Adriano Cressoni Araújo

Metabolic Syndrome (MetS) is a complex and multifactorial condition characterized by insulin resistance, visceral obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which contribute to increased cardiovascular risk. Central to its pathophysiology is metainflammation, a persistent inflammatory state closely linked to oxidative stress and mitochondrial dysfunction. This review aims to provide an integrated and updated overview of the interplay between metainflammation, oxidative stress, mitochondrial dysfunction, and organokine signaling in the development and progression of MetS and its cardiovascular complications. Current evidence indicates that mitochondrial dysfunction plays a pivotal role by promoting excessive production of reactive oxygen species (ROS), impairing ATP synthesis, and disrupting redox balance, thereby exacerbating insulin resistance and endothelial dysfunction. In parallel, dysregulated secretion of organokines—including adipokines, myokines, hepatokines, cardiokines, osteokines, and renokines—alters interorgan communication and amplifies pro-inflammatory and atherogenic pathways. Additionally, gut microbiota contributes to metabolic homeostasis through the production of short-chain fatty acids, whereas dysbiosis is associated with worsening metabolic parameters. Collectively, these interconnected mechanisms establish a self-perpetuating cycle that drives metabolic dysfunction and cardiovascular disease progression. This review highlights the central role of the metainflammation–mitochondrial dysfunction axis and emphasizes the importance of organokine-mediated crosstalk as a key regulator of systemic metabolism. Targeting these pathways may represent a promising strategy for the prevention and management of MetS and its associated complications.

Metabolic syndrome (MetS) is a complex and multifactorial condition characterized by insulin resistance, visceral obesity, dyslipidemia, hypertension, and chronic low-grade inflammation, all of which contribute to increased cardiovascular risk. Central to its pathophysiology is metainflammation, a persistent inflammatory state closely linked to oxidative stress and mitochondrial dysfunction. This review aims to provide an inte-grated and updated overview of the interplay between metaflammation, oxidative stress, mitochondrial dysfunction, and organokine signaling in the development and progression of MetS and its cardiovascular complications. Current evidence indicates that mitochondrial dysfunction plays a pivotal role by promoting excessive production of reactive oxygen species (ROS), impairing ATP synthesis, and disrupting redox bal-ance, thereby exacerbating insulin resistance and endothelial dysfunction. In parallel, dysregulated secretion of organokines—including adipokines, myokines, hepatokines, cardiokines, osteokines, and renokines—alters interorgan communication and ampli-fies pro-inflammatory and atherogenic pathways. Additionally, gut microbiota con-tributes to metabolic homeostasis through the production of short-chain fatty acids, whereas dysbiosis is associated with worsening metabolic parameters. Collectively, these interconnected mechanisms establish a self-perpetuating cycle that drives meta-bolic dysfunction and cardiovascular disease progression. This review highlights the central role of the metainflammation–mitochondrial dysfunction axis and emphasizes the importance of organokine-mediated crosstalk as a key regulator of systemic me-tabolism. Targeting these pathways may represent a promising strategy for the pre-vention and management of MetS and its associated complications.

Apitherapy is a complementary therapeutic approach based on the use of bee-derived products, particularly bee venom (BV), also known as apitoxin. Bee venom is a complex mixture of biologically active compounds, including peptides, enzymes, and biogenic amines, that exhibit diverse pharmacological activities. Major bioactive constituents such as melittin, apamin, adolapin, and phospholipase A2 have attracted increasing scientific interest due to their anti-inflammatory, antioxidant, antimicrobial, analgesic, and immunomodulatory properties. This review provides a comprehensive overview of the biological effects and therapeutic potential of bee venom in the management of chronic diseases, particularly diabetes, cancer, and neurological disorders. Evidence from experimental and clinical studies suggests that BV and its components can modulate multiple molecular pathways associated with oxidative stress, inflammation, apoptosis, and immune responses. These mechanisms contribute to potential benefits in glycemic control, tumor suppression, neuroprotection, and pain management. Additionally, bee venom has been investigated for its capacity to influence signaling pathways involved in cellular proliferation and survival, highlighting its potential as a complementary strategy in the treatment of complex diseases such as neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Despite these promising therapeutic effects, the clinical use of BV remains limited due to safety concerns, particularly the risk of allergic reactions, systemic toxicity, and anaphylaxis. Recent advances in drug delivery systems and nanotechnology may help improve the safety and efficacy of BV-based therapies by enabling targeted delivery and controlled dosing. Overall, bee venom represents a promising source of bioactive compounds with potential applications in translational and integrative medicine; however, further well-designed clinical trials and mechanistic studies are necessary to establish its safety, efficacy, and long-term therapeutic value.

Mitochondrial dysfunction is a key contributor to cognitive impairment, directly affecting neuronal viability, synaptic function, and energy metabolism. In the central nervous system, where energy demand is particularly high, disturbances in mitochondrial dynamics, including impaired oxidative phosphorylation (OxPhos), increased reactive oxygen species (ROS) production, and reduced ATP availability, can compromise synaptic transmission and accelerate cognitive decline. These alterations are commonly observed in neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD), in which mitochondrial dysfunction is closely associated with oxidative stress and neuroinflammatory processes. This review aims to investigate the role of mitochondrial dysfunction in cognitive impairment and the effects of physical exercise as a non-pharmacological strategy to mitigate these alterations. Current evidence indicates that exercise promotes mitochondrial biogenesis through activation of the AMPK/PGC-1α pathway, enhances oxidative metabolism, and improves mitochondrial efficiency. Furthermore, exercise reduces oxidative stress and inflammation while stimulating the release of neurotrophic factors, such as brain-derived neurotrophic factor which support neurogenesis, synaptic plasticity, and neuronal survival. Overall, these findings reinforce the importance of mitochondrial integrity in maintaining cognitive function and highlight physical exercise as a promising strategy to counteract mitochondrial dysfunction and delay the progression of neurodegenerative diseases.

Central nervous system disorders drive disability, yet many neuroactive candidates fail because the brain is a hard compartment to dose. Plant-derived molecules spanning polyphenols, alkaloids, terpenoids, and cannabinoids are attractive because their pleiotropic actions can engage oxidative stress, neuroinflammation, and circuit dysfunction. In practice, the blood–brain barrier (BBB) restricts most native phytochemicals through tight-junction selectivity, rapid metabolism, low solubility, and transporter-mediated efflux. Key gaps include poor standardization of exposure metrics, limited human-relevant BBB models, and few head-to-head studies that compare delivery platforms on the same payload and outcome. This review tackles the mismatch between mechanistic promise and reliable brain exposure that stalls translation. The objectives are to link phytochemical liabilities to enabling strategies in nanomedicine, alternative routes, and transporter-targeted prodrugs, and to propose decision-grade endpoints for translation. We synthesize evidence on BBB transport logic, nanocarrier families, targeting ligands, intranasal delivery, focused ultrasound-mediated opening, and prodrug approaches that hijack influx transporters, while foregrounding safety and chemistry, manufacturing, and controls (CMC) constraints. Here we highlight that effective neurotherapeutics emerge when chemistry, carrier, route, and measurement are co-designed rather than optimized in isolation. This framework can guide platform selection, de-risk first in-human studies, and sharpen trial endpoints. More broadly, it offers a transferable playbook for barrier-limited drug development across neurology, psychiatry, and oncology.

Central nervous system disorders drive disability, yet many neuroactive candidates fail because the brain is a hard compartment to dose. Plant derived molecules spanning polyphenols, alkaloids, terpenoids, and cannabinoids are attractive because their pleiotropic actions can engage oxidative stress, neuroinflammation, and circuit dysfunction. In practice, the blood-brain barrier (BBB) restricts most native phytochemicals through tight-junction selectivity, rapid metabolism, low solubility, and transporter-mediated efflux. Key gaps include poor standardization of exposure metrics, limited human relevant BBB models, and few head-to-head studies that compare delivery platforms on the same payload and outcome. This review tackles the mismatch between mechanistic promise and reliable brain exposure that stalls translation. The objectives are to link phytochemical liabilities to enabling strategies in nanomedicine, alternative routes, and transporter-targeted prodrugs, and to propose decision-grade endpoints for translation. We synthesize evidence on BBB transport logic, nanocarrier families, targeting ligands, intranasal delivery, focused ultrasound mediated opening, and prodrug approaches that hijack influx transporters, while foregrounding safety and chemistry, manufacturing, and controls (CMC) constraints. Here we highlight that effective neurotherapeutics emerge when chemistry, carrier, route, and measurement are co designed rather than optimized in isolation. This framework can guide platform selection, de-risk first in-human studies, and sharpen trial endpoints. More broadly, it offers a transferable playbook for barrier-limited drug development across neurology, psychiatry, and oncology.

Background and Objectives: Obesity has been increasing sharply worldwide and is related to diabetes, cardiovascular diseases, liver disease, and cancer. Sleeve gastrectomy is the most used surgical approach to reduce body weight and treat metabolic implications observed in patients with moderate-to-severe obesity. On the other hand, this procedure affects the musculoskeletal system, and investigating skeletal muscle is not routinely recommended for bariatric surgery. This study aimed to evaluate the psoas muscle in patients in the preoperative period of sleeve gastrectomy and six months after the procedure using abdominal computed tomography scans. Materials and Methods: This clinical, exploratory, and observational study, with a prospective longitudinal observational study design, was conducted at a single center with 31 women who underwent sleeve gastrectomy. The evaluations were performed before and after six months of the procedures. Results: Anthropometric, muscle strength, hepatic ultrasound, and psoas computerized tomography evaluations were performed. A significant reduction in body weight, body mass index, waist, neck, and calf circumference was observed. There was also a substantial reduction in right-hand strength and the area and index of the psoas muscle (but with an increase in density). Most presented a routine abdominal ultrasound. Conclusions: Our results suggest that muscle evaluation provides valuable information for clinical monitoring before and after bariatric surgery, helping to identify potential risks and guide multidisciplinary follow-up. Psoas muscle area and psoas muscle index decreased, but psoas muscle density increased, all significantly. These results indicate that conducting a muscle evaluation is helpful for patients undergoing bariatric surgery, supporting the use of the clinical approach before and after the procedure, predicting possible complications, and providing more accurate prognoses.

In the face of population aging, sarcopenia has emerged as a significant muscle disorder characterized by the progressive loss of muscle mass, strength, and function. Chronic inflammation, oxidative stress, and mitochondrial dysfunction contribute to sarcopenia and help explain its association with comorbidities such as type 2 diabetes, obesity, and neurodegenerative diseases. Despite extensive research, there remains a need to integrate current knowledge on interventions that target these interconnected mechanisms. This review synthesizes recent evidence on the effects of resistance exercise, nutritional supplementation (high-protein intake, leucine, vitamin D, omega-3 fatty acids), and probiotic use on muscle function and inflammatory status in older adults with sarcopenia. Literature was critically analyzed to evaluate the efficacy of multicomponent strategies. The reviewed studies consistently report that combining resistance training with anti-inflammatory nutrition and targeted supplementation improves muscle strength, reduces pro-inflammatory cytokines, and supports mitochondrial function. These findings suggest that an integrated, multicomponent approach represents a promising strategy for attenuating the progression of sarcopenia and reducing its associated comorbidities.

Melatonin is indispensable for the homeostasis of plants and animals. In humans, it can help prevent or be an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of circadian rhythm, regulation of the immunological system, epilepsy control, delaying the aging process, and diminishing hormones related to cancer. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The results showed it can present scavenging of free radicals, reducing inflammatory cytokines, and modulating the immune system. Moreover, it can improve insulin resistance, blood pressure, LDL-c, adipose tissue mass, adhesion molecules, endothelial impairment, and plaque formation. These effects result in neuro- and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may be more cost-effective and present fewer adverse events than synthetic. However, more clinical trials should be performed to show adequate doses, formulation, and treatment time.

Melatonin was primarily identified for its indispensable roles in animals. Recently, it has been described as a potent regulator of several physiological pathways in plants. In humans, it has shown effects in the prevention or as an adjuvant treatment for several diseases mainly related to the immune system, inflammation, and oxidative stress. Moreover, a melatonin-rich diet is linked to several health benefits, such as regulation of the circadian rhythm, regulation of the immunological system, epilepsy control, reduced allergic reactions, delaying the aging process, diminishing hormones related to cancer, and delaying Alzheimer’s and Parkinson’s disease symptoms. This review aimed to show the effects of melatonin in diseases beyond its traditional use. The outcome of clinical trials showed that it can present scavenging of free radicals (reducing reactive oxygen species) and inflammation (reducing the synthesis of inflammatory cytokines modulating the immune system. Moreover, it can minimize apoptosis, insulin resistance, blood pressure, LDL-c, body mass index, adipose tissue mass, waist circumference, adhesion molecules, endothelial impairment, plaque formation, and muscle atrophy. It can also reduce hyperleptinemia, alanine aminotransferase, and liver fat. These effects result in neuro and cardioprotection, improvement of liver diseases, rheumatoid arthritis, dermatitis, COVID-19, polycystic ovaries, dermatitis, and sepsis. We conclude that plant melatonin can benefit patients with many diseases besides sleep problems and neurodegeneration. Plant melatonin may also be more cost-effective, less adverse, and more sustainable than synthetic; therefore, it is better than the typical already sold. However, more clinical trials should show adequate doses, formulation, and treatment time.