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The American Journal of Clinical... Dec 2023Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD)....
BACKGROUND
Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification.
OBJECTIVE
This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA).
METHODS
Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics.
RESULTS
RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations.
CONCLUSIONS
These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact.
Topics: Adult; Child; Female; Humans; Folic Acid; Cross-Sectional Studies; Chromatography, Liquid; Tandem Mass Spectrometry; Neural Tube Defects; Diet; Nutrition Surveys; Erythrocytes; Food, Fortified
PubMed: 37839706
DOI: 10.1016/j.ajcnut.2023.10.006 -
Medicine Nov 2023Idiopathic granulomatous mastitis is a benign, inflammatory disease of breasts characterized by non-caseating granulomas. Our study aims to identify distinguishing...
Idiopathic granulomatous mastitis is a benign, inflammatory disease of breasts characterized by non-caseating granulomas. Our study aims to identify distinguishing clinical and histopathological features of relapsing disease compared to those in complete remission. We queried databases at our institution (1990-2021) to include females ≥18 years with biopsy-proven diagnosis of idiopathic granulomatous mastitis, excluding patients with breast cancer, lymphoproliferative disorders, solid organ malignancy, foreign body reaction in breast, plasma cell mastitis, and ductal ectasia. Remission was defined as a 3-month period without recurrence of symptoms or imaging findings. Relapse was defined as recurrence after 3 months of remission. Clinical and histopathological features were compared using 2-sample t tests and chi-squared tests. Of the 27 patients that met our inclusion criteria, the mean age at diagnosis was 35.8 years (± standard deviation 9.4 years) with a mean body mass index of 31.7 kg/m2 (± standard deviation 6.7 kg/m2). 11 (41%) were Hispanic, 25 (93%) had at least one previous full-term pregnancy prior to diagnosis and 8 (30%) were on oral contraceptives. Remission was seen in 18 patients (66%) and 9 (33%) had relapse. Six of these patients received steroids after antibiotics, while 5 patients received methotrexate. Three (33%) patients with relapse and 14 (77%) with remission, had abscess formation confirmed on histopathology (P = .04). Patients with remission had a higher number of abscesses on histopathology and history of oral contraceptive use was associated with more relapse. By identifying key clinical and histopathological findings in this population may guide prognosis and treatment of these patients.
Topics: Female; Humans; Granulomatous Mastitis; Neoplasm Recurrence, Local; Breast; Methotrexate; Breast Neoplasms; Chronic Disease
PubMed: 37933043
DOI: 10.1097/MD.0000000000035679 -
Frontiers in Immunology 2023Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to...
Folate receptor delta (FRδ) has been used as a biomarker for regulatory T cells (Tregs), because its expression is limited to Tregs and ovum. Although FRδ is unable to bind folate, we have used molecular docking software to identify a folate congener that binds FRδ with high affinity and have exploited this FRδ-specific ligand to target attached drugs (imaging agents, immune activators, and immune suppressors) specifically to Tregs in murine tumor xenografts. Analysis of treated tumors demonstrates that targeting of a Toll-like receptor 7 agonist inhibits Treg expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor growth and repolarization of other tumor-infiltrating immune cells to more inflammatory phenotypes. Targeting of the immunosuppressive drug dexamethasone, in contrast, promotes enhanced tumor growth and shifts the tumor-infiltrating immune cells to more anti-inflammatory phenotypes. Since Tregs comprise <1% of cells in the tumor masses examined, and since the targeted drugs are not internalized by cancer cells, these data demonstrate that Tregs exert a disproportionately large effect on tumor growth. Because the targeted drug did not bind to Tregs or other immune cells in healthy tissues, the data demonstrate that the immunosuppressive properties of Tregs in tumors can be manipulated without causing systemic toxicities associated with global reprogramming of the immune system.
Topics: Humans; Animals; Mice; T-Lymphocytes, Regulatory; Molecular Docking Simulation; Neoplasms; Transcription Factors; Immunosuppressive Agents; Folic Acid
PubMed: 37928524
DOI: 10.3389/fimmu.2023.1274199 -
Journal of the International AIDS... Sep 2023Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial.
INTRODUCTION
Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development.
METHODS
We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020.
RESULTS
A total of 229 children aged ≥6 years were included in the sub-study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up.
CONCLUSIONS
Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels.
Topics: Male; Child; Adolescent; Humans; Female; Folic Acid; Vitamin B 12; Erythrocyte Indices; HIV Infections
PubMed: 37766505
DOI: 10.1002/jia2.26174 -
Biomedicine & Pharmacotherapy =... Oct 2023Neurogenesis is a process of generating neural stem cells (NSCs) as functional neurons can be decreased after chemotherapy treatments. Methotrexate (MTX) is a folate...
Neurogenesis is a process of generating neural stem cells (NSCs) as functional neurons can be decreased after chemotherapy treatments. Methotrexate (MTX) is a folate antagonist that is used for cancer treatment but has negative effects, including oxidative stress, neuronal apoptosis and cognitive impairments. Hesperidin (Hsd), a flavonoid found in citrus fruits, has antioxidant and neuroprotection properties. This study investigated whether Hsd could attenuate impairments of hippocampal neural stem cells related to apoptosis induced by MTX. Spraque-Dawley rats (n = 24) were divided into 4 groups: (1) Vehicle group received propylene glycol (21 days) and 0.9% normal saline (day 8 and 15), (2) Hsd group received 100 mg/kg (21 days), (3) MTX group received 75 mg/kg (days 8 and 15) and (4) MTX+Hsd group received MTX, 75 mg/kg (day 8 and 15) and Hsd 100 mg/kg (21 days). Our results showed that MTX decreased hippocampal neural stem cells including SRY (sex determining region Y)-box 2 (SOX2) and nestin. MTX diminished vascular related (VR) Ki-67 positive cells in the hippocampus but not non-vascular related (NVR) Ki-67. Additionally, MTX reduced SOX2, nestin, postsynaptic density protein 95 (PSD-95) and B-cell lymphoma-2 family of proteins (Bcl-2), whereas Bax and caspase-3 were enhanced in the hippocampal tissues. Interestingly, co-treatment with Hsd and MTX revealed upregulation of SOX2, nestin and VR Ki-67 positive cells as well as elevated SOX2, nestin, PSD-95 and Bcl-2 proteins. Moreover, receiving both Hsd and MTX significantly suppressed increased Bax and caspase-3. These results confirm that Hsd can ameliorate MTX-induced impairments of hippocampal NSC proliferation and neuronal apoptosis.
Topics: Animals; Rats; Hesperidin; Methotrexate; Caspase 3; Nestin; Ki-67 Antigen; bcl-2-Associated X Protein; Apoptosis; Neural Stem Cells; Disks Large Homolog 4 Protein; Hippocampus
PubMed: 37597319
DOI: 10.1016/j.biopha.2023.115329 -
Systematic Reviews Nov 2023To determine the effectiveness and safety of photoactivated chromophore-corneal cross-linking (PACK-CXL) adjuvant in infectious keratitis by April 5, 2022. (Meta-Analysis)
Meta-Analysis Review
AIM
To determine the effectiveness and safety of photoactivated chromophore-corneal cross-linking (PACK-CXL) adjuvant in infectious keratitis by April 5, 2022.
METHODS
We searched randomized controlled trials (RCTs) comparing standard antibiotic treatment (SAT) plus PACK-CXL to SAT in infectious keratitis in Embase, MEDLINE with PubMed, Web of Science, and Cochrane Library. We independently screened and extracted data using predesigned tables. Cochrane's risk-of-bias tool was utilized to examine the quality of RCTs. A random-effects model was employed to determine the overall effect size of the meta-analyses. Grading of Recommendations, and Assessment, Development and Evaluations (GRADE) was also performed to examine the quality of evidence.
RESULTS
Seven eligible RCTs with 283 patients were acquired. Adjuvant PACK-CXL reduced the time needed to perform corneal healing in fungal keratitis (- 1.33 months; 95% CI, - 1.83 to - 0.42, I = 0%, P < 0.05) as compared to SAT alone. The risks of adverse events were not significantly different both in fungal and bacterial keratitis. Due to the substantial heterogeneity among studies, such as population, the type and severity of infectious keratitis, drug regimens of SAT, PACK-CXL protocol, and the judgment of subjective outcomes, the evidence grade was low.
CONCLUSION
Adjuvant PACK-CXL accelerates fungal keratitis healing as compared to SAT alone. But more rigorous RCTs are required to determine the clinical effectiveness and safety.
Topics: Humans; Corneal Cross-Linking; Photosensitizing Agents; Riboflavin; Collagen; Keratitis; Anti-Bacterial Agents
PubMed: 37951953
DOI: 10.1186/s13643-023-02380-5 -
Biomolecules Jul 2023RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic...
RadH is one of the flavin-dependent halogenases that has previously exhibited promising catalytic activity towards hydroxycoumarin, hydroxyisoquinoline, and phenolic derivatives. Here, we evaluated new functional homologs of RadH and expanded its specificities for the halogenation of non-tryptophan-derived, heterocyclic scaffolds. Our investigation revealed that RadH could effectively halogenate hydroxyquinoline and hydroxybenzothiophene. Assay optimization studies revealed the need to balance the various co-factor concentrations and where a GDHi co-factor recycling system most significantly improves the conversion and efficiency of the reaction. A crystal structure of RadH was also obtained with a resolution of 2.4 Å, and docking studies were conducted to pinpoint the binding and catalytic sites for substrates.
Topics: Oxidoreductases; Halogenation; Catalytic Domain; Flavins
PubMed: 37509117
DOI: 10.3390/biom13071081 -
PloS One 2023Maternal folic acid supplementation is protective against the development of neural tube defects (NTDs) in babies. However, recent public-facing communications have...
BACKGROUND
Maternal folic acid supplementation is protective against the development of neural tube defects (NTDs) in babies. However, recent public-facing communications have raised concerns about a causal relationship between folic acid supplementation, particularly after the first trimester, and ankyloglossia (tongue-tie) in infants. Non-evidence-based communications are potentially harmful because they could adversely affect adherence to folic acid supplementation, increasing NTD occurrence. This study aimed to review evidence on the relationships between maternal folic acid supplementation during preconception and/or pregnancy and the risk of ankyloglossia in infants.
METHODS
We searched the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Scopus. We searched for observational, and interventional studies, and systematic reviews investigating the effect of maternal folic acid supplementation during preconception or pregnancy on the occurrence of ankyloglossia in offspring. The search was registered on PROSPERO on 01/12/2022, ID: CRD42022375862.
RESULTS
The database searches yielded 93 articles. After removing duplicates and screening titles and abstracts, 26 remained. One article was judged relevant for inclusion in analyses; a case-control study that directly mentions the relationship between folic acid supplementation and ankyloglossia. This study reported that regular intake of folic acid supplements was higher in women with infants with ankyloglossia. However, this study has limitations regarding design, selection bias, and confounding, calling the findings into question.
CONCLUSIONS
Insufficient evidence exists for a relationship between folic acid supplementation and ankyloglossia. Currently, the benefits of folic acid supplementation far outweigh the risks. This must be clearly communicated to patients by their clinicians during preconception and antenatal care.
Topics: Female; Pregnancy; Infant; Humans; Ankyloglossia; Case-Control Studies; Folic Acid; Dietary Supplements; Neural Tube Defects; Tongue
PubMed: 37922258
DOI: 10.1371/journal.pone.0294042 -
Journal of Integrative Neuroscience Aug 2023Many studies have shown that the levels of homocysteine (Hcy), vitamin B12 (Vit B12), and folate (FA) are abnormal in patients with Parkinson's disease (PD), but the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many studies have shown that the levels of homocysteine (Hcy), vitamin B12 (Vit B12), and folate (FA) are abnormal in patients with Parkinson's disease (PD), but the results have not been consistent. Therefore, we conducted this meta-analysis to summarize the features of Hcy, Vit B12, and FA in PD patients.
METHODS
A systematic literature search was conducted on PubMed, Cochrane Library, Web of Science, and Embase databases.
RESULTS
A total of 71 studies were included. The analysis showed the following. (1) PD patients had significantly increased Hcy level (standardized mean difference [SMD] 0.80, 95% confidence interval [CI] [0.61, 0.99]; < 0.001), and decreased Vit B12 (SMD -0.33, 95% CI [-0.43, -0.22]; <0.001) and FA levels (SMD -0.13, 95% CI [-0.19, -0.06]; < 0.001) compared to healthy controls. (2) Higher Hcy level (SMD 0.48, 95% CI [0.30, 0.67]; < 0.001) was found in Dopaminergic medications treated PD patients than in untreated patients. (3) PD patients with cognitive impairment had higher Hcy level (SMD 0.71, 95% CI [0.50, 0.92]; < 0.001) and lower Vit B12 (SMD -0.22, 95% CI [-0.34, -0.09]; = 0.001) and FA levels (SMD -0.17, 95% CI [-0.29, -0.04]; = 0.009) than those with no cognitive impairment. (4) PD patients with neuropathy had significantly increased Hcy level (SMD 0.87, 95% CI [0.43, 1.31]; < 0.001) and decreased Vit B12 level (SMD -0.40, 95% CI [-0.81, -0.00]; = 0.049) compared to PD patients with no neuropathy.
CONCLUSIONS
In conclusion, PD patients may have higher Hcy levels and lower Vit B12 and FA levels than the healthy population. Thus, Hcy, Vit B12, and FA may play a role in cognitive impairment and neuropathy in PD patients.
Topics: Humans; Vitamin B 12; Parkinson Disease; Cognitive Dysfunction; Folic Acid; Homocysteine
PubMed: 37735121
DOI: 10.31083/j.jin2205115 -
Nutrients Mar 2024Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis.... (Review)
Review
Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.
Topics: Animals; Mice; Humans; Dietary Supplements; Folic Acid; Neural Tube Defects; Family; Drug-Related Side Effects and Adverse Reactions
PubMed: 38474883
DOI: 10.3390/nu16050755