Search Results (311)

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

Melanoma is one of the most aggressive skin cancers and requires innovative therapeutic strategies to overcome the limitations of conventional therapies. In this work, upconversion nanoparticles coated with mesoporous silica and functionalized with folic acid (UCNP@mSiO₂-FA) were developed as a targeted nanocarrier system for the delivery of doxorubicin (DOX). The UCNPs were synthesized via thermal decomposition, coated with mesoporous silica shells, and functionalized with folic acid (FA) to enable receptor-mediated targeting. DOX was then loaded into the mesoporous silica coating by adsorption, yielding UCNP@mSiO₂-FA-DOX. The different UCNPs were characterized for size, composition, colloidal stability, and loading and release of DOX. This comprehensive physicochemical characterization confirmed a high DOX loading efficiency and a slightly increased drug release under acidic conditions, mimicking the tumour microenvironment. In vitro assays using four melanoma cell lines (A375, B16-F10, MNT-1, and SK-MEL-28) revealed an excellent biocompatibility of UCNP@mSiO₂-FA and a significantly higher cytotoxicity of UCNP@mSiO₂-FA-DOX compared to unloaded UCNPs, in a dose-dependent manner. Cell cycle analysis demonstrated G2/M phase arrest after treatment with UCNP@mSiO₂-FA-DOX, confirming its antiproliferative effect. Overall, UCNP@mSiO₂-FA-DOX represents a promising nanoplatform for targeted melanoma therapy, combining active tumour targeting and enhanced anticancer efficacy. Full article

Objectives: Neural tube defects such as myelomeningocele (MMC) remain a significant public health concern despite prevention efforts. Public health measures have reduced the global MMC incidence, but socioeconomic disparities may limit their impact. Puerto Rico (PR) is a United States (US) territory; however, its socioeconomic landscape is vastly different, which may contribute to differences in MMC incidence. In this study, we aimed to compare the differences in MMC incidence and annual variability between PR and the US. Materials and Methods: Data on MMC incidence for the US was obtained from the Centers for Disease Control’s National Vital Statistics Reports, and data for PR from the Puerto Rico Birth Defects Surveillance and Prevention System. Annual percentage change (APC) was used to evaluate year-to-year variation, and multiple linear regression analysis was applied to compare incidence rates. Results: The mean annual MMC incidence in 1996–2020 was 4.88 per 10,000 live births in PR (SD = 1.86), and 1.78 (SD = 0.35) in the US, with an estimated mean difference of 3.11 (p < 0.001). APCs during this period varied significantly, ranging from +200% to −63%. A subgroup analysis after folic acid fortification efforts in PR (1999–2020) showed a persistently elevated incidence in PR (mean = 4.41, SD = 1.33) vs. US (mean = 1.67, SD = 0.25), with an estimated mean difference of 2.72 (p < 0.001). Conclusions: Despite folic acid fortification and public health interventions, MMC incidence in PR remains higher and more variable. These findings underscore the need for improved disease reporting and targeted, region-specific preventive strategies. Full article

Chitosan (CS) has emerged as a versatile biopolymer for designing drug delivery systems (DDS) in colorectal cancer (CRC) therapy due to its biocompatibility, mucoadhesive properties, and ability to be surface-functionalized. This scoping review systematically analyzed current experimental studies on CS-based DDS for CRC, comparing non-targeted formulations with ligand-modified systems to identify advances in targeting efficiency, drug release behavior, and biological outcomes. Among the twenty-five initially identified studies, divided into two categories, non-targeted CS-based DDSs and ligand-modified CS-DDSs, five fulfilled the inclusion criteria for ligand-functionalized systems. These incorporated targeting moieties, such as folic acid (FA), hyaluronic acid (HA), and galactose (Gal), to achieve receptor-mediated uptake via FRα, CD44, and ASGP receptors, respectively. Ligand modification consistently enhanced cellular uptake, reduced IC₅₀ values, and improved tumor-selective cytotoxicity compared to non-targeted systems. However, in vivo validation remains scarce, with only one study confirming tumor accumulation in xenograft models. Moreover, no clinical trials currently assess CS-based nanocarriers for the treatment of CRC. Overall, CS represents a promising modular platform for targeted nanomedicine, but translational progress requires bridging preclinical success with comprehensive in vivo and clinical evaluation. Full article

Breast cancer is the most common cancer in women worldwide, with a high mortality rate. Moreover, the treatments currently used to address this disease are sometimes ineffective and cause numerous side effects. For this reason, the search for new treatments that can overcome these challenges is a growing field of research. One potential solution under investigation is the use of mesoporous silica nanoparticles (MSNs). These materials possess excellent properties, making them attractive as starting platforms for various compounds. In this study, different compounds with distinct properties were anchored onto these nanoplatforms. The first is polyethyleneimine (PEI), which, when formulated within the nanoparticle, increases its bioavailability. The second is folic acid (FA), a molecule that enables active targeting of tumor cells. Finally, an organotin(IV) complex was incorporated via two different anchoring strategies to provide therapeutic action. This multifunctional platform thus combines three activities simultaneously. MTT assay studies revealed that the final material, MSN-TEDTH-PEI-FA-TR-Sn, demonstrates potential against the MCF-7 tumor cell line while showing no toxicity to the healthy Hek 293T cell line. These findings make it an interesting candidate for future in vivo trials. Full article

In colorectal carcinoma (CRC), 5-fluorouracil (5-FU) remains the cornerstone of adjuvant systemic therapy, with folic acid (FA) serving as an essential adjunct. Expression of genes related to the metabolism and action of 5-FU and FA can be influenced by patient- and tumor-specific biological factors. In this study, we explore differential gene expression profiles of 180 genes representing 14 different gene sets associated with different 5-FU and FA metabolism processes, at both gene and pathway levels across clinical and molecular subgroups. In 71 patients with CRC, paired tumors and normal colonic tissues were analyzed. In CRC tissue, several gene sets (including Cell Cycle Checkpoint, Oxidative Stress Response, and Signaling Pathway, etc.) were upregulated, while three gene sets (Apoptotic, Tumor Suppressor, and Endoplasmic Reticulum Stress) were downregulated. Kirsten rat sarcoma virus (KRAS), tumor protein p53 (TP53), and microsatellite instability (MSI) status impacted gene expression across molecular subgroups. At the individual gene level, among cell cycle genes, the BUB3 mitotic checkpoint protein (BUB3) was upregulated in MSI tumors compared to MSS, whereas SMAD family member 4 (SMAD4) was downregulated in MSS tumors compared to MSI. DNA fragmentation factor alpha (DFFA) was downregulated in MSI and upregulated in MSS. Notably, thymidylate synthetase (TYMS) was more upregulated in MSI tumors (1.65-fold; 95% CI: 1.27–2.13) compared to MSS (1.19-fold; 95% CI: 1.02–1.39). Dysregulation of these genes across these factors will broaden our understanding of 5-FU-based treatment in CRC. Furthermore, targeting dysregulated pathways could form the basis for improved precision therapies tailored to CRC subtypes. Full article

Background/Objectives: In Pakistan, 41.7% of women of reproductive age and 53.7% of children aged 6–59 months are anaemic. This study aimed to evaluate the effectiveness of a nutritional supplementation programme, underpinned with behaviour change communication and implemented through Lady Health Workers (LHWs), in reducing anaemia among pregnant and lactating women as well as 6–59-month-old children. Methods: This study used a quasi-experimental design with an intervention and a control group. A total of 2821 and 2410 pregnant and lactating women and 3397 and 3277 children aged 6–59 months participated in the baseline and endline surveys, respectively. The study areas were matched for demographic and economic characteristics, and both had routine public-sector health and nutrition programmes, including iron–folic acid supplementation during pregnancy. The participants in the intervention group received additional nutritional support. Throughout the pregnancy and in the first six months of exclusive breast feeding, women were provided 5 kg (165 g/day) of wheat soya blend (WSB) per month. Children aged 6–23 months received lipid-based nutrient supplements (LNS), and those aged 24–59 months received micronutrient powder. We applied a difference-in-difference (DID) analysis with kernel propensity score matching to assess the impact on anaemia, a secondary outcome of a stunting prevention programme. Results: Maternal anaemia (both pregnant and breastfeeding women) declined substantially in the intervention areas from 80.4% to 62.6% compared with a smaller reduction in the control areas (80.0% to 72.9%). The DID estimate showed a 10.7-percentage-point (pp) greater decline in maternal anaemia (p ≤ 0.001). Both pregnant and lactating women benefited, with DID reductions of 16.7 pp (p ≤ 0.001) and 9.4 pp (p = 0.005), respectively. The largest gains occurred among women in higher-wealth quintiles, with reductions up to 22.6 pp (p ≤ 0.001). In contrast, childhood anaemia showed no overall significant difference between intervention and control areas (DID = −0.7 pp, p = 0.73). However, significant improvements were observed among male children (DID = −10.3 pp, p = 0.001) and those in higher-wealth quintiles (DID = −15.0 pp, p = 0.002). Conclusions: Overall, the findings suggest that LHWs can effectively reduce maternal anaemia when iron–folic acid supplementation is complemented with WSB and targeted behaviour change communication. Full article

Breast cancer continues to rank among the most common and complex cancers worldwide. A promising approach is the direct delivery of drugs to cancer cells via specially designed nanocarriers that can target specific receptors on their surface, like folate receptors. When combined with other therapies, these functionalized nanocarriers can increase the effectiveness of treatment by more precisely targeting cancer cells than traditional methods that rely on passive targeting. Folate receptors are glycoproteins with four isoforms, for which both laboratory and animal models have shown encouraging results in research. The numerous chemical methods for attaching folic acid (FA) and enhancing drug delivery in folic acid-modified nanocarriers for breast cancer are examined in this review. Additionally, it examines how these smart carriers combine chemotherapy with alternative therapies like photodynamic therapies and state-of-the-art theranostics. The review highlights how important it is to carry out comprehensive testing to ensure that these innovations can successfully move from the lab to real clinical settings, even though the potential is evident. Full article

Treating bacterial infections has become increasingly difficult due to the rise in antibiotic-resistant bacterial strains. Strategies involving the targeted delivery of antibiotics have been proposed to minimize the administered antibiotic doses. This study aims to develop the first double-modified nanovehicle capable of increasing bacterial membranes’ permeability while specifically targeting Staphylococcus aureus, one of the foremost pathogens responsible for global mortality rates. Thus, polymeric NPs composed of poly(lactic-co-glycolic acid) (PLGA) were produced, and their surface was modified with TAT peptide to increase the membranes’ permeability and folic acid (FA) to direct the NPs to S. aureus. The nanosystem showed spherical morphology with sizes of 174 ± 4 nm, a monodisperse population (polydispersity index of 0.08 ± 0.02), and a zeta potential of −2.5 ± 0.1 mV. The NPs remained stable for up to four months during storage. Fluorescence-based flow cytometry analysis proved that the double modification of PLGA NPs increased the interaction of the NPs with S. aureus, with fluorescence increasing from 71 ± 3% to 87 ± 1%. The nanosystem slightly affected the growth curve of S. aureus by extending both the lag time (from 2.5 ± 0.2 to 2.88 ± 0.4 h) and the exponential phase, as evidenced by an increase in the half-maximum growth time (from 3.9 ± 0.2 to 4.4 ± 0.1 h). Furthermore, the nanocarrier showed no toxicity for human dermal fibroblast cells, maintaining a 100% cell viability at the highest concentration tested (100 µM). Therefore, the proposed FA/TAT-functionalized nanocarrier presented promising features to be successfully used as a delivery vehicle of antimicrobials to fight S. aureus. Full article

Background: Glioma remains an intractable and highly aggressive brain tumor, mainly due to the daunting obstacle presented by the blood–brain barrier (BBB). To overcome this challenge and enhance therapeutic efficacy, a dual-drug delivery system was engineered. This system co-encapsulated curcumin, a nutraceutical with multitargeted anticancer potential, with atorvastatin calcium, a repurposed anticancer agent, within lipidic nanocapsules (LNCs). Methods: LNCs were prepared via the phase inversion temperature method and optimized using a Box–Behnken design. The optimized LNCs were subsequently functionalized with folic acid (FA) to enable active targeting. FA-LNCs were characterized using XPS, TEM, in vitro release, and MTT cytotoxicity assays. Atorvastatin and curcumin were radiolabeled separately with iodine-131 to evaluate the in vivo pharmacokinetics in a glioma-bearing mouse model. Results: The optimized LNCs and FA-LNCs displayed a mean particle size of 97.98 ± 2.27 nm and 181.60 ± 2.83 nm, a polydispersity index of 0.32 ± 0.07 and 0.40 ± 0.02, and a zeta potential of −15.85 ± 1.35 mV and −11.90 ± 2.80, respectively. XPS and FTIR analyses verified FA conjugation. Both LNCs and FA-LNCs enhanced the in vitro cytotoxicity compared to free drugs; however, the most pronounced effect of FA functionalization was observed in vivo. Most significantly, FA-LNCs achieved markedly greater glioma accumulation than non-functionalized LNCs, with AUC values 2.0-fold higher for atorvastatin and 2.6-fold higher for curcumin. When compared to the free drug solutions, this efficiency was even more pronounced, with atorvastatin and curcumin showing enhancements of 8.2 and 12.4 times, respectively. Conclusions: FA-LNCs markedly improved glioma targeting efficiency and reduced systemic clearance, which underscores the therapeutic potential of integrating nutraceuticals with repurposed agents to achieve effective glioma therapy. Full article

Sepsis remains one of the major challenges in modern intensive care, characterized by high mortality and complex metabolic and immunological disturbances. Given the limited effectiveness of current therapeutic strategies, increasing attention has been directed toward supportive interventions aimed at restoring metabolic homeostasis. Particular interest has been focused on selected vitamins that exhibit pleiotropic biological effects. Thus, we summarized the current evidence on the role of selected vitamins (C, D, B1, B9, B12) in the treatment and supportive management of sepsis, highlighting their mechanisms of action, potential clinical benefits, and limitations derived from available studies. A comprehensive analysis of the literature was performed, including clinical trials and meta-analyses evaluating the efficacy of vitamin supplementation in sepsis, with particular emphasis on combined interventions and randomized controlled trials in severe sepsis and septic shock. Vitamin D might demonstrate the greatest therapeutic potential, particularly in patients with severe sepsis and respiratory failure, with benefits associated with achieving appropriate therapeutic concentrations. Thiamine (vitamin B1) appears to provide potential advantages primarily in deficient patients, improving mitochondrial function and reducing the risk of renal failure. Evidence regarding folic acid (vitamin B9) and cobalamin (vitamin B12) remains inconclusive, as both deficiency and elevated serum levels have been linked to adverse outcomes. Vitamin C, despite its well-documented antioxidant and microcirculatory effects, has not yet shown consistent evidence of mortality reduction. In conclusion, current evidence suggests that vitamin supplementation might represent an adjunct to standard sepsis therapy, particularly within a personalized approach that considers nutritional status and metabolic phenotype. The development of standardized dosing protocols and well-designed clinical trials is essential to determine the efficacy and safety of phenotype-driven individualized approaches in sepsis management. Full article

Gelatin microparticles (GMPs) can load functional active substances, but they tend to redissolve in high-temperature aqueous solutions during food processing. In this study, a new loading system adapted to food processing and digestive environments was constructed through the crosslinking of tea polyphenols (TP) on GMPs. The effects of pH, temperature, and crosslinking time on the methylene blue (MB) retention rate in crosslinked gelatin microparticles (cGMPs) were investigated, resulting in optimized crosslinking conditions. Compared with GMPs, the surface of cGMPs was denser and smoother. ATR-FTIR results showed that the N–H groups were involved in the formation of hydrogen bonds during the crosslinking process. The crosslinking effect of TP significantly disrupted the triple-helical structure of gelatin. The melting temperature ($T_m$) of cGMPs is 147.79 °C, which is significantly higher than that of GMPs (87.11 °C), indicating a marked improvement in thermal stability. In high-temperature aqueous solutions, Folic acid-loaded cGMPs (FA-cGMPs) maintained morphological integrity for 2 h (at 40 °C) and 0.5 h (at 60 °C). In vitro digestion simulations revealed excellent sustained-release characteristics of FA-cGMPs, with a release rate of only 4.91% in simulated gastric fluid and 88.13% in simulated intestinal fluid. This study provides an ideal carrier with food processing stability and intestinal-targeted release capabilities for functional active substances. Full article

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with a high recurrence rate and mortality. A major obstacle to the effective treatment of GBM is the blood–brain barrier (BBB), which hinders the transfer of therapeutic cargo to the tumor lesion. Polysorbate-coated drug carriers are known to efficiently cross the BBB via apolipoprotein E (ApoE)-mediated transcytosis. In this study, we developed cancer-targeted nanocarriers using folic acid (FA)-conjugated polysorbate (Tween 80, T80) for safe and efficient chemo-sonodynamic combination therapy against GBM. T80-based nanocarriers effectively co-encapsulated doxorubicin (DOX, chemotherapeutic agent) and oxygen-deficient MnWOx nanoparticles (sonosensitizer). FA-conjugated T80 nanocarriers encapsulating DOX and MnWOx (FA-T-DOX@MnWOx) boosted the cellular uptake of DOX in human glioblastoma U87MG cells. The efficient ability of the T80-based drug carriers to cross the BBB was demonstrated using an in vitro transwell BBB model. In addition, sonosensitizer MnWOx nanoparticles in the T80-based carriers triggered GSH depletion, synergistically enhancing intracellular reactive oxygen species (ROS) generation in U87MG cells upon US irradiation. As a result, FA-T-DOX@MnWOx combined with US triggered significant apoptosis in U87MG cells. This study demonstrated that FA-conjugated, MnWOx-loaded, T80-based nanocarriers capable of crossing the BBB hold significant potential for treating GBM through a combined chemo-sonodynamic therapy. Full article

Objectives: The aim of this study was to assess nutrient intake among individuals adhering to the Christian Orthodox Church (COC) fasting and to investigate potential differences in dietary intake according to Body Mass Index (BMI) classification. Methods: This cross-sectional study enrolled participants through announcements at public universities, churches, and monasteries, targeting both urban and religious adult populations. A total of 228 adults with a BMI exceeding 25 kg/m² were enrolled. Of these, 121 had followed COC fasting practices for at least 10 years or since childhood, while 107 non-fasters were age-matched. Exclusion criteria included age under 18 years, refusal to provide consent, absence from measurements, non-communicable diseases, food allergies, pregnancy, or lactation. Results: Overweight and obesity rates were similar in both groups. Furthermore, there were no statistically significant differences in body composition measurements [body fat %, fat mass (kg), fat free mass (kg), waist circumference]. Diastolic and systolic blood pressure was significantly higher in non-fasters. Non-fasters reported higher intake of sugar, dietary protein, fats (saturated and polyunsaturated), and cholesterol. Fasters consumed lower amounts of vitamin A, vitamins B (B2, B3, B6, B12, folate, pantothenic acid), iron, phosphorus, sodium, zinc, and calcium. Serum folic acid levels were higher, and fasting glucose and phosphorus levels were lower in fasters. Distinct dietary patterns were observed between groups, with fasters consuming more fish and traditional plant-based foods, while non-fasters consumed higher amounts of meat, dairy products, and alcohol. Conclusions: COC fasting is associated with favorable dietary and metabolic profiles, including improved glucose regulation. However, its impact on weight status appears limited. Full article