Immunity training is the epigenetic and metabolic remodulation of the innate immune system in response to primary stimuli, ultimately enhancing or attenuating secondary immune responses. Modulating immune training has emerged as a revolutionary approach to treating cancer and infectious diseases through nanomedicines and drug delivery systems. Nanomedicines and drug delivery systems offer effective strategies to overcome the limitations of conventional therapies by enhancing safety, biocompatibility, and targeted delivery of immunomodulators within a patient-oriented framework. In this mini-review, we discuss the immune training modulating mechanism through epigenetic reprogramming and metabolic remodeling. We have highlighted recent preclinical approaches to modulate immune training using nanomedicine and drug delivery systems, and have finally addressed their challenges and future perspectives.
PCOS is the most prevalent heterogeneous endocrine disorder, characterized by hyperandrogenism, anovulation, ovarian dysfunction, and polycystic ovarian morphology. Its pathogenesis involves interconnected pathways, including neuroendocrine dysregulation, elevated GnRH pulsatility, insulin resistance, alterations in ovarian steroidogenesis, an imbalance in LH/FSH ratios, adiposity, and chronic inflammation. This review provides a comprehensive overview of the epidemiology and pathophysiology of PCOS, along with current pharmacological and non-pharmacological management strategies. Recent advances in drug repurposing and the emergence of novel therapeutic targets, such as kisspeptin pathways, neurokinin B receptor modulators, glucagon-like peptide (GLP-1) agonists, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, highlight promising approaches for developing more precise and individualized therapies. However, further research is needed to establish phenotype-specific, long-term clinical-outcomes-based treatments that can more effectively address menstrual irregularity, metabolic dysregulation, and infertility associated with PCOS.
Fluvoxamine maleate (FM) is a selective serotonin reuptake inhibitor (SSRI) that has attracted increased attention owing to its strong agonistic activity at the sigma 1 receptor (61R). This review consolidates the current understanding of its processes highlighting 61R-mediated chaperone activity in the endoplasmic reticulum (ER), which alleviates protein misfolding, ER stress, and neuroinflammation in mental and neurological illnesses. Fluvoxamine demonstrates one of the highest affinities for 61R among SSRIs, exceeding those of sertraline and fluoxetine, via dissociating 61R from BiP chaperones to improve protein refolding and cellular resilience. Preclinical experiments illustrate its inhibition of unfolded protein response indicators, reinstatement of glutamatergic transmission, and stimulation of parvalbumin interneurons, resulting in antipsychotic-like effects in schizophrenia and neuroprotection against ketamine-induced impairments. In addition to serotonin reuptake inhibition, fluvoxamine influences inflammation, apoptosis, and extracellular matrix dynamics. Supplementary activities include advantages against tardive dyskinesia and cognitive improvement in depression by mitigating stress induced neuronal atrophy. Repurposing initiatives underscore fluvoxamine's potential beyond obsessive compulsive disorder (OCD) and depression. 61R agonism is fundamental to its effectiveness in disorders caused by ER stress, such as schizophrenia and tardive dyskinesia, and in neuropsychiatric sequelae associated with protracted COVID. Clinical translation encounters obstacles in dose optimization and 61R selectivity; yet, current studies highlight its multimodal efficacy in neurodegeneration, fibrosis, and psychopharmacology.
