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Nutrients May 2024Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have...
BACKGROUND
Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension.
OBJECTIVE
The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City.
RESULTS
In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age.
CONCLUSIONS
Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.
Topics: Humans; Female; Zinc; Adolescent; Pregnancy; Folic Acid; Gestational Weight Gain; Erythrocytes; Birth Weight; Infant, Newborn; Mexico; Infant, Small for Gestational Age; Pregnancy in Adolescence
PubMed: 38892565
DOI: 10.3390/nu16111632 -
Nutrients May 2024Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Methylfolate, Pyridoxal-5'-Phosphate, and Methylcobalamin (Soloways) Supplementation on Homocysteine and Low-Density Lipoprotein Cholesterol Levels in Patients with Methylenetetrahydrofolate Reductase, Methionine Synthase, and Methionine Synthase Reductase Polymorphisms: A Randomized...
Exploring the link between genetic polymorphisms in folate metabolism genes (MTHFR, MTR, and MTRR) and cardiovascular disease (CVD), this study evaluates the effect of B vitamin supplements (methylfolate, pyridoxal-5'-phosphate, and methylcobalamin) on homocysteine and lipid levels, potentially guiding personalized CVD risk management. In a randomized, double-blind, placebo-controlled trial, 54 patients aged 40-75 with elevated homocysteine and moderate LDL-C levels were divided based on MTHFR, MTR, and MTRR genetic polymorphisms. Over six months, they received either a combination of methylfolate, P5P, and methylcobalamin, or a placebo. At the 6 months follow-up, the treatment group demonstrated a significant reduction in homocysteine levels by 30.0% (95% CI: -39.7% to -20.3%) and LDL-C by 7.5% (95% CI: -10.3% to -4.7%), compared to the placebo ( < 0.01 for all). In the subgroup analysis, Homozygous Minor Allele Carriers showed a more significant reduction in homocysteine levels (48.3%, 95% CI: -62.3% to -34.3%, < 0.01) compared to mixed allele carriers (18.6%, 95% CI: -25.6% to -11.6%, < 0.01), with a notable intergroup difference (29.7%, 95% CI: -50.7% to -8.7%, < 0.01). LDL-C levels decreased by 11.8% in homozygous carriers (95% CI: -15.8% to -7.8%, < 0.01) and 4.8% in mixed allele carriers (95% CI: -6.8% to -2.8%, < 0.01), with a significant between-group difference (7.0%, 95% CI: -13.0% to -1.0%, < 0.01). Methylfolate, P5P, and methylcobalamin supplementation tailored to genetic profiles effectively reduced homocysteine and LDL-C levels in patients with specific MTHFR, MTR, and MTRR polymorphisms, particularly with homozygous minor allele polymorphisms.
Topics: Humans; Middle Aged; Homocysteine; Female; Male; Dietary Supplements; Methylenetetrahydrofolate Reductase (NADPH2); Double-Blind Method; 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Cholesterol, LDL; Aged; Vitamin B 12; Pyridoxal Phosphate; Adult; Ferredoxin-NADP Reductase; Tetrahydrofolates; Polymorphism, Genetic; Vitamin B Complex
PubMed: 38892484
DOI: 10.3390/nu16111550 -
International Journal of Molecular... May 2024Tumor recurrence and drug resistance are responsible for poor prognosis in colorectal cancer (CRC). DNA mismatch repair (MMR) deficiency or elevated interleukin-8 (IL-8)...
Tumor recurrence and drug resistance are responsible for poor prognosis in colorectal cancer (CRC). DNA mismatch repair (MMR) deficiency or elevated interleukin-8 (IL-8) levels are characteristics of CRCs, which have been independently correlated with treatment resistance to common therapies. We recently demonstrated significantly impaired therapeutical response and increased IL-8 release of CRC cell lines with reduced expression of MMR protein MLH1 as well as cytoskeletal non-erythrocytic spectrin alpha II (SPTAN1). In the present study, decreased intratumoral MLH1 and SPTAN1 expression in CRCs could be significantly correlated with enhanced serum IL-8. Furthermore, using stably reduced SPTAN1-expressing SW480, SW620 or HT-29 cell lines, the RASmediated RAFMEKERK pathway was analyzed. Here, a close connection between low SPTAN1 expression, increased IL-8 secretion, enhanced extracellular-signal-regulated kinase (ERK) phosphorylation and a mesenchymal phenotype were detected. The inhibition of ERK by U0126 led to a significant reduction in IL-8 secretion, and the combination therapy of U0126 with FOLFOX optimizes the response of corresponding cancer cell lines. Therefore, we hypothesize that the combination therapy of FOLFOX and U0126 may have great potential to improve drug efficacy on this subgroup of CRCs, showing decreased MLH1 and SPTAN1 accompanied with high serum IL-8 in affected patients.
Topics: Humans; Colorectal Neoplasms; Interleukin-8; Fluorouracil; Butadienes; Nitriles; Cell Line, Tumor; Organoplatinum Compounds; Leucovorin; Antineoplastic Combined Chemotherapy Protocols; Female; Male; Extracellular Signal-Regulated MAP Kinases; HT29 Cells; MAP Kinase Signaling System; MutL Protein Homolog 1; Middle Aged; Aged; Gene Expression Regulation, Neoplastic; Phosphorylation
PubMed: 38891846
DOI: 10.3390/ijms25115658 -
International Journal of Molecular... May 2024FOLFOXIRI chemotherapy is a first-line therapy for advanced or metastatic colorectal cancer (CRC), yet its therapeutic efficacy remains limited. Immunostimulatory...
FOLFOXIRI chemotherapy is a first-line therapy for advanced or metastatic colorectal cancer (CRC), yet its therapeutic efficacy remains limited. Immunostimulatory therapies like oncolytic viruses can complement chemotherapies by fostering the infiltration of the tumor by immune cells and enhancing drug cytotoxicity. In this study, we explored the effect of combining the FOLFOXIRI chemotherapeutic agents with the oncolytic coxsackievirus B3 (CVB3) PD-H in the CRC cell line Colo320. Additionally, we examined the impact of the drugs on the expression of microRNAs (miRs), which could be used to increase the safety of oncolytic CVB3 containing corresponding miR target sites (miR-TS). The measurement of cytotoxic activity using the Chou-Talalay combination index approach revealed that PD-H synergistically enhanced the cytotoxic activity of oxaliplatin (OX), 5-fluorouracil (5-FU) and SN-38. PD-H replication was not affected by OX and SN-38 but inhibited by high concentrations of 5-FU. MiR expression levels were not or only slightly elevated by the drugs or with drug/PD-H combinations on Colo320 cells. Moreover, the drug treatment did not increase the mutation rate of the miR-TS inserted into the PD-H genome. The results demonstrate that the combination of FOLFOXIRI drugs and PD-H may be a promising approach to enhance the therapeutic effect of FOLFOXIRI therapy in CRC.
Topics: Humans; Colorectal Neoplasms; Cell Line, Tumor; Fluorouracil; Oncolytic Virotherapy; MicroRNAs; Oncolytic Viruses; Antineoplastic Combined Chemotherapy Protocols; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Enterovirus B, Human; Combined Modality Therapy; Irinotecan
PubMed: 38891807
DOI: 10.3390/ijms25115618 -
Journal of Cancer Research and Clinical... Jun 2024Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, often arising from hepatitis induced by the hepatitis B virus (HBV) in China. However, effective...
PURPOSE
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor, often arising from hepatitis induced by the hepatitis B virus (HBV) in China. However, effective biomarkers for early diagnosis are lacking, leading to a 5-year overall survival rate of less than 20% among patients with advanced HCC. This study aims to identify serum biomarkers for early HCC diagnosis to enhance patient survival rates.
METHODS
We established an independent cohort comprising 27 healthy individuals, 13 patients with HBV-induced cirrhosis, 13 patients with hepatitis B-type HCC, and 8 patients who progressed from cirrhosis to hepatocellular carcinoma during follow-up. Serum metabolic abnormalities during the progression from cirrhosis to HCC were studied using untargeted metabolomics. Liquid chromatography-mass spectrometry-based metabolomics methods characterized the subjects' serum metabolic profiles. Partial least squares discriminant analysis (PLS-DA) was employed to elucidate metabolic profile changes during the progression from cirrhosis to HCC. Differentially expressed metabolites (DEMs) between cirrhosis and HCC groups were identified using the LIMMA package in the R language. Two machine learning algorithms, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest Classifier (RF), were used to identify key metabolic biomarkers involved in the progression from cirrhosis to HCC. Key metabolic biomarkers were further validated using targeted metabolomics in a new independent validation cohort comprising 25 healthy individuals and 25 patients with early-stage hepatocellular carcinoma.
RESULTS
A total of 155 serum metabolites were identified, of which 21/54 metabolites exhibited significant changes in HCC patients compared with cirrhosis patients and healthy individuals, respectively. PLS-DA clustering results demonstrated a significant change trend in the serum metabolic profile of patients with HBV-induced cirrhosis during the progression to HCC. Utilizing LASSO regression and RF algorithms, we confirmed 10 key metabolic biomarkers. Notably, 1-Methylnicotinamide (1-MNAM) exhibited a persistent and significant decrease in healthy individuals, cirrhosis, and HCC patients. Moreover, 1-MNAM levels in developing patients were significantly higher during the cirrhosis stage than in the HCC stage. Targeted metabolomic validation in an external cohort further confirmed the good diagnostic performance of 1-MNAM in early HCC detection.
CONCLUSION
Our findings imply that 1-MNAM may be a specific biomarker for the progression of cirrhosis to HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Liver Cirrhosis; Disease Progression; Male; Biomarkers, Tumor; Female; Middle Aged; Niacinamide; Adult; Metabolomics; Cohort Studies; Aged
PubMed: 38890166
DOI: 10.1007/s00432-024-05848-6 -
Cancer Medicine Jun 2024Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to...
BACKGROUND
Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies.
METHODS
In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics.
RESULTS
By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively).
CONCLUSIONS
Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.
Topics: Humans; Male; Female; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Aged; Colorectal Neoplasms; Fluorouracil; Immune Checkpoint Inhibitors; Pilot Projects; Bevacizumab; Antibodies, Monoclonal, Humanized; Leucovorin; DNA Mismatch Repair; Adult; Microsatellite Instability; Oxaliplatin; Neoadjuvant Therapy; Tumor Microenvironment; Organoplatinum Compounds; Programmed Cell Death 1 Receptor; Treatment Outcome
PubMed: 38888366
DOI: 10.1002/cam4.7224 -
BMC Gastroenterology Jun 2024Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD...
BACKGROUND
Inflammatory bowel disease (IBD), a chronic inflammatory condition, is caused by several factors involving aberrant immune responses. Genetic factors are crucial in IBD occurrence. Mendelian randomization (MR) can offer a new perspective in understanding IBD's genetic background.
METHODS
Single nucleotide polymorphisms (SNPs) were considered instrumental variables (IVs). We analyzed the relationship between 731 immunophenotypes, 1,400 metabolite phenotypes, and IBD. The total effect was decomposed into indirect and direct effects, and the ratio of the indirect effect to the total effect was calculated.
RESULTS
We identified the causal effects of HLA-DR-expressing CD14 + monocytes on IBD through MR analysis. The phenotype "HLA-DR expression on CD14 + monocytes" showed the strongest association among the selected 48 immune phenotypes. Chiro-inositol metabolites mediated the effect of CD14 + monocytes expressing HLA-DR on IBD. An increase in Chiro-inositol metabolites was associated with a reduced risk of IBD occurrence, accounting for 4.97%.
CONCLUSION
Our findings revealed a new pathway by which HLA-DR-expressing CD14 + monocytes indirectly reduced the risk of IBD occurrence by increasing the levels of Chiro-inositol metabolites. The results provided a new perspective on the immunoregulatory mechanisms underlying IBD, laying a theoretical foundation for developing new therapeutic targets in the future.
Topics: Humans; Monocytes; Lipopolysaccharide Receptors; Inflammatory Bowel Diseases; HLA-DR Antigens; Polymorphism, Single Nucleotide; Inositol; Mendelian Randomization Analysis; Phenotype; Immunophenotyping; Female; Male
PubMed: 38886630
DOI: 10.1186/s12876-024-03271-2 -
Scientific Reports Jun 2024Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and...
Crocin is a carotenoid compound in saffron with anti-cancer properties. However, its therapeutic application is limited by its low absorption, bioavailability, and stability, which can be overcome through nanocarrier delivery systems. This study used surface-modified Nano-crystalline cellulose (NCC) to deliver crocin to cancer cells. NCC modified with CTAB were loaded with crocin and then conjugated with folic acid (NCF-CR-NPs). The synthesized nanoparticles (NPs) were characterized using FTIR, XRD, DLS, and FESEM. The crystallinity index of NCC was 66.64%, higher than microcrystalline cellulose (61.4%). The crocin loading and encapsulation efficiency in NCF-CR-NPs were evaluated. Toxicity testing by MTT assay showed that NCF-CR-NPs had higher toxicity against various cancer cell lines, including colon cancer HT-29 cells (IC50 ~ 11.6 μg/ml), compared to free crocin. Fluorescent staining, flow cytometry, and molecular analysis confirmed that NCF-CR-NPs induced apoptosis in HT-29 cells by increasing p53 and caspase 8 expression. The antioxidant capacity of NCF-CR-NPs was also evaluated using ABTS and DPPH radical scavenging assays. NCF-CR-NPs exhibited high free radical scavenging ability, with an IC50 of ~ 46.5 μg/ml for ABTS. In conclusion, this study demonstrates the potential of NCF-CR-NPs to deliver crocin to cancer cells effectively. The NPs exhibited enhanced anti-cancer and antioxidant activities compared to free crocin, making them a promising nanocarrier system for crocin-based cancer therapy.
Topics: Carotenoids; Folic Acid; Humans; Cellulose; Nanoparticles; Apoptosis; Antineoplastic Agents; HT29 Cells; Drug Carriers; Antioxidants; Cell Line, Tumor; Drug Delivery Systems; Cell Survival
PubMed: 38886450
DOI: 10.1038/s41598-024-64758-2 -
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