Early-Life Exposure to Commercial Formulation Containing Deltamethrin and Cypermethrin Insecticides Impacts Redox System and Induces Unexpected Regional Effects in Rat Offspring Brain

Several studies have shown that the oxidative impact of pesticides is most prevalent in rural environments where they are intensively used. At different levels, pyrethroids are reported to promote neurodegeneration; they share the ability to promote oxidative stress, and to induce mitochondrial impairments, a-synuclein overexpression and neuronal cell loss. The present study evaluates the impact of early-life exposure to a commercial formulation containing deltamethrin (DM) and cypermethrin (CYP) at a dose of 1/100 LD50 (1.28 and 2.5 mg/kg, respectively). Rats aged 30 days old, treated from the 6th to the 21st day of life, were tested for brain antioxidant activity and a-synuclein levels. Four regions of the brain were analyzed: the striatum, cerebellum, cortex and hippocampus. Our data demonstrated a significant increase in catalase (CAT), superoxide dismutase (SOD) and glutathione (GSH) antioxidant levels in the brain regions compared to the controls. Pups exhibited no significant changes in protein carbonyl levels and lipid peroxidation. Striatal a-synuclein expression was significantly reduced in the rats exposed to DM + CYP, while the treatment resulted in a non-significant increase in the other brain areas. These findings indicate unexpected effects of postnatal treatment with the commercial formulation containing DM and CYP on brain redox state and a-synuclein expression, suggesting an adaptive response

Can Early Life Exposure to Permethrin lead to intergenerational effects?

Pesticides are largely used in agriculture against pests and consequently are present in fruits and vegetables. The wide presence of pesticide residues in breast milk underline the risk for the population, focalizing the long-term consequence of early life pyrethroid exposure. The significant presence of pyrethroid metabolites in the urine of population over the world confirms that their presence in food is a global problem. It has been demonstrated that there is a correlation between the environmental exposure to pesticides and the development of neurodegenerative diseases. Neonatal exposure to Permethrin (PERM), a member of the family of synthetic pyrethroids, can induce neurodegeneration (i.e. Parkinson’s –like disease) and it can cause some alterations in striatum of rats, involving both genetic and epigenetic pathways. The aim of this study was to evaluate if the rat offspring (F1 generation) exposed to a low dose of PERM from postnatal day 6 to 21, presents alterations in Nurr1 gene expression as previously observed in early life permethrin treated male rats. Moreover, global DNA methylation was analyzed in untreated early life exposed mothers and offspring (F1 generation). Methods Through Nurr1gene expression analysis and global DNA methylation assessment in both PERM-treated parents and their untreated offspring, we investigated on the prospective intergenerational effect of this pesticide. Results 33% of progeny presents the same Nurr1 alteration as rats exposed to permethrin in early life. A decrease in global genome-wide DNA methylation was measured in mothers exposed in early life to permethrin as well as in their offspring, whereas untreated rats have a hypermethylated genomic DNA. Conclutions Intergenerational PERM-induced damage on progenies has been identified for the first time. On the light of these results, pesticide residues in the food could represent a risk factor for the health of children especially in early life when the brain is still in the developing phase. Further studies are needed to elucidate the molecular mechanisms associated with the damage

Advances on the Antioxidant Peptides from Nuts: A Narrow Review

Antioxidant peptides extracted from natural foods have been studied for their potential use in the development of additives, nutraceuticals, and therapeutic agents. Nut proteins are considered an excellent source of plant-derived proteins for the human diet, due to their high protein content and digestibility of up to 86.22%. Furthermore, compared with grain and soybean proteins, nut proteins have a special amino acid composition, which makes their protein structure different, and promotes their disparate functional characteristics and great bioactivity potential. This review presents the most remarkable studies on antioxidant peptides from nuts, to gain insights into feasible production methods, different evaluation indexes within in vivo or in vitro systems, high bioavailability, and the complex structure-activity relationship resulting from the particularity of their protein structure and amino acid composition. Previously published studies mainly focused on the effects of the production methods/processes of nut-derived peptides on antioxidant activity, and proved that nut-extracted antioxidant peptides can resist the degradation of acid, alkali, and gastrointestinal enzymes, have high antioxidant activity in vitro and in vivo, and also have the potential to cross small intestinal epithelial cells in a stable and integral manner. However, the structure-activity relationship of antioxidant peptides from nuts has not been fully established, and the structure information of antioxidant peptides obtained from various nut protein sources is still unclear. The findings presented in this review can be used to provide the theoretical basis for the design and production of nut-derived antioxidant peptides

Plant-Derived Epi-Nutraceuticals as Potential Broad-Spectrum Anti-Viral Agents

Although the COVID-19 pandemic appears to be diminishing, the emergence of SARS-CoV-2 variants represents a threat to humans due to their inherent transmissibility, immunological evasion, virulence, and invulnerability to existing therapies. The COVID-19 pandemic affected more than 500 million people and caused over 6 million deaths. Vaccines are essential, but in circumstances in which vaccination is not accessible or in individuals with compromised immune systems, drugs can provide additional protection. Targeting host signaling pathways is recommended due to their genomic stability and resistance barriers. Moreover, targeting host factors allows us to develop compounds that are effective against different viral variants as well as against newly emerging virus strains. In recent years, the globe has experienced climate change, which may contribute to the emergence and spread of infectious diseases through a variety of factors. Warmer temperatures and changing precipitation patterns can increase the geographic range of disease-carrying vectors, increasing the risk of diseases spreading to new areas. Climate change may also affect vector behavior, leading to a longer breeding season and more breeding sites for disease vectors. Climate change may also disrupt ecosystems, bringing humans closer to wildlife that transmits zoonotic diseases. All the above factors may accelerate the emergence of new viral epidemics. Plant-derived products, which have been used in traditional medicine for treating pathological conditions, offer structurally novel therapeutic compounds, including those with anti-viral activity. In addition, plant-derived bioactive substances might serve as the ideal basis for developing sustainable/efficient/cost-effective anti-viral alternatives. Interest in herbal antiviral products has increased. More than 50% of approved drugs originate from herbal sources. Plant-derived compounds offer diverse structures and bioactive molecules that are candidates for new drug development. Combining these therapies with conventional drugs could improve patient outcomes. Epigenetics modifications in the genome can affect gene expression without altering DNA sequences. Host cells can use epigenetic gene regulation as a mechanism to silence incoming viral DNA molecules, while viruses recruit cellular epitranscriptomic (covalent modifications of RNAs) modifiers to increase the translational efficiency and transcript stability of viral transcripts to enhance viral gene expression and replication. Moreover, viruses manipulate host cells' epigenetic machinery to ensure productive viral infections. Environmental factors, such as natural products, may influence epigenetic modifications. In this review, we explore the potential of plant-derived substances as epigenetic modifiers for broad-spectrum anti-viral activity, reviewing their modulation processes and anti-viral effects on DNA and RNA viruses, as well as addressing future research objectives in this rapidly emerging field

Obesity and Cardiometabolic Risk Factors: From Childhood to Adulthood

Obesity has become a major epidemic in the 21st century. It increases the risk of dyslipidemia, hypertension, and type 2 diabetes, which are known cardiometabolic risk factors and components of the metabolic syndrome. Although overt cardiovascular (CV) diseases such as stroke or myocardial infarction are the domain of adulthood, it is evident that the CV continuum begins very early in life. Recognition of risk factors and early stages of CV damage, at a time when these processes are still reversible, and the development of prevention strategies are major pillars in reducing CV morbidity and mortality in the general population. In this review, we will discuss the role of well-known but also novel risk factors linking obesity and increased CV risk from prenatal age to adulthood, including the role of perinatal factors, diet, nutrigenomics, and nutri-epigenetics, hyperuricemia, dyslipidemia, hypertension, and cardiorespiratory fitness. The importance of 'tracking' of these risk factors on adult CV health is highlighted and the economic impact of childhood obesity as well as preventive strategies are discussed

Codrugs linking L-Dopa and sulfur-containing antioxidants: new pharmacological tools against Parkinson’s Disease

A series of multifunctional codrugs (1-6) were synthesized to overcome the pro-oxidant effect associated with L-dopa (LD) therapy. Target compounds release LD and dopamine (DA) in human plasma after enzymatic hydrolysis, displaying an antioxidant effect superior to that of N-acetylcysteine (NAC). After intracerebroventricular injection of codrug 4, the levels of DA in the striatum were higher than those in LD-treated groups, indicating that this compound has a longer half-life in brain than LD

KDR receptor: A key marker defining hematopoietic stem cells

Studies on pluripotent hematopoietic stem cells (HSCs) have been hindered by lack of a positive marker, comparable to the CD34 marker of hematopoietic progenitor cells (HPCs). In human postnatal hematopoietic tissues, 0.1 to 0.5% of CD34+cells expressed vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR). Pluripotent HSCs were restricted to the CD34+KDR+cell fraction. Conversely, lineage-committed HPCs were in the CD34+KDR-subset. On the basis of limiting dilution analysis, the HSC frequency in the CD34+KDR+fraction was 20 percent in bone marrow (BM) by mouse xenograft assay and 25 to 42 percent in BM, peripheral blood, and cord blood by 12-week long-term culture (LTC) assay. The latter values rose to 53 to 63 percent in LTC supplemented with VEGF and to greater than 95 percent for the cell subfraction resistant to growth factor starvation. Thus, KDR is a positive functional marker defining stem cells and distinguishing them from progenitors

Psychosocial and environmental risk factors of obesity and hypertension in children and adolescents—a literature overview

Childhood obesity has become a worldwide epidemic in the 21st century. Its treatment is challenging and often ineffective, among others due to complex, often not obvious causes. Awareness of the existence and meaning of psychosocial and environmental risk factors seems to be an essential element in the prevention and treatment of obesity and its complications, especially arterial hypertension. In this review, we will discuss the role of that risk factors linking obesity and increased cardiovascular disorders including the role of nutritional factors (including the role of unhealthy diet, inadequate hydration), unhealthy behaviors (e.g. smoking, alcohol and drugs, sedentary behavior, low physical activity, disrupted circadian rhythms, sleep disorders, screen exposure), unfavorable social factors (such as dysfunctional family, bullying, chronic stress, mood disorders, depression, urbanization, noise, and environmental pollution), and finally differences in cardiovascular risk in girls and boy

Effects of deletion of the Streptococcus pneumoniae lipoprotein diacylglyceryl transferase gene lgt on ABC transporter function and on growth in vivo

Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the corresponding gene potentially allows the characterisation of the overall importance of lipoproteins for specific bacterial functions. We have used a Δlgt mutant strain of Streptococcus pneumoniae to investigate the effects of loss of lipoprotein attachment on cation acquisition, growth in media containing specific carbon sources, and virulence in different infection models. Immunoblots of triton X-114 extracts, flow cytometry and immuno-fluorescence microscopy confirmed the Δlgt mutant had markedly reduced lipoprotein expression on the cell surface. The Δlgt mutant had reduced growth in cation depleted medium, increased sensitivity to oxidative stress, reduced zinc uptake, and reduced intracellular levels of several cations. Doubling time of the Δlgt mutant was also increased slightly when grown in medium with glucose, raffinose and maltotriose as sole carbon sources. These multiple defects in cation and sugar ABC transporter function for the Δlgt mutant were associated with only slightly delayed growth in complete medium. However the Δlgt mutant had significantly reduced growth in blood or bronchoalveolar lavage fluid and a marked impairment in virulence in mouse models of nasopharyngeal colonisation, sepsis and pneumonia. These data suggest that for S. pneumoniae loss of surface localisation of lipoproteins has widespread effects on ABC transporter functions that collectively prevent the Δlgt mutant from establishing invasive infection

Three Thousand Years of Continuity in the Maternal Lineages of Ancient Sheep (Ovis aries) in Estonia

lthough sheep (Ovis aries) have been one of the most exploited domestic animals in Estonia since the Late Bronze Age, relatively little is known about their genetic history. Here, we explore temporal changes in Estonian sheep populations and their mitochondrial genetic diversity over the last 3000 years. We target a 558 base pair fragment of the mitochondrial hypervariable region in 115 ancient sheep from 71 sites in Estonia (c. 1200 BC – AD 1900s), 19 ancient samples from Latvia, Russia, Poland and Greece (6800 BC – AD 1700), as well as 44 samples of modern Kihnu native sheep breed. Our analyses revealed: (1) 49 mitochondrial haplotypes, associated with sheep haplogroups A and B; (2) high haplotype diversity in Estonian ancient sheep; (3) continuity in mtDNA haplotypes through time; (4) possible population expansion during the first centuries of the Middle Ages (associated with the establishment of the new power regime related to 13th century crusades); (5) significant difference in genetic diversity between ancient populations and modern native sheep, in agreement with the beginning of large-scale breeding in the 19th century and population decline in local sheep. Overall, our results suggest that in spite of the observed fluctuations in ancient sheep populations, and changes in the natural and historical conditions, the utilisation of local sheep has been constant in the territory of Estonia, displaying matrilineal continuity from the Middle Bronze Age through the Modern Period, and into modern native sheep