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Organization of the neural retina. ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; NFL, nerve fiber layer

Organization of the neural retina. ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer; NFL, nerve fiber layer

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Folic acid (FA), also termed folate, is an essential vitamin for health at all ages since it participates in the biosynthesis of nucleotides, amino acids, neurotransmitters, and certain vitamins. It is therefore crucial for rapidly growing tissues such as those of the fetus. It is becoming clear that FA deficiency and impaired folate pathways are i...

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... Interestingly, canakinumab (a selective anti-IL-1b monoclonal antibody) decreased neutrophil counts to lower NLR, which in turn decreased adverse endpoint events of cardiovascular disease with no discernible effect from lipid levels, which may indicate that neutrophil played a more vital role (26). Folic acid, also known as vitamin B9, must be formed through food intake and converted by gut microbes through digestion (27). As a coenzyme in the production of purines and pyrimidines, as well as in the conversion of one-carbon units and the methylation cycle, folic acid performs a variety of roles in the body (28). ...
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Background Coronary artery disease (CAD) is still a lethal disease worldwide. This study aims to identify clinically relevant diagnostic biomarker in CAD and explore the potential medications on CAD. Methods GSE42148, GSE180081, and GSE12288 were downloaded as the training and validation cohorts to identify the candidate genes by constructing the weighted gene co-expression network analysis. Functional enrichment analysis was utilized to determine the functional roles of these genes. Machine learning algorithms determined the candidate biomarkers. Hub genes were then selected and validated by nomogram and the receiver operating curve. Using CIBERSORTx, the hub genes were further discovered in relation to immune cell infiltrability, and molecules associated with immune active families were analyzed by correlation analysis. Drug screening and molecular docking were used to determine medications that target the four genes. Results There were 191 and 230 key genes respectively identified by the weighted gene co-expression network analysis in two modules. A total of 421 key genes found enriched pathways by functional enrichment analysis. Candidate immune-related genes were then screened and identified by the random forest model and the eXtreme Gradient Boosting algorithm. Finally, four hub genes, namely, CSF3R, EED, HSPA1B, and IL17RA, were obtained and used to establish the nomogram model. The receiver operating curve, the area under curve, and the calibration curve were all used to validate the accuracy and usefulness of the diagnostic model. Immune cell infiltrating was examined, and CAD patients were then divided into high- and low-expression groups for further gene set enrichment analysis. Through targeting the hub genes, we also found potential drugs for anti-CAD treatment by using the molecular docking method. Conclusions CSF3R, EED, HSPA1B, and IL17RA are potential diagnostic biomarkers for CAD. CAD pathogenesis is greatly influenced by patterns of immune cell infiltration. Promising drugs offers new prospects for the development of CAD therapy.
... Folic acid is another necessary nutrient for mothers and is widely known for its role in preventing neural tube defects [7,12,13]. Folic acid plays a fundamental role in cellular division as a DNA and RNA synthesis cofactor [13]. In the US, the Centers for Disease Control and Prevention (CDC) recommends that women of reproductive age prophylactically supplement their diet with 400 mcg of folic acid daily [14]. ...
... In the US, the Centers for Disease Control and Prevention (CDC) recommends that women of reproductive age prophylactically supplement their diet with 400 mcg of folic acid daily [14]. In the eye, folate receptors exist predominantly in the retina, including the Müller cells, ganglion cells, outer limiting membrane, and the outer plexiform layer, but also in the lens and other parts of the eye [12,13,15]. Low levels of folate have presented with sequelae, including amblyopia, central scotomas, and optic neuropathy [12]. ...
... In the eye, folate receptors exist predominantly in the retina, including the Müller cells, ganglion cells, outer limiting membrane, and the outer plexiform layer, but also in the lens and other parts of the eye [12,13,15]. Low levels of folate have presented with sequelae, including amblyopia, central scotomas, and optic neuropathy [12]. During embryonic development in mice, maternal folic acid deficiency led to smaller eyes and morphological changes to the lens and the retina [16]. ...
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The intricate steps of human ocular embryology are impacted by cellular and genetic signaling pathways and a myriad of external elements that can affect pregnancy, such as environmental, metabolic, hormonal factors, medications, and intrauterine infections. This review focuses on presenting some of these factors to recognize the multifactorial nature of ocular development and highlight their clinical significance. This review is based on English-language articles sourced from PubMed, Web of Science, and Google Scholar; keywords searched included “ocular development in pregnancy,” “ocular embryology,” “maternal nutrition,” “ophthalmic change,” and “visual system development.” While some animal models show the disruption of ocular embryology from these external factors, there are limited post-birth assessments in human studies. Much remains unknown about the precise mechanisms of how these external factors can disrupt normal ocular development in utero, and more significant research is needed to understand the pathophysiology of these disruptive effects further. Findings in this review emphasize the importance of additional research in understanding the dynamic association between factors impacting gestation and neonatal ocular development, particularly in the setting of limited resources.
... Maternal folic acid deficiency is associated with several congential anomalies such as cleft lip, congenital heart disease, and spina bifida. Folic acid deficiency may also lead to eye problems as it is required for optimal eye health [64]. ...
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Micronutrient deficiencies refer to insufficiencies in essential vitamins and minerals required for optimal physiological function. These vital nutrients, including vitamins A, C, D, and minerals such as iron, zinc, and calcium, play a crucial role in supporting various bodily functions. Micronutrient deficiencies can arise due to inadequate dietary intake, dietary restrictions, or underlying medical conditions, and their repercussions extend far beyond dietary concerns, significantly impacting overall health. The link between micronutrient deficiencies and health outcomes is profound, influencing diverse aspects of well-being. This chapter explores the critical issue of nutritional deficiencies and highlights their significance in maintaining optimal health. It emphasizes the crucial role of a balanced diet and lifestyle adjustments in effectively addressing these deficiencies. By focusing on dietary patterns and maximizing nutrient intake through the consumption of balanced meals and appropriate supplementation, individuals can mitigate the adverse effects of nutritional deficiencies. However, challenges related to the affordability and accessibility of nutritious food persist, necessitating comprehensive government-led initiatives and nutrition education programs. The chapter delves into the various causes of nutritional deficiencies, including inadequate dietary intake and underlying medical conditions. It underscores the importance of addressing these deficiencies to prevent the onset of various health conditions and improve skeletal-muscular health. Additionally, the chapter discusses the potential interactions between medications and dietary supplements, emphasizing the need for caution and awareness. Overall, this chapter provides valuable insights into the significance of nutrition in maintaining optimal health and offers practical strategies to effectively address nutritional deficiencies.
... Folate is an essential water-soluble B vitamin (B9) [1] that is not synthesized in mammalian cells and can only be obtained by diet or from supplementation [2]. as a crucial nutrient for normal reproduction and pregnancy, women in many countries are recommended to start folic acid (Fa) supplementation from one month before conception and throughout the first trimester of pregnancy due to the increased physiological need for this vitamin to support rapid fetal growth and placental development [3][4][5]. ...
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Background As folates are essential for embryonic development and growth, it is necessary to accurately determine the levels of folates in plasma and red blood cells (RBCs) for clinical intervention. The aims of this study were to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantitation of folates in plasma and RBCs and to examine the association between plasma and RBC folate concentrations and gestational diabetes mellitus (GDM), gestational hypertension (GH) and preeclampsia (PE). Methods With the in-house developed LC-MS/MS, a retrospective cross-sectional study was conducted. The healthy pregnant women of first- (n = 147), second- (n = 84) and third-trimester (n = 141) or the women diagnosed with GDM (n = 84), GH (n = 58) or PE (n = 23), that were aged between 22 and 46 years old and registered at our institute, were subjected for measurement of folic acid (FA) and 5-methyltetrahydrofolate (5-MTHF), followed by appropriate statistical association analysis. Results The assay for simultaneous quantitation of FA and 5-MTHF in plasma and RBCs was linear, stable, with imprecision less than 15% and recoveries within ±10%. The lower limits of quantification for FA and 5-MTHF measurement in whole blood were 0.57 and 1.09 nmol/L, and in plasma were 0.5 and 1 nmol/L, respectively. In the association analysis, the patients with lower RBC folate level (<906 nmol/L) presented higher risks of PE development (OR 4.861 [95% CI 1.411–16.505]) by logistic regression and restricted cubic spline (RCS) regression in a nonlinear fashion. In addition, higher level of plasma folates in pregnancy was significantly associated with GH risk but may be protective for the development of GDM. Conclusions The in-house developed LC-MS/MS method for folates and metabolites in plasma or RBC showed satisfactory analytical performance for clinical application. Further, the levels of folates and metabolites were diversely associated with GDM, GH and PE development.
... However, further progress is necessary to reduce the rates of mortality and morbidity related to ALI and ARDS (6). nutrient that plays a crucial role in DNA synthesis, cell division, and other cellular processes (7). It is essential during rapid cell growth and division, such as pregnancy. ...
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... In addition, folic acid salts promote increased bone alkaline phosphatase activity, which determines normal bone development. Metal complexes with FA also promote bone cell replication [20][21][22][23]. ...
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The research has been conducted to obtain scaffolds for cancellous bone regeneration. Polylactide scaffolds were made by the phase inversion method with a freeze-extraction variant, including gelling polylactide in its non-solvent. Substitutes made of polylactide are hydrophobic, which limits cell adhesion. For this reason, the scaffolds were modified using chitosan and folic acid by forming gel-like coatings on the surface. The modification aimed to improve the material's surface properties and increase cell adhesion. Analyses of obtained scaffolds confirmed the effectiveness of performed changes. The presence of chitosan and folic acid was confirmed in the modified scaffolds, while all scaffolds retained high open porosity, which is essential for proper cell growth inside the scaffold and the free flow of nutrients. Hydrostatic weighing showed that the scaffolds have high mass absorbability, allowing them to be saturated with biological fluids. There were also cytotoxicity tests performed on 24 h extracts of the materials obtained, which indicated a lack of cytotoxic effect.
... Consequently, deficiency in vitamin B12 can manifest as hematological, neurological, and neuropsychiatric disorders (17). Folic acid (FA), another essential nutrient, underpins various physiological processes, including nucleotide and amino acid biosynthesis, neurotransmitter function, and vitamin metabolism (18). The significance of zinc lies in its role in facilitating immune system activities through enzyme functionality (19). ...
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Objective: Thalassemia major, an autosomal recessive genetic disorder, represents a significant healthcare concern worldwide. The hallmark of this condition is the deficiency in hemoglobin synthesis, resulting in chronic anemia and necessitating regular blood transfusions. This study endeavors to delve into the realm of pediatric patients afflicted by thalassemia major, with a particular focus on investigating potential vitamin and mineral deficiencies. By exploring these deficiencies, we aim to contribute to the broader understanding of the physiological implications of thalassemia major on growing individuals, shedding light on aspects that could impact their overall health and well-being. Material Methods: The current study constitutes a retrospective analysis of a meticulously curated dataset comprising 112 pediatric patients diagnosed with thalassemia major. The patients were drawn from diverse backgrounds and were subjected to rigorous assessment and evaluation. Comprehensive medical records, encompassing demographic information, clinical history, and laboratory findings, were meticulously reviewed. Results: The patients had a mean age of 8.14±12 years; among them, 59 (52.7%) were girls. The median hemoglobin and ferritin levels were 8.5 g/dL (range 6.5-10.6) and 2497 ml/ng (range 170-7417), respectively. The frequency of erythrocyte suspension (ES) transfusion in the patients was 1:2.7 weeks. The mean serum levels were 423.7 pg/mL (range 166-755) for vitamin B12, 6.6 ng/mL (range 1.55-16.4) for folic acid, 79.4 mg/dL (range 51-167) for zinc, and 111.07 mg/dL (range 67-190) for copper. Among the patients, 7 (6.25%) had a vitamin B12 deficiency, 35 (31.25%) had a folic acid deficiency, 27 (24.1%) had a zinc deficiency, and 10 (8.9%) had a copper deficiency. Conclusion: The exploration into pediatric thalassemia major unveils a landscape where folic acid and zinc deficiencies play a significant role. The detected prominence of these deficiencies prompts a call for focused interventions to address the potential health implications. Amid the intricate fabric of thalassemia major, the spotlight on folic acid and zinc deficiencies highlights an avenue for proactive healthcare strategies. By targeting these deficiencies, we hold the potential to improve the well-being and future prospects of young patients grappling with thalassemia major.
... Consequently, the primary sources of this nutrient are FA-fortified foods and FA-containing dietary supplements. However, FA is inactive in the human body, and consequently, it must be converted into the active molecule 5-methyltetrahydrofolate (5-MTHF) by the human liver [19,20]. 5-MTHF is associated with many metabolic reactions and functions as a methyl donor. ...
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Background: SARS-CoV-2 is a life-threatening RNA virus that may cause an acute respiratory syndrome associated with extremely high morbidity and mortality rates. Folic acid (FA), also known as folate, is an essential vitamin vital for human homeostasis, participating in many biochemical pathways, and its deficiency has been associated with viral infection vulnerability. In this review, we investigated the association between FA intake and SARS-CoV-2 infection, along with the existence of any potential impact of FA on the health outcome of patients suffering from this new viral infection. Methods: Studies included were patients' and in silico and molecular docking studies. Results: Data from in silico studies and molecular docking support that FA inhibits SARS-CoV-2 entry into the host and viral replication, binding at essential residues. Accordingly, in patients' studies, a protective role of FA supplementation against SARS-CoV-2 infection is indicated. However, contradictory data from observational studies indicate that FA supplementation, often linked to deficits during systemic inflammation due to SARS-CoV-2, increases the risk of post-infection mortality. Conclusions: Future randomized controlled trial studies, including the FA pharmacological group, are needed to better understand the role of FA as a potential protective or mortality risk indicator in COVID-19 patients.
... Merging the 74 IMPC genes and the 114 MAC spectrum genes using STRING revealed a cluster of interrelated genes that are involved in serine-glycine biosynthesis within the folate cycle. While folate deficiency is associated with eye defects, and components of the serine-glycine pathway have been known to cause congenital eye disease [31][32][33][34], the serine-glycine pathway has never previously been associated with the MAC spectrum disorder. Our query also uncovered three novel genes (Mthfd2, Phgdh, Slc25a1) not previously recognized as an underlying fundamental mechanistic factor in MAC spectrum disease and associated with this pathway (Additional file 1: Fig. S2). ...
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Background: Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. Results: Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. Conclusions: Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.
... It takes participation in several functions like biosynthesis of amino acids, nucleotides, neurotransmitters, and certain vitamins. So, it is required at all age health group (Sijilmassi, 2019) [55] . Three chemical structures together make folic acid are (1) pteridine ring (2) p-aminobenzoic acid (PABA) and (3) glutamic acid. ...
... It takes participation in several functions like biosynthesis of amino acids, nucleotides, neurotransmitters, and certain vitamins. So, it is required at all age health group (Sijilmassi, 2019) [55] . Three chemical structures together make folic acid are (1) pteridine ring (2) p-aminobenzoic acid (PABA) and (3) glutamic acid. ...