Maternal nutrition and its effects on fetal neurodevelopment.

Herein, we present a thorough examination of the impact of maternal nutrition on fetal and infant neurodevelopment, focusing on specific nutrients and their critical roles in perinatal and pediatric health. Through a comprehensive narrative review of the literature, this study highlights the importance of a balanced maternal diet rich in nutrients like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), folic acid, iron, and iodine in shaping children's neurological functions. Key findings underscore the influence of maternal nutrition during pregnancy and the peri-gestational period on children's cognitive, motor, speech, and socio-emotional development. Deficiencies in essential nutrients, such as DHA, are linked to adverse long-lasting outcomes such as premature birth and intrauterine growth restriction, where a suitable intake of iron and folic acid is vital to prevent neural tube defects and promote healthy brain development. We highlight areas requiring further investigation, particularly regarding iodine's impact and the risks associated with alcohol consumption during pregnancy. In conclusion, this research sheds light on our current understanding of maternal nutrition and child neurodevelopment, offering valuable insights for health professionals and researchers.

Therapeutic potential of psychedelics: History, advancements, and unexplored frontiers.

Psychedelics (serotonergic hallucinogens) are psychoactive substances that can alter perception and mood, and affect cognitive functions. These substances activate 5-HT2A receptors and may exert therapeutic effects. Some of the disorders for which psychedelic-assisted therapy have been studied include depression, addiction, anxiety and post-traumatic stress disorder. Despite the increasing number of studies reporting clinical effectiveness, with fewer negative symptoms and, additionally, minimal side effects, questions remain to be explored in the field of psychedelic medicine. Although progress has been achieved, there is still little understanding of the relationship among human brain and the modulation induced by these drugs. The present article aimed to describe, review and highlight the most promising findings in the literature regarding the (putative) therapeutic effects of psychedelics.

Stem Cells and Tissue Engineering-Based Therapeutic Interventions: Promising Strategies to Improve Peripheral Nerve Regeneration.

Unlike the central nervous system, the peripheral one has the ability to regenerate itself after injury; however, this natural regeneration process is not always successful. In fact, even with some treatments, the prognosis is poor, and patients consequently suffer with the functional loss caused by injured nerves, generating several impacts on their quality of life. In the present review we aimed to address two strategies that may considerably potentiate peripheral nerve regeneration: stem cells and tissue engineering. In vitro studies have shown that pluripotent cells associated with neural scaffolds elaborated by tissue engineering can increase functional recovery, revascularization, remyelination, neurotrophin expression and reduce muscle atrophy. Although these results are very promising, it is important to note that there are some barriers to be circumvented: the host's immune response, the oncogenic properties attributed to stem cells and the duration of the pro-regenerative effects. After all, more studies are still needed to overcome the limitations of these treatments; those that address techniques for manipulating the lesion microenvironment combining different therapies seem to be the most promising and proactive ones.

The gut microbiota in neurodegenerative diseases: revisiting possible therapeutic targets for cannabidiol.

Understanding the pathophysiology of Alzheimer's disease (AD) is essential to improve the efficacy of treatments and, consequently, patients' lives. Unfortunately, traditional therapeutic strategies have not been effective. There is therefore an urgent need to discover or develop alternative treatment strategies. Recently, some pieces of the puzzle appear to emerge: on a hand, the gut microbiota (GM) has gained attention since intestinal dysbiosis aggravates and generates some of the pathological processes of AD; on the other hand, cannabidiol (CBD), a phytocannabinoid, attenuates intestinal inflammation and possesses neuroprotective properties. Intestinal dysbiosis (increased population of proinflammatory bacteria) in AD increases plasma lipopolysaccharide and Aß peptide levels, both responsible for increasing the permeability of the blood-brain barrier (BBB). A leaky BBB may facilitate the entry of peripheral inflammatory mediators into the central nervous system and ultimately aggravate neuroinflammation and neuronal death due to chronic activation of glial cells. Studies investigating the GM reported a strong relationship between intestinal dysbiosis and AD. In this review we conjecture that the GM is a promising therapeutic target for CBD in the context of AD.

Acute autonomic effects of rose oxide on cardiovascular parameters of Wistar and spontaneously hypertensive rats.

AIMS: Anti-inflammatory molecules, such as rose oxide (RO), are likely to exert therapeutic effects in systemic arterial hypertension (SAH), a disease associated with abnormal immune responses. We aimed to investigate acute autonomic effects of RO on hemodynamic parameters of Wistar and spontaneously hypertensive rats (SHR). METHODS: Rats were anesthetized and femoral artery and veins were cannulated. Next day, blood pressure (BP) and heart rate (HR) were recorded. Acute effects of RO (1.25, 2.5, or 5.0 mg/kg; iv) on BP, HR, and variability of systolic arterial pressure (SAP) and pulse interval (PI) were assessed. The effects of RO were also investigated in SHR, which received atropine (2 mg/kg), propranolol (4 mg/kg), or hexamethonium (20 mg/kg) 15 min before receiving RO. Vasorelaxant effects of RO (10-10 to 10-4 M) on aortic rings of rats were also assessed. KEY FINDINGS: In Wistar rats, none of the RO doses evoked significant changes in BP, HR, and variability of SAP and PI. On the other hand, in SHR, RO elicited reduction in mean arterial pressure (MAP), and prevented the increase in the low frequency power (LF) of the SAP spectra. Pretreatment with atropine or propranolol did not alter hypotension, but attenuated RO-induced bradycardia. Hexamethonium prevented RO-induced hypotension and bradycardia. RO exerted vasorelaxant effects on aortic rings with (Wistar and SHR) or without functional endothelium (SHR only). SIGNIFICANCE: Rose oxide, a monoterpene with anti-inflammatory properties, acts as an antihypertensive molecule due to its ability to acutely promote hypotension and bradycardia in spontaneously hypertensive rats.

Efficacy of low-level laser therapy in nerve injury repair-a new era in therapeutic agents and regenerative treatments.

BACKGROUND: Traumatic nerve injuries may result in severe motor dysfunctions. Although the microenvironment of peripheral axons favors their regeneration, regenerative process is not always successful. PURPOSE: We reviewed and discussed the main findings obtained with low-level laser therapy (LLLT), a therapeutic intervention that has been employed in order to achieve an optimized regeneration process in peripheral axons. SCOPE: Disseminating the best available evidence for the effectiveness of this therapeutic strategy can potentially improve the statistics of success in the clinical treatment of nerve injuries. We found evidence that LLLT optimizes the regeneration of peripheral axons, improving motor function, especially in animal models. Nonetheless, further clinical evidence is still needed before LLLT can be strongly recommended. Although the results are promising, the elucidation of the mechanisms of action and safety assessment are necessary to support highquality clinical studies. CONCLUSION: The present careful compilation of findings with consistent pro-regenerative evidence and published in respected scientific journals can be valuable for health professionals and researchers in the field, possibly contributing to achieve more promising results in future randomized controlled trials and interventions, providing better prognosis for clinical practice.

Revisiting the Role of Biologically Active Natural and Synthetic Compounds as an Intervention to Treat Injured Nerves.

Traumatic lesions in nerves present high incidence and may culminate in sensorimotor and/or autonomic dysfunctions or a total loss of function, affecting the patient's quality of life. Although the microenvironment favors peripheral nerve regeneration, the regenerative process is not always successful. Some herbs, natural products, and synthetic drugs have been studied as potential pro-regenerative interventions. We reviewed and discussed the most recent articles published over the last ten years in high impact factor journals. Even though most of the articles contemplated in this review were in vitro and animal model studies, those with herbs showed promising results. Most of them presented antioxidant and anti-inflammatory effects. Drugs of several pharmacological classes also showed optimistic outcomes in nerve functional recovery, including clinical trials. The results are hopeful; however, mechanisms of action need to be elucidated, and there is a need for more high-quality clinical studies. The study presents careful compilation of findings of dozens of compounds with consistent pro-regenerative evidence published in respected scientific journals. It may be valuable for health professionals and researchers in the field.

Nanotherapeutic approach to tackle chemotherapeutic resistance of cancer stem cells.

Estimates indicate that cancer will become the leading cause of mortality worldwide in the future. Tumorigenesis is a complex process that involves self-sufficiency in signs of growth, insensitivity to anti-growth signals, prevention of apoptosis, unlimited replication, sustained angiogenesis, tissue invasion, and metastasis. Cancer stem cells (CSCs) have an important role in tumor development and resistance. Here we will approach phenotypic plasticity capacity, highly efficient DNA repair systems, anti-apoptotic machinery, sustained stemness features, interaction with the tumor microenvironment, and Notch, Wnt, and Hedgehog signaling pathways. The researches about CSCs as a target in cancer treatment has been growing. Many different options have pointed beneficial results, such as pathways and CSC-surface markers targeting. Besides its limitations, nanotherapeutics have emerged as a potential strategy in this context since they aim to improve pharmacokinetics, biodistribution, and reduce the side effects observed in traditional treatments. Nanoparticles have been studied in this field, mostly for drug delivery and a multitherapy approach. Another widely researched approaches in this area are related to heat therapy, such as photothermal therapy, photodynamic therapy and magnetic hyperthermia, besides molecular targeting. This review will contemplate the most relevant studies that have shown the effects of nanotherapeutics. In conclusion, although the studies analyzed are mostly preclinical, we believe that there is strong evidence that nanoparticles can increase the chances of a better prognosis to cancer in the future. It is also essential to transpose these findings to the clinic to confirm and better understand the role of nanotherapeutics in this context.

Role of hydrogen sulfide in ventilatory responses to hypercapnia in the medullary raphe of adult rats.

NEW FINDINGS: What is the central question of this study? There is evidence that H2 S plays a role in the control of breathing: what are its actions on the ventilatory and thermoregulatory responses to hypercapnia via effects in the medullary raphe, a brainstem region that participates in the ventilatory adjustments to hypercapnia? What is the main finding and its importance? Hypercapnia increased the endogenous production of H2 S in the medullary raphe. Inhibition of endogenous H2 S attenuated the ventilatory response to hypercapnia in unanaesthetized rats, suggesting its excitatory action via the cystathionine ß-synthase-H2 S pathway in the medullary raphe. ABSTRACT: Hydrogen sulfide (H2 S) has been recently recognized as a gasotransmitter alongside carbon monoxide (CO) and nitric oxide (NO). H2 S seems to modulate the ventilatory and thermoregulatory responses to hypoxia and hypercapnia. However, the action of the H2 S in the medullary raphe (MR) on the ventilatory responses to hypercapnia remains to be elucidated. The present study aimed to assess the role of H2 S in the MR (a brainstem region that contains CO2 -sensitive cells and participates in the ventilatory adjustments to hypercapnia) in the ventilatory responses to hypercapnia in adult unanaesthetized Wistar rats. To do so, aminooxyacetic acid (AOA; a cystathionine ß-synthase (CBS) enzyme inhibitor), propargylglycine (PAG; a cystathionine γ-lyase enzyme inhibitor) and sodium sulfide (Na2 S; an H2 S donor) were microinjected into the MR. Respiratory frequency (fR ), tidal volume (VT ), ventilation ( V̇E ), oxygen consumption ( V̇O2 ) and body temperature (Tb ) were measured under normocapnic (room air) and hypercapnic (7% CO2 ) conditions. H2 S concentration within the MR was determined. Microinjection of the drugs did not affect fR , VT and V̇E during normocapnia when compared to the control group. However, the microinjection of AOA, but not PAG, attenuated fR and V̇E during hypercapnia in comparison to the vehicle group, but had no effects on Tb . In addition, we observed an increase in the endogenous production of H2 S in the MR during hypercapnia. Our findings indicate that endogenously produced H2 S in the MR plays an excitatory role in the ventilatory response to hypercapnia, acting through the CBS-H2 S pathway.

Exploitation of Marine-Derived Robust Biological Molecules to Manage Inflammatory Bowel Disease.

Naturally occurring biological entities with extractable and tunable structural and functional characteristics, along with therapeutic attributes, are of supreme interest for strengthening the twenty-first-century biomedical settings. Irrespective of ongoing technological and clinical advancement, traditional medicinal practices to address and manage inflammatory bowel disease (IBD) are inefficient and the effect of the administered therapeutic cues is limited. The reasonable immune response or invasion should also be circumvented for successful clinical translation of engineered cues as highly efficient and robust bioactive entities. In this context, research is underway worldwide, and researchers have redirected or regained their interests in valorizing the naturally occurring biological entities/resources, for example, algal biome so-called "treasure of untouched or underexploited sources". Algal biome from the marine environment is an immense source of excellence that has also been demonstrated as a source of bioactive compounds with unique chemical, structural, and functional features. Moreover, the molecular modeling and synthesis of new drugs based on marine-derived therapeutic and biological cues can show greater efficacy and specificity for the therapeutics. Herein, an effort has been made to cover the existing literature gap on the exploitation of naturally occurring biological entities/resources to address and efficiently manage IBD. Following a brief background study, a focus was given to design characteristics, performance evaluation of engineered cues, and point-of-care IBD therapeutics of diverse bioactive compounds from the algal biome. Noteworthy potentialities of marine-derived biologically active compounds have also been spotlighted to underlying the impact role of bio-active elements with the related pathways. The current review is also focused on the applied standpoint and clinical translation of marine-derived bioactive compounds. Furthermore, a detailed overview of clinical applications and future perspectives are also given in this review.

Acetylcholinesterase inhibition prevents alterations in cardiovascular autonomic control and gastric motility in L-NAME-induced hypertensive rats.

AIMS: Autonomic dysfunction in arterial hypertension affects cardiorespiratory control and gastric motility and has been characterized by increased sympathetic and reduced parasympathetic activity. In the present work we investigated the effects of anticholinesterase drugs [donepezil (DON) or pyridostigmine (PYR)] on cardiovascular, autonomic, and gastric parameters in L-NAME-induced hypertensive rats. MATERIALS AND METHODS: Daily oral gavage of L-NAME (70 mg/kg/day) was performed over 14 days in male Wistar rats (180-220 g), whereas daily oral gavage of DON or PYR (1.6 and 22 mg/kg/day, respectively) started 2 days after the L-NAME treatment initiation and lasted 12 days. The development of hypertension was verified by tail plethysmography technique. After the end of treatments, the animals were subjected to experimental protocols (6-12 animals per group; total number of animals used: 78). KEY FINDINGS: L-NAME hypertensive animals had no alterations in heart rate (HR) and intrinsic HR, but showed reduction in baroreflex sensitivity, parasympathetic tone, and gastric motility; and the sympathetic tone, chemoreflex sensitivity, and the LF (low frequency) band of systolic arterial pressure (SAP) variability were increased. DON or PYR attenuated the increase in mean arterial pressure (MAP) induced by L-NAME. Both anticholinesterase drugs were effective in preventing the decrease in baroreflex sensitivity, parasympathetic tone and gastric motility, and also prevented the increases in peripheral chemoreflex response and cardiac sympathetic tone. SIGNIFICANCE: Acetylcholinesterase inhibition with DON or PYR is a promising pharmacological approach to increase parasympathetic function, thus preventing the hypertension-induced alterations in the cardiovascular, gastrointestinal and autonomic systems.

Marine-Derived Biologically Active Compounds for the Potential Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with a prevalence rate of up to 1% and is significantly considered a common worldwide public health concern. Commercially, several traditional formulations are available to treat RA to some extent. However, these synthetic compounds exert toxicity and considerable side effects even at lower therapeutic concentrations. Considering the above-mentioned critiques, research is underway around the world in finding and exploiting potential alternatives. For instance, marine-derived biologically active compounds have gained much interest and are thus being extensively utilized to confront the confines of in practice counterparts, which have become ineffective for 21st-century medical settings. The utilization of naturally available bioactive compounds and their derivatives can minimize these synthetic compounds' problems to treat RA. Several marine-derived compounds exhibit anti-inflammatory and antioxidant properties and can be effectively used for therapeutic purposes against RA. The results of several studies ensured that the extraction of biologically active compounds from marine sources could provide a new and safe source for drug development against RA. Finally, current challenges, gaps, and future perspectives have been included in this review.

Anxiolytic-like effect of hydrogen sulfide (H2S) in rats exposed and re-exposed to the elevated plus-maze and open field tests.

Hydrogen sulfide (H2S), an endogenous gaseous mediator, modulates many physiological functions in mammals but evidence of its involvement in emotional and behavioral aspects is currently scarce. We hypothesized that this gas plays a modulatory role in behavioral parameters in rats submitted to tests (for 5min) in the open field (OF) and elevated plus-maze (EPM - test and retest). Male Wistar rats (200-250g) were intraperitoneally injected with saline or Na2S (a H2S donor; 4, 8 and 12mg/kg) either once or for 8days, and submitted to the OF test or to the EPM test and retest. A third group (naïve) was not injected but exposed to the same experimental protocols. In the OF test, Na2S injected for 8days caused a decrease in self-cleaning (4, 8 and 12mg/kg) and freezing behaviors (8 and 12mg/kg), and a rise in the rate of line crossings in the central part of the arena (12mg/kg). In the EPM test and retest, Na2S at 12mg/kg for 8days caused an increase in the number of open arm entries and in the percentage of time spent on open arms. Our data are consistent with the notion that H2S exerts anxiolytic-like effects in rats submitted to the EPM and OF tests. Moreover, this gaseous modulator reduces aversive learning in the EPM retest.

Amblyopia: neural basis and therapeutic approaches.

Abnormalities in visual processing caused by visual deprivation or abnormal binocular interaction may induce amblyopia, which is characterized by reduced visual acuity. Occlusion therapy, the conventional treatment, requires special attention as occlusion of the fellow normal eye may reduce its visual acuity and impair binocular vision. Besides recovering visual acuity, some researchers have recommended restoration of stereoacuity and motor fusion and reverse suppression in order to prevent diplopia. Recent studies have documented that the amblyopic visual cortex has a normal complement of cells but reduced spatial resolution and a disordered topographical map. Changes occurring in the late sensitive period selectively impact the parvocellular pathway. Distinct morphophysiologic and psychophysical deficits may demand individualization of therapy, which might provide greater and longer-lasting residual plasticity in some children.

Amblyopia: neural basis and therapeutic approaches / Ambliopia: bases neurais e intervenções terapêuticas

ABSTRACT Abnormalities in visual processing caused by visual deprivation or abnormal binocular interaction may induce amblyopia, which is characterized by reduced visual acuity. Occlusion therapy, the conventional treatment, requires special attention as occlusion of the fellow normal eye may reduce its visual acuity and impair binocular vision. Besides recovering visual acuity, some researchers have recommended restoration of stereoacuity and motor fusion and reverse suppression in order to prevent diplopia. Recent studies have documented that the amblyopic visual cortex has a normal complement of cells but reduced spatial resolution and a disordered topographical map. Changes occurring in the late sensitive period selectively impact the parvocellular pathway. Distinct morphophysiologic and psychophysical deficits may demand individualization of therapy, which might provide greater and longer-lasting residual plasticity in some children.

RESUMO Anormalidades nos processamentos visuais causadas por privação visual ou interação binocular anormal podem gerar ambliopia, caracterizada por redução da acuidade visual. A terapia de oclusão (tratamento convencional) necessita de cuidados especiais, pois a oclusão do olho normal (não-amblíope) pode reduzir a acuidade visual do mesmo e prejudicar a visão binocular. Além de recuperar a acuidade visual, alguns pesquisadores alertam para a necessidade em potencial de se restaurar a estereoacuidade e a fusão motora, bem como reverter a supressão a fim de impedir diplopia. Estudos recentes revelam que nos córtices visuais de amblíopes há uma quantidade normal de células, mas com resolução espacial reduzida e mapa topográfico desorganizado. Alterações ocorridas durante o período crítico tardio do desenvolvimento visual humano impactam seletivamente a via parvocelular. Déficits morfofisiológicos e psicofísicos distintos podem exigir programas de tratamento potencialmente seletivos e poderiam explicar a plasticidade residual maior e mais duradoura em algumas crianças.

[Pharmacotherapy and analysis of gaseous mediators in hypertensive patients]. / Farmacoterapia e análise de mediadores gasosos em pacientes hipertensos.

OBJECTIVE: To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS: Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS: It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p<0.03) and the hydrogen sulphide concentration was significantly higher in hypertensive plasma in use of calcium channel antagonists (p<0.002). CONCLUSION: The findings suggest that these medications have as additional action mechanism the improvement of endothelial dysfunction by elevate plasma levels of vasodilatory substances.

Pharmacotherapy and analysis of gaseous mediators in hypertensive patients / Farmacoterapia y análisis de mediadores gaseosos en pacientes hipertensos / Farmacoterapia e análise de mediadores gasosos em pacientes hipertensos

OBJECTIVE To evaluate the effect of using antihypertensive classes of drugs of the calcium channel antagonists and inhibitors of angiotensin-converting enzyme in plasma concentrations of hydrogen sulfide and nitric oxide in patients with hypertension. METHODS Cross-sectional study with quantitative approach conducted with hypertensive patients in use of antihypertensive classes of drugs: angiotensin-converting enzyme inhibitors or calcium channel antagonists. RESULTS It was found that the concentration of plasma nitric oxide was significantly higher in hypertensive patients that were in use of angiotensin-converting enzyme inhibitors (p<0.03) and the hydrogen sulphide concentration was significantly higher in hypertensive plasma in use of calcium channel antagonists (p<0.002). CONCLUSION The findings suggest that these medications have as additional action mechanism the improvement of endothelial dysfunction by elevate plasma levels of vasodilatory substances. .

OBJETIVO Evaluar el efecto del uso de antihipertensivos pertenecientes a las clases medicamentosas antagonistas de canales de calcio e inhibidores de la enzima convertidora de angiotensina en las concentraciones plasmáticas de ácido sulfhídrico y óxido nítrico en portadores de hipertensión arterial sistémica. MÉTODO Estudio transversal con abordaje cuantitativo realizado con hipertensos que toman antihipertensivos de las clases de inhibidores de la enzima convertidora de angiotensina o antagonistas de los canales de calcio. RESULTADOS Se verificó que la concentración de óxido nítrico plasmático fue significativamente mayor en hipertensos que estaban usando inhibidores de la enzima convertidora de angiotensina (p<0.03) y que la concentración de ácido sulfhídrico plasmático fue significativamente mayor en hipertensos en uso de antagonistas de los canales de calcio (p<0.002). CONCLUSIÓN Los hallazgos sugieren que dichos fármacos tienen como mecanismo de acción adicional la mejora de la disfunción endotelial al elevar los niveles plasmáticos de sustancias vasodilatadoras. .

OBJETIVO Avaliar o efeito do uso de anti-hipertensivos pertencentes às classes medicamentosas antagonistas de canais de cálcio e inibidores da enzima conversora de angiotensina nas concentrações plasmáticas de ácido sulfídrico e óxido nítrico em portadores de hipertensão arterial sistêmica. MÉTODO Estudo transversal com abordagem quantitativa realizado com hipertensos em uso de anti-hipertensivos das classes inibidores da enzima conversora de angiotensina ou antagonistas dos canais de cálcio. RESULTADOS Verificou-se que a concentração de óxido nítrico plasmático foi significativamente maior em hipertensos que estavam em uso de inibidores da enzima conversora de angiotensina (p<0.03) e que a concentração de ácido sulfídrico plasmático foi significativamente maior em hipertensos em uso de antagonistas dos canais de cálcio (p<0.002). CONCLUSÃO Os achados sugerem que essas medicações possuem como mecanismo de ação adicional a melhora da disfunção endotelial por elevar os níveis plasmáticos de substâncias vasodilatadoras. .