Search Results (324)

Background: Overactive bladder (OAB) is a common functional disorder in paediatric populations and is associated with significant psychological burden and impaired quality of life. Although oxybutynin is widely used as first-line pharmacological therapy, a substantial proportion of children exhibit incomplete symptom control or limited tolerability. Emerging evidence suggests that targeting metabolic dysfunction, oxidative stress, and neuromuscular excitability may provide additional therapeutic benefit. This retrospective observational study evaluated the clinical impact of an adjunctive nutraceutical formulation containing myo-inositol, microlipodispersed magnesium, folic acid, and vitamin C (LEVIGON™ PRO, Sanitpharma; Milan, Italy) in children with OAB receiving oxybutynin. Methods: Medical records of children diagnosed with OAB were retrospectively reviewed. After applying inclusion and exclusion criteria, 120 patients aged 5–15 years were included and allocated to two groups based on documented treatment: oxybutynin plus LEVIGON™ PRO (Group A, n = 60) or oxybutynin alone (Group B, n = 60). The primary outcome was complete daytime urinary continence at Day 112. Secondary outcomes included weekly incontinence episodes, voiding frequency, bladder wall thickness, uroflowmetry parameters, and Patient Perception of Bladder Condition (PPBC) scores. An exploratory subgroup analysis was performed in 34 children with impaired fasting glucose (ifg), assessing fasting glucose, insulin, and homa-ir. results: by day 112, complete daytime continence was achieved in 61.7% of patients in group a and 48.3% in group b (absolute risk difference 13.4%; nnt ≈ 7.5; p = 0.14). across secondary endpoints, the combination therapy group showed significantly greater longitudinal improvements (group × time interaction, p < 0.05), including reductions in weekly incontinence episodes, voiding frequency, post-void residual volume, and ppbc scores, as well as increases in mean voided volume, qmax, and reductions in bladder wall thickness. in the ifg subgroup, greater reductions in fasting glucose, fasting insulin, and homa-ir were observed in group a compared with group b (p < 0.01). Both treatments were well tolerated, with no serious adverse events reported. conclusions: adjunctive nutraceutical therapy combined with oxybutynin was associated with greater improvements in several clinically relevant secondary outcomes in children with OAB, with a favourable tolerability profile. Although the primary endpoint did not reach statistical significance, the overall pattern of findings may suggest a possible additive benefit; however, these findings may be influenced by residual confounding inherent to the retrospective observational design. Therefore, the results should be considered hypothesis generating and require confirmation in prospective randomized controlled trials. Full article

With increasing environmental pollution and a high incidence of respiratory infections, pulmonary nodules (PN) are being detected more frequently. Although most are benign, they are often accompanied by chronic inflammation and localized fibrosis, which may predispose patients to progression toward idiopathic pulmonary fibrosis (IPF). However, the biological relationship between benign pulmonary nodules (BPNs) and IPF remains poorly understood. Therefore, this study aims to investigate the shared molecular mechanisms and identify potential biomarkers linking BPN and IPF, with the goal of elucidating the pathogenic transition from BPN to IPF. In this study, microarray data from GEO datasets were systematically analyzed to explore shared molecular mechanisms, immune infiltration characteristics, and potential early intervention strategies linking BPN and IPF. Differential expression analysis, protein–protein interaction (PPI) networks, weighted gene co-expression network analysis (WGCNA), and integrative machine learning approaches identified MME and ANKRD23 as key hub genes associated with the transition from BPN to IPF. Both genes demonstrated strong diagnostic performance, with Area Under the Curve (AUC) values exceeding 0.7, and were significantly correlated with immune cell infiltration, particularly effector memory CD8⁺ T cells. Functional enrichment and gene set enrichment analyses indicated that these genes were mainly involved in immune-related processes in BPN, while in IPF, ANKRD23 was linked to cytoskeletal organization and genomic stability, and MME was enriched in profibrotic pathways such as TGF-β signaling. The diagnostic value of these biomarkers was further validated in a bleomycin-induced IPF mouse model using quantitative polymerase chain reaction (qPCR). In addition, drug–gene interaction prediction and molecular docking analyses highlighted several naturally derived compounds with favorable binding affinity and anti-inflammatory properties, among which folic acid, curcumin, and arbutin emerged as promising candidates for safe early intervention. Collectively, these findings identify MME and ANKRD23 as potential biomarkers for early identification of BPN patients at risk of developing IPF and provide a theoretical basis for early diagnosis and targeted preventive strategies. Full article

Background: Cancer is a major health concern that significantly impacts the global population. Selective chemotherapeutic delivery is needed to improve the efficacy of cancer therapy while minimizing side effects in healthy cells. This study investigated the potential of gold nanoclusters (AuNCs) functionalized with poly(amidoamine) dendrimers (PAMAM) and folic acid (FA) to selectively deliver doxorubicin (DOX) to cancer cells that express the folate receptor (FR). Methods: AuNC synthesis was confirmed via UV–visible and Fourier transform infrared spectroscopy, nanoparticle tracking analysis, and transmission electron microscopy. Folic acid (FA) was incorporated for cell surface receptor targeting, while the triphenylphosphonium cation (TPP⁺) was added to improve mitochondrial localization. Cytotoxicity (MTT), apoptosis, caspase 3/7, mitopotential, and oxidative stress assays were assessed using human MCF-7 (breast adenocarcinoma), HeLa (cervical carcinoma), Caco-2 (colon adenocarcinoma), MDA-MB-231 (epithelial breast cancer), and the embryonic kidney (HEK293) cells. Results: Favorable DOX loading (>78%), with more than 90% of the drug released at pH 4.5, was achieved. A dose-dependent increase in cytotoxicity was observed, with IC50 values lower in cancer cells than HEK293 cells, indicating selective toxicity and minimal off-target effects. Targeting nanocomplexes produced the best responses in the mitopotential, caspase, and oxidative stress assays in HeLa and MCF-7 cells. Conclusions: The improved cytotoxicity in cancer cells may be due to folate-receptor-mediated cellular uptake, as well as the mitochondrial uptake of TPP⁺ nanocomplexes. This highlighted the potential of the drug–AuNC nanocomplexes to limit systemic side effects, proposing a potential novel strategy for drug delivery to cancer cells. Full article

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, with a five-year survival rate of only 26%, primarily due to late-stage diagnosis and limited treatment options. Exosomes, nanosized extracellular vesicles released by nearly all cell types, have emerged as promising tools in both diagnostics and therapeutics. Their unique composition containing proteins, lipids, and nucleic acids reflects the molecular profile of their cell of origin, making them excellent candidates for non-invasive early detection biomarkers. For therapeutic applications, exosomes offer biocompatible, low-immunogenicity platforms capable of delivering diverse therapeutic agents, including small molecules, siRNAs, and antimetabolites, directly to tumor cells while minimizing systemic toxicity. Functionalization strategies, such as folic acid tagging, have further enhanced tumor specificity, especially in cancers with high folate receptors. However, clinical translation is hindered by challenges including lack of standardized isolation and characterization methods, high production costs, and regulatory uncertainties. Despite these limitations, ongoing research continues to optimize exosome production, targeting, and integration with conventional therapies. Milk- and colostrum-derived exosomes have shown promising potential due to their abundance, scalability, oral bioavailability, and safety. Collectively, exosomes represent a transformative approach in lung cancer management, with the potential to improve early diagnosis, enhance therapeutic efficacy, and reduce adverse effects, thereby offering a path toward more personalized and effective cancer care. Full article

Background: Co-delivery of two drugs with diverse physicochemical properties and a specific administration sequence holds great importance in cancer theranostics to overcome drug resistance and reduce side effects. Paclitaxel (PTX) and hydroxycamptothecin (HCPT) have long been used clinically as chemotherapeutic agents for Nasopharyn-geal carcinoma (NPC). However, their clinical application is severely restricted by low water solubility, poor stability, and systemic adverse reactions. Nanoparticle-based drug delivery systems provide a promising platform for combination cancer therapy. Methods: In this study, folic acid-modified and dual drug-loaded self-assembled HCPT/PTX@FA@p-PS-SPIONs were successfully fabricated via the emulsification–solvent evaporation method using amphiphilic phosphorylated polystyrene (p-PS). The characterization, cellular uptake, and in vivo pharmacokinetic profiles of the nanoparticles in NPC models were systematically investigated. Result: HCPT/PTX@FA@p-PS-SPIONs were successfully prepared with p-PS as the copolymer backbone. The nanoparticles exhibited a uniform particle size of 196.9 ± 5.5 nm and a zeta potential of −7.3 ± 0.7 mV. The encapsulation efficiency (EE) was 81.4 ± 2.5% for PTX and 67.6 ± 4.1% for HCPT. The drug loading (DL) efficiency was 18.4 ± 1.5% for PTX and 12.2 ± 1.0% for HCPT. HCPT/PTX@FA@p-PS-SPIONs showed favorable biocompatibility. Sustained and sequential release of the two drugs contributed to an enhanced therapeutic effect. Moreover, under magnetic field (MF) guidance, HCPT/PTX@FA@p-PS-SPIONs exhibited stronger inhibitory effects on NPC cells than single-drug, cocktail, or dual-drug groups, demonstrating the superiority of the combined therapy. Pharmacokinetic studies in rats revealed that the half-lives of PTX and HCPT were 3.9 ± 1.2 h and 4.7 ± 1.1 h, respectively, confirming that HCPT/PTX@FA@p-PS-SPIONs could resist rapid metabolism and clearance in vivo. Conclusions: The long-circulating, folic acid-targeted nanoparticles HCPT/PTX@FA@p-PS-SPIONs show great potential for the targeted therapy of nasopharyngeal carcinoma. Full article

Background: Liver cancer is a complex malignant tumor; gambogic acid (GA) has significant anti-cancer potential, but poor water solubility and low bioavailability limit its clinical application. In this paper, by integrating nanocrystal (NC) technology and an active targeting strategy, a new nanoagent—folic acid-modified phospholipid–gambogic acid nanocrystals (GA-NCs@FA)—was developed to improve the delivery efficiency and therapeutic effect of GA in the treatment of liver cancer. Methods: GA-NCs@FA was prepared by the CO₂-assisted precipitation method and the thin-film hydration method. The in vitro anti-tumor activity of GA-NCs@FA was evaluated by cytotoxicity, as well as a scratch and uptake test. A HepG2 tumor-bearing nude mouse model was established to investigate the in vivo distribution and tumor targeting of GA. The in vivo anti-tumor activity was evaluated by the tumor inhibition rate, and the pathological changes of organs in each group were observed by H&E staining. Results: GA-NCs@FA significantly reduced HepG2 cell viability (IC₅₀: 0.50 μg·mL⁻¹) and migration ability (48 h healing rate: 11.50%) and enhanced intracellular fluorescence intensity. In vivo analysis showed that GA-NCs@FA significantly increased the accumulation of drugs in tumor tissues by active targeting and achieved a tumor growth inhibition rate of 70.9%. Histopathology confirmed that GA-NCs@FA induced the most obvious nuclear pyknosis and necrosis in tumor tissues while maintaining good biosafety. Conclusions: GA-NCs@FA significantly prolongs the systemic circulation time of the drug and enhances intratumoral accumulation; therefore, it is a method that can be considered for active targeting and treatment of liver cancer. Full article

Objectives: To summarize the best evidence regarding folic acid supplementation for preventing neural tube defects (NTDs) in women of childbearing age and to develop a structured evidence summary for guiding clinical practice. Methods: We systematically searched multiple databases and professional websites from 1 January 2013 to 18 September 2025. Sources included 7 databases and 20 professional websites. The search targeted clinical guidelines, expert consensuses, best practices, and recommended practices on folic acid supplementation for NTD prevention in women of childbearing age. The retrieved literature underwent quality assessment, evidence extraction, and summarization. Results: The review included 17 publications: 10 guidelines, 4 expert consensuses, 2 recommended practices, and 1 best practice. From these, 14 distinct evidence statements were synthesized and organized into five thematic dimensions: risks of neural tube defects and the role of folic acid, time window of neural tube closure, timing and dosage of folic acid supplementation, relationship between dietary folic acid and folic acid tablets, and folic acid-related testing. The key recommendations include initiating supplementation at least 3 months preconception, with daily doses of 0.4 mg for low-risk, 1.0 mg for moderate-risk, and 4.0–5.0 mg for high-risk women, continuing through the first trimester, emphasizing that dietary intake alone is insufficient, and advising against routine folate testing. Conclusions: This study synthesized the best available evidence regarding folic acid supplementation for preventing NTDs in women of childbearing age, providing an evidence-based foundation to inform clinical practice, particularly for healthcare systems and populations in regions without mandatory folic acid food fortification. Full article

The inadequate biosafety of MRI contrast agents (CAs) remains a challenging issue. Both increasing the magnetic relaxivity of CAs and targeting them through conjugation with folates are promising approaches to addressing this issue. Silica nanoparticles (SNs) with Mn²⁺ ions specifically localized in the outer layer were selected as the target for further surface modification for the covalent attachment of folates. It was shown that when Mn-containing SNs are conjugated with folates via preliminary amino modification of the surface silanol groups, the folate-conjugated SNs suffer from colloidal instability. Thus, precoating Mn-containing SNs with unfolded BSA exposes surface amino groups that successfully conjugate with folates without loss of colloidal stability. Partial washout of surface-localized Mn²⁺ follows folate conjugation of Mn-containing SNs, although residual Mn²⁺ ions provide r₁₍₂₎ relaxivities of 62.1 (160.4) mM⁻¹s⁻¹ at 0.47 T. Full article

Oxaliplatin (OXA) is a chemotherapeutic agent that suffers from poor pharmacokinetics and off-target toxicity. To enable controlled OXA release, we engineered a multi-functional iron oxide nanoparticle (IONPs) drug delivery system, based on pH-responsive mesoporous Fe₃O₄ (Fe₃O₄@MSN-NH₂) nanoparticles (NPs), conjugated with folic acid (FA) for receptor-mediated targeting and guided by a magnetic robot platform (MRP) under simulated physiologically relevant dynamic circulation/flow system. For FA-conjugated NPs (Fe₃O₄@MSN-NH₂/FA), ~29.73% OXA loading was achieved compared to ~10.3% in controls (Fe₃O₄@MSN-NH₂/OXA), quantified by ICP-OES. Under dynamic circulation flow over 48 h, MRP enhanced pH-responsive OXA release (quantified by HPLC-UV), reaching ~92% and 88% (Fe₃O₄@MSN-NH₂/OXA and Fe₃O₄@MSN-NH₂/FA, respectively) at pH 5, versus 47% and 40% (Fe₃O₄@MSN-NH₂/OXA and Fe₃O₄@MSN-NH₂/FA, respectively) without MRP, demonstrating precise control in acidic tumor-mimicking conditions. MRI relaxometry exhibited strong T2-weighted contrast (T2 = 0.015 s at 50 μg/mL for Fe₃O₄@MSN-NH₂/FA/OXA), confirming theranostic potential. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) studies revealed variable Folate receptor alpha (FOLR1) expression among colorectal cancer cell lines (Caco2, SW620, SW48, and T84), with Caco2 demonstrating high levels. MTT assays indicated selective targeting of FOLR1-positive cells by FA-functionalized NPs (Fe₃O₄@MSN-NH₂/FA). This multi-functional drug delivery system integrates targeted delivery, MRP release, and real-time imaging, offering a promising technique for precision oncology. Full article

Kidney disease, be it acute or chronic, has a complex pathology and is a significant human health problem. Increasing interest has been focused on exploring therapeutic targets that can be used to safeguard kidney function under a variety of detrimental conditions. In this article, we review the protective effects of 5-methoxytryptophan (5-MTP), a tryptophan metabolite, on kidney injury. Published studies indicate that serum 5-MTP level is decreased in patients with chronic kidney disease (CKD), suggesting that 5-MTP is a biomarker for CKD and has therapeutic values. Indeed, rodent models of kidney injury induced by folic acid, lipopolysaccharide (LPS), unilateral ureteral obstruction (UUO), and ischemia/reperfusion all demonstrate that exogenous 5-MTP exhibits nephroprotective effects. The underlying mechanisms involve antioxidative damage via activating antioxidant systems such as heme oxygenase-1, anti-inflammation, anti-fibrosis, and enhanced mitophagy. To further explore the underlying mechanisms and the potential of 5-MTP as a kidney therapeutic compound, future studies need to include more rodent models of kidney injury induced by a variety of insults. Moreover, how to boost endogenous 5-MTP content and its potential synergistic effects with other therapeutic approaches aiming to combat kidney diseases also remain to be explored. Full article

Background: Congenital anomalies are influenced by genetic and environmental factors. While interventions including folic acid supplementation have reduced neural tube defects, data on modifiable socio-demographic risk factors remain limited. Aim: This study aimed to assess variation in the prevalence of selected congenital anomalies across the United States according to socio-demographic factors. Methods: A population-based analysis was conducted using CDC-WONDER natality data from 2016 to 2023. Included anomalies were anencephaly, spina bifida, cyanotic heart disease, diaphragmatic hernia, omphalocele, gastroschisis, limb reduction, cleft lip/palate, Down syndrome, chromosomal disorders, and hypospadias. Associations with maternal age, BMI, race, tobacco use, diabetes, and fertility treatments were analyzed. Prevalence rates were calculated per 1000 live births. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Joinpoint regression was used to assess annual percent changes (APCs), with p < 0.05 considered significant. Results: Among 3,482,944 singleton live births in 2023, the overall prevalence of the selected congenital anomalies was 3.3 per 1000. Compared to Caucasian mothers, risk was lower in Asian (RR 0.57; 95% CI: 0.52–0.63) and Black (RR 0.81; 95% CI: 0.76–0.85) infants and higher in American Indian/Alaska Native infants. Significant risk factors included pre-pregnancy diabetes (RR 2.41; 95% CI: 2.16–2.69), maternal age > 45 (RR 2.95; 95% CI: 2.36–3.69), and tobacco use (RR 1.78; 95% CI: 1.64–1.94). A significant decline in prevalence was observed from 2016 to 2023 (APC: −0.6%; 95% CI: −1.1 to −0.2; p = 0.006). Conclusions: Significant disparities and modifiable maternal risk factors were associated with the prevalence of selected congenital anomalies in the U.S. from 2016 to 2023. A modest statistically significant decline in overall prevalence was observed during the study period, supporting the importance of continued national surveillance and targeted preconception and prenatal interventions to reduce risk and address inequities. Full article

Gadolinium-doped hydroxyapatite nanoparticles (HapGd NPs) have emerged as promising multifunctional platforms for biomedical applications due to their unique combination of biocompatibility, structural tunability, and magnetic responsiveness. In this work, HapGd nanoparticles were synthesized using a microwave-assisted method and subsequently functionalized with curcumin and folic acid to enhance therapeutic efficiency and selective targeting. The synthesized nanostructures were characterized using various techniques, including X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and relaxometry. Structural analyses revealed successful incorporation of Gd³⁺ ions into the Hap lattice, resulting in reduced unit cell volume and slight lattice distortion, while preserving the apatite crystalline framework. Surface functionalization with curcumin and folic acid was confirmed through spectroscopic characterization, demonstrating effective molecular attachment. Nuclear Magnetic Resonance (NMR) relaxation measurements indicated that Gd doping endowed paramagnetic behavior suitable for contrast enhancement in magnetic resonance imaging (MRI). Relaxometry studies revealed a strong linear correlation between 1/T₁ and the Gd³⁺ concentration, especially in the functionalized samples, with performance comparable to the commercial contrast agent Omniscan™. The developed HapGd-based nanoplatform exhibits integrated diagnostic and therapeutic potential, providing a foundation for future research in biomedical applications. Full article

Folate receptor alpha is expressed at low levels in normal tissues, but is elevated in aggressive breast cancer types and can be utilized for targeted nanoparticle delivery. Hence, we prepared a hybrid nanocarrier based on in-house synthesized mesoporous silica nanoparticles (MSNs) which were further lipid-coated and reinforced with folic acid (FA). Thorough physicochemical evaluation was performed including dynamic light scattering (DLS), powder x-ray diffraction (PXRD), thermogravimetric analysis (TGA), and nitrogen physisorption. In vitro dissolution of the model drug doxorubicin was carried out in release media with pH 7.4 and pH 5.5. The cytotoxic potential and cellular uptake were investigated in MCF-7 breast cancer cells via the MTT assay, doxorubicin fluorescence measurement, and microscopy. The potential amelioration of doxorubicin’s cardiotoxicity was evaluated in vitro on the H9c2 cell line. The results showed MSNs with significant pore volume (1.38 cm³/g) and relatively small sizes (98.05 ± 1.34 nm). The lipid coat and FA attachment improved the physicochemical stability and sustained release pattern over 24 h. MSNs were non-toxic, while when doxorubicin-loaded, they caused moderate cytotoxicity. The highest cytotoxic activity was observed with folate-functionalized, doxorubicin-loaded nanoparticles (NPs). Even though non-loaded folate-functionalized NPs exhibited significant cytotoxicity, their physical mixture with doxorubicin was inferior in MCF-7 cytotoxicity as opposed to the corresponding loaded nanocarrier. Fluorescence-based quantification showed a higher intracellular accumulation of doxorubicin when delivered via NPs. These results demonstrate the potential to use folate-functionalized NPs as carriers for doxorubicin delivery in breast cancer cells. Its cardiotoxicity was significantly reduced in the case of loading onto the folic acid-functionalized lipid-coated MSNs. All these findings provide a promising proof-of-concept, although further experimental validation, particularly regarding targeting selectivity and safety, is required. Full article

Perinatal depression (PND) is a severe mood disorder affecting mothers during pregnancy and postpartum, with implications for both maternal and neonatal health. Emerging evidence suggests that gut microbiota-derived metabolites play a critical role in neuroinflammation and neurotransmission. In this study, we employed an in silico approach to evaluate the pharmacokinetic and therapeutic potential of metabolites produced by Lactobacillus helveticus and Bifidobacterium longum in targeting key proteins implicated in PND, including BDNF, CCL2, TNF, IL17A, IL1B, CXCL8, IL6, IL10. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles of selected microbial metabolites, including acetate, lactate, formate, folic acid, riboflavin, kynurenic acid, γ-aminobutyric acid, and vitamin B12 were assessed using computational tools to predict their bioavailability and safety. Enrichment analysis was performed to identify biological pathways and molecular mechanisms modulated by these metabolites, with a focus on neuroinflammation, stress response, and neurogenesis. Additionally, molecular docking studies were conducted to evaluate the binding affinities of these metabolites toward the selected PND-associated targets, providing insights into their potential as neuroactive agents. Our findings suggest that specific microbial metabolites exhibit favorable ADMET properties and strong binding interactions with key proteins implicated in PND pathophysiology. These results highlight the therapeutic potential of gut microbiota-derived metabolites in modulating neuroinflammatory and neuroendocrine pathways, paving the way for novel microbiome-based interventions for perinatal depression. Further experimental validation is warranted to confirm these computational predictions and explore the clinical relevance of these findings. Full article

Nano- and submicron particles (NSPs) with folate for targeting are actively used for the treatment and diagnosis of cancer and inflammatory diseases. Albumin-containing systems have enhanced biocompatibility, circulation time, and colloidal stability, which are important for medical applications. The outstanding binding properties of albumin allow the transport of numerous therapeutic and/or imaging agents. This review summarizes multiple aspects of binding a folate residue (or folic acid) to NSPs and the functioning of folate-albumin-NSPs. Special attention in the review is given to the types of bonds between folic acid and albumin, i.e., covalent and non-covalent, and to the confirmation and quantification of binding by different physicochemical methods. The process of binding, the qualitative and quantitative characteristics of binding and forming product, and its functioning are interconnected with the binding conditions; thus, an analysis of reaction conditions is provided. For the proper functioning of folate-albumin-NSPs, the state of albumin within them is important; thus, considerable focus in the review is placed on the features of structure modification of serum albumin in folate-albumin binding, i.e., the amino acid residues involved in this process and the conformational state of the protein. The stability and the functioning of the protein within folate-albumin-NSPs are discussed. Also, the effectiveness of targeting by folate is viewed as dependent on many characteristics of folate-albumin-NSPs, particularly on the peculiarities of binding between the folic acid residue and albumin. Furthermore, the authors discussed and suggested solutions concerning the shortcomings highlighted in the studies devoted to obtaining folate-modified albumin-containing NSPs. Full article