Differences in the Interleukin Profiles in Inattentive ADHD Prepubertal Children Are Probably Related to Conduct Disorder Comorbidity.

Inflammatory cytokines are involved in attention deficit hyperactivity disorder (ADHD), a highly prevalent neurodevelopmental disorder. To quantify the baseline levels of pro- and anti-inflammatory cytokines and their changes after methylphenidate (MPH), a total of 31 prepubertal children with ADHD were recruited and subclassified into only two ADHD presentations-ADHD attention deficit ( = 13) or ADHD combined ( = 18). The children were also screened for oppositional defiant conduct disorder (ODCD) and anxiety disorder.

Inflamma-miRs Profile in Myelodysplastic Syndrome Patients.

Etiological factors involved in myelodysplastic syndrome (MDS) include immunologic, oxidative stress and inflammatory factors, among others, and these are targets for microRNAs (miRNs). Here, we evaluated whether some miRNs may affect tumor development comparing untreated and 5-azacitidine (5-AZA) MDS-treated patients. Peripheral blood samples were collected from 20 controls and 24 MDS patients, and selected miRNs related to redox balance and inflammation (inflamma-miRs), including miR-18a, miR-21, miR-34a and miR-146a, were isolated and measured by quantitative real-time polymerase chain reaction (qRTPCR).

Zebrafish as a Human Muscle Model for Studying Age-Dependent Sarcopenia and Frailty.

Currently, there is an increase in the aging of the population, which represents a risk factor for many diseases, including sarcopenia. Sarcopenia involves progressive loss of mass, strength, and function of the skeletal muscle. Some mechanisms include alterations in muscle structure, reduced regenerative capacity, oxidative stress, mitochondrial dysfunction, and inflammation.

Harbingers of Hope: Scientists and the Pursuit of World Peace.

The ongoing wars in many regions-such as the conflict between Israel and Hamas-as well as the effects of war on communities, social services, and mental health are covered in this special editorial. This article emphasizes the need for international efforts to promote peace, offer humanitarian aid, and address the mental health challenges faced by individuals and communities affected by war and violence.

Changes in Cortisol and in Oxidative/Nitrosative Stress Indicators after ADHD Treatment.

Although ADHD is one of the most prevalent diseases during childhood, we still do not know its precise origin; oxidative/nitrosative stress and the hypothalamic-pituitary-adrenal axis are suggested contributors. Methylphenidate, among others, is the main drug used in ADHD patients, but its effects on relevant markers and structures remain unclear. This study, involving 59 patients diagnosed with ADHD according to DSM-5 criteria, aimed to assess changes in cortisol levels (using cortisol awakening response, CAR) and oxidative/nitrosative status with the treatment.

From Chronodisruption to Sarcopenia: The Therapeutic Potential of Melatonin.

Sarcopenia is an age-related condition that involves a progressive decline in muscle mass and function, leading to increased risk of falls, frailty, and mortality. Although the exact mechanisms are not fully understood, aging-related processes like inflammation, oxidative stress, reduced mitochondrial capacity, and cell apoptosis contribute to this decline. Disruption of the circadian system with age may initiate these pathways in skeletal muscle, preceding the onset of sarcopenia.

Targeting NR1D1 in organ injury: challenges and prospects.

Nuclear receptor subfamily 1, group D, member 1 (NR1D1, also known as REV-ERBα) belongs to the nuclear receptor (NR) family, and is a heme-binding component of the circadian clock that consolidates circadian oscillators. In addition to repressing the transcription of multiple clock genes associated with circadian rhythms, NR1D1 has a wide range of downstream target genes that are intimately involved in many physiopathological processes, including autophagy, immunity, inflammation, metabolism and aging in multiple organs. This review focuses on the pivotal role of NR1D1 as a key transcription factor in the gene regulatory network, with particular emphasis on the milestones of the latest discoveries of NR1D1 ligands.

The Relationship between Clock Genes, Sirtuin 1, and Mitochondrial Activity in Head and Neck Squamous Cell Cancer: Effects of Melatonin Treatment.

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, which generates rhythmic changes in many physiological processes, including mitochondrial activity. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases such as cancer. Melatonin, whose production and secretion oscillates according to the light-dark cycle, is the principal regulator of clock gene expression.

Patient-derived tumor models in cancer research: Evaluation of the oncostatic effects of melatonin.

The development of new anticancer therapies tends to be very slow. Although their impact on potential candidates is confirmed in preclinical studies, ∼95 % of these new therapies are not approved when tested in clinical trials. One of the main reasons for this is the lack of accurate preclinical models.

iMS-Bmal1 mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies.

Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in Bmal1 clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible Bmal1 knockout mice (iMS-Bmal1 ) were examined by phenotypic tests and light and electron microscopy.

PIK3CG Regulates NLRP3/GSDMD-Mediated Pyroptosis in Septic Myocardial Injury.

Cardiac insufficiency is a common complication of sepsis with high mortality. Inflammatory programmed cell death (pyroptosis) executed by NLRP3/gasdermin D (GSDMD) is intrinsically correlated with septic myocardial injury. However, it remains unclear whether PIK3CG, a classical target of septic myocardial injury, can affect pyroptosis by regulating NLRP3/GSDMD signaling.

Insights into the Role of Plasmatic and Exosomal microRNAs in Oxidative Stress-Related Metabolic Diseases.

A common denominator of metabolic diseases, including type 2 diabetes Mellitus, dyslipidemia, and atherosclerosis, are elevated oxidative stress and chronic inflammation. These complex, multi-factorial diseases are caused by the detrimental interaction between the individual genetic background and multiple environmental stimuli. The cells, including the endothelial ones, acquire a preactivated phenotype and metabolic memory, exhibiting increased oxidative stress, inflammatory gene expression, endothelial vascular activation, and prothrombotic events, leading to vascular complications.

The NLRP3 inflammasome: contributions to inflammation-related diseases.

The NOD-like receptor protein 3 (NLRP3) inflammasome is a protein complex that regulates innate immune responses by activating caspase-1 and the inflammatory cytokines interleukin (IL)-1β and IL-18. Multiple studies have demonstrated the importance of the NLRP3 inflammasome in the development of immune and inflammation-related diseases, including arthritis, Alzheimer's disease, inflammatory bowel disease, and other autoimmune and autoinflammatory diseases. This review first explains the activation and regulatory mechanism of the NLRP3 inflammasome.

Chronodisruption and Loss of Melatonin Rhythm, Associated with Alterations in Daily Motor Activity and Mitochondrial Dynamics in Parkinsonian Zebrafish, Are Corrected by Melatonin Treatment.

Beyond sleep/wake, clock genes regulate the daily rhythms of melatonin production, motor activity, innate immunity, and mitochondrial dynamics, among others. All these rhythms are affected in Parkinson's disease (PD), suggesting that chronodisruption may be an early stage of the disease. The aim of this study was to evaluate the connection between clock genes and these rhythms in PD, and whether melatonin administration reestablished the normal clock function.

Role of Melatonin in Cancer: Effect on Clock Genes.

The circadian clock is a regulatory system, with a periodicity of approximately 24 h, that generates rhythmic changes in many physiological processes. Increasing evidence links chronodisruption with aberrant functionality in clock gene expression, resulting in multiple diseases, including cancer. In this context, tumor cells have an altered circadian machinery compared to normal cells, which deregulates the cell cycle, repair mechanisms, energy metabolism and other processes.

Identification of PIK3CG as a hub in septic myocardial injury using network pharmacology and weighted gene co-expression network analysis.

Sepsis causes multiple organ injuries, among which the heart is one most severely damaged organ. Melatonin (MEL) alleviates septic myocardial injury, although a systematic and comprehensive approach is still lacking to understand the precise protective machinery of MEL. This study aimed to examine the underlying mechanisms of MEL on improvement of septic myocardial injury at a systematic level.

A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in surgical patients with severe sepsis admitted to the intensive care unit.

To determine whether IV melatonin therapy improves redox status and inflammatory responses in surgical patients with severe sepsis, a unicenter, phase II double-blind, randomized, placebo-controlled trial was carried out. The study included patients with severe sepsis marked by infectious systemic inflammatory response syndrome (SIRS), associated with organ dysfunction, hypoperfusion or hypotension requiring surgical intervention. IV melatonin at a daily dose of 60 mg, which was dissolved in 500 ml of 5% dextrose serum, was continuously administered to the patients for over 30 min starting on the day of the diagnoses during a 5-day period.

Role of c-miR-21, c-miR-126, Redox Status, and Inflammatory Conditions as Potential Predictors of Vascular Damage in T2DM Patients.

The development of type 2 diabetes mellitus (T2DM) vascular complications (VCs) is associated with oxidative stress and chronic inflammation and can result in endothelial dysfunctions. Circulating microRNAs play an important role in epigenetic regulation of the etiology of T2DM. We studied 30 healthy volunteers, 26 T2DM patients with no complications, and 26 T2DM patients with VCs, to look for new biomarkers indicating a risk of developing VCs in T2DM patients.

Deciphering clock genes as emerging targets against aging.

The old people often suffer from circadian rhythm disturbances, which in turn accelerate aging. Many aging-related degenerative diseases such as Alzheimer's disease, Parkinson's disease, and osteoarthritis have an inextricable connection with circadian rhythm. In light of the predominant effects of clock genes on regulating circadian rhythm, we systematically present the elaborate network of roles that clock genes play in aging in this review.

Understanding the Mechanism of Action of Melatonin, Which Induces ROS Production in Cancer Cells.

Reactive oxygen species (ROS) constitute a group of highly reactive molecules that have evolved as regulators of important signaling pathways. In this context, tumor cells have an altered redox balance compared to normal cells, which can be targeted as an antitumoral therapy by ROS levels and by decreasing the capacity of the antioxidant system, leading to programmed cell death. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects.

Melatonin drives apoptosis in head and neck cancer by increasing mitochondrial ROS generated via reverse electron transport.

The oncostatic effects of melatonin correlate with increased reactive oxygen species (ROS) levels, but how melatonin induces this ROS generation is unknown. In the present study, we aimed to elucidate the two seemingly opposing actions of melatonin regarding its relationship with free radicals. We analyzed the effects of melatonin on head and neck squamous cell carcinoma cell lines (Cal-27 and SCC-9), which were treated with 0.

The Zebrafish, an Outstanding Model for Biomedical Research in the Field of Melatonin and Human Diseases.

The zebrafish has become an excellent model for the study of human diseases because it offers many advantages over other vertebrate animal models. The pineal gland, as well as the biological clock and circadian rhythms, are highly conserved in zebrafish, and melatonin is produced in the pineal gland and in most organs and tissues of the body. Zebrafish have several copies of the clock genes and of and genes, the latter involved in melatonin synthesis.

Age and Chronodisruption in Mouse Heart: Effect of the NLRP3 Inflammasome and Melatonin Therapy.

Age and age-dependent inflammation are two main risk factors for cardiovascular diseases. Aging can also affect clock gene-related impairments such as chronodisruption and has been linked to a decline in melatonin synthesis and aggravation of the NF-κB/NLRP3 innate immune response known as inflammaging. The molecular drivers of these mechanisms remain unknown.