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Frontiers in Immunology 2024SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to...
BACKGROUND
SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.
METHODS
We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.
RESULTS
Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.
CONCLUSION
Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.
Topics: Humans; Toll-Like Receptor 4; Lupus Erythematosus, Systemic; Monocytes; Transcobalamins; Cell Proliferation; Female; Folic Acid; Male; Adult; Inflammation; Middle Aged; THP-1 Cells; Carbon; Vitamin B 12; Case-Control Studies
PubMed: 38881906
DOI: 10.3389/fimmu.2024.1339680 -
Medicine Jun 2024Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study Observational Study
BACKGROUND
Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea.
METHODS
The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point.
RESULTS
At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DA + DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DA + DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks.
CONCLUSION
Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.
Topics: Humans; Donepezil; Male; Female; Aged; Double-Blind Method; Drug Therapy, Combination; Glycerylphosphorylcholine; Nootropic Agents; Ginkgo biloba; Indans; Alzheimer Disease; Piperidines; Plant Extracts; Republic of Korea; Acetylcarnitine; Cognitive Dysfunction; Mental Status and Dementia Tests; Treatment Outcome; Aged, 80 and over; Cognition; Ginkgo Extract
PubMed: 38875437
DOI: 10.1097/MD.0000000000038067 -
PloS One 2024Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far,...
BACKGROUND
Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab.
PATIENTS AND METHODS
15 German and Austrian centers prospectively recruited 50 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM).
RESULTS
Using random forests, we developed a predictive machine learning model that discriminated between the situations of "no progress within 100 days before radiological progress" and "progress within 100 days before radiological progress". We could further identify a combination of ten out of the 102 CAF markers, which fulfilled this task with 78.2% accuracy, 71.8% sensitivity, and 82.5% specificity.
CONCLUSIONS
We identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Leucovorin; Antineoplastic Combined Chemotherapy Protocols; Female; Organoplatinum Compounds; Male; Fluorouracil; Middle Aged; Aged; Drug Resistance, Neoplasm; Prospective Studies; Adult; Neoplasm Metastasis; Biomarkers, Tumor
PubMed: 38875244
DOI: 10.1371/journal.pone.0304324 -
Nature Communications Jun 2024People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces... (Randomized Controlled Trial)
Randomized Controlled Trial
People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. -10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed.
Topics: Humans; Peripheral Arterial Disease; Niacinamide; Male; Female; Aged; Pyridinium Compounds; Double-Blind Method; Resveratrol; Middle Aged; Walking; Treatment Outcome; Oxidative Stress
PubMed: 38871717
DOI: 10.1038/s41467-024-49092-5 -
Scientific Reports Jun 2024Thiamin is a vital nutrient that acts as a cofactor for several enzymes primarily localized in the mitochondria. These thiamin-dependent enzymes are involved in energy...
Thiamin is a vital nutrient that acts as a cofactor for several enzymes primarily localized in the mitochondria. These thiamin-dependent enzymes are involved in energy metabolism, nucleic acid biosynthesis, and antioxidant machinery. The enzyme HMP-P kinase/thiamin monophosphate synthase (TH1) holds a key position in thiamin biosynthesis, being responsible for the phosphorylation of HMP-P into HMP-PP and for the condensation of HMP-PP and HET-P to form TMP. Through mathematical kinetic model, we have identified TH1 as a critical player for thiamin biofortification in rice. We further focused on the functional characterization of OsTH1. Sequence and gene expression analysis, along with phylogenetic studies, provided insights into OsTH1 bifunctional features and evolution. The indispensable role of OsTH1 in thiamin biosynthesis was validated by heterologous expression of OsTH1 and successful complementation of yeast knock-out mutants impaired in thiamin production. We also proved that the sole OsTH1 overexpression in rice callus significantly improves B1 concentration, resulting in 50% increase in thiamin accumulation. Our study underscores the critical role of OsTH1 in thiamin biosynthesis, shedding light on its bifunctional nature and evolutionary significance. The significant enhancement of thiamin accumulation in rice callus upon OsTH1 overexpression constitutes evidence of its potential application in biofortification strategies.
Topics: Oryza; Thiamine; Plant Proteins; Phylogeny; Gene Expression Regulation, Plant
PubMed: 38866808
DOI: 10.1038/s41598-024-62326-2 -
Journal of Cellular and Molecular... Jun 2024Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded...
Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.
Topics: Female; Paclitaxel; Micelles; Albendazole; Ovarian Neoplasms; Humans; Animals; Cell Line, Tumor; Drug Carriers; Polyethylene Glycols; Vitamin E; Folic Acid; Mice; Drug Liberation; Particle Size; Polyvinyls; Polymers; Xenograft Model Antitumor Assays
PubMed: 38864691
DOI: 10.1111/jcmm.18389 -
Scientific Reports Jun 2024Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to...
Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to counter iron deficiency anemia and neural tube anomalies. Although Iron Folic Acid supplementation is integral to Ethiopian antenatal care, one in four women in Ethiopia experiences anemia during pregnancy suggesting poor compliance. This study aimed to investigate compliance level and associated factors of Iron Folic Acid supplementation among pregnant women attending antenatal care in Wuchale Woreda of North Shoa Zone, Ethiopia. An institutional-based cross-sectional study was conducted among 302 pregnant women from March 20 to April 5, 2021, who were selected using a systematic random sampling technique. Data were collected through face-to-face interview, entered epi-data, and exported to Statistical Package for the Social Sciences for analysis. A multivariable logistic regression was used to identify factors associated with compliance level. All the results were presented with 95% confidence intervals. The compliance with Iron Folic Acid supplementation was 47.0%. Residing nearest to the health facility (AOR = 2.46; 95% CI 1.32, 4.57), initiating antenatal care at health center (AOR = 2.23; 95% CI 1.17, 4.51), having a family size of 4 and above (AOR = 4.99; 95% CI 2.43, 10.24), and receiving information from health extension workers (AOR = 5.52; 95% CI 1.30, 23.54) increased compliance with Iron Folic Acid supplementation. Less than half of the pregnant women were compliant with Iron Folic Acid utilization. There is a need to prioritize promoting the importance of Iron Folic Acid supplementation through health education particularly by targeting pregnant women with identified factors.
Topics: Humans; Female; Folic Acid; Pregnancy; Ethiopia; Adult; Dietary Supplements; Cross-Sectional Studies; Iron; Prenatal Care; Anemia, Iron-Deficiency; Young Adult; Adolescent; Pregnant Women; Patient Compliance
PubMed: 38862566
DOI: 10.1038/s41598-024-63111-x -
BMJ Open Jun 2024This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and... (Meta-Analysis)
Meta-Analysis
Weekly iron-folic acid supplementation and its impact on children and adolescents iron status, mental health and school performance: a systematic review and meta-analysis in sub-Saharan Africa.
OBJECTIVE
This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and educational outcomes of children and adolescents in sub-Saharan Africa.
DESIGN
A systematic review and meta-analysis was used.
DATA SOURCES
Five databases, namely, MEDLINE, Scopus, Web of Science, Cochrane Library and Google Scholar, were systematically searched for relevant articles up to 23 August 2023.
ELIGIBILITY CRITERIA
It was focused on randomised controlled trials involving children and adolescents in sub-Saharan Africa, exploring the effects of iron supplementation on various outcomes, such as serum ferritin and haemoglobin levels, anaemia, mental health and school performance.
DATA EXTRACTION AND SYNTHESIS
The Joanna Briggs Institute Critical Appraisal tools were used for quality assessment, with two independent reviewers thoroughly evaluating each paper. Using the Cochrane risk of bias tool, we evaluated the certainty of evidence such as the risk of bias, inconsistency, indirectness, imprecision and publication bias.
RESULTS
A systematic review of 10 articles revealed that WIFAS significantly increased serum ferritin levels in adolescent girls (Hedge's g=0.53, 95% CI 0.28 to 0.78; heterogeneity I=41.21%, p<0.001) and haemoglobin levels in school-aged children (Hedge's g=0.37, 95% CI 0.01 to 0.73; heterogeneity I=91.62%, p<0.001). The analysis further demonstrated a substantial reduction in the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; heterogeneity I=28.12%, p<0.001).
CONCLUSION
WIFAS proved effective in enhancing serum ferritin and haemoglobin concentrations and lowering the risk of anaemia in school-aged children and adolescents compared with a placebo. Similarly, there are not enough studies to examine the effects of WIFAS on school performance. However, information regarding mental health problems, mortality and potential side effects remains insufficient.
PROSPERO REGISTRATION NUMBER
CRD42023397898.
Topics: Humans; Child; Adolescent; Dietary Supplements; Africa South of the Sahara; Mental Health; Iron; Folic Acid; Ferritins; Anemia, Iron-Deficiency; Hemoglobins; Randomized Controlled Trials as Topic; Female; Nutritional Status
PubMed: 38862227
DOI: 10.1136/bmjopen-2024-084033 -
Biomedical Engineering Online Jun 2024Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric...
BACKGROUND
Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis.
METHODS
In this paper, we constructed a new type of hollow nanocomposites, @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite.
RESULTS
This report demonstrates that @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future.
CONCLUSIONS
In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.
Topics: Stomach Neoplasms; Animals; Nanocomposites; Magnetic Resonance Imaging; Mice; Cell Line, Tumor; Neoplasm Metastasis; Humans; Folic Acid; Manganese Compounds; Optical Imaging; Mice, Nude; Oxides
PubMed: 38858706
DOI: 10.1186/s12938-024-01248-6 -
Annals of Medicine Dec 2024To outline the prevalence of vitamin D and vitamin B deficiencies in enuretic children.
PURPOSE
To outline the prevalence of vitamin D and vitamin B deficiencies in enuretic children.
METHODS
An analytical descriptive study was conducted on enuretic children who were followed up at the outpatient clinic for nocturnal enuresis at the Children's Hospital, Cairo University. Sociodemographic and clinical data were recorded. The levels of vitamin D and vitamin B were assessed and correlated with the severity of enuresis.
RESULTS
Two hundred and eighty-eight children were enrolled. Insufficiency of Vitamin D predominated ( = 139; 48.3%). Vitamin D deficiency was present in 31.3%, = 90 and it was normal in 20.5%, = 59). Vitamin B deficiency was observed in 25% of the studied children, = 72). The one-sample Wilcoxon signed-rank test was significant for both vitamins (P value =0.001). Vitamin D showed a stronger inverse correlation with the number of enuresis episodes per day than vitamin B (-0.680 vs. -0.219 respectively). A cut-off of 13.7 ng/ml for vitamin D was detected, below which the child was predicted to have failed dry nights. Using multivariate logistic regression, higher vitamin D levels and behavioural treatment coexistence were significant protective factors for the absence of dry nights.
CONCLUSION
Low levels of vitamin D and B were detected in children with primary nocturnal enuresis, which could be considered a burden on the clinical severity of enuresis.
Topics: Humans; Child; Male; Female; Nocturnal Enuresis; Cross-Sectional Studies; Vitamin D; Vitamin B 12; Vitamin D Deficiency; Vitamin B 12 Deficiency; Prevalence; Egypt; Child, Preschool; Adolescent
PubMed: 38857176
DOI: 10.1080/07853890.2024.2352030