Advancements in addressing drug dependence: A review of promising therapeutic strategies and interventions.

Substance dependence represents a pervasive global concern within the realm of public health. Presently, it is delineated as a persistent and recurrent neurological disorder stemming from drug-triggered neuroadaptations in the brain's reward circuitry. Despite the availability of various therapeutic modalities, there has been a steady escalation in the mortality rate attributed to drug overdoses. Substantial endeavors have been directed towards the exploration of innovative interventions aimed at mitigating cravings and drug-induced repetitive behaviors. Within this review, we encapsulate the most auspicious contemporary treatment methodologies, accentuating meta-analyses of efficacious pharmacological and non-pharmacological approaches: including gabapentin, topiramate, prazosin, physical exercise regimens, and cerebral stimulation techniques.

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.

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.

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.

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.