Search Results (1,037)

Autoimmune diseases are driven by chronic inflammation and oxidative stress, thus requiring innovative therapeutic approaches. Polymeric nanotherapeutics incorporating antioxidant bioactive compounds offer a promising strategy for immune modulation and enhanced drug delivery. This review explores the application of polymer-based nanocarriers for improving the solubility, bioavailability, and targeted delivery of antioxidant compounds in autoimmune disease treatment. A comprehensive analysis of recent advancements in polymeric nanoformulations, including poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), chitosan, and hyaluronic acid, was conducted. The therapeutic efficacy of various antioxidant-loaded nanoparticles has been assessed in both preclinical and clinical studies. Phenolic antioxidants, such as resveratrol, curcumin, quercetin, and epigallocatechin-3-gallate, exhibit potent anti-inflammatory effects; however, their poor solubility limits their clinical application. Nanocarriers such as dendrosomes, tannic acid-based reactive oxygen species (ROS)-scavenging nanoparticles, and folic acid-functionalized systems enhance drug stability, controlled drug release, and macrophage targeting. Carotenoid and bilirubin nanoparticles further demonstrate immunomodulatory effects in multiple sclerosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Polymeric antioxidant nanotherapeutics provide targeted and sustained drug delivery, offering improved efficacy and reduced toxicity. Future research should focus on optimizing these nanocarriers for clinical translation and patient-centered therapeutic strategies. Full article

This review paper highlights the importance of educating current and future professionals about epigenetic mechanisms and recognizing epigenetics as a crucial model for protection against ionizing radiation. Two basic models for radiation-induced DNA damage are currently in use. The association between mutations and chromosomal aberrations provides a framework for analyzing risks at low radiation doses and exposure to small doses. However, there is no monitoring of epigenetic changes in professionals exposed to low doses of ionizing radiation. Epigenetic events regulate gene activity and expression not only during cell development and differentiation but also in response to environmental stimuli, such as ionizing radiation. Furthermore, the potential occurrence of malignant and hereditary diseases at low doses of ionizing radiation is linearly correlated and is considered a scientifically accepted assumption, despite recognized scientific limitations associated with this assessment. The aim of this review is to integrate novel and intriguing radiobiological paradigms regarding the effects of ionizing radiation on DNA methylation and epigenetic regulation of the DNA molecule. Several hypothesized biological responses to ionizing radiation are examined, linking them to epigenetic mechanisms involved in health risk assessment for professionals. The second part of the review includes published research related to epigenetics, supplementation, and virus reactivation in the context of epigenetic modifications of the DNA molecule. We hypothesize that different cycles lead to changes in the epigenome, which may be associated with the reactivation of certain viruses and the deficiency of specific dietary elements. These findings are linked to minimal deficiencies in vitamin B12 and folic acid, which may contribute to epigenomic changes. This aspect is crucial for the immune status of individuals working in high-risk environments. Full article

Background/Objectives: Acute kidney injury (AKI) remains an unsolved medical problem due to the lack of effective treatments, high mortality, and increased susceptibility to progression to chronic kidney disease (CKD), especially in the elderly. Cellular senescence has been described in AKI, CKD, and aging and has been proposed as a promising therapeutic target. The senolytic drug combination of dasatinib plus quercetin (D&Q) is beneficial in some pathological conditions, including experimental CKD, but there are no data for AKI. Methods: The effect of D&Q combination was tested in folic acid-induced nephrotoxicity (FAN-AKI), a murine AKI model. Results: D&Q pretreatment did not prevent renal dysfunction in the acute phase of FAN-AKI, as determined by serum creatinine and BUN levels at 48 h. Moreover, gene expression of the kidney damage biomarkers Lcn2 and Havcr1, the Cdkn1a gene, which encodes p21, and some genes encoding components of the senescent cell secretome were significantly increased in response to D&Q treatment. The number of senescent p21-positive cells in injured kidneys was similar in untreated or D&Q-treated FAN mice. In addition, D&Q did not prevent the downregulation of the antiaging factor Klotho in damaged kidneys. Conclusions: D&Q treatment was not protective in FAN-AKI, exacerbating some deleterious responses. These results suggest caution when exploring the clinical translation of D&Q senolytic activity. Full article

Human papillomavirus (HPV) infection represents one of the most common sexually transmitted infections worldwide. However, the lack of effective therapeutic strategies to counteract viral infection and its persistence still makes the management of HPV a medical concern. Persistence is indeed a crucial issue in the context of HPV, as it may increase the risk of viral DNA integration into the host genome, thus exposing patients to tumoral progression. This clinical study aims to evaluate the effectiveness of a dietary supplement containing epigallocatechin gallate (EGCG), folic acid (FA), vitamin B12 (B12), and hyaluronic acid (HA) in improving HPV clearance and HPV-induced cervical lesions, and in counteracting viral persistence. A total of 106 patients who tested positive for HPV DNA were enrolled in this study and were treated daily for 6 months with a tablet containing EGCG (200 mg), FA (400 μg), B12 (1 mg), and HA (50 mg) (Pervistop^®, Lo.Li. Pharma, Rome, Italy). A 6-month treatment with such combined molecules demonstrated a viral clearance in 85.8% of enrolled patients, while 92.3% of participants exhibited no more cervical lesions. Furthermore, 71.8% of patients with persistent infection tested negative to HPV DNA test after 6 months of treatment. The obtained data in this large population strongly support previous evidence on the efficacy of such molecules in the management of HPV infection by improving both viral clearance and related cervical lesions, and by targeting viral persistence. Full article

Background and Aims: Colorectal cancer (CRC) remains the third most common cancer worldwide and a leading cause of cancer-related death. Chemoprevention through widely used pharmaceutical agents has garnered increasing interest due to its potential cost-effectiveness and accessibility. This review summarizes current evidence from observational studies, randomized controlled trials, and meta-analyses on the association between commonly prescribed medications and CRC incidence and survival, with particular emphasis on low-dose aspirin and oral anticoagulants (OACs). Scope: Aspirin is the most extensively studied agent, with substantial evidence supporting its protective effect on CRC-specific survival, particularly in long-term users, those with COX-2 overexpression, or PIK3CA mutations. OACs have recently gained attention due to their association with increased gastrointestinal bleeding, which may facilitate earlier CRC detection. While emerging evidence suggests a possible survival benefit through this mechanism, data remain heterogeneous and affected by methodological challenges such as lead-time bias. Metformin is associated with improved CRC outcomes, primarily in patients with type 2 diabetes, though its direct anti-tumor potential remains under investigation. Corticosteroids, statins, and beta-blockers have both limited and inconclusive evidence. Finally, recent studies on vitamin D, calcium, and folic acid suggest inconsistent associations, often confounded by lifestyle factors or underlying comorbidities. Conclusions: While promising, chemoprevention strategies require further validation in well-designed, mechanistically informed studies that account for confounding variables, treatment duration, and tumor biology. Personalized prevention—guided by genetic, molecular, and clinical risk factors—represents a promising path forward. Full article

Cancer remains a prevalent global health concern, with key factors such as diet, environment, and genetics playing significant roles in its progression. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play a critical role in cancer progression by degrading the extracellular matrix, thereby facilitating tumor growth and metastasis. Wine contains various bioactive compounds, including caffeic acid, gallic acid, kaempferol, naringenin, quercetin, myricetin, resveratrol, epigallocatechin gallate, riboflavin, and folic acid, which have shown promise in inhibiting cancer cell proliferation and metastasis. These compounds have been reported to downregulate the activity and/or expression of MMP-2 and MMP-9, thus potentially suppressing tumor progression. However, excessive alcohol consumption can lead to addiction and elevate the risk of various health complications, including fatty liver disease, cardiovascular damage, stroke, and kidney failure. Despite these concerns, moderate wine consumption has been associated with potential anticancer properties by restricting tumor growth and metastasis. In this review, we summarize and discuss how bioactive molecules in wine regulate MMP-2 and MMP-9 through bioactive compounds derived from wine and explore their implications for cancer treatment. Full article

In this study, we developed a multifunctional graphene oxide (GO)-based nanoprobe co-loaded with antisense peptide nucleic acid (PNA) and the chemotherapeutic agent doxorubicin (DOX). The nanoplatform was strategically functionalized with folic acid ligands to enable folate receptor-mediated tumor targeting. Upon cellular internalization, the antisense PNA component selectively hybridized with human telomerase reverse transcriptase (hTERT) mRNA through sequence-specific recognition, inducing structural detachment from the GO surface. This displacement restored the fluorescence signal of previously quenched fluorophores conjugated to the PNA strand, thereby enabling the real-time in situ detection and quantitative fluorescence imaging of intracellular hTERT mRNA dynamics. The antisense PNA component effectively reduced the hTERT mRNA level and downregulated telomerase activity via an antisense gene regulation pathway, while the pH-responsive release of DOX induced potent cancer cell apoptosis through chemotherapeutic action. This combinatorial therapeutic strategy demonstrated enhanced anticancer efficacy compared to single-modality treatments, achieving a 60% apoptosis induction in HeLa cells through coordinated gene silencing and chemotherapy. This study establishes GO as a promising dual-drug nanocarrier platform for developing next-generation theranostic systems that integrate molecular diagnostics with multimodal cancer therapy. Full article

Background/Objectives: The aim of this systematic review and meta-analysis was to investigate the effect of dietary supplements on male infertility. Methods: PubMed, Embase, and CENTRAL were searched from inception to May 2024. Randomized controlled trials with treatment durations of ≥12 weeks investigating the effect of dietary supplements on male infertility compared to placebo were included. Primary outcomes were pregnancy and live birth, while secondary outcomes were sperm concentration, sperm count, total motility, progressive motility, normal morphology, and DNA Fragmentation Index. Risk of bias was assessed using the revised Cochrane risk of bias (RoB2) tool. Data were meta-analyzed using random effects-restricted maximum likelihood models. Certainty of evidence was evaluated using the grading of recommendations, assessment, development and evaluation (GRADE) approach. Results: Of the 3137 articles identified, 50 were included. No effect on pregnancy and live birth was found. Different supplements improved single sperm parameters: Zinc and folic acid and ≥3 substance dietary supplements improved sperm concentration, selenium, carnitine, and coenzyme Q10 improved motility and alpha-lipoic acid improved normal morphology. Vitamin D, vitamin E, and omega-3 fatty acids showed no improvement in sperm parameters. The majority of studies had some concerns or high risk of bias, and certainty of evidence was generally low or very low. Conclusions: This study found no convincing evidence of an effect of any dietary supplements on male infertility. Larger and more well-conducted randomized controlled trials focusing on specific supplements and considering pregnancy outcomes are needed. Full article

Background and clinical significance: Osteonecrosis of the femoral head (ONFH) is a disease of the epiphysis caused by the death of osteocytes and osteoblasts, resulting in debilitating pain. ONFH can be traumatic or nontraumatic, with prolonged glucocorticoid use being the leading cause of nontraumatic ONFH. Atopic dermatitis (AD) is a chronic inflammatory skin condition typically treated with topical corticosteroids. ONFH following topical corticosteroid treatment is exceedingly rare, with limited documentation in the literature. We present a case of an under-recognized complication of prolonged topical corticosteroid treatment. Case presentation: We report a case of a 29-year-old Caucasian male patient with sharp right hip pain. Plain radiographs, a CT scan, and an MRI indicated Ficat and Arlet stage 3 ONFH. The patient reported the prolonged uncontrolled use of topical mometasone furoate for five years due to AD. Following the diagnosis, topical corticosteroids were discontinued, and the treatment was shifted to tacrolimus and, subsequently, to oral methotrexate with folic acid. The patient underwent a total hip arthroplasty in June 2022. Given his young age and poor response to previous treatments, he was transitioned to upadacitinib, which led to significant improvement without skin flare-ups or postoperative hip pain. Conclusions: This case highlights the rare, but serious, risk of ONFH associated with long-term topical corticosteroid use. It underscores the importance of monitoring systemic side effects in dermatological therapies and educating patients on proper corticosteroid use. Alternative treatments, such as upadacitinib, should be considered in young male patients to prevent severe complications. Full article

Background/Objectives: Neonatal outcomes, including low birth weight, preterm birth, and neonatal mortality, pose significant global health challenges, particularly in low- and middle-income countries. Prenatal care has emerged as a critical intervention in mitigating these risks through medical, nutritional, and psychosocial support. This study aimed to systematically assess the effectiveness of prenatal care interventions in preventing neonatal outcomes across diverse settings. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines, with the protocol registered in PROSPERO (CRD42024601066). Fourteen peer-reviewed studies were included following a comprehensive search across five major databases. Eligible studies reported quantitative neonatal outcomes associated with prenatal care interventions, including nutritional supplementation, mental health services, telehealth, and routine antenatal care. Random-effects models were used for meta-analysis, and the risk of bias was assessed using RoB 2 and the Newcastle–Ottawa Scale. Results: Nutritional interventions, especially folic acid and iron supplementation, significantly reduced neonatal mortality by up to 40% (RR = 0.60, 95% CI: 0.54–0.68). High-quality prenatal care was associated with a 41% reduction in neonatal mortality. Psychosocial support reduced the risk of low birth weight and preterm birth, while telehealth interventions lowered NICU admissions in low-risk populations (RR = 0.88, 95% CI: 0.75–1.03). Heterogeneity was substantial (I² = 70%), and publication bias was suggested. Conclusions: Comprehensive prenatal care, integrating medical, nutritional, and mental health interventions, significantly improves neonatal outcomes. The global implementation of accessible, high-quality prenatal services is essential, particularly in underserved populations, to reduce neonatal morbidity and mortality. Full article

Cellular communication network factor 2 (CCN2, also known as CTGF) is a complex protein that regulates numerous cellular functions. This biomolecule exhibits dual functions, depending on the context, and can act as a matricellular protein or as a growth factor. CCN2 is an established marker of fibrosis and a well-known mediator of kidney damage, involved in the regulation of inflammation, extracellular matrix remodeling, cell death, and activation of tubular epithelial cell (TECs) senescence. In response to kidney damage, cellular senescence mechanisms are activated, linked to regeneration failure and progression to fibrosis. Our preclinical studies using a total conditional CCN2 knockout mouse demonstrate that CCN2 plays a significant role in the development of a senescence phenotype after exposure to a nephrotoxic agent. CCN2 induces cell growth arrest in TECs, both in the early phase and in the chronic phase of folic acid nephropathy (FAN), associated with cell-death/necroinflammation and fibrosis, respectively. Renal CCN2 overexpression was found to be linked to excessive collagen accumulation in tubulointerstitial areas, microvascular rarefaction, and a decline in renal function, which were observed three weeks following the initial injury. All these findings were markedly diminished in conditional CCN2 knockout mice. In the FAN model, injured senescent TECs are associated with microvascular rarefaction, and both were modulated by CCN2. In primary cultured endothelial cells, as previously described in TECs, CCN2 directly induced senescence. The findings collectively demonstrate the complexity of CCN2, highlight the pivotal role of cellular senescence as an important mechanism in renal injury, and underscore the critical function of this biomolecule in kidney damage progression. Full article

The radiation sterilization of polymer-based drug solutions can change the characteristics that determine the efficiency of drug targeting, such as particle sizes in the solution and their surface potential. The effect of E-beam treatment at doses of 3 and 8 kGy in a Xe or air atmosphere on the hydrodynamic properties of dilute solutions of polyvinylpyrrolidone (PVP) conjugate with fullerene C₆₀ and folic acid (FA-PVP-C₆₀) was studied and compared with native PVP K30. The capillary viscometry method was used to determine the intrinsic viscosity of solutions. The particle sizes (R_h) were determined using the DLS method. The zeta potential of the particles was determined using the PALS method. The morphological features of the conjugate surface irradiated in a Xe atmosphere with a dose of 8 kGy FA-PVP-C₆₀ were studied by AFM. The functionalization of FA-PVP-C₆₀ and PVP during E-beam treatment was examined using UV- and FTIR-spectrometry. When the diluted solutions of FA-PVP-C₆₀ and PVP were irradiated in air with a dose of 3 kGy, destruction of polymer chains occurred predominantly, but when the dose was increased to 8 kGy, intermolecular cross-linking occurred, leading to an increase in the characteristic viscosity and particle size in the solution. It was shown that the average particle sizes, amounting to 3 and 8 nm for PVP and 4 and 20 nm for FA-PVP-C₆₀, did not change significantly under E-beam irradiation in a Xe atmosphere in the considered dose range. The zeta potential of the particles remained virtually unchanged for both PVP and FA-PVP-C₆₀ under all irradiation conditions. The obtained results indicate the possibility of performing radiation sterilization of FA-PVP-C₆₀ conjugate solutions in an inert gas atmosphere in the range of studied doses. Full article

Background: Neurobehavioral developmental disorders significantly affect children’s future well-being and contribute to the global disease burden. While prenatal micronutrient supplementation is crucial for fetal neural development, their individual and combined effects on subsequent neurobehavioral outcomes in childhood remain poorly understood. This study aimed to examine the individual and combined effects of prenatal micronutrient supplementation on neurobehavioral developmental disorders in preschool children, and to explore their effects across specific developmental domains. Methods: 15,636 mother-child dyads were recruited from the 2022 children’s survey in Shenzhen, China. Mothers provided information on prenatal supplementation of calcium, folic acid, iron, and multivitamins. Five domains of children’s neurobehavioral functioning were assessed using the Ages and Stages Questionnaire-Third Edition (communication, gross motor, fine motor, problem-solving, and personal-social status). Logistic regression models were used to estimate the effect of micronutrient supplementations on NDDs across crude, adjusted, and full-inclusion models. Combined effects were assessed by multiplicative and additive interactions calculated from crossover analysis. Results: 11.7% of preschool children were identified as at risk for neurobehavioral developmental disorders, with the highest prevalence in the gross motor domain. Prenatal multivitamin supplementation showed a protective effect against neurobehavioral developmental disorders (OR = 0.73, 95% CI = 0.66–0.81). Interaction analysis revealed that the combination of iron and multivitamins further enhanced this protection, with both multiplicative (IOR = 1.26, 95% CI = 1.02–1.57) and additive interactions (RERI = 0.18, 95% CI = 0.02–0.35). The problem-solving domain consistently showed the greatest benefit from the supplementation of these micronutrients individually and in combination. Conclusions: Prenatal multivitamin supplementation reduces the risk of neurobehavioral developmental disorders, especially when combined with iron supplementation. These findings highlight the potential benefits of prenatal co-supplementation strategies to improve neurobehavioral outcomes in offspring. Further studies are recommended to confirm these findings and explore underlying mechanisms. Full article

Purpose: to identify evidence on the effectiveness of web-based interventions for lifestyle modification among women or couples of reproductive ages wishing to conceive. Methods: A systematic search was conducted in February 2023 across CENTRAL, PubMed, Web of Science, Embase, Emcare, ClinicalTrials.gov, and WHO ICTRP. Data from four randomized controlled trials involving 1965 preconception women were narratively synthesized following risk of bias assessment. Interventions included a web-based conversational agent system, an email-based mobile service, and a mobile app providing lifestyle-related information. Results: Despite diverse assessment tools, benefits were observed for systolic blood pressure, serum folate levels, and physical activity. However, no significant effects were found for intake of vegetables and fruit, folic acid supplementation, smoking, alcohol consumption, waist circumference, weight, BMI, overweight status, HbA1c, total cholesterol, HDL, stress, depression, anxiety, or pregnancy outcomes. Conclusions: Web-based interventions show potential in improving certain health behaviors among preconception women. Further high-quality studies are needed to assess their effectiveness on a broader range of outcomes, including dietary habits, physical activity, and substance use, and to inform their integration into preconception care strategies. Registration: We registered the study protocol with PROSPERO (CRD42023488277). Full article

Background/Objectives: In 1998 choline was identified as an essential nutrient by the United States Institute of Medicine. Choline is known primarily for its roles in neurotransmitter production, cell membrane formation, and methyl and lipid metabolism. Since this discovery the relevance of choline to maternal, fetal, and infant health has been studied intensively. This narrative review provides a coherent update of the latest evidence for field clinicians and healthcare professionals. Methods: A PubMed/ScienceDirect search for human clinical evidence restricted to meta-analysis and systematic/review publications from the last 10 years was undertaken. Results: Meta-analysis and review publications highlight the importance of choline in supporting maternal health and fetal development during pregnancy by showing promising roles for choline in relation to neurological development, brain and liver function, reduced neural tube defect risk, and adverse pregnancy outcome risk. However, there are clear present-day gaps between habitual choline intakes and intake recommendations with the majority of pregnant and lactating women not meeting adequate intake recommendations for choline. This gap is anticipated to widen given transitions towards plant-based diets which tend to be lower in choline. Conclusions: Alongside folic acid recommendations, choline supplementation should be considered in dietary recommendations by clinicians during crucial life stages such as pregnancy and lactation when physiological demands for this critical nutrient substantially increase. Full article