Effects of maternal folic acid supplementation during pregnancy on infant neurodevelopment at 1 month of age: a birth cohort study in China.

PURPOSE: This study aimed to explore effects of maternal folic acid (FA) supplementation during pregnancy on neurodevelopment in 1-month-old infants and to determine whether effects may be related to maternal circulating inflammatory cytokine concentrations. METHODS: This birth cohort study recruited 1186 mother-infant pairs in Tianjin, China, between July 2015 and July 2017. The women completed interviewer-administered questionnaires on their lifestyles and FA supplementation during pregnancy. Neurodevelopment was assessed in 1-month-old infants using a standard neuropsychological examination table. In 192 women, serum homocysteine (Hcy) and inflammatory cytokine concentrations were measured at 16-18 weeks of gestation. RESULTS: The infants whose mothers took FA supplements during pregnancy had a significantly higher development quotient (DQ) compared with those whose mothers were non-users (P < 0.05). After adjustment for maternal characteristics, supplementary FA use for 1-3 months, 3-6 months, and > 6 months were associated with the increases of 7.7, 11.0, and 7.4 units in the scale of infant DQ score compared with women reporting no supplement use, respectively (P < 0.05). FA supplementation was associated with a decreased serum concentration of Hcy (ß = [Formula: see text] 0.19), which was correlated with women's serum inflammatory cytokine concentrations at 16-18 weeks of gestation (ß = 0.57). Serum inflammatory cytokine concentrations were inversely related to DQ score in the 1-months-old offspring (ß = [Formula: see text] 0.22). CONCLUSIONS: Maternal FA supplementation during pregnancy favors neurodevelopment in the offspring at 1-month-old. This association may be mediated by changes in serum Hcy and inflammatory cytokine concentrations throughout pregnancy.

The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells.

EZR, a member of the ezrin-radixin-moesin (ERM) family, is involved in multiple aspects of cell migration and cancer. SMYD3, a histone H3-lysine 4 (H3-K4)-specific methyltransferase, regulates EZR gene transcription, but the molecular mechanisms of epigenetic regulation remain ill-defined. Here, we show that antisense lncRNA EZR-AS1 was positively correlated with EZR expression in both human esophageal squamous cell carcinoma (ESCC) tissues and cell lines. Both in vivo and in vitro studies revealed that EZR-AS1 promoted cell migration through up-regulation of EZR expression. Mechanistically, antisense lncRNA EZR-AS1 formed a complex with RNA polymerase II to activate the transcription of EZR. Moreover, EZR-AS1 could recruit SMYD3 to a binding site, present in a GC-rich region downstream of the EZR promoter, causing the binding of SMYD3 and local enrichment of H3K4me3. Finally, the interaction of EZR-AS1 with SMYD3 further enhanced EZR transcription and expression. Our findings suggest that antisense lncRNA EZR-AS1, as a member of an RNA polymerase complex and through enhanced SMYD3-dependent H3K4 methylation, plays an important role in enhancing transcription of the EZR gene to promote the mobility and invasiveness of human cancer cells.

A three-lncRNA signature predicts overall survival and disease-free survival in patients with esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence shows that dysregulated long non-coding RNAs (lncRNAs) can serve as potential biomarkers for cancer prognosis. However, lncRNA signatures, as potential prognostic biomarkers for esophageal squamous cell carcinoma (ESCC), have been seldom reported. METHODS: Based on our previous transcriptome RNA sequencing analysis from 15 paired ESCC tissues and adjacent normal tissues, we selected 10 lncRNAs with high score rank and characterized the expression of those lncRNAs, by qRT-PCR, in 138 ESCC and paired adjacent normal samples. These 138 patients were divided randomly into training (n = 77) and test (n = 59) groups. A prognostic signature of lncRNAs was identified in the training group and validated in the test group and in an independent cohort (n = 119). Multivariable Cox regression analysis evaluated the independence of the signature in overall survival (OS) and disease-free survival (DFS) prediction. GO and KEGG pathway analysis, combined with cell transwell and proliferation assays, are applied to explore the function of the three lncRNAs. RESULTS: A novel three-lncRNA signature, comprised of RP11-366H4.1.1 (ENSG00000248370), LINC00460 (ENSG00000233532) and AC093850.2 (ENSG00000230838), was identified. The signature classified patients into high-risk and low-risk groups with different overall survival (OS) and disease-free survival (DFS). For the training group, median OS: 23.1 months vs. 39.1 months, P < 0.001; median DFS: 15.2 months vs. 33.3 months, P < 0.001. For the test group, median OS: 23 months vs. 59 months, P < 0.001; median DFS: 16.4 months vs. 50.8 months, P < 0.001. For the independent cohort, median OS: 22.4 months vs. 60.4 months, P < 0.001). The signature indicates that patients in the high-risk group show poor OS and DFS, whereas patients with a low-risk group show significantly better outcome. The independence of the signature was validated by multivariable Cox regression analysis. GO and KEGG pathway analysis for 588 protein-coding genes-associated with the three lncRNAs indicated that the three lncRNAs were involved in tumorigenesis. In vitro assays further demonstrated that the three lncRNAs promoted the migration and proliferation of ESCC cells. CONCLUSIONS: The three-lncRNA signature is a novel and potential predictor of OS and DFS for patients with ESCC.

Inhibitory effect of homocysteine on rat neural stem cell growth in vitro is associated with reduced protein levels and enzymatic activities of aconitase and respiratory complex III.

Increased blood plasma concentration of the sulphur amino acid homocysteine (Hcy) is considered as an independent risk factor of the neurodegenerative diseases. However, the detailed molecular mechanisms by which Hcy leads to neurotoxicity have yet to be clarified. Recent research has suggested that neurotoxicity of Hcy may involve negative regulation of neural stem cell (NSC) proliferation. In the current study, primary NSCs were isolated from neonatal rat brain hippocampus and the inhibition in cell growth was observed after exposure to l50 µM and 500 µM L-Hcy. The changes in protein expression were monitored with densitometric 2D-gel electrophoresis coupled with MALDI-TOF mass spectrometry. Proteomic analysis revealed that the expression levels of two mitochondrial proteins, cytochrome bc1 complex2 (UQCRC2, the major component of electron transport chain complex III) and aconitase (an enzyme involved in the tricarboxylic acid cycle), were decreased in Hcy treatment group, compared to control group. Protein expression was further verified by Western blot, and their enzymatic activities were also down-regulated in NSCs after Hcy treatment. Restoration of aconitase and UQCRC2 protein levels using their expression vectors could partly rescue the cell viability inhibition caused by Hcy. Moreover, Hcy caused the increase in the intracellular levels of reactive oxygen species (ROS) and the decrease in ATP content, which are known to play important roles in the cellular stress response of the cell growth. Altogether, the results suggest that the decreased expression and enzymatic activities of the mitochondrial proteins may be possible causes of the overproduction of ROS and depletion of ATP. The inhibition in cell growth at the end of Hcy treatment was probably due to the changes in protein expression and mitochondrial dysfunction in vitro cultures of NSCs.

Effectiveness of Antibiotic Use Management in Tianjin (2011-2013): A Quasi-Experimental Study.

BACKGROUND In this study we investigated changes in the status of antibiotic use in Tianjin since the implementation of the Antibiotic Stewardship Program (ASP) (2011-2013), as well as existing problems, strategies, and outcomes to promote rational clinical antibiotic use. MATERIAL AND METHODS A quasi-experimental study was performed to investigate situations of antibiotic use in secondary and tertiary general hospitals in Tianjin from April 2011 to 2013. Five major indicators were analyzed: percentage of antibiotic use in inpatient cases (%), antibacterial use density (AUD), proportion of prophylactic antibiotic application for type I surgical incision, compliance rate of medication administration 0.5-2.0 h before such procedures, and antibiotic prophylaxis for ≤24 h in patients receiving these surgeries. RESULTS There was a decrease in the percentage of antibiotic use across general hospitals (60.38% to 46.88%), in AUD (51.60% to 35.37%), and in the proportion of prophylactic antibiotic applications for type I incisions (86.67% to 25.08%). For patients undergoing these procedures, there was an increased compliance rate of medication administration of 0.5-2.0 h prior to surgery (86.38% to 100%), and of antibiotic prophylactic use for ≤24 h (40.30% to 96.37%). CONCLUSIONS Implementation of the ASP campaign has reduced irrational antibiotic use, promoted rational antibiotic use, and delayed antibiotic resistance.

Periconceptional Folic Acid Supplementation in Chinese Women: A Cross-sectional Study.

OBJECTIVE: To investigate the status of folic acid (FA) supplementation and determinants of its use in pregnant Chinese women. METHODS: In this cross-sectional study, questionnaires were used to collect information of participants and FA supplementation. Women were recruited between 6 and 12 weeks postpartum in Tianjin, China, between July 2015 and July 2016. RESULTS: A total of 1,921 women were recruited in the study. Approximately 93.1% of the study participants used FA, while 14.4% of the women taking FA from three months prior to preconception to three months post-conception. Women who took FA for three months prior to preconception through at least three months into their pregnancy were more likely to be between 30 and 34 years old (OR = 2.91, 95% CI: 1.15, 7.33), employed (OR = 2.07, 95% CI: 1.17, 3.67), primigravida (OR = 5.20, 95% CI: 3.02, 8.96), married to spouses with an intermediate education level (OR = 2.92, 95% CI: 1.45, 5.89), and earn a high family income (OR = 3.19, 95% CI: 1.57, 6.49). CONCLUSION: The prevalence of periconceptional FA intake was far below the requirements of the National Health and Family Planning Commission of China; therefore, knowledge of FA supplementation should be strengthened among women who are or planning to become pregnant.

circular RNA circ-231 promotes protein biogenesis of TPI1 and PRDX6 through mediating the interaction of eIF4A3 with STAU1 to facilitate unwinding of secondary structure in 5' UTR, enhancing progression of human esophageal squamous cell carcinoma (ESCC).

Background: The nuclear cap-binding complex (CBC)-dependent translation (CT) is an important initial translation pathway for 5'-cap-dependent translation in normal mammal cells. Eukaryotic translation initiation factor 4A-III (eIF4A3), as an RNA helicase, is recruited to CT complex and enhances CT efficiency through participating in unwinding of secondary structure in the 5' UTR. However, the detailed mechanism for eIF4A3 implicated in unwinding of secondary structure in the 5' UTR in normal mammal cells is still unclear. Specially, we need to investigate whether the kind of mechanism in normal mammal cells extrapolates to cancer cells, e.g. ESCC, and further interrogate whether and how the mechanism triggers malignant phenotype of ESCC, which are important for identifying a potential therapeutic target for patients with ESCC. Methods: Bioinformatics analysis, RNA immunoprecipitation and RNA pulldown assays were performed to detect the interaction of circular RNA circ-231 with eIF4A3. In vitro and in vivo assays were performed to detect biological roles of circ-231 in ESCC. RNA immunoprecipitation, RNA pulldown, mass spectrometry analysis and co-immunoprecipitation assays were used to measure the interaction of circ-231, eIF4A3 and STAU1 in HEK293T and ESCC. In vitro EGFP reporter and 5' UTR of mRNA pulldown assays were performed to probe for the binding of circ-231, eIF4A3 and STAU1 to secondary structure of 5' UTR. Results: RNA immunoprecipitation assays showed that circ-231 interacted with eIF4A3 in HEK293T and ESCC. Further study confirmed that circ-231 orchestrated with eIF4A3 to control protein expression of TPI1 and PRDX6, but not for mRNA transcripts. The in-depth mechanism study uncovered that both circ-231 and eIF4A3 were involved in unwinding of secondary structure in 5' UTR of TPI1 and PRDX6. More importantly, circ-231 promoted the interaction between eIF4A3 and STAU1. Intriguingly, both circ-231 and eIF4A3 were dependent on STAU1 binding to secondary structure in 5' UTR. Biological function assays revealed that circ-231 promoted the migration and proliferation of ESCC via TPI1 and PRDX6. In ESCC, the up-regulated expression of circ-231 was observed and patients with ESCC characterized by higher expression of circ-231 have concurrent lymph node metastasis, compared with control. Conclusions: Our data unravels the detailed mechanism by which STAU1 binds to secondary structure in 5' UTR of mRNAs and recruits eIF4A3 through interacting with circ-231 and thereby eIF4A3 is implicated in unwinding of secondary structure, which is common to HEK293T and ESCC. However, importantly, our data reveals that circ-231 promotes migration and proliferation of ESCC and the up-regulated circ-231 greatly correlates with tumor lymph node metastasis, insinuating that circ-231 could be a therapeutic target and an indicator of risk of lymph node metastasis for patients with ESCC.

Establishment and validation of novel nomograms to predict muscle quality in colorectal cancer patients.

OBJECTIVES: The skeletal muscle mass index and skeletal muscle radiodensity have promise as specific diagnostic indicators for muscle quality. However, the difficulties in measuring low skeletal muscle mass index and low skeletal muscle radiodensity limit their use in routine clinical practice, impeding early screening and diagnosis. The objective of this study is to develop a nomogram that incorporates preoperative factors for predicting low skeletal muscle mass index and low skeletal muscle radiodensity. METHODS: A total of 1692 colorectal cancer patients between 2015 and 2021 were included. The patients were randomly divided into a training cohort (n = 1353) and a validation cohort (n = 339). Nomogram models were calibrated using the area under the curve, calibration curves, and the Hosmer-Lemeshow test to assess their predictive ability. Finally, a decision curve was applied to assess the clinical usefulness. RESULTS: In a prediction model for low skeletal muscle mass index, age, body mass index, and grip strength were incorporated as variables. For low skeletal muscle radiodensity, age, sex, body mass index, serum hemoglobin level, and grip strength were included as predictors. In the training cohort, the area under the curve value for low skeletal muscle mass index was 0.750 (95% CI, 0.726-0.773), whereas for low skeletal muscle radiodensity, it was 0.763 (95% CI, 0.739-0.785). The Hosmer-Lemeshow test confirmed that both models fit well in both cohorts. Decision curve analysis was applied to assess the clinical usefulness of the model. CONCLUSIONS: The incorporation of preoperative factors into the nomogram-based prediction model represents a significant advancement in the muscle quality assessment. Its implementation has the potential to early screen patients at risk of low skeletal muscle mass index and low skeletal muscle radiodensity.

Physical exercise frequency and cognition: a multicenter cross-sectional cohort study.

Background and aims: Dementia imposes a heavy burden on society and families, therefore, effective drug treatments, exploring and preventing factors associated with dementia, are paramount. To provide reference points for the best frequency of physical exercise (physical exercise), we investigated the association between frequency of PE and cognition in Chinese old adults. Methods: 16,181 Chinese participants aged 65 years or older were included in this study. Associations between PE and cognition were estimated multivariate logistic and linear regression analyses. Associations were further investigated across dementia subtypes (Alzheimer dementia, vascular dementia, and other types of dementia). Subgroup analyses were performed in different age groups, in populations with and without stroke, and those with and without hypertension. Results: PE associated with dementia after adjusting for full covariates (OR: 0.5414, 95% CI: 0.4536-0.6491, p < 0.001). Exercise performed at ≥3 times/week associated with lower risk of dementia (OR: 0.4794-0.6619, all p value <0.001). PE was associated with improved cognition (ß: 12851, p < 0.001), and any PE frequency contributed to cognitive improvement (p values for exercise performed ≥1 time/week were <0.001). Similar conclusions were identified when we repeated analyses in different dementia subtypes and age groups. Subgroup analyses suggested that the cognition of individuals without hypertension also benefitted from exercising 1-2 times/week (OR: 0.6168, 95% CI: 0.4379-0.8668, p = 0.005). Conclusion: The best exercise frequency is exercising ≥3 times/week for individuals from different dementia subtypes and age groups. While for those without hypertension, PE at 1-2 times /week is also beneficial.

Serum uric acid and appropriate cutoff value for prediction of metabolic syndrome among Chinese adults.

The relation between serum uric acid and metabolic syndrome is observed not only with frank hyperuricemia but also with serum uric acid levels within the normal range. The current "normal" range set for hyperuricemia often fails to identify patients with potential metabolic disorders. We investigate the association between serum uric acid within the normal range and incident metabolic syndrome risk, and further to determine the optimal cut-off value of serum uric acid for the diagnosis or prediction of metabolic syndrome. A total of 7399 Chinese adults (2957 men and 4442 women; ≥20 years) free of metabolic syndrome were followed for 3 years. During the 3-year follow-up, 1190 normouricemic individuals developed metabolic syndrome (16.1%). After adjusting the associated variables, the top quartile of serum uric acid levels was associated with higher metabolic syndrome development compared with the bottom quartile in men (hazard ratio (HR), 1.29; p<0.05) and women (HR, 1.62; p<0.05). ROC curve analysis indicated that the optimal cut-off values for serum uric acid to identify metabolic syndrome were 6.3 mg/dl in men and 4.9 mg/dl in women. Our results suggested that high baseline serum uric acid levels within the normal range predict future development of metabolic syndrome after 3 y of follow-up.

Analysis of Trapping Effect on Large-Signal Characteristics of GaN HEMTs Using X-Parameters and UV Illumination.

GaN high-electron-mobility transistors (HEMTs) have attracted widespread attention for high-power microwave applications, owing to their superior properties. However, the charge trapping effect has limitations to its performance. To study the trapping effect on the device large-signal behavior, AlGaN/GaN HEMTs and metal-insulator-semiconductor HEMTs (MIS-HEMTs) were characterized through X-parameter measurements under ultraviolet (UV) illumination. For HEMTs without passivation, the magnitude of the large-signal output wave (X21FB) and small-signal forward gain (X2111S) at fundamental frequency increased, whereas the large-signal second harmonic output wave (X22FB) decreased when the device was exposed to UV light, resulting from the photoconductive effect and suppression of buffer-related trapping. For MIS-HEMTs with SiN passivation, much higher X21FB and X2111S have been obtained compared with HEMTs. It suggests that better RF power performance can be achieved by removing the surface state. Moreover, the X-parameters of the MIS-HEMT are less dependent on UV light, since the light-induced performance enhancement is offset by excess traps in the SiN layer excited by UV light. The radio frequency (RF) power parameters and signal waveforms were further obtained based on the X-parameter model. The variation of RF current gain and distortion with light was consistent with the measurement results of X-parameters. Therefore, the trap number in the AlGaN surface, GaN buffer, and SiN layer must be minimized for a good large-signal performance of AlGaN/GaN transistors.

Magnetic cryopreservation for dental pulp stem cells.

Magnetic cryopreservation has been successfully used for tooth banking with satisfactory implantation outcomes, suggesting that the method preserves human periodontal ligament cells and dental pulp stem cells (DPSCs). Therefore, magnetic cryopreservation may be applied for the preservation of DPSCs; however, this method has not been evaluated yet. A reliable cryopreservation method for live-cell preservation is important for the clinical applications of regenerative medicine. The conventional slow-freezing procedure with 10% dimethylsulfoxide (DMSO) may not be appropriate for stem cell-based therapies because DMSO is cytotoxic. The objective of this study was to investigate whether magnetic cryopreservation can be applied for DPSC cryopreservation. Cells isolated from human dental pulp were subjected to magnetic cryopreservation. Postthawing cell viability, adhesion, proliferation, expression of markers for mesenchymal stem cells (MSCs), differentiation ability of magnetically cryopreserved DPSCs and DNA stability were compared to those of cells subjected to the conventional slow-freezing method. The results indicated that a serum-free cryopreservation medium (SFM) containing 3% DMSO is optimal for magnetic cryopreservation. Post-thaw magnetically cryopreserved DPSCs express MSC markers, and perform osteogenesis and adipogenesis after induction similarly to fresh MSCs. No significant DNA damage was found in magnetically cryopreserved DPSCs. Magnetic cryopreservation is thus a reliable and effective method for storage of DPSCs. The smaller amount of DMSO required in SFM for cryopreservation is beneficial for the clinical applications of post-thaw cells in regenerative medicine.

linc01305 promotes metastasis and proliferation of esophageal squamous cell carcinoma through interacting with IGF2BP2 and IGF2BP3 to stabilize HTR3A mRNA.

Evidence shows that long noncoding RNAs (lncRNAs) modulate mRNAs of multiple genes by post-transcriptional regulation. However, in esophageal squamous cell carcinoma, lncRNAs involvement in post-transcriptional regulation of mRNAs have been rarely reported. In this study, we investigated a novel mechanism of linc01305 promoting metastasis and proliferation of ESCC. The results for real-time quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization showed that linc01305 was highly expressed and predominantly located in cytoplasm of human esophageal cancer cells. Transwell and colony formation assays confirmed that linc01305 promoted migration and proliferation of esophageal cancer cells. RNA-seq, linc01305 pulldown, mass spectrometry, RNA immunoprecipitation and mRNA stability assays demonstrated that linc01305 stabilized mRNA of target gene HTR3A through interacting with IGF2BP2 and IGF2BP3. Taken together, our data unveils a novel mechanism in which cytoplasmic linc01305 stabilizes HTR3A mRNA through interacting with IGF2BP2 and IGF2BP3 and thereby promotes metastasis and proliferation of ESCC.

Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.

Integrated single-cell transcriptome analysis reveals heterogeneity of esophageal squamous cell carcinoma microenvironment.

The tumor microenvironment is a highly complex ecosystem of diverse cell types, which shape cancer biology and impact the responsiveness to therapy. Here, we analyze the microenvironment of esophageal squamous cell carcinoma (ESCC) using single-cell transcriptome sequencing in 62,161 cells from blood, adjacent nonmalignant and matched tumor samples from 11 ESCC patients. We uncover heterogeneity in most cell types of the ESCC stroma, particularly in the fibroblast and immune cell compartments. We identify a tumor-specific subset of CST1+ myofibroblasts with prognostic values and potential biological significance. CST1+ myofibroblasts are also highly tumor-specific in other cancer types. Additionally, a subset of antigen-presenting fibroblasts is revealed and validated. Analyses of myeloid and T lymphoid lineages highlight the immunosuppressive nature of the ESCC microenvironment, and identify cancer-specific expression of immune checkpoint inhibitors. This work establishes a rich resource of stromal cell types of the ESCC microenvironment for further understanding of ESCC biology.

Folate stimulates ERK1/2 phosphorylation and cell proliferation in fetal neural stem cells.

Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays central roles in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In this study, we have investigated the effect of folate on extracellular signal-regulated kinase (ERK1/2) phosphorylation, cell proliferation and apoptosis in fetal NSCs. The results showed that treatment of neurospheres with folate increased ERK1/2 phosphorylation and cell proliferation in a concentration-dependent manner. Folate also decreased the percentage of apoptotic cells. All of these effects of folate were prevented by a selective inhibitor (U0126) of mitogen-activated/ERK kinase 1/2. In conclusion, fetal NSCs respond to folate with ERKl/2 phosphorylation, cell proliferation and decreased apoptosis. This mechanism may mediate the regulation by folate of neurogenesis in the central nervous system.

Purification and antitumour activity of a lipopeptide biosurfactant produced by Bacillus natto TK-1.

An antitumour lipopeptide biosurfactant purified from Bacillus natto TK-1 was able to inhibit the proliferation of MCF-7 human breast-cancer cells in a dose- and time-dependent manner. The activity of lactate dehydrogenase release showed no significant difference between MCF-7 cells treated with lipopeptide and untreated controls. The antitumour activity of the lipopeptide in MCF-7 cells was associated with cell apoptosis determined by typical morphological changes and sub-G(1) peak in cell growth-phase distribution. The cell cycle was arrested at G(2)/M phase. In addition, the caspase activity assay revealed that lipopeptide-induced apoptosis in MCF-7 cells was associated with caspase 3.

Folate deficiency induces neural stem cell apoptosis by increasing homocysteine in vitro.

Cellular events for neural progenitor cells, such as proliferation and differentiation, are regulated by multiple intrinsic and extrinsic cell signals. Folate plays a central role in central nervous system development, so folate, as an extrinsic signal, may affect neural stem cell (NSC) proliferation and differentiation. In the present study, we investigated the effects of folate deficiency on the cell proliferation, cell apoptosis and homocysteine concentrations in NSCs. NSCs were isolated from fetal rats and identified as NSCs by their expression of immunoreactive nestin. Cell proliferation was quantitated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were detected and confirmed by flow cytometric analysis. We measured homocysteine concentrations in NSCs by high performance liquid chromatography and detected the expression of caspase-3 by western blot method. Folate deficiency not only decreased cell proliferation, but also increased the apoptotic rate of NSCs as demonstrated by the increased expression of early apoptotic markers such as caspase-3, compared to control group (p<0.05). Furthermore, There was a statistically significant increase in homocysteine concentration during folate deficiency in NSCs (p<0.05). These data suggest that folate affects the cell proliferation, apoptosis and homocysteine generation in NSC cells.

Association between Pre-pregnancy Body Mass Index and Offspring Neuropsychological Development from 1 to 24 Months of Age: A Birth Cohort Study in China.

OBJECTIVE: To explore the interactions between pre-pregnancy body mass index (BMI) and age on offspring neuropsychological development from 1 to 24 months in China. METHODS: In this birth cohort study, a total of 2,253 mother-child pairs were enrolled in Tianjin, China, between July 2015 and May 2018. The China Developmental Scale for Children was used to assess developmental quotient (DQ) of children aged from 1 to 24 months. RESULTS: Mixed-models analysis revealed significant age × pre-pregnancy BMI interactions for total DQ and five neurobehavioral domains (gross motor, fine motor, adaptive, language, and social; P < 0.001). Age × pre-pregnancy BMI ⪖ 25 kg/m2 was associated with a negative effect on total DQ and five neurobehavioral domains, as compared to pre-pregnancy BMI < 25 kg/m2 (P < 0.01). Multiple comparisons showed pre-pregnancy BMI ⪖ 25 kg/m2 of mothers had a positive effect on child total DQ at the age of 1 month but a negative effect at 24 months (P < 0.05). CONCLUSION: This study supported the age × pre-pregnancy BMI interaction on offspring neuropsychological development. It also revealed a short-term positive impact of high pre-pregnancy BMI on neuropsychological development at 1 month of age, but a long-term negative effect (from 1 to 24 months).

[Effects of folic acid, vitamin B(6) and vitamin B(12) on learning and memory function in cerebral ischemia rats].

OBJECTIVE: To investigate the effects of folic acid, vitamin B(6) and B(12) on plasma homocysteine and on learning and memory functions in focal cerebral ischemia rats. METHODS: Sprague-Dawley rats were randomly divided into four groups. They were sham operation group (Sham OP), middle cerebral artery occlusion model group (MCAO), MCAO + folic acid group (MCAO + FA) and MCAO + compound vitamin (folate, vitamin B(6) and B(12)) group (MCAO + CV). Plasma homocysteine was measured before and after supplementation and after ischemia. RESULTS: The level of plasma homocysteine in MCAO + FA and MCAO + CV groups were significantly lower than those in Sham OP and MCAO groups after supplementation and ischemia (6.92 +/- 1.04) micromol/L and (5.49 +/- 1.00) micromol/L vs (9.33 +/- 1.11) micromol/L, (10.90 +/- 2.03 micromol/L), P < 0.05. While in MCAO + CV group was lower than that in MCAO + FA group (5.49 +/- 1.00) micromol/L vs (6.92 +/- 1.04) micromol/L, P < 0.05. The neurological deficit scores and shock times in Y-type maze of MCAO + FA and MCAO + CV groups were lower than those in MCAO group (1.75 +/- 0.46 and 1.38 +/- 0.52 vs 2.62 +/- 0.52; 123.50 +/- 39.77 and 86.25 +/- 21.39 vs 173.25 +/- 46.32, P < 0.05). The correct times of MCAO + CV group in Y-type maze was higher than that in MCAO group (3.75 +/- 0.42 vs 2.12 +/- 0.45, P < 0.05). CONCLUSION: Folic acid intake could not only reduce plasma homocysteine concentration but also promote the recovery of the learning and memory functions of rats with cerebral ischemia. The effects of folic acid combined with vitamin B(6) and vitamin B(12) on cerebral ischemia rats was better than that of single folate.