Mioara Desdemona Stepan

Cyclodextrins (CDs) have gained increasing attention as versatile platforms for enhancing drug delivery to the central nervous system, particularly in overcoming the restrictive properties of the blood–brain barrier (BBB). Owing to their unique cyclic oligosaccharide structure, CDs are capable of forming inclusion complexes with a wide range of therapeutic agents, thereby improving their solubility, stability, and bioavailability. In addition to their role as excipients, growing evidence indicates that CDs can actively modulate biological processes, including membrane fluidity and cholesterol homeostasis, which are critical factors in neurological disorders. This review explores the application of CDs in facilitating drug transport across the BBB through multiple mechanisms, including carrier-mediated transport, receptor-mediated transcytosis, and nanoparticle-based delivery systems. Special emphasis is placed on their use in the treatment of neurodegenerative and neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, Niemann–Pick type C disease, and other central nervous system disorders. In these contexts, CD-based formulations have demonstrated the ability to enhance brain targeting, reduce pathological protein aggregation, and improve therapeutic outcomes in preclinical models. This review uniquely integrates cyclodextrin’s physicochemical properties with specific blood–brain barrier transport mechanisms, proposing a structure–transport–therapy framework that enables a more predictive understanding of brain-targeted drug delivery.

Metabolic abnormalities are frequently associated with hepatic steatosis and low-grade inflammation, yet the contributions of iron metabolism and genetic susceptibility are not fully understood. We aimed to investigate the relationship between serum ferritin, hepatic steatosis, metabolic risk clustering, and the PNPLA3 rs738409 gene variant in children. A total of 68 children aged 6–14 years underwent anthropometric, biochemical, imaging, and genetic assessment. Hepatic steatosis was present in 72.1% of participants, with fibrosis greater than F1 in 42.6%. Serum ferritin showed a strong correlation with echographic liver steatosis severity (ρ = 0.804, p < 0.001) and a moderate correlation with the number of metabolic risk components (ρ = 0.482, p < 0.001). The highest metabolic burden occurred in children with low iron and elevated ferritin. While PNPLA3 status did not independently predict ferritin levels, carriers had a significantly higher prevalence of hypertension (50.0% vs. 25.0%, p = 0.038) and a non-significant trend toward low HDL-C (65.0% vs. 42.9%, p = 0.070). Ferritin was associated with metabolic clustering and ultrasound-defined hepatic steatosis, acting as a nonspecific marker of combined metabolic and hepatic alterations. PNPLA3 genotype was not independently related to ferritin or fibrosis in early pediatric disease. Given the cross-sectional design and the relatively small sample size, these findings should be interpreted as exploratory and further studies including larger populations and direct inflammatory markers should be conducted.

This review critically examines how cyclodextrins modulate regulated cell death pathways and the implications for immunometabolism and therapeutic translation. Increasing evidence, however, indicates that cyclodextrins exert intrinsic biological activity by modulating cellular lipid homeostasis, membrane organization, and intracellular trafficking. In recent years, these properties have positioned cyclodextrins as unexpected regulators of regulated cell death (RCD) pathways, with broad implications for immunometabolism and therapeutic innovation. This review provides a comprehensive overview of the mechanisms by which native and chemically modified cyclodextrins influence major forms of regulated cell death, including apoptosis, autophagy-dependent cell death, pyroptosis, ferroptosis, and necroptosis. Particular attention is given to cholesterol sequestration, lipid raft disruption, lysosomal cholesterol mobilization, and transcriptional reprogramming via pathways such as TFEB (transcription factor EB) and AMPK (AMP-activated protein kinase), which collectively shape cell fate decisions. We further examine how cyclodextrin-mediated modulation of RCD intersects with immune metabolism, especially macrophage polarization and inflammasome activity, thereby influencing inflammatory responses and disease progression. Translational implications are discussed across diverse pathological contexts, including cancer, cardiovascular diseases, neurodegenerative disorders, inflammatory and autoimmune conditions, infectious diseases, and lysosomal storage disorders. Finally, emerging cyclodextrin-based delivery platforms, ranging from inclusion complexes to nanoparticles and polymeric systems, are evaluated with respect to their ability to achieve targeted modulation of cell death while minimizing off-target toxicity. Importantly, we critically discuss dose-dependent cytotoxicity, sterol depletion–related adverse effects, and formulation-dependent variability, which currently limit the clinical translation of cyclodextrin-mediated cell death modulation. By integrating mechanistic insights with pharmaceutical formulation strategies, this review delineates key challenges and opportunities for the rational design of cyclodextrin-based therapeutics. Overall, this review highlights cyclodextrins as bioactive modulators rather than inert carriers, underscoring their potential to inspire novel pharmacological strategies that integrate drug delivery, immunometabolism, and regulated cell death.

Background: Acne in adult women is increasingly recognized as a condition with systemic endocrine–metabolic correlates. Evidence linking acne to thyroid-related abnormalities and cardiometabolic risk markers remains mixed, and integrated real-world evaluations combining thyroid biochemistry, ultrasound metrics, inflammatory indices, and lipid profile are limited. Methods: We performed a cross-sectional observational analysis of 80 women with acne who underwent routine laboratory testing and thyroid ultrasound assessment. Thyroid status was defined using TSH (reference 0.4–4.5 mIU/L) and free T4 (0.8–1.8 ng/dL), with an additional TSH-only sensitivity definition (high TSH >4.5 mIU/L). Low HDL-cholesterol (HDL-C) was defined as 4.5 mIU/L) was strongly associated with low HDL-C (OR 13.13, 95% CI 1.48–116.04; p = 0.020). In a minimal adjusted model including NLR, high TSH remained associated with low HDL-C (adjusted OR 12.93, 95% CI 1.44–115.70; p = 0.022). HDL-C showed an inverse association with NLR (ρ = −0.28; p = 0.023). Endocrine profiling suggested a positive association between ACTH and log(TSH) (ρ = 0.62; p = 0.004), although this did not remain significant after FDR correction. Thyroid ultrasound metrics showed limited correspondence with thyroid biochemistry. Conclusions: In women with acne, elevated TSH is associated with substantially higher odds of low HDL-C, independent of inflammatory burden as proxied by NLR, while thyroid ultrasound morphology contributes limited functional information. These findings support integrated thyroid–metabolic assessment in adult female acne and motivate prospective studies incorporating acne severity measures and standardized testing to clarify clinical implications.

Childhood obesity has emerged as a major global health challenge, with a marked increase in prevalence. Defined by excessive fat accumulation, it is associated with an increased risk of developing metabolic syndrome (MetS) and metabolic dysfunction-associated steatotic liver disease (MASLD). These conditions share common pathophysiological mechanisms, involving chronic low-grade inflammation, adipose tissue dysfunction, and insulin resistance. Excess weight contributes to the development of MetS even in the pediatric population through abdominal fat accumulation, dyslipidemia, hypertension, and hyperglycemia, while also creating a pro-inflammatory state that enhances hepatic fat accumulation, leading to MASLD. It is a bidirectional relationship, with MASLD increasing the risk of hypertension and the development of MetS individual components and as a whole. Adipose tissue, especially visceral fat, acts as a metabolic and immunologic organ, producing pro-inflammatory cytokines, which further accentuate insulin resistance and hepatic injury. The “three-strike” hypothesis illustrates the progression of MASLD. Several inflammatory biomarkers, including C-reactive protein, interleukins, adipokines, and serum ferritin, have been studied to monitor and predict disease progression in pediatrics. However, their diagnostic value in children remains limited due to age-related variability and lack of standardized pediatric cut-off points. A unified definition of pediatric MetS and MASLD is crucial to improve study comparability and clinical applicability. Such standardization would support the development of targeted strategies for early identification and intervention.

This study analyzed the relationship between obesity, metabolic syndrome (MetS) and its individual components, iron metabolism, and hepatic alterations in a pediatric group of patients. We mostly concentrated on the role of serum ferritin as a marker of inflammation. We conducted a retrospective study, in which we determined the presence of MetS and hepatic ultrasound changes in a cohort of 68 pediatric patients and examined the changes in serum iron and ferritin levels. MetS prevalence was significantly higher in obese children (64%) compared to those with average weight (11.1%). Abdominal circumference, triglycerides, and high-density lipoprotein cholesterol were the most relevant MetS criteria. Serum iron levels were significantly lower, while ferritin levels increased proportionally with MetS number of components. Liver ultrasound findings confirmed a strong association between hepatic steatosis and MetS, with advanced ultrasonographic scores correlating with increased ferritin and serum iron deficiency. These results reinforce the interplay between iron metabolism and inflammation in pediatric MetS. Given this study’s unicentric design and limited ethnic diversity, further large-scale, longitudinal studies are needed to confirm these findings and improve early screening strategies for pediatric metabolic complications.

Pathogenic variants in the NEXMIF gene are associated with a broad neurodevelopmental phenotype, including autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. However, the role of NEXMIF in specific epileptic syndromes remains insufficiently explored. We present the case of an 11.9-year-old Romanian girl diagnosed with ASD, attention-deficit/hyperactivity disorder (ADHD), mild ID, and Jeavons syndrome (generalized epilepsy characterized by eyelid myoclonia, absence seizures, and photosensitivity). Genetic testing identified a pathogenic NEXMIF variant: c.1882C>T (p.Arg628*), a pathogenic variant rarely reported in the literature, with only two documented cases to date. To better understand the genotype–phenotype correlation, we conducted a systematic review of NEXMIF-associated disorders and compared our findings with previously reported cases. Our analysis suggests that NEXMIF variants may contribute to a broader spectrum of epileptic syndromes, including photosensitive epilepsy such as Jeavons syndrome. This highlights the need for a greater awareness of atypical seizure presentations in individuals with NEXMIF-related disorders. This study underscores the importance of genetic testing in individuals with overlapping ASD and epilepsy phenotypes as early diagnosis may facilitate targeted therapeutic interventions and genetic counseling. Further research is needed to clarify the molecular mechanisms linking NEXMIF dysfunction to epileptic syndromes and neurodevelopmental disorders.

Cyclodextrin (CD)-based drug delivery systems have emerged as a promising strategy to overcome limitations commonly encountered in antidepressant therapy, including low bioavailability, poor solubility, and suboptimal penetration of the blood–brain barrier. This review synthesizes current evidence demonstrating that complexing various classes of antidepressants—such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and atypical antidepressants—with β-CD or its derivatives significantly enhances drug solubility and stability. In addition, encapsulation with CDs can diminish systemic toxicity and improve pharmacokinetics, thereby helping to optimize dosage regimens and reduce adverse effects. Analysis of published in vitro and in vivo studies indicates that CD formulations not only boost therapeutic efficacy but also enable sustained or targeted release, which is critical for drugs requiring precise plasma and tissue concentrations. When compared to other carriers (e.g., liposomes, polymeric nanoparticles, dendrimers), CD-based systems often stand out for their ease of formulation, biocompatibility, and cost-effectiveness, although limited drug-loading capacity can be a drawback. We recommend expanding in vivo trials to substantiate the clinical benefits of CD–antidepressant complexes, particularly for treatment-resistant cases or specific subpopulations (e.g., elderly and pediatric patients). Additional investigations should also explore hybrid systems—combining CDs with advanced nano- or macroparticles—to amplify their advantages and address any limitations. Ultimately, integrating CDs into antidepressant regimens holds substantial potential to refine therapy outcomes, reduce adverse events, and pave the way for more personalized, effective interventions for depression.

Background: Respiratory distress syndrome (RDS) is the primary cause of respiratory failure in preterm infants, but it also affects 5–7% of term infants. Dysfunctions in pulmonary surfactant metabolism, resulting from mutations of the lung surfactant genes, are rare diseases, ranging from fatal neonatal RDS to interstitial lung disease, associated with increased morbidity and mortality. This study aims to clarify the clinical significance of ABCA3 variants found in a specific family case, as existing data in the literature are inconsistent. Material and Methods: A family case report was conducted; targeted panel genetic testing identified a variant of the SFTPB gene and two variants of ABCA3 genes. Comprehensive research involving a systematic review of PubMed, Google Scholar databases, and genome browsers was used to clarify the pathogenicity of the two ABCA3 variants found in the index patient. Advanced prediction tools were employed to assess the pathogenicity of the two ABCA3 variants, ensuring the validity and reliability of our findings. Results: The index case exhibited fatal neonatal RDS. Genetic testing revealed the presence of the SFTPB p.Val267Ile variant, which was not previously reported but is a benign variant based on family genetic testing and history. Additionally, two ABCA3 gene variants were identified: c.697C>T, not yet reported, and c.838C>T. These variants were found to affect ABCA3 protein function and were likely associated with neonatal RDS. Prediction tools and data from nine other cases in the literature supported this conclusion. Conclusions: Based on in silico predictors, an analysis of the presented family, and cases described in the literature, it is reasonable to consider reclassifying the two ABCA3 variants identified in the index case as pathogenic/pathogenic. Reclassification will improve genetic counseling accuracy and facilitate correct diagnosis.

Obesity is linked to the increasing prevalence of metabolic syndrome (MetS), even among the pediatric population. Some inflammatory and cardioembolic indexes derived from routine laboratory tests have captivated the attention of the medical community. Objectives: The aim of our study was to evaluate whether these markers are effective in distinguishing varying degrees of obesity and MetS in children and adolescents. Methods: We conducted a retrospective study. A total of 71 children and adolescents, aged between 6 and 16, were included in the study. Among them, 5 were overweight, 35 had obesity, and 31 had severe obesity. According to the NCEP ATP III criteria, 32 individuals had Metabolic Syndrome (MetS), while 39 did not have MetS. Results: The MetS positive group had higher values of TG/HDL-C (p < 0.001), TC/HDL-C (p < 0.001), MHR (p = 0.015), LHR (p = 0.001), NHR (p = 0.001), atherogenic index of plasma (p < 0.001), and PHR (p < 0.001). ESR, NLR, PLR, and SII did not progressively increase with the number of MetS criteria. The ROC curve analysis demonstrated that markers such as TG/HDL-C, the atherogenic index of plasma, TC/HDL-C, LHR, NHR, and PHR were effective in identifying MetS in children and adolescents with obesity. Conclusions: In conclusion, we determined that some novel inflammatory and cardioembolic indexes are useful in assessing MetS and obesity in children and adolescents.