Co-delivery of temozolomide and quercetin with folic acid-conjugated exosomes in glioblastoma treatment.

Aim: The study aims to improve glioblastoma multiforme (GBM) treatment by combining temozolomide (TMZ) and quercetin (Qct), using folic acid (FA)-conjugated exosomes to overcome TMZ resistance and enhance blood-brain barrier (BBB) penetration.Methods: Exosomes were isolated and after characterizing and modifying their surfaces with FA, drug loading of TMZ and Qct into exosomes was done. In vitro assays, including cell viability tests, RT-PCR, Western-blotting and flow-cytometry, were performed using U87MG and U251MG GBM cell lines. In vivo analysis included administering exosome-drug formulations to glioblastoma-bearing Wistar rats, monitored through optical imaging and PET scans, followed by post-mortem immunohistochemistry and histological examination.Results: The results showed successful exosome isolation and FA conjugation, with drug release studies indicating accelerated release of TMZ and Qct in acidic conditions, enhancing cytotoxicity. Immunofluorescence indicated greater exosome uptake in GBM cells due to FA conjugation. Cell viability assays demonstrated increased toxicity of the combination therapy, correlating with elevated apoptosis. In vivo studies revealed significant tumor size reduction, alongside increased apoptosis and reduced angiogenesis, particularly in the TMZ-Qct-Exo-FA group.Conclusion: FA-conjugated exosomes loaded with TMZ and Qct represent a promising strategy to enhance GBM treatment efficacy by improving drug delivery, apoptosis induction and inhibiting the PI3K/Akt/mTOR pathway.

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Folic acids promote in vitro maturation of bovine oocytes by inhibition of ferroptosis via upregulated glutathione and downregulated Fe2+ accumulation.

Bovine embryos by in vitro fertilization have become the primary source of commercial embryo transfers globally. However, the developmental capacity of in vitro maturation (IVM) oocytes is considerably lower than that of in vivo maturation (IVO) oocytes, owing to the production of reactive oxygen species (ROS) via mitochondrial metabolism, which was higher in IVM oocytes than in IVO oocytes. To avoid the negative effects of ROS on embryo quality, folic acid (FA) was supplemented directly into the IVM medium to antagonize ROS production, however, the mechanisms remain unknown. In the present study, five levels of FA (0, 25, 50, 100, and 200 µM) were supplemented into the bovine oocyte culture medium. The maturation, cleavage, and blastocyst formation rates increased by 8.95 %, 6.94 %, and 4.36 %, respectively, in the 50 µM group compared to the 0 µM group. Moreover, 7904 differential genes were identified between 0 µM and 50 µM groups by transcriptome sequencing, and they were mainly enriched in 8 pathways. The glutathione, ROS, and Fe2+ levels in oocytes were found to be associated with ferroptosis. Our results revealed that 50 µM FA promoted the IVM of bovine oocytes and affected the expression of genes involved in the ferroptosis pathway. The downregulation of TFR1 and STEAP3 led to a decrease in intracellular Fe2+ accumulation, and the upregulation of GCL increased oocyte GSH levels, thereby reducing the production of ROS in the ferroptosis pathway. Our study provides a new insight into the molecular mechanisms by which FA promotes bovine oocyte development in vitro.

Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Effects of Oral Folic Acid and Iron Tablets Intake on the Prevalence and Severity of Anemia in Pregnant Women in a Public Sector Hospital in Delhi.

OBJECTIVE: To study the effects of oral folic acid, iron tablets, and tea consumption on the prevalence and severity of anemia in pregnancy. METHODS: This cross-sectional study was conducted on 430 women who fulfilled the eligibility criteria in the second and third trimesters of pregnancy attending the antenatal clinic of a public sector hospital in Delhi. RESULTS: The mean age, parity, BMI, and gestation were 26.2 ± 4.5 years, 1.8 ± 1.2, 22.5 ± 4.5 kg/m2, and 32.2 ± 3.4 weeks, respectively. Out of 430 patients, the prevalence of anemia was found in 210 (48.84%) patients, with mild anemia in 111 (25.81%), moderate in 68 (15.81%), severe in 30 (6.98%), and very severe in one (0.24%) patient. Significantly more women (97, 46.19%) in the anemia group did not take oral folic acid tablets as compared to the normal hemoglobin (Hb) group (83, 37.72%) (p = 0.04). Similarly, significantly more (103, 49.04%) women in the anemia group did not take oral iron tablets as compared to the normal Hb group (19, 8.63%) (p = 0.02) with even more patients being in the severe anemia group (29, 93.55%) (p = 0.001). Intake of two or more cups of tea per day was a significant risk factor for anemia, with 147 (70%) anemic vs. 134 (60.9%) with normal Hb (p = 0.05). CONCLUSION: The prevalence of anemia during pregnancy was found to be high in 210 (48.84%) patients. Non-intake of oral folic acid and iron tablets and consumption of two or more cups of tea were significant risk factors for anemia in pregnancy.

High Bioavailability of Spinach Folate Evaluated by Functional Biomarkers in a Folate Depletion-Repletion Mouse Model.

The bioavailability of natural folates is 50% lower than that of synthetic folic acid (FA); however, it remains unclear whether this value is universally applicable to all foods. Therefore, the present study investigated the bioavailability of folate from spinach using multiple biomarkers in a folate depletion-repletion mouse model. Mice were fed a folate-deficient diet for 4 wk and subsequently divided into three groups: folate-deficient, FA, and spinach folate. The folate repletion group received either FA or spinach folate at 2 mg/kg diet for 9 d. On the 7th day of repletion, half of each group underwent low-dose total body X-ray irradiation to induce chromosomal damage in bone marrow. Folate bioavailability biomarkers included measurements of folate levels in plasma, liver, and bone marrow along with an analysis of plasma homocysteine levels and chromosome damage, both of which are functional biomarkers of body folate. The consumption of a folate-deficient diet led to decreased tissue folate levels, increased plasma homocysteine levels, and chromosomal damage. Repletion with spinach folate restored folate levels in plasma, liver, and bone marrow to 69, 13, and 68%, respectively, of FA levels. Additionally, spinach folate repletion reduced plasma homocysteine levels and chromosome damage to 83% and 93-117%, respectively, of FA levels. Collectively, the present results demonstrated that the bioavailability of spinach folate exceeded 83% of FA, particularly when assessed using functional biomarkers.

Electrochemical detection of folic acid in food extracts using molecularly imprinted polyacrylonitrile imbued graphite electrode.

The present study elucidates the effectiveness of a molecularly imprinted polyacrylonitrile-imbued graphite-base electrode (MAN@G) for the selective detection of folic acid (FA) in food samples. The prime objective of the recognition and quantification of vitamin compounds like FA is the overall quality assessment of vegetables and fruits. The cost-effective, reproducible, and durable MAN@G electrode has been fabricated using acrylonitrile (AN) as the monomer and FA as the template over graphite-base. The characterization of the synthesized MAN@G electrode material has been accomplished by utilizing UV-visible (UV-vis) spectroscopy and scanning electron microscopy (SEM). A tri-electrode system based on differential pulse voltammetry (DPV) and cyclic voltammetry (CV) techniques was employed to explore the analytical performance of the synthesized electrode. Rigorous analyses divulged that a widespread linearity window could be exhibited by the electrode under an optimized experimental environment, ranging from 20 µM to 400 µM concentrations with an acceptable lower limit of detection (LOD) and limit of quantification (LOQ) of 18 nM, and 60 nM respectively. Additionally, this electrode exhibits high reproducibility, good stability, and high repeatability, with RSD values of 1.72 %, 1.32 %, and 1.19 %, respectively. The detection efficacy of the proposed electrode has been further examined in food extracts, namely orange, spinach, papaya, soybean, and cooked rice, which endorsed high accuracy compared to the high-performance liquid chromatography (HPLC) method. Moreover, the statistical results obtained from the t-test analysis were also satisfactory for the FA concentrations present in those five samples.

Neurosurgical Advocacy in the Prevention of Neural Tube Defects: Impacting Global Fortification Policies Through Leadership, Collaboration, and Stakeholder Engagement.

The G4 Alliance and its member organizations formed a delegation that participated in the 76th World Health Assembly (WHA) in 2023, which unanimously adopted the resolution to address micronutrient deficiencies through safe, effective food fortification to prevent congenital disorders such as spina bifida and anencephaly, the first neurosurgery-led resolution since the founding of the World Health Organization. The WHA included other resolutions and side events by the G4 Alliance and other organizations relevant to neurosurgery. An opportunity exists for neurosurgeons to harness the momentum from this resolution to promote initiatives to prevent neurosurgical disease or expand access to neurosurgical care.

Direct Immobilization of Folic Acid Molecules on Hydroxyapatite Nanoparticles with Substitution and Coordination Phenomena.

We successfully synthesized folic acid (FA) immobilized hydroxyapatite (HA) nanoparticles without using a mediative reagent (e.g., silane coupling agent), and the immobilization states were evaluated and discussed. The HA nanoparticles with higher biocompatibility have two different planes, namely, c- and m-planes. These plane surfaces are rich in phosphate groups (P-site) and Ca2+ ions (C-site), respectively. We suggested that during the synthesis of the HA nanoparticles, the P-site substitution and C-site coordination with the addition of organic molecules containing -COO- ions can occur. Thus, it is possible to simultaneously immobilize two molecules to one HA nanoparticle. In this study, we successfully synthesized FA-immobilized HA nanoparticles by P-site substitution and C-site coordination reactions, which were named as substitution type and coordination type. In the substitution type, when FA was reacted with HA during the nucleation stage, the PO43- ions of HA decreased as the FA ratio of coverage surface area increased, and the crystalline phase was changed significantly from the Ca deficient HA to the carbonated HA phase. Accordingly, it was indicated that FA was immobilized on HA by the P-site substitution. In the coordination type, since FA was reacted with HA after the completion of crystal growth, the crystalline phase was changed slightly as the FA ratio of coverage surface area increased, indicating that FA was immobilized on HA by the C-site coordination. From the above, we controlled the FA immobilization states on the HA nanoparticles by the P-site substitution and the C-site coordination through the FA addition timing in the synthesis. Since the -COO- ions in FA could be selectively substituted with the P-site in HA, it is possible to directly coordinate the foreign organic molecules to the Ca2+ ions in HA. Therefore, the immobilization technique of this study is expected to achieve two different drug molecules with diagnosis and therapy functions (i.e., theranostics) on one nanoparticle.

Valproate-Autism Labyrinth.

Valproate and Autism complexity is manifold. From an established environmental risk factor for autism, to a translational animal model, valproate's composite mode of action might unfold to address core autistic domains transcending mere aggressive behavioural control.

Folic Acid and Selected Risk Factors for Fetal Heart Defects-Preliminary Study Results.

BACKGROUND: The available data on the relationship between diet/folic acid and congenital heart disease (CHD) are not consistent. This study aimed to investigate the relationship between the intake and supplementation of folic acid and other selected factors in mothers and the risk of congenital heart defects in fetuses. METHODS: A case-control study was conducted. The study group included pregnant women with fetuses from singleton pregnancies with prenatally diagnosed heart defects in the fetus (n = 79) and pregnant women whose course of pregnancy was normal with no heart defects or other developmental anomalies diagnosed in the fetus (n = 121). The patients were diagnosed at a reference center in Poland. The women completed a lifestyle questionnaire and FFQ and precisely described their use of dietary supplements. A univariate logistic regression model was used to evaluate the association between folic acid and selected risk factors and CHD. The association was significant and included such risk factors such as nutritional status, medications taken, smoking, and alcohol consumption. Additionally, the time of starting folic acid supplementation turned out to be statistically significant. The reference period of supplementation was the period before pregnancy. RESULTS: Lack of supplementation increases the risk of heart defects in children by more than four times compared to supplementation before pregnancy (OR = 4.19; p = 0.0117), whereas supplementation beyond the eighth week of gestation increases the risk almost threefold (OR = 2.90; p = 0.0474). The presence of congenital defects in the family is also an important factor. CONCLUSIONS: A history of congenital heart defects or other defects, lack of periconceptional folic acid supplementation, and lack of dietary supplementation before pregnancy were associated with congenital heart defects in the fetus. Place of residence, parents' education, lifestyle habits such as smoking and alcohol consumption, nutritional status before pregnancy, and mother's diseases did not show a significant relationship with congenital heart defects in the children. There is an urgent need to develop preventive strategies and conduct extensive public education.

Non-Covalent Interaction of Folic Acid and 5-Methyltetrahydrofolate with Caseinates Improves the Folates Stability Studied by Multi-Spectroscopic Analysis and Molecular Docking.

Folates, a crucial B-group vitamin, serve as a significant functional food supplement. Nevertheless, considerable obstacles persist in improving folates stability in liquid products. In this study, folic acid (FA) and 5-methyltetrahydrofolate (MTFA), two approved sources of folates, were encapsulated with sodium caseinate (NaCas) to enhance their stability. The protective effect of NaCas on folate molecules was investigated using experimental and computational methods. Meanwhile, the influence of divalent calcium ion (Ca2+) on the properties of the NaCas-MTFA complex was examined to evaluate the potential application of calcium 5-methyltetrahydrofolate (CaMTFA). Fluorescence tests showed both folates had static quenching behavior and bound to NaCas with a binding constant of 104-105 M-1. Hydrophobic interactions were crucial in NaCas-FA complex formation, while hydrogen bonding drove NaCas-MTFA binding. The encapsulation of caseinate notably slowed down the degradation of folates under both light and dark conditions. Moreover, the addition of a low concentration of Ca2+ did not adversely impact the binding mechanism of the NaCas-MTFA complex or the degradation curve of MTFA. The results of this study could serve as a valuable resource for the utilization of caseinates in incorporating folates, specifically MTFA, in the creation of natural liquid dietary supplements.

Folic Acid as a Potential Vitamin in Glycemic Control: A Systematic Review.

PURPOSE: This systematic review aims to examine the relationship between serum folate level and folic acid supplements with glycemic control parameters (fasting blood glucose (FBG), insulin level, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and Hemoglobin A1C (HbA1c)) in adult individuals with current studies. METHODS: In this study, which was designed as a systematic review, the searches were performed on Web of Science, Science Direct, Medline, Wiley, and Cochrane Library databases between April 10, 2023, and May 10, 2023, and the searches were updated between October 16, 2023, and November 14, 2023. Of the 1855 studies obtained from the screening, 17 met the criteria and were included in the systematic review. The PROSPERO system registered the study protocol (ID: CRD42023472434). RECENT FINDINGS: Although no significant correlation was found between serum folate levels and glycemic control parameters in most of the cross-sectional studies included in this systematic review, most of the randomized controlled trials showed that glycemic control parameters (FBG, insulin, HOMA-IR) decreased significantly in the intervention group receiving folic acid supplementation compared to the control group. However, study durations were short, and HbA1c needed to be evaluated in most studies. This makes it difficult to get information about the long-term effects of folic acid supplementation. More comprehensive studies should be conducted to draw more precise conclusions about the relationship between folic acid levels and folic acid supplementation with glycemic control parameters.

Influence of different forms of folic acid supplementation on pregnancy outcomes under various exposure factors.

BACKGROUND: Folic acid supplementation has been shown to provide benefits in preventing neural tube defects and other birth defects, as well as reducing adverse pregnancy outcomes. OBJECTIVE: This study aimed to examine the impact of various folic acid supplementation methods on pregnancy. METHODS: TaqMan-MGB technology was used to detect polymorphisms in the folate metabolism-related genes, MTHFR C677T and A1298C. Blood-related biochemical indicators, including HCY levels and history of adverse pregnancy, were examined in relation to different exposure factors (MTHFR gene polymorphism, HCY levels, and adverse pregnancy history) and their impact on pregnancy outcomes. Various forms of folic acid intervention were implemented in a population with an adverse pregnancy history and high HCY levels to analyze the effects of reducing HCY levels and improving pregnancy outcomes. RESULTS: Exposure factors, such as adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were closely associated with pregnancy outcomes. Interestingly, methylfolate efficiently reduced the serum HCY levels. More importantly, the methylfolate group exhibited a significantly lower incidence of adverse pregnancies than the synthetic folic acid group. CONCLUSION: In this study, the risk factors, including adverse pregnancy history, HCY, and medium-to-high risk of gene metabolism, were confirmed to lead to the poorer pregnancy outcomes in our cohort. 5-methyltetrahydrofolate may be an effective approach for decreasing the incidence of adverse pregnancy outcomes.

Enhanced anti-inflammatory activity of chlorogenic acid via folic acid-TPGS-modified liposomes encapsulation: characterization and In vivo evaluation on colitis mice.

Introduction: Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity. Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism. Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1ß, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae. Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.

Folic acid-conjugated bovine serum albumin-coated selenium-ZIF-8 core/shell nanoparticles for dual target-specific drug delivery in breast cancer.

Methotrexate (MTX), a frequently used chemotherapeutic agent, has limited water solubility, leading to rapid clearance even in local injections. In the present study, we developed folic acid-conjugated BSA-stabilized selenium-ZIF-8 core/shell nanoparticles for targeted delivery of MTX to combat breast cancer. FT-IR, XRD, SEM, TEM, and elemental mapping analysis confirmed the successful formation of FA-BSA@MTX@Se@ZIF-8. The developed nano-DDS had a mean diameter, polydispersity index, and zeta potential of 254.8 nm, 0.17, and - 16.5 mV, respectively. The release behavior of MTX from the nanocarriers was pH-dependent, where the cumulative release percentage at pH 5.4 was higher than at pH 7.4. BSA significantly improved the blood compatibility of nanoparticles so that after modifying their surface with BSA, the percentage of hemolysis decreased from 12.67 to 5.12%. The loading of methotrexate in BSA@Se@ZIF-8 nanoparticles reduced its IC50 on 4T1 cells from 40.29 µg/mL to 16.54 µg/mL, and by conjugating folic acid on the surface, this value even decreased to 12.27 µg/mL. In vivo evaluation of the inhibitory effect in tumor-bearing mice showed that FA-BSA@MTX@Se@ZIF-8 caused a 2.8-fold reduction in tumor volume compared to the free MTX, which is due to the anticancer effect of selenium nanoparticles, the pH sensitivity of ZIF-8, and the presence of folic acid on the surface as a targeting agent. More importantly, histological studies and animal body weight monitoring confirmed that developed nano-DDS does not have significant organ toxicity. Taking together, the incorporation of chemotherapeutics in folic acid-conjugated BSA-stabilized selenium-ZIF-8 nanoparticles may hold a significant impact in the field of future tumor management.

Maternal Folic Acid and Dietary Folate Intake in Relation to Sex Ratio at Birth and Sex-Specific Birth Weight in China.

BACKGROUND: It is well-established that prenatal folic acid supplements can reduce neural tube defects. However, the associations between folic acid supplementation, dietary folate intake, and overall folate intake with sex-specific birth outcomes are not yet fully understood. OBJECTIVES: This study aims to investigate the association of periconceptional folic acid supplement, dietary folate, and total folate intake with the sex ratio at birth and sex-specific birth weight. METHODS: Data were sourced from a cross-sectional survey conducted between August and December 2013 in Northwest China, involving 7318 infants and their mothers, recruited using a stratified multistage random sampling method. Folic acid supplements (400 µg/d) were ascertained via a retrospective in-person interview. Dietary folate was evaluated using a validated food frequency questionnaire. Birth outcomes, including sex and weight at birth, were obtained from the Medical Certificate of Birth. Generalized linear models were employed to calculate relative risks (RRs) or differences with 95% confidence intervals (CIs). RESULTS: No association or dose-response relationship was observed between folic acid supplement, dietary folate, and total folate intake during periconception and the likelihood of male births. However, women who took folic acid supplements during pre- and post-conception were associated with an increased male birth weight by 52.8 (8.1 to 97.5) g. Additionally, the total folate intake during periconception was associated with birth weight for males (upper vs. lower tertile: ß = 38.8, 95%CI: 5.0 to 72.5 g, p-trend = 0.024) and females (upper vs. lower tertile: ß = 42.4, 95%CI: 6.7 to 78.1; p-trend = 0.022). CONCLUSIONS: Our findings indicate that periconceptional total folate intake does not correlate with sex ratio at birth but was positively linked to infant birth weights, regardless of gender. These findings offer novel insights into potential benefits of total folate intake, beyond the prevention of neural tube defects, for policymakers and public health.

Design of casein-based nanocarriers for targeted delivery of daunorubicin to leukemia cells.

Daunorubicin (DAU) is a chemotherapy drug approved for the treatment of some cancers. However, the clinical compatibility of DAU is limited due to its lack of specificity and its highly toxic effects, which interfere with normal cells. This toxicity can be reduced with nanocarriers and targeted drug delivery systems. In this study, to develop the drug delivery of DAU, the surface of synthesized nanoparticles was modified by folic acid to target cancer cells optimally. Encapsulation of DAU in protein sodium caseinate (NaCAS) was done by adding calcium ions to bring the casein (CAS) in the solution to a micellar structure to synthesize dense nanoparticles. Fourier-transform infrared spectroscopy transmission, fluorescence spectroscopy, UV-Vis spectroscopy, field emission scanning electron microscopy, and zeta potential studies designed and distinguished the synthesized nanocomplexes. The results showed that CAS nanoparticles successfully encapsulated DAU, and the protein surface was targeted by folic acid. Light scattering analysis determined that the particles with a scattering index number of 306.0 and an average size of 8.117 nm were synthesized. The zeta potential of CAS micelles is more harmful than CAS nanoparticles. This is because calcium ions are added during the formation of CAS nanoparticles during the drug-loading stages. These studies prove that the synthesized "NaCAS-DAU" and "NaCAS-DAU-folic acid" complexes can be favorable carriers in the targeted drug delivery of cancer drugs.

Dynamic changes in the real-time glomerular filtration rate and kidney injury markers in different acute kidney injury models.

In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Supplementation with Folic Acid or 5-Methyltetrahydrofolate and Prevention of Neural Tube Defects: An Evidence-Based Narrative Review.

Background: Folic acid (FA), which in its chemical form is pteroylglutamic acid, is the fully oxidised, water-soluble, monoglutamic form of vitamin B9. This compound is part of the folate group but with higher bioavailability, and it is found in vitamin supplements and fortified foods and drugs. Folate metabolism is complex and associated with various metabolic pathways, all of which confer protection on the cell and allow its survival. Methods: We conducted a non-systematic search of articles published in English and Spanish including controlled trials, cohort studies, systematic re-views, and meta-analyses were included, as well as key studies in animal models related to pharmacokinetic studies. Search terms encompassed: "folic acid", "folates", "5-metyltetrahydrofolate", "5-MTHF", "neural tube defects", "supplementation", "fortification", AND "homocysteine" Results: A crucial role demonstrated for FA is to help prevent neural tube defects (NTDs). However, more studies are definitely still needed to establish 5-MTHF as a safe and effective therapeutic approach comparable with FA. Moreover, there is a lack of clinical studies that evaluate the efficacy of 5-MTHF supplementation in the prevention of NTDs. The present evidence-based narrative review discusses differences between FA and 5-MTHF in terms of structure, metabolism, bioavailability, clinical efficacy, and safety. Conclusions: Despite the potential value of 5-MTHF as an alternative to FA, clinical studies would be urgently needed to support the efficacy, dosage, timing, and/or safety of its use as a supplement.