Search Results (1,399)

The lung is increasingly recognized as an organ with dual endocrine and respiratory roles, participating in a complex bidirectional crosstalk with systemic hormones and local/paracrine activity. Endocrine and paracrine pathways regulate lung development, ventilation, immunity, and repair, while pulmonary cells express hormone receptors and secrete mediators with both local and systemic effects, defining the concept of the “endocrine lung”. This narrative review summarizes current evidence on the endocrine–pulmonary axis. Thyroid hormones, glucocorticoids, sex steroids, and metabolic hormones (e.g., insulin, leptin, adiponectin) critically influence alveologenesis, surfactant production, ventilatory drive, airway mechanics, and immune responses. Conversely, the lung produces mediators such as serotonin, calcitonin gene-related peptide, endothelin-1, leptin, and keratinocyte growth factor, which regulate vascular tone, alveolar homeostasis, and immune modulation. We also describe the respiratory manifestations of major endocrine diseases, including obstructive sleep apnea and lung volume alterations in acromegaly, immunosuppression and myopathy in Cushing’s syndrome, hypoventilation in hypothyroidism, restrictive “diabetic lung”, and obesity-related phenotypes. In parallel, chronic pulmonary diseases such as chronic obstructive pulmonary disease, interstitial lung disease, and sleep apnea profoundly affect endocrine axes, promoting insulin resistance, hypogonadism, GH/IGF-1 suppression, and bone metabolism alterations. Pulmonary neuroendocrine tumors further highlight the interface, frequently presenting with paraneoplastic endocrine syndromes. Finally, therapeutic interactions are discussed, including the risks of hypothalamic–pituitary–adrenal axis suppression with inhaled corticosteroids, immunotherapy-induced endocrinopathies, and inhaled insulin. Future perspectives emphasize mapping pulmonary hormone networks, endocrine phenotyping of chronic respiratory diseases, and developing hormone-based interventions. Full article

Dumping Syndrome (DS) is a significant complication following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). This condition is characterised by gastrointestinal and vasomotor symptoms resulting from altered anatomy and hormonal dysregulation, notably accelerated gastric emptying and an exaggerated release of gut peptides. Based on the timing of symptom onset after food ingestion, DS is classified as early (EDS) or late (LDS). The critical roles of peptides such as GLP-1, GIP, insulin, and YY peptide are highlighted, along with the involvement of neuroendocrine pathways in symptom manifestation. Diagnosis relies on a combination of clinical evaluation and dynamic testing, with the oral glucose tolerance test (OGTT) often considered a key reference standard for diagnosis. Initial management involves dietary modifications, emphasising the glycaemic index of foods and meal distribution. In cases where nutritional interventions are insufficient, pharmacotherapy with agents such as acarbose, somatostatin analogues (octreotide and pasireotide), GLP-1 receptor agonists (liraglutide), calcium channel blockers (verapamil), and emerging therapies, including herbal medicine, may be considered. For refractory cases, surgical options like bypass reversal or partial pancreatectomy are reserved, although their efficacy can be variable. Despite advancements in understanding and treating DS, further large-scale, randomised controlled trials are essential to validate novel strategies and optimise long-term management. This review provides an updated and comprehensive overview of the aetiology, pathophysiological mechanisms, diagnostic approaches, and current management strategies for DS. Full article

Hidradenitis suppurativa (HS) is a chronic, recurrent, and highly debilitating inflammatory disorder of the pilosebaceous unit. Its pathogenesis is considered multifactorial, involving genetic, environmental, hormonal, lifestyle, and microbiome-related factors. The microbiota, defined as the collection of microorganisms, their genomes, and their interactions within a given environment, colonizes multiple sites of the healthy human body, which include the skin and gut, where it contributes to the maintenance of homeostasis. In HS, both skin and gut microbiota exhibit disruptions in composition and diversity, a state referred to as dysbiosis. Alterations in the expression of antimicrobial peptides in HS further implicate the microbiome in disease pathophysiology. In addition, chronic inflammation, bacterial biofilm formation, and dysbiosis are thought to contribute to the severity and recurrence of HS. Although the precise role of dysbiosis in HS pathogenesis remains unclear, several studies have demonstrated a reduction in cutaneous microbial diversity in HS patients, distinguished by an increased abundance of anaerobic and opportunistic bacteria and a reduction in commensal species. The intestinal microbiome has been even less thoroughly investigated, but available evidence suggests decreased overall diversity and richness, with enrichment of pro-inflammatory and depletion of anti-inflammatory bacterial taxa. This review aims to provide an overview of the current knowledge regarding the role of the microbiome in HS, with the goal of informing the direction of future research, including the potential utility of the microbiome as a biomarker for diagnosis and severity stratification in HS. Full article

One of the main targets for snake venoms in animal and human organisms is the circulatory system. Mechanisms of circulatory system injury within the victim’s body include, among others, the direct effect of snake toxins on structures in blood vessel walls. The interaction of a toxin with cells and the extracellular matrix of the vessel wall may manifest as cytotoxicity, leading to cell death by necrosis or apoptosis, and damage to vascular wall structures. Such interactions may increase capillary permeability, promoting hemorrhage or edema, and may also induce alterations in vascular tone, resulting in changes in blood pressure. Snake toxins may also affect the growth, function, and regenerative ability of the endothelium, thus modulating angiogenesis; some toxins exert protective or anti-atherosclerotic effects. Toxins interacting with the vasculature may be classified as enzymes (phospholipases A₂, metalloproteinases, L-amino acid oxidases, and hyaluronidases), proteins without enzymatic activity (vascular endothelial growth factors, disintegrins, C-type lectins and snaclecs, three-finger toxins, etc.), peptides (bradykinin-potentiating peptides, natriuretic peptides, sarafotoxins), and low-molecular-weight substances. This review summarizes the data on the vascular effects, particularly on the blood vessel wall, exhibited by various classes and groups of snake toxins. Full article

Despite growing recognition of the role of the gut microbiome in host health and in modulating pathogen activity, the dynamic and reciprocal relationship between enteric viruses and the gut microbial ecosystem remains insufficiently defined and requires further exploration. This comprehensive review examines the bidirectional interplay between the gut microbiome and enteric viral infections by addressing (i) viruses associated with gastrointestinal alterations, (ii) how enteric viral infections alter the composition and function of the gut microbiome, (iii) how the gut microbiome modulates viral infectivity and host susceptibility, and (iv) current microbial-based approaches for preventing or treating enteric viral infections. Gastrointestinal viral infections induce gut microbiome dysbiosis, marked by reductions in beneficial bacteria and increases in potentially pathogenic populations. Specific gut microorganisms can modulate host susceptibility, with certain bacterial genera increasing or decreasing infection risk and disease severity. Pattern recognition receptors in the intestinal epithelium detect microbial signals and trigger antimicrobial peptides, mucus, and interferon responses to control viral replication while maintaining tolerance to commensal bacteria. The gut microbiome can indirectly facilitate viral infections by creating a tolerogenic environment, suppressing antiviral antibody responses, and modulating interferon signaling, or directly enhance viral replication by stabilizing virions, promoting host cell attachment, and facilitating coinfection and viral recombination. In turn, commensal gut bacteria can inhibit viral entry, enhance host antiviral responses, and strengthen mucosal barrier function, contributing to protection against gastrointestinal viral infections. Probiotics and fecal microbiota transplantation constitute potential microbial-based therapeutics that support antiviral defenses, preserve epithelial integrity, and restore microbial balance. In conclusion, the role of the gut microbiome in modulating enteric viral infections represents a promising area of future investigation. Therefore, integrating microbiome insights with virology and immunology could enable predictive and personalized strategies for prevention and treatment. Full article

Agrobacterium tumefaciens (A. tumefaciens), the causal agent of crown gall disease on several plant species, is responsible for substantial yield losses worldwide. The limitations of conventional pesticides in controlling this disease highlight the need for alternative antibacterial solutions. Phage biocontrol can be an option, effectively managing bacterial plant diseases, by reducing pathogen loads while driving evolutionary trade-offs, often enhancing synergy with other antibacterial strategies. In this study, we aimed to explore and develop a sustainable strategy to control A. tumefaciens, by combining Agrobacterium phage PAT1 with the natural antimicrobial peptide “Ascaphin 8” and leveraging the fitness trade-offs resulting from phage resistance. In vitro and in planta investigations showed that PAT1 in combination with Ascaphin 8 at the sublethal concentration of 3 μM could effectively eradicate A. tumefaciens in YPG broth and reduce tumor formation by 46.33% on tomato plants, unlike their individual applications, indicating that the combination was synergistic against A. tumefaciens. This synergy was attributed to the fitness trade-offs in A. tumefaciens induced by phage resistance, which led to increased sensitivity to antimicrobial peptides, slower growth rate, and an 89.96% attenuation of virulence in the PAT1-resistant mutant (AT-M1). Transmission electron microscopy analyses showed that treatment with 1 µM of Ascaphin 8 induced cytoplasmic condensation in 80% of AT-M1 cells, whereas only 16% of the wild-type CFBP 5770 cells exhibited similar alterations under identical conditions. Furthermore, proteomic analyses performed on AT-M1 and CFBP 5770 revealed that the mutant AT-M1 exhibited a loss of DNA-binding protein HupB and downregulation of SDR family oxidoreductase and superoxide dismutase. These molecular alterations are potentially associated with the reduced virulence and heightened AT-M1 sensitivity. This study investigated the fitness costs associated with phage resistance in A. tumefaciens and laid the first foundation for potential biocontrol of plant bacterial diseases, particularly A. tumefaciens infections, using phage–peptide combination. Full article

Background: The pathophysiology of Alzheimer’s disease (AD) is strongly linked to damage to the cholinergic systems of the central nervous system (CNS), mainly due to the formation of β-amyloid peptide plaques, which trigger intense inflammatory responses and are currently the main cause of the symptoms of the disease. Among the therapeutic strategies under investigation, classes of natural products with immunomodulatory properties, action on the CNS, and potent antioxidant activity, which contribute to neuroprotection, stand out. Methods: We aimed to evaluate the flavonoid quercetin using in silico, in vitro, and in vivo methods for the treatment of AD. Initially, the compounds were selected, and molecular dynamics simulations were performed. The in vitro assays included tests of antioxidant activity (DPPH), enzymatic inhibition of acetylcholinesterase (AChE), and prediction of oral toxicity. The in vivo studies investigated the effects on scopolamine-induced learning deficits and conducted histopathological analysis of the brain. Results: Quercetin showed structural stability in the complex with (AChE), with no significant alterations in the Root Mean Square Deviation (RMSD), SASA and radius of gyration (Rg) parameters. Through the same method it was possible to predict stability between the quercetin and inducible nitric oxide synthase (iNOS) complex, a possible mechanism for quercetin immunomodulation in the CNS. In the AChE inhibition test, the IC₅₀ obtained for quercetin was 59.15 μg mL⁻¹, while in the antioxidant test with DPPH, the concentration of 33.1 µM exhibited 50% of the scavenging of reactive oxygen species. This corroborates the perspective of quercetin having neuroprotective activity. This activity was also corroborated in vivo, in a zebrafish model, in which quercetin reduced the cognitive deficit induced by scopolamine. Histopathological analysis revealed its ability to prevent atrophy, caused by scopolamine, in the nervous tissue of animals, reinforcing the potential of quercetin as a neuroprotective agent. Conclusions: The results of the tests carried out with quercetin suggest that this molecule has antioxidant, AChE inhibitory, and neuroprotective activities, making it a good candidate for use in future clinical trials to ensure its efficacy and safety. Full article

The gastrointestinal (GI) tract is increasingly recognized as an important regulator of energy balance and metabolism, extending beyond its traditional digestive functions. This review synthesizes current research on how modifications to the GI tract, particularly those induced by metabolic bariatric surgery (MBS), influence hormonal and physiological processes involved in glucose regulation and appetite control. MBS procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), induce significant and sustained weight loss, but also elicit adaptive morphological and functional changes within the intestines. These alterations include intestinal hypertrophy, increased mucosal surface area, changes in nutrient transit time, and modifications in enzyme activity. Such changes enhance the secretion of key gut hormones, including glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), which play vital roles in promoting insulin secretion, suppressing appetite, and improving blood glucose regulation. The benefits stem from the exposure of undigested nutrients to different intestinal segments, which stimulates enteroendocrine activity and positively influences systemic metabolism. These hormonal adaptations contribute significantly to the metabolic improvements observed post-surgery, independent of weight loss alone. Understanding how gut structural and functional changes drive hormonal responses provides valuable insights into the mechanisms underlying the success of MBS. Moreover, elucidating these processes may facilitate the development of less invasive therapies that mimic the metabolic benefits of surgery. Ultimately, this research advances our understanding of gut-mediated regulation of energy and glucose homeostasis and holds promise for improving treatment strategies for obesity and related metabolic disorders. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated neurodegenerative disorder marked by inflammation, demyelination, and neuronal loss within the central nervous system. Despite advances in diagnostics, current tools remain insufficiently sensitive and specific. Metabolomics has emerged as a promising approach to explore MS pathophysiology and discover novel biomarkers. This PRISMA-guided systematic review included 29 original studies using validated metabolomic techniques in adult patients with MS. Biological samples analyzed included serum, cerebrospinal fluid, and feces. Consistent metabolic alterations were identified across several pathways. The kynurenine pathway demonstrated a shift toward neurotoxic metabolites, alongside reductions in microbial-derived indoles, indicating inflammation and gut dysbiosis. Energy metabolism was impaired, with changes in glycolysis, tricarboxylic acid (TCA) cycle, and mitochondrial function. Lipid metabolism showed widespread dysregulation involving phospholipids, sphingolipids, endocannabinoids, and polyunsaturated fatty acids, some modulated by treatments such as ocrelizumab and interferon-β. Nitrogen metabolism was also affected, including amino acids, peptides, and nucleotides. Non-classical and xenobiotic metabolites, such as myo-inositol, further reflected host–microbiome–environment interactions. Several studies demonstrated the potential of metabolomics-based machine learning to distinguish MS subtypes. These findings highlight the value of metabolomics for biomarker discovery and support its integration into personalized therapeutic strategies in MS. Full article

Atherosclerosis (AS), a major contributor to cardiovascular disease, hypertension, and stroke, is associated with significant morbidity and mortality. Antimicrobial peptides (AMPs) 3-13, W3R6, and chensinin-1b were engineered based on the sequence of chensinin-1, originally isolated from the skin secretion of Rana chensinensis. This study investigated their therapeutic potential in ApoE^-/- AS mice and THP-1-derived foam cells, focusing on the regulation of cholesterol metabolism. AMP 3-13 markedly reduced body weight gain, aortic root plaque formation, and plasma cholesterol levels in ApoE^-/- mice. Transcriptomic analysis revealed that AMP 3-13 significantly altered gene expression related to cholesterol metabolism and the PPAR signaling pathway. Specifically, AMP 3-13 upregulated PPARγ, ABCA1, and ABCG1, while downregulating CD36 in aortic root plaques. In THP-1-derived foam cells, AMP 3-13 and its analogs activated the PPARγ–ABCA1/ABCG1 axis, enhancing cholesterol efflux. Concurrently, they inhibited CD36 expression by competing with PPARγ for promoter binding, thereby reducing ox-LDL uptake. These findings suggested that AMP 3-13 and its analogs represented promising therapeutic agents for AS through their ability to reduce cholesterol accumulation in foam cell. Full article

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, and immune cell regulation. This review summarizes current knowledge on adropin’s biological functions and its relevance in conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren’s syndrome, osteoarthritis, psoriasis, Behçet’s disease, and Kawasaki disease. We discuss how adropin interacts with various signaling pathways and highlight its potential role in macrophage polarization, regulatory T cell activity, and fibrotic remodeling. Although data remain limited and sometimes conflicting, altered adropin levels have been observed across several ARDs, suggesting potential utility as a biomarker or therapeutic target. Further research is needed to clarify its clinical significance and translational potential in immune-mediated diseases. Full article

With the increase in global life expectancy, preserving skeletal muscle (SM) health is essential for the overall well-being of older adults. Gradual decline in muscle mass, strength, and physical performance significantly contributes to frailty, reduced mobility, and heightened vulnerability to chronic diseases. These challenges underscore the need to formulate innovative strategies for safeguarding muscle health in aging demographics. This review analyzes the major biological and lifestyle factors influencing age-related changes, establishing a framework for understanding SM deterioration. The review focuses on structural and functional alterations of SM extracellular matrix components to identify potential intervention points for muscle waste mitigation. Additionally, we discuss novel interventions designed to preserve muscle mass and functionality. In older individuals, emerging pharmacological strategies, including innovative peptides and natural compounds, may mitigate catabolic processes, enhance muscle regeneration, and increase resilience. Concurrent lifestyle interventions, including specialized exercise regimens, nutritional enhancement, and stress reduction, augment these pharmacological approaches. This review provides a thorough resource for researchers, clinicians, and healthcare professionals focused on functional capacity enhancement in older adults. Full article

Skeletal muscle is the largest insulin-sensitive tissue in the human body, playing a crucial role in glucose homeostasis, body mobility and overall metabolic health. In obesity and type 2 diabetes (T2D), skeletal muscle undergoes structural, functional, and metabolic alterations, including reduced muscle mass, impaired contractile function, increased myosteatosis, mitochondrial dysfunction, and chronic low-grade inflammation. Incretin-based therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are highly effective treatments for T2D and obesity, producing substantial weight loss. While clinical trials suggest proportional loss of fat and lean mass when using incretin-based therapies, emerging preclinical and translational data indicate potential muscle-specific beneficial effects such as attenuation of atrophy, improved myogenesis, enhanced mitochondrial function and reduced myosteatosis. This review comprehensively summarizes the current preclinical and clinical evidence on the impact of incretin-based therapies on skeletal muscle mass, composition, metabolism, and performance, focusing on mechanistic insights from animal models and translational findings from human studies. Full article

Mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), are among the leading causes of disability worldwide and are frequently associated with treatment resistance, functional impairment, and high comorbidity with metabolic dysfunction. Increasing evidence implicates insulin resistance (IR) as a key pathophysiological factor linking metabolic and psychiatric illness. IR is associated with chronic low-grade inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, impaired neuroplasticity, mitochondrial dysfunction, and altered reward processing mechanisms that may contribute to core depressive features such as anhedonia, cognitive slowing, and emotional dysregulation. These processes are further exacerbated by the metabolic side effects of many psychotropic medications, creating a self-perpetuating cycle that worsens both psychiatric and physical health outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes and obesity, have emerged as promising candidates to address this metabolic–psychiatric interface. Beyond improving glycemic control and promoting weight loss, GLP-1 RAs exert central actions relevant to mood disorders, including modulation of dopaminergic reward pathways, enhancement of hippocampal neurogenesis, attenuation of neuroinflammation, and regulation of appetite and energy balance. Preclinical studies demonstrate that GLP-1 RAs reduce microglial activation, promote hippocampal neurogenesis, and normalize stress-induced behavioral changes. Early clinical trials in patients with metabolic disorders suggest improvements in depressive symptoms, quality of life, and cognitive function, with some effects independent of weight loss or glycemic outcomes. Observational evidence also indicates reduced antidepressant use and psychological distress in diabetic and obese populations receiving GLP-1 RAs. While these findings are promising, large randomized controlled trials in primary psychiatric populations are lacking. Key challenges include clarifying dose–response relationships, disentangling central from peripheral effects, and addressing safety and adherence concerns in individuals with comorbid psychiatric conditions. Future research should focus on biomarker-informed stratification, comparative trials with standard treatments, and integration of GLP-1 RAs into multimodal care frameworks. Overall, GLP-1 RAs represent a biologically plausible and clinically relevant approach to bridging metabolic and psychiatric care, with the potential to improve outcomes in patients with mood disorders who carry a high metabolic burden. Full article

The COVID-19 pandemic has revealed significant secondary complications affecting musculoskeletal (MSK) health, especially in patients with pre-existing conditions. This review synthesizes data from clinical and experimental studies on key MSK biomarkers, including cartilage oligomeric matrix protein (COMP), hyaluronic acid (HA), osteocalcin, alkaline phosphatase (ALP), procollagen type I N-terminal peptide (PINP), osteopontin (OPN), matrix metalloproteinases (MMP-3 and MMP-9), myostatin, IGF-1, follistatin, and creatine kinase. COVID-19 is associated with decreased COMP and osteocalcin levels, indicating cartilage degradation and impaired bone formation, alongside elevated HA, ALP, PINP, OPN, and MMPs, reflecting increased joint inflammation, bone remodeling, and tissue breakdown. Changes in myostatin, IGF-1, follistatin, and creatine kinase levels have been shown to be linked with COVID-19-related sarcopenia. These biomarker alterations provide insight into the underlying mechanisms of MSK damage in COVID-19 patients and highlight the potential for using these markers in early diagnosis and management of post-COVID musculoskeletal disorders. Further longitudinal research is essential to develop targeted therapies aimed at mitigating long-term MSK complications in affected individuals. Full article