Targeting Monkeypox Virus Methyltransferase: Virtual Screening of Natural Compounds from Middle-Eastern Medicinal Plants.

Monkeypox is an infectious disease resulting from the monkeypox virus, and its fatality rate varies depending on the virus clade and the location of the outbreak. In monkeypox virus, methyltransferase (MTase) plays a crucial role in modifying the cap structure of viral mRNA. This alteration assists the virus in evading the host's immune system, enhances viral protein synthesis, and ultimately enables successful infection and replication within host cells. Given the significance of MTase in viral infection and spread within the host, our study aimed to identify a natural inhibitor for this enzyme using docking and molecular dynamic (MD) simulations. We collected a total of 12,971 natural compounds from 200 medicinal plants in the Middle East. After eliminating duplicate compounds, we had 5,749 unique ligand conformers, which we then subjected to high-throughput virtual screening against MTase. The most promising hits were further evaluated using the extra-precision (XP) tool. The affinity of these hits was also assessed by Prime-Molecular Mechanics/Generalized Born Surface Area (MMGBSA) tool. The analysis revealed that two standard controls (sinefungin and TO1119) and two Middle-Eastern compounds (folic acid and 1,2,4,6-tetragalloylglucose) exhibited the best XP docking scores. According to Prime MMGBSA calculations, the Middle-Eastern compounds showed higher affinities, with values of - 60.61 kcal/mol for 1,2,4,6-tetragalloylglucose and - 51.87 kcal/mol for folic acid, surpassing the controls (TO1119 at - 35.71 kcal/mol and sinefungin at - 31.51 kcal/mol). In the majority of Molecular dynamic (MD) simulations, folic acid exhibited demonstrated greater stability than sinefungin. Further investigation revealed that folic acid occupied a critical position in the active site of MTase, which reduced its interaction with the mRNA substrate. Based on these findings, it can be concluded that folic acid is a highly promising natural compound for potential use in the cost-effective treatment of monkeypox virus. The identification of folic acid as a potential antiviral agent highlights the importance of nature in providing new therapeutic uses that have significant implications for global health, particularly in regions where monkeypox viral outbreaks are prevalent. However, it is essential to note that further wet-lab validations are necessary to confirm its efficacy for treatment in a medical context.

Sensitive electrochemical determination of quercetin and folic acid with cobalt nanoparticle functionalized multi-walled carbon nanotube.

A nanocomposite of cobalt nanoparticle (CoNP) functionalized carbon nanotube (Co@CNT) was prepared and used to modify a glassy carbon electrode (Co@CNT/GCE). Characterization indicates the morphology of Co@CNT is CoNPs adhering on CNTs. With the nano-interface, Co@CNT provides large surface area, high catalytic activity, and efficient electron transfer, which makes Co@CNT/GCE exhibiting satisfactory electrochemical response toward quercetin (QC) and folic acid (FA). The optimum pH values for the detection of FA and QC are 7.0 and 3.0, respectively. The saturated absorption capacity (Γ*) and catalytic rate constant (kcat) of Co@CNT/GCE for QC and FA are calculated as 1.76 × 10-9, 3.94 × 10-10 mol∙cm-2 and 3.04 × 102, 0.569 × 102 M-1∙s-1. The linear range for both FA and QC is estimated to be 5.0 nM-10 µM, and the LODs (3σ/s) were 2.30 nM and 2.50 nM, respectively. The contents of FA and QC in real samples determined by Co@CNT/GCE are comparable with the results determined by HPLC. The recoveries were in the range 90.5 ~ 114% and the total RSD was lower than 8.67%, which further confirms the reliability of the proposed electrode for practical use.

A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Public perception of folate-biofortified genetically modified lettuce varieties in Brazil.

Lettuce is one of the most widely consumed vegetables in the world, commonly eaten fresh in salads, sandwiches, wraps, and as a garnish in various dishes. Consequently, it is a very promising vehicle to deliver vitamins, such as folate (vitamin B9), to a specific population using biofortified varieties generated by conventional or molecular breeding. A new genetically modified lettuce was generated with increased folate content. However, some issues related to public perception regarding this technology should still be evaluated. The aim of this study was to analyze whether consumers are willing to accept a folate-biofortified GM lettuce that could become available to the Brazilian market. A questionnaire involving several issues regarding lettuce consumption was answered by 2,391 people from almost all Brazilian states. When informed that the folic acid biofortified lettuce is a transgenic plant, 46.1% of respondents stated that they would eat it and 30.5% stated that it would be a possibility. This study demonstrated that if there is any explanation regarding the advantage in relation to the use of biotechnology, like enrichment with folic acid, the number of people who accept it increases.

Folate Receptor ß (FRß) Expression on Myeloid Cells and the Impact of Reticuloendothelial System on Folate-Functionalized Nanoparticles' Biodistribution in Cancer.

Folate uptake is largely mediated by folate receptor (FR)ß, encoded by FOLR2 gene, in myeloid immune cells such as granulocytes, monocytes, and especially in macrophages that constitute the reticuloendothelial system (RES) and infiltrate the tumor microenvironment. Since the myeloid immune compartment dynamically changes during tumorigenesis, it is critical to assess the infiltration status of the tumors by FRß-expressing myeloid cells to better define the targeting efficacy of folate-functionalized drug delivery systems. On the other hand, clearance by RES is a major limitation for the targeting efficacy of nanoparticles decorated with folate. Therefore, the aims of this study are (i) to determine the amount and subtypes of FRß+ myeloid cells infiltrating the tumors at different stages, (ii) to compare the amount and subtype of FRß+ myeloid cells in distinct organs of tumor-bearing and healthy animals, (iii) to test if the cancer-targeting efficacy and biodistribution of a prototypic folate-functionalized nanoparticle associates with the density of FRß+ myeloid cells. Here, we report that myeloid cell infiltration was enhanced and FRß was upregulated at distinct stages of tumorigenesis in a mouse breast cancer model. The CD206+ subset of macrophages highly expressed FRß, prominently both in tumor-bearing and healthy mice. In tumor-bearing mice, the amount of all myeloid cells, but particularly granulocytes, was remarkably increased in the tumor, liver, lungs, spleen, kidneys, lymph nodes, peritoneal cavity, bone marrow, heart, and brain. Compared with macrophages, the level of FRß was moderate in granulocytes and monocytes. The density of FRß+ immune cells in the tumor microenvironment was not directly associated with the tumor-targeting efficacy of the folate-functionalized cyclodextrin nanoparticles. The lung was determined as a preferential site of accumulation for folate-functionalized nanoparticles, wherein FRß+CD206+ macrophages significantly engulfed cyclodextrin nanoparticles. In conclusion, our results demonstrate that the tumor formation augments the FR levels and alters the infiltration and distribution of myeloid immune cells in all organs which should be considered as a major factor influencing the targeting efficacy of nanoparticles for drug delivery.

Targeted biocompatible Zn-metal-organic framework nanocomposites for intelligent chemotherapy of breast cancer cells.

Finding a novel drug delivery system (DDS) represents one of the most challenging endeavors in cancer therapy. Hence, in this study, we developed a new biocompatible and biodegradable zinc-based nanoscale metal-organic framework (Zn-NMOF) coated with folic acid (FA) functionalized chitosan (CS) to facilitate targeted delivery of doxorubicin (D), a standard chemotherapeutic agent, into breast cancer cells. The synthesis of the NMOF-CS-FA-D nanocomposite preceded its comprehensive characterization via FT-IR, DLS, XRD, SEM, and TEM analyses. Subsequent in vitro studies were conducted on MCF-7 breast cancer cells and HFF-1 normal cells, encompassing assessments of cell viability, expression levels of apoptotic and autophagy genes, cell cycle arrest, and apoptotic analyses. The size of the NMOF-CS-FA-D particles was determined to be less than 80 nm, with a drug loading efficiency of 72 ± 5%. The release kinetics of DOX from the nanocomposite were investigated, revealing controlled release behavior at pH 7.4 and accelerated release at pH 5.0, which is conducive to drug delivery into cancer cells. In vitro results indicated a 17.39% ± 6.34 cell viability after 24 h of treatment with a 40 nM concentration of the NMOF-CS-FA-D nanocomposite. Furthermore, the expression levels of Caspase-9 and BAX, key apoptotic genes, along with BECLIN1, an autophagy gene, were found to increase by two-fold, four-fold, and two-fold, respectively, following 5 h of treatment with the nanocomposite. Additionally, analysis of cell cycle distribution revealed 15.4 ± 2% of cells in the sub-G1 phase, indicative of apoptotic cells, and 31.9% of cells undergoing early and late apoptosis in MCF-7 cells. Collectively, these findings underscore the potential of the NMOF-CS-FA-D nanocomposite in inhibiting cancer cell proliferation with low side effects.

Prevalence and Factors Associated with Adherence to Iron-Folic Acid Supplementation Among Pregnant Women in Eastern Sudan: A Cross-Sectional Study.

Purpose: The present study was conducted to determine the prevalence and factors associated with adherence to iron-folic acid supplementation (IFAS) among pregnant women in eastern Sudan. Methods: A cross-sectional survey was conducted among pregnant women who obtained antenatal care (ANC) at Gadarif Maternal Hospital in eastern Sudan between May 1 and August 31, 2023. Face-to-face interview questionnaires were used to gather sociodemographic, obstetric, and clinical data (age, parity, education, residence, and previous medical diseases). Knowledge of anemia and IFAS was assessed. Multivariate analysis was performed to adjust for confounders. Results: A total of 568 pregnant women were enrolled in the present study. Among them, 449 (79.0%) adhered to the IFAS. The multivariate analysis showed that the adjusted odds ratio (AOR) of IFAS adherence increased with ANC visits > 4 (AOR = 1.68, 95.0% CI = 1.01-2.77) and knowledge of anemia (AOR = 2.06, 95.0% CI = 1.437-3.276). In the univariate analysis, maternal occupation and knowledge of IFAS adherence were the only factors associated with IFAS adherence. Maternal age, parity, gestational age, education, residence, occupation, medical insurance, medical disease, and husband's occupation were not associated with IFAS. Forgetfulness (71.0%), frustration from taking many drugs (54.6%), and unpleasant tests of the supplement (50.7%) were the main reasons for not taking the IFAS. Conclusion: About four out of five pregnant women adhered to the IFAS, indicating a good level of adherence, especially among women who attended more than four ANC visits and those with good knowledge of anemia. More attention is needed to encourage ANC to increase adherence to IFAS.

Qualitative evaluation of a package of implementation strategies codesigned to support the introduction of multiple micronutrient supplementation (MMS) for pregnant women in Bamako, Mali.

Mali national policy recommends that women take iron and folic acid supplements (IFA) from the time of the first antenatal care (ANC) visit, throughout pregnancy and during the first 3 months after delivery. In 2020, the World Health Organization (WHO) updated their ANC guidelines to recommend the United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP) formulation of multiple micronutrient supplements (MMS) in the context of rigorous research, including implementation research. In Bamako, Mali, a codesign process was used to tailor antenatal care MMS packaging and counselling materials aimed at optimizing delivery and uptake of and adherence to MMS. This paper presents the codesign process along with the results of a post-intervention qualitative assessment to evaluate the behaviour change intervention. At the conclusion of the intervention, we conducted semistructured qualitative interviews with 24 women who had received the intervention and six pharmacy managers from the six health centres participating in the study. We conducted two focus groups with midwives who had delivered the intervention and two group discussions with family members of women who had received the intervention. Respondent perspectives reveal an easy experience transitioning from previously used IFA. Women and providers concur that the intervention counselling materials and visual aids were instrumental in influencing the perceived benefit and uptake of MMS. Family members play an influential role in pregnant women's decision-making regarding MMS uptake. MMS and the associated implementation strategies developed through the codesign process were found to be a highly acceptable intervention.

Amine-Rich Carbon Dots Synthesized from Kappa-Carrageenan and l-Lysine as a Dual Probe for Detection of Folic Acid and Tumor-Targeted Delivery of Therapeutics.

Strategically designed, heteroatom-rich surface functionalized blue fluorescent carbon dots (CDs) were synthesized for high-throughput detection of folic acid (vitamin B9). The highly stable CDs could particularly detect vitamin B9 in the presence of 35 analytes, even up to 40 nM of the vitamin. The versatile CDs were found to have a high affinity for folic acid in wastewater, folic acid tablets, and food samples enriched with folic acid. The hemocompatibility of the CDs was also studied by using a hemolysis assay, confirming the CDs to be nontoxic to human blood samples up to 400 µg/mL. The CDs were then covalently conjugated to biotin, which possesses receptors that are overexpressed in tumor cells. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye) assay and confocal bioimaging studies proved the biotin-modified CDs (CDBT) were remarkably nontoxic in healthy cell lines (HEK-293) and highly target-specific toward tumor cells (HeLa), including triple-negative breast cancer cells (MDA-MB-231). The cytotoxicity assay of 5-fluorouracil encapsulated CDs (CDBTFu) showed the IC50 value to be 81 µM in HeLa cells and 185 µM in MDA-MB-231 cells, respectively, and significantly higher in HEK-293 cells (over 300 µM), owing to high specificity toward tumor cells.

Folic acid for the primary prevention of stroke: a systematic review and meta-analysis.

Objectives: Results from studies were inconsistent with regard to the effect of folic acid on the primary prevention of stroke. The aim of this study was to analyze the association between folic acid and the primary prevention of stroke using the data from observational studies and randomized controlled trials (RCTs). Methods: Eligible publications published until June 2024 were searched in the database of PubMed, Web of Science and Embase. This study included all observational studies and RCTs of folic acid with first stroke as the reporting endpoints. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled in the random-effects model to assess the effect of folic acid on the primary prevention of stroke. Results: Results from 12 observational publications with 16 research, including 312,320 participants, were combined to explore the association between dietary folic acid intake and the primary prevention of stroke. The results showed that high dietary folic acid intake was associated with a 17% reduction in stroke incidence (RR:0.83; 95% CI: 0.73-0.94), and the effect of dietary folic acid was greater in areas without grain fortification (RR:0.80; 95% CI: 0.67-0.95). The pooled results from 12 RCTs, totaling 75,042 participants, indicated that folic acid supplementation was not associated with the stroke primary prevention (RR:0.92; 95% CI: 0.80-1.05), but folic acid supplementation was effective in areas without grain fortification (RR:0.78; 95% CI: 0.68-0.89). Conclusion: Our meta-analysis demonstrated that dietary folic acid is effective in stroke primary prevention, and folic acid supplementation is effective in stroke primary prevention only in areas without grain fortification. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024516991.

Evaluation of Folic Acid-Containing Mouthrinse and Chlorhexidine Mouthrinse as an Adjunct to Scaling and Root Planing in Patients With Periodontal Disease.

BACKGROUND: Periodontal disease is a host-mediated inflammation caused due to microbial challenge. Hence, mechanisms involving the control of host-associated mediators can be a potential target. The conventional nonsurgical periodontal treatment modality includes scaling and root planing (SRP), which is often combined with adjunctive chemical plaque control agents for effective disease control. Chlorhexidine (CHX) is the most common chemical plaque control agent used. Recent research is now being focused on exploring other medicinal substitutes that may benefit control of inflammation and tissue healing. Folic acid is an important nutrient that increases the ability of oral epithelial cells to resist local irritants and inflammation if supplemented either systemically or locally. AIM: The current study aimed to evaluate the effect of folic acid and CHX mouthwash as an adjunct to scaling and root planing for treating patients with chronic periodontitis. METHODOLOGY: In this study, 30 patients with chronic periodontitis were included and assigned to either of the two groups: Group A (receiving folic acid-containing mouthrinse) and Group B (receiving CHX mouthrinse). Periodontal measurements, including plaque index, probing pocket depth, gingival index, and healing index, were evaluated at baseline and again four weeks after scaling and root planing. RESULTS: Significant reduction was detected in all clinical parameters (plaque index, gingival index, probing pocket depth, healing index) for both groups (p<0.05) when evaluated from baseline to four weeks. CONCLUSION: Both mouthrinses were effective when used as an adjunct to scaling and root planing in the treatment of periodontitis. Hence, folic acid-containing mouthrinse can be used in patients with chronic periodontitis.

Advances in DNA methylation of imprinted genes and folic acid regulation of growth and development.

DNA methylation is closely related to folate levels and acts as a mechanism linking developmental disorders to chronic diseases. Folic acid supplementation can impact DNA methylation levels of imprinted genes crucial for neonatal development. Imprinted genes are vital for regulating embryonic and postnatal fetal growth. This review summarizes imprinted genes, DNA methylation, folic acid's influence on growth and development and their correlation. It aims to provide a comprehensive overview of research advancements on imprinted genes, DNA methylation and folic acid regulation concerning growth and development.

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Folic acid supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, 2023: A cross-sectional study.

Background: Supplementing folic acid (FA) before and in the first month of conception is an essential preventive factor, especially for neural tube defects (NTDs) and other congenital anomalies. Aim: The research aimed to assess FA supplement prescribing practice during the protective period and its associated factors among health professionals in selected governmental health centers in Addis Ababa, Ethiopia, in 2023. Methods: An institutionalized cross-sectional survey was carried out in Addis Ababa public health centers with a total sample size of 396 in February 2023. Systematic random sampling methods were used, and after each respondent's signed consent, a row of data was gathered using pretested self-administered questionnaires. The data was coded, interred to Epi Data 4.6.0.6 and transferred to Statistical Package for Social Sciences 27 software. Then a binary and multivariable logistic regression analysis method was used to show the associated variables with FA prescribing practice using a confidence interval (CI) of 95% and a significance value < 0.05. Results: The total prevalence of FA prescribing practice during the periconceptional period was 64.4% [95% CI (59.68-69.12)]. But those prescribed during the protective period were 26.7%. Ever since the birth of a neonate with NTDs, not prescribing a dose of 4 mg of FA for women with NTD, the type of women for whom FA was prescribed were associated with FA prescribing practice during the protective period. Conclusion: The healthcare professional's prescribing practice during the protective period was still low and needs more attention to strengthen FA supplements.

Genetically predicted lipid traits mediate the association between folic acid and atherosclerosis.

Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.

Association of maternal ABO blood type with lesion level and birthweight of children with spina bifida: a descriptive study.

The etiology of spina bifida, a neural tube birth defect, is largely unknown, but a majority of cases are thought to be genetic in origin. Although maternal blood type was found not to be associated with the occurrence of spina bifida, the analysis was never extended to other aspects of the disorder. The purpose of this descriptive study was to determine if maternal blood type was related to characteristics of children with spina bifida. The blood type of 221 mothers of children with spina bifida enrolled on the Arkansas Spinal Cord Disability Registry from 1995 to 2008 was obtained by mailed questionnaire. All children were community-dwelling and from singleton pregnancies. As expected, analysis of mother-child data showed that the distribution of mothers' blood type was not statistically different from the general population (chi-squared, P = 0.9203). However, the blood type of these mothers was associated with their child's lesion level (chi-squared, P = 0.011). Mothers with blood type A more frequently had children with thoracic lesions; mothers with non-A blood types more frequently had children with lumbar and sacral lesions. In addition, mean birthweight differed by mothers' blood type (analysis of variance, P = 0.025). Children of mothers with blood type A had the highest mean birthweight, while those of mothers with blood type AB had the lowest. Also, hydrocephalus was present more frequently in children with thoracic lesions compared to those with lumbar and sacral lesions (chi-squared, P = 0.001). Interestingly, these results were significant for female children but not for male children. In conclusion, maternal blood type was associated with lesion level and birthweight of children with spina bifida.

αvß3 Integrin and Folate-Targeted pH-Sensitive Liposomes with Dual Ligand Modification for Metastatic Breast Cancer Treatment.

The advent of pH-sensitive liposomes (pHLips) has opened new opportunities for the improved and targeted delivery of antitumor drugs as well as gene therapeutics. Comprising fusogenic dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS), these nanosystems harness the acidification in the tumor microenvironment and endosomes to deliver drugs effectively. pH-responsive liposomes that are internalized through endocytosis encounter mildly acidic pH in the endosomes and thereafter fuse or destabilize the endosomal membrane, leading to subsequent cargo release into the cytoplasm. The extracellular tumor matrix also presents a slightly acidic environment that can lead to the enhanced drug release and improved targeting capabilities of the nano-delivery system. Recent studies have shown that folic acid (FA) and iRGD-coated nanocarriers, including pH-sensitive liposomes, can preferentially accumulate and deliver drugs to breast tumors that overexpress folate receptors and αvß3 and αvß5 integrins. This study focuses on the development and characterization of 5-Fluorouracil (5-FU)-loaded FA and iRGD surface-modified pHLips (FA-iRGD-5-FU-pHLips). The novelty of this research lies in the dual targeting mechanism utilizing FA and iRGD peptides, combined with the pH-sensitive properties of the liposomes, to enhance selective targeting and uptake by cancer cells and effective drug release in the acidic tumor environment. The prepared liposomes were small, with an average diameter of 152 ± 3.27 nm, uniform, and unilamellar, demonstrating efficient 5-FU encapsulation (93.1 ± 2.58%). Despite surface functionalization, the liposomes maintained their pH sensitivity and a neutral zeta potential, which also conferred stability and reduced aggregation. Effective pH responsiveness was demonstrated by the observation of enhanced drug release at pH 5.5 compared to physiological pH 7.4. (84.47% versus 46.41% release at pH 5.5 versus pH 7.4, respectively, in 72 h). The formulations exhibited stability for six months and were stable when subjected to simulated biological settings. Blood compatibility and cytotoxicity studies on MDA-MB-231 and SK-BR3 breast cancer cell lines revealed an enhanced cytotoxicity of the liposomal formulation that was modified with FA and iRGD compared to free 5-FU and minimal hemolysis. Collectively, these findings support the potential of FA and iRGD surface-camouflaged, pH-sensitive liposomes as a promising drug delivery strategy for breast cancer treatment.

The Impact of the Dietary Intake of Vitamin B12, Folic Acid, and Vitamin D3 on Homocysteine Levels and the Health-Related Quality of Life of Levodopa-Treated Patients with Parkinson's Disease-A Pilot Study in Romania.

BACKGROUND AND OBJECTIVES: Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). MATERIALS AND METHODS: An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. RESULTS: Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). CONCLUSIONS: The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support.

Thermoresponsive lipids engineered magnetic nanoparticles for spatiotemporal delivery of hesperidin to inflammatory sites in animal model.

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis (p < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication (p < 0.05, p < 0.01, and p < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

The effect of folic acid intake on congenital anomalies. A systematic review and meta-analysis.

Background: Congenital anomalies pose a significant challenge to global health and result in considerable morbidity and mortality in early childhood. With the decline of other causes of death among children under five, the burden of congenital anomalies is rising, emphasizing the need for improved prenatal care, screening, and nutrition for pregnant women. This systematic review and meta-analysis aim to estimate the pooled effect of folic acid intake on congenital anomalies. Methods: To identify relevant research published up until December 30/2023, we conducted electronic searches of PubMed/Medline, PubMed Central, Hinary, Google, African Journals Online, Web of Science, Science Direct, and Google Scholar databases using predefined eligibility criteria. We used Excel to extract data and evaluated the studies using the JBI appraisal checklist. We computed the pooled effect size with 95% confidence intervals for maternal folic acid intake on congenital anomalies using STATA version 17 and the DerSimonian and Laird random effects meta-analysis model. We assessed statistical heterogeneity using Cochran's Q-test, I 2 statistic, and visual examination of the funnel plot. Results: The review included 16 case-control, cohort, and cross-sectional studies. According to the results of this systematic review and meta-analysis, maternal folic acid intake significantly lowers the incidence of congenital anomalies (odds ratio (OR), 0.23; confidence interval (CI), 0.16, 0.32). Among the included studies, both the Cochrane Q-test statistic (χ2 = 118.82, p < 0.001) and I 2 test statistic (I 2 = 87.38%, p < 0.001) revealed statistically significant heterogeneity. Egger's weighted regression (p < 0.001) and funnel plot show evidence of publication bias in this meta-analysis. Conclusion: The results of the recent meta-analysis and systematic review have demonstrated a significant association between maternal folic acid intake and the risk of congenital anomalies. Specifically, children whose mothers received periconceptional folic acid supplementation had a 77% reduced risk of congenital anomalies. To further investigate the correlation between maternal folic acid supplementation and the occurrence of various congenital anomalies, particularly in developing countries, it is recommended that a comprehensive prospective study be conducted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42024511508).

Hybrid Nanoparticles Based on Mesoporous Silica and Functionalized Biopolymers as Drug Carriers for Chemotherapeutic Agents.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan-dopamine and hyaluronic acid-folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments.