ethanol-phospholipid system was developed for the entrapment and delivery of polyprenols for potential commercial applications in food supplement and cosmetic industries. Full article

Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM).
Material and Methods. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay.
Results. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values.
Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes. Full article

Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6‑OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease. Full article