DNA methylation was traditionally viewed as a static mechanism required during cell fate determination. This view has been challenged and it is now accepted that DNA methylation is involved in the ...regulation of genomic responses in mature neurons, particularly in cognitive functions. The evidence for a role of DNA methylation in memory formation and maintenance comes from the increasing number of studies that have assessed the effects of manipulation of DNA methylation modifiers in the ability to form and maintain memories. Moreover, insights from genome-wide analyses of the hippocampal DNA methylation status after neuronal activity show that DNA methylation is dynamically regulated. Despite all the experimental evidence, we are still far from having a clear picture of how DNA methylation regulates long-term adaptations. This review aims on one hand to describe the findings that led to the confirmation of DNA methylation as an important player in memory formation. On the other hand, it tries to integrate these discoveries into the current views of how memories are formed and maintained.
Cognitive abilities decline in normal aging, yet the underlying molecular mechanisms are poorly understood. We found that aging was associated with a decrease in the expression of the DNA ...methyltransferase Dnmt3a2 in the hippocampus and that rescuing Dnmt3a2 levels restored cognitive functions. Moreover, we found that Dnmt3a2 is an activity-regulated immediate early gene that is partly dependent on nuclear calcium signaling and that hippocampal Dnmt3a2 levels determine cognitive abilities in both young adult and aged mice.
Biomarkers of inflammation, muscle damage, and oxidative stress after high-intensity exercise have been described previously; however, further understanding of their role in the postexercise recovery ...period is necessary. Because these markers have been implicated in cell signaling, they may be specifically related to the training adaptations induced by high-intensity exercise. Thus, a clear model showing their responses to exercise may be useful in characterizing the relative recovery status of an athlete. The purpose of this study was twofold: (a) to investigate the time course of markers of muscle damage and inflammation in the blood from 3 to 72 hours after combined training exercises and (b) to investigate indicators of oxidative stress and damage associated with increased reactive oxygen species production during high-intensity exercise in elite athletes. Nineteen male athletes performed a combination of high-intensity aerobic and anaerobic training exercises. Samples were acquired immediately before and at 3, 6, 12, 24, 48, and 72 hours after exercise. The appearance and clearance of creatine kinase and lactate dehydrogenase in the blood occurred faster than previous studies have reported. The neutrophil/lymphocyte ratio summarizes the mobilization of 2 leukocyte subpopulations in a single marker and may be used to predict the end of the postexercise recovery period. Further analysis of the immune response using serum cytokines indicated that high-intensity exercise performed by highly trained athletes only generated inflammation that was localized to the skeletal muscle. Biomarkers are not a replacement for performance tests, but when used in conjunction, they may offer a better indication of metabolic recovery status. Therefore, the use of biomarkers can improve a coach's ability to assess the recovery period after an exercise session and to establish the intensity of subsequent training sessions.
Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been ...responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses.
In the context of the 21st century, the integration of diverse perspectives within the circular economy framework, encompassing waste management, economic growth, and environmental sustainability, ...stands out as a paramount challenge. Addressing this challenge, an innovative avenue emerges through the application of microbial oil to replace traditional petroleum in the synthesis of essential commodity chemicals. This groundbreaking study takes a significant step toward this goal by introducing a pioneering polyester material boasting an exceptionally high renewable content. This material is synthesized through melt polycondensation, utilizing a novel primary feedstock derived from the oily residue extracted post‐distillation of β‐farnesene (FDR). The ingenious approach involves fermenting sugarcane syrup using a genetically engineered yeast strain of Saccharomyces cerevisiae. The outcome of this study reveals the creation of an amorphous polymer with rubber‐like attributes. These attributes include a Young's modulus of 3.9 MPa, with a maximum elastic strain and tensile stress values of 185.4% and 510 KPa, respectively, along with distinctive strain‐hardening characteristics. Remarkably, this material also exhibits indications of shape memory behavior in a temperature range spanning from −47 to 12°C, as discerned from dynamic mechanical analysis. Evidently, this novel polymer demonstrates exceptional promise in the realm of low‐temperature applications. Its intrinsic ability to uphold mechanical integrity, even when subjected to substantial deformations within its service conditions, positions it as an invaluable resource for various components requiring resilience in challenging environments.
Scheme illustrating the farnesene distillation residue (FDR) derived from a fermentation process utilizing sugarcane syrup, which underwent winterization, epoxidation, and hydroxylation for the synthesis of polyols. These bio‐polyols served as the foundational material for the production of an elastomeric polyester.
In the last decade, selectively tuned bio-based polyesters have been increasingly used for their clinical potential in several biomedical applications, such as tissue engineering, wound healing, and ...drug delivery. With a biomedical application in mind, a flexible polyester was produced by melt polycondensation using the microbial oil residue collected after the distillation of β-farnesene (FDR) produced industrially by genetically modified yeast,
After characterization, the polyester exhibited elongation up to 150% and presented
of -51.2 °C and
of 169.8 °C. In vitro degradation revealed a mass loss of about 87% after storage in PBS solution for 11 weeks under accelerated conditions (40 °C, RH = 75%). The water contact angle revealed a hydrophilic character, and biocompatibility with skin cells was demonstrated. 3D and 2D scaffolds were produced by salt-leaching, and a controlled release study at 30 °C was performed with Rhodamine B base (RBB, 3D) and curcumin (CRC, 2D), showing a diffusion-controlled mechanism with about 29.3% of RBB released after 48 h and 50.4% of CRC after 7 h. This polymer offers a sustainable and eco-friendly alternative for the potential use of the controlled release of active principles for wound dressing applications.
Epigenetic mechanisms have gained increasing attention as regulators of synaptic plasticity and responsiveness to drugs of abuse. In particular, it has been shown that the activity of the DNA ...methyltransferase 3a (Dnmt3a) mediates certain long-lasting effects of cocaine. Here we examined the role of the Dnmt isoforms,
and
, within the nucleus accumbens (NAc) on transcriptional activity of immediate early genes (IEGs) and acute and long-lasting responsiveness to cocaine and cocaine conditioned cues. Using primary striatal cultures, we show that transcription of
, but not that of
, is activated by dopamine D1 receptor signaling and that knockdown of
using viral vector-mediated expression of Dnmt3a2-specific shRNAs impairs induction of the IEGs,
,
, and
Acute cocaine administration increases expression of
but not that of
in the NAc shell. In contrast, in the NAc core, expression of
and
was unaffected by cocaine administration. shRNA-mediated knockdown of
impairs the induction of IEGs, including
and
indicating that Dnmt3a2 regulates cocaine-dependent expression of plasticity genes in the rat NAc shell. Cocaine self-administration experiments in rats revealed that Dnmt3a2 regulates drug cue memories that drive reinstatement of cocaine seeking as well as incubation of this phenomenon within the NAc shell. Dnmt3a2 does not influence the primary reinforcing effects of cocaine. Thus, Dnmt3a2 mediates long-lasting cocaine cue memories within the NAc shell. Targeting
expression or function may interfere with cocaine craving and relapse.
In humans, drug craving can occur in response to conditioned cues, even after extended periods of abstinence. In rats, cue-induced cocaine seeking has been shown to increase progressively during the first 2 months of abstinence from drug self-administration. This phenomenon, referred to as incubation of cocaine seeking, is consistent with the hypothesis that in humans craving increases over time and remains high following prolonged abstinence. Those long-lasting behavioral changes are likely to be mediated by epigenetic effects and neuroplastic changes within the mesolimbic brain reward system. Here we show that a specific isoform of DNA-methyltransferases in the NAc shell regulates drug cue memories that drive reinstatement of cocaine seeking after both early abstinence and incubation of cocaine craving.
Gedunin is an important limonoid present in several genera of the Meliaceae family, mainly in seeds. Several biological activities have been attributed to gedunin, including antibacterial, ...insecticidal, antimalarial, antiallergic, anti-inflammatory, anticancer, and neuroprotective effects. The discovery of gedunin as a heat shock protein (Hsp) inhibitor represented a very important landmark for its application as a biological therapeutic agent. The current study is a critical literature review based on the several biological activities so far described for gedunin, its therapeutic effect on some human diseases, and future directions of research for this natural compound.
The coronavirus disease (COVID-19) affected virtually all countries. Uncertain about the health risk and an increasing financial loss will contribute to widespread emotional distress and an increased ...risk of psychiatric disorders shortly. Posttraumatic, anxiety, and depression disorders are expected during and aftermath of the pandemic. Some groups, like children, have more susceptibility to having long term consequences in mental health. Herein, we made a comprehensive and non-systematic search in four databases (PubMed, Scopus, SciELO, and Google Scholars) to answer the question: What are children's and adolescents' mental health effects of the pandemic? Furthermore, which features are essential for mental health in a pandemic? Results: Seventy-seven articles were selected for full text read, and 51 were included. Children answer stress differently, depending on the development stage. High rates of anxiety, depression, and post-traumatic symptoms were identified among children. Discussion: Symptoms were as expected. New supportive strategies have appeared during this pandemic, but there is no measure of its effectiveness. Some groups seem to be more vulnerable to the mental health burden of the COVID-19 pandemic, and the mitigation actions should prioritize them. The school's role appears to be revalued by society. This review seems to pick good targets to prioritize mitigation actions aiming to spare children not only from the severe cases of COVID-19 but also to help them to deal with the mental health burden of the pandemics.
•Anxiety, depression, and post-traumatic symptoms were observed in children and adolescents.•Children answer stress differently, depending on the development stage during pandemic.•The schools' role appears to be reevaluated by the society during the pandemic.•Mitigation actions should target the vulnerable groups.
Timely and spatially-regulated injectable hydrogels, able to suppress growing tumors in response to conformational transitions of proteins, are of great interest in cancer research and treatment. ...Herein, we report rapidly responsive silk fibroin (SF) hydrogels formed by a horseradish peroxidase (HRP) crosslinking reaction at physiological conditions, and demonstrate their use as an artificial biomimetic three-dimensional (3D) matrix. The proposed SF hydrogels presented a viscoelastic nature of injectable hydrogels and spontaneous conformational changes from random coil to β-sheet conformation under physiological conditions. A human neuronal glioblastoma (U251) cell line was used for screening cell encapsulation and in vitro evaluation within the SF hydrogels. The transparent random coil SF hydrogels promoted cell viability and proliferation up to 10 days of culturing, while the crystalline SF hydrogels converted into β-sheet structure induced the formation of TUNEL-positive apoptotic cells. Therefore, this work provides a powerful tool for the investigation of the microenvironment on the programed tumor cells death, by using rapidly responsive SF hydrogels as 3D in vitro tumor models.
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