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AIM:To observe the effect of folic acid(FA)on C2C12 myoblast proliferation and differentia-tion,and to explore its mechanism.METHODS:During the proliferation stage,C2C12 myoblasts were treated with vari-ous concentrations of FA(0,2.5,5,10 and 20 μmol/L).The cell status was observed under a microscope,cell viability was detected using the MTT method,and cell proliferation was assessed using the EdU method.In the differentiation stage,C2C12 cells were divided into control(Ctrl)group(0 μmol/L FA)and FA group(10 μmol/L FA).On day 2 or 4 of differentiation,immunofluorescence staining and Western blot were employed to detect the expression of myoblast differen-tiation-related proteins,myoblast determination protein 1(MyoD),myogenin(MyoG)and myosin heavy chain(MyHC).The myotubule formation in each group was analyzed.On day 4 of differentiation,C2C12 cells were treated with FA for 0,1,3 and 6 h,and the protein levels of p-JNK,JNK,p-p38 MAPK and p38 MAPK at each time point were detected by Western blot.Additionally,C2C12 cells after 4-day differentiation were divided into Ctrl group,FA group,FA+ SP600125(specific inhibitor of JNK)group,and FA+SB203580(specific inhibitor of p38)group.The cells in FA+ SP600125 and FA+SB203580 groups were treated with 10 μmol/L SP600125 or SB203580 for 1 h,followed by treatment with 10 μmol/L FA for 24 h.The cells in FA group were treated with 10 μmol/L FA for 24 h,while the cells in Ctrl group were left untreated.The protein levels of p-JNK,JNK,p-p38 MAPK,p38 MAPK and MyHC were detected by Western blot.RESULTS:(1)Compared with 0 μmol/L FA group,the number of the cells in other concentration groups in-creased,cell viability was raised(P＜0.05 or P＜0.01),and the rate of EdU positive cells increased(P＜0.05).(2)Com-pared with Ctrl group,the expression levels of MyoD,MyoG and MyHC in FA group were increased(P＜0.05),and the myotube fusion index was raised(P＜0.05 or P＜0.01).(3)Compared with 0 h group,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK were elevated after FA treatment for 1,3 and 6 h(P＜0.05 or P＜0.01),and showed a trend of gradual increase with the extension of treatment time.(4)After FA treatment,the ratios of p-JNK/JNK and p-p38 MAPK/p38 MAPK,and the expression of MyHC were elevated(P＜0.01).Treatment with SP600125 decreased the ratio of p-JNK/JNK and the expression of MyHC(P＜0.05),while SB203580 intervention cut down the ratio of p-p38 MAPK/p38 MAPK and the expression of MyHC(P＜0.05 or P＜0.01).CONCLUSION:Folic acid can promote the differentiation of C2C12 myoblasts by activating the JNK/p38 MAPK signaling pathway.
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ObjectiveThis study aims to investigate the effectiveness and potential mechanism of Erxian Decoction （二仙汤） for late-onset depression （LOD）. MethodsForty Wistar male rats of 7-8 weeks were divided into 20 each of normal group and youth depression group. Sixty Wistar male rats of 20 months were divided into 20 each of elder group， LOD group and Erxian Decoction group. The rats in youth depression group were modelled with chronic unpredictable mild stress （CUMS） for 6 weeks to build a depression model， and the elder rats in LOD group and Erxian Decoction group were modelled with CUMS for 6 weeks to build a LOD model， with no interventions in the normal group and the elder group. Gastric administration was carried out at the same time of modelling， rats in Erxian Decoction group were given 8 g/（kg·d） of Erxian Decoction by gavage， and rats in the normal group， youth depression group， elder group， and LOD group were given 4 ml/（kg·d） of pure water by gavage， for 6 weeks in each group. Sugar water preference experiment and forced swimming experiment were used to evaluate the depression-like behaviour of rats， absent field experiment was used to evaluate the spontaneous activity ability of rats， and T-maze experiment was used to evaluate the cognitive function of rats； Western blot assay was used to detect neuronal nuclei （NeuN）， nestin， doublecortin （DCX） in hippocampal tissue， and zonula occludens-l （ZO-1）， folate receptor α （FRα）， reduced folate carrier （RFC）， and protoncoupledfolate transporter （PCFT） protein expression in choroid plexus； immunofluorescence was used to detect the number of double-positive cells for Ki-67/nestin， the number of double-positive cells for 5-bromodeoxyuracil nucleoside （BrdU）/DCX in hippocampal dentate gyrus， and the protein expression of ZO-1， FRα， RFC， and PCFT in choroid plexus tissues； ELISA technique was used to detect plasma， cerebrospinal fluid， 5-methyltetrahydrofolate （5-MTHF） in hippocampal tissues； Pearson correlation analysis was used to correlate the 5-MTHF content in cerebrospinal fluid and hippocampal tissues and the expression of nestin， DCX， and NeuN proteins in hippocampal tissues of rats in youth depression group and LOD group. ResultsCompared with normal group， rats in youth depression group and LOD group showed reduced sugar water preference， reduced total distance travelled in the absent field， reduced number of times through the grid， prolonged forced swimming immobilisation， reduced hippocampal NeuN， nestin and DCX protein expression， reduced number of Ki-67/nestin double-positive cells in hippocampal dentate gyrus， reduced number of BrdU/DCX double-positive cells in hippocampal dentate gyrus， and reduced expression of ZO-1 and FRα proteins and fluorescence intensity （P＜0.05 or P＜0.01）； the correct rate of T-maze on days 3 and 4 in the rats of youth depression group and on days 2 to 4 in the rats of LOD group significantly decreased， and the content of 5-MTHF in the cerebrospinal fluid and hippocampal tissues of the rats of LOD group significantly decreased as well （P＜0.05 or P＜0.01）. Compared with youth depression group， rats in LOD group showed a decrease in total distance travelled in absenteeism， number of times through the grid， a significant decrease in the correct rate of the T-maze on day 1-4， a decrease in NeuN， nestin， DCX protein expression of hippocampal tissue and the number of Ki-67/nestin double-positive cells， BrdU/DCX double-positive cells of hippocampal dentate gyrus （P＜0.05 or P＜0.01）. Compared with LOD group， rats in Erxian Decoction group had elevated sugar-water preference and total distance travelled in absenteeism and number of times through the grid， shorter forced swimming immobility time， significantly higher correct rate of the T-maze on day 3-4， elevated expression of NeuN， nestin， and DCX proteins in hippocampal tissues， increased number of Ki-67/nestin double-positive cells and BrdU/DCX double-positive cells in hippocampal dentate gyrus， and increased 5-MTHF content in cerebrospinal fluid and hippocampal， and ZO-1， FRα， RFC， PCFT protein expression and fluorescence intensity increased in choroid plexus （P＜0.05 or P＜0.01）. Correlation analysis showed that there was a positive correlation between 5-MTHF content in cerebrospinal fluid （r = 0.466）， hippocampal tissue （r = 0.522） and nestin expression in hippocampal tissue （P＜0.05）. ConclusionErxian Decoction could improve depressive-like behaviour and cognitive impairment in LOD model rats， and its mechanism may promote hippocampal neurogenesis by alleviating structural damage to the choroid plexus of the brain tissue， and improving impaired choroid plexus folate transport.
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As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.
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Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.
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BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.
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Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Fosfatasa 1 de Especificidad Dual/farmacología , Proliferación Celular , Proteínas Quinasas p38 Activadas por Mitógenos/farmacología , Metilación , Apoptosis , Línea Celular TumoralRESUMEN
Objective:To investigate the clinical efficacy of Danggui Shaoyao powder combined with folic acid tablets in the treatment of chronic atrophic gastritis. Methods:A total of 90 patients with chronic atrophic gastritis who were treated at Longyou Branch, Sir Run Run Shaw Hospital, Zhejiang University from March 2021 to March 2022 were included in this study. They were randomly divided into a control group and an experimental group, with 45 patients per group. The control group was treated with folic acid tablets, while the experimental group was treated with Danggui Shaoyao powder combined with folic acid tablets. Before and after treatment, traditional Chinese medicine syndrome scores, gastroscopy and pathology scores, and inflammatory factor levels were compared between the two groups. Clinical efficacy was compared between the two groups. Results:The amplitudes of decreases in traditional Chinese medicine syndrome score in the experimental group [acid reflux (0.57 ± 0.19) points and epigastric pain (0.84 ± 1.36) points] were significantly greater than those in the control group [acid reflux (1.46 ± 0.39) points, epigastric pain (1.52 ± 1.41) points, t = 4.86, 6.52, both P < 0.05]. Inflammatory factor levels in the experimental group [tumor necrosis factor-α (1.03 ± 0.11) μg/L, interleukin-6 (8.15 ± 1.42) ng/L, C-reactive protein (6.55 ± 0.98) mg/L] were significantly lower than those in the control group [tumor necrosis factor-α (1.73 ± 0.14) μg/L, interleukin-6 (12.24 ± 1.48) ng/L, C-reactive protein (10.23 ± 1.03) mg/L, t = 4.52, 7.66, 6.95, all P < 0.05]. The gastroscopy and pathological scores in the experimental group [intestinal metaplasia (0.78 ± 0.35) points, dysplasia (0.30 ± 0.10) points] were significantly lower than those in the control group [intestinal metaplasia (1.31 ± 0.38) points, dysplasia (0.68 ± 0.12) points, t = 4.13, 3.85, both P < 0.05]. The overall response rate in the experimental group was 93.33% (42/45), which was significantly higher than 77.78% (35/45) in the control group ( χ2 = 4.40, P < 0.05). Conclusion:Danggui Shaoyao powder combined with folic acid tablets in the treatment of chronic atrophic gastritis can effectively improve traditional Chinese medicine syndromes, reduce the level of inflammatory factors, and have a good clinical effect.
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ObjectiveThis research focused on examining the distinctive characteristics of nutrient intake and dietary patterns among long-lived elderly individuals. Additionally， the study was aimed to explore the specific dietary components that may impact the skeletal muscle mass in this particular group. MethodsThis study was conducted in the Chongming area of Shanghai， China. A total of 206 long-lived elderly individuals aged 90 or above were recruited. The 3-day 24-hour dietary recall method was used to collect dietary information and general demographic data through face-to-face interviews with professional nutritionists. The skeletal muscle mass index（SMI） was measured by bioelectrical impedance analysis（BIA）， and low skeletal muscle mass was diagnosed based on the 2019 Asian Working Group for Sarcopenia criteria. T-test analysis， chi-square test， and logistic regression were used to analyze the relationship between dietary nutrient intake and skeletal muscle mass. ResultsIn terms of food intake categories， compared with the long-lived elderly people with normal muscle mass， the intake of cereals containing miscellaneous beans and vegetables in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. In terms of the nutrient intake， compared with the long-lived elderly people with normal muscle mass， the intake of total energy， carbohydrate， dietary fiber， vitamin D， folic acid， phosphorus， potassium， magnesium， iron， and manganese in the long-lived elderly people with low muscle mass was significantly lower（P<0.05）. After continuous adjustment for the covariates， multivariate logistic regression analysis found that the intake levels of folic acid and dietary fiber were important factors influencing skeletal muscle mass， Individuals with lower intake levels of folic acid and dietary fiber are at a higher risk of low muscle mass in long-lived elderly individuals ［ORfolic acid T1， dietary fiber T1 （95%CI）： 2.90 （1.11‒7.61）； 4.09 （1.53‒10.91）］. ConclusionThe consumption of cereals that include a variety of beans and vegetables was noticeably lower in the long-lived elderly individuals with lower muscle mass when compared to those with normal muscle mass. Furthermore， low levels of folic acid and dietary fiber intake are associated with an increased risk of low skeletal muscle mass.
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Objective To investigate the effect of folic acid–modified liposome quercetin (FLQ) on the proliferation and apoptosis of triple negative breast cancer (TNBC) cells and explore its underlying mechanism. Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability. Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation. Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis, the levels of intracellular ROS, and mitochondrial membrane potential. Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins. Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells (P=0.023, P<0.001). It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells (P=0.003, P=0.034); inhibited the phosphorylation levels of JAK2 and STAT3; upregulated the expression levels of the proapoptotic proteins Bax, Bak, cytochrome C, and Cleaved-Caspase-3 (P<0.001, P<0.001); and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL (P=0.037, 0.028). Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells. These effects may be related to the activation of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.
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Resumen OBJETIVO: Determinar la relación entre el nivel de conocimiento y la adhesión al régimen prescrito de sulfato ferroso y ácido fólico para prevenir o tratar la anemia gestacional en pacientes atendidas en un hospital público del Perú. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, de serie de casos, transversal y prospectivo llevado a cabo entre febrero y abril de 2022 en pacientes en el puerperio inmediato con diagnóstico de anemia gestacional establecido dos meses antes del término del embarazo. Se evaluaron los conocimientos mediante un cuestionario y la adhesión mediante la prueba de Morisky-Green-Levine, ambos instrumentos validados y fiables. El análisis estadístico se procesó en el programa STATA; se utilizaron χ2 de Pearson y el modelo lineal generalizado de la familia de Poisson con varianza robusta y nivel de confianza del 95%. RESULTADOS: Se estudiaron 217 pacientes; 2 de cada 10 tenían diagnóstico de anemia gestacional y cumplían el tratamiento. En conjunto, el 71.89% de las participantes tenía un conocimiento adecuado de la importancia del tratamiento con sulfato ferroso y ácido fólico, y el 23.96% alcanzó un nivel intermedio. La relación entre el nivel de conocimientos y el apego se aproximó a la significación estadística (p = 0.05 RPa:1.63; IC95%: 0.99-2.71), establecida mediante análisis ajustado. El conocimiento de la importancia del tratamiento antianémico para la madre multiplicó por tres la prevalencia de la adherencia (p = 0.04; RPa: 3.17; IC95%: 1.04-9.72). CONCLUSIÓN: El conocimiento por parte de las madres de la importancia del tratamiento antianémico aumentó significativamente la adherencia.
Abstract OBJECTIVE: To determine the relationship between the level of knowledge and adherence to the prescribed regimen of ferrous sulfate and folic acid to prevent or treat gestational anemia in patients attended in a public hospital in Peru. MATERIALS AND METHODS: Observational, descriptive, case series, cross-sectional and prospective study carried out between February and April 2022 in patients in the immediate postpartum period with a diagnosis of gestational anemia established two months before the end of pregnancy. Knowledge was assessed by means of a questionnaire and adherence by means of the Morisky-Green-Levine test, both validated and reliable instruments. Statistical analysis was performed with the STATA program; Pearson's χ2 and the generalized linear model of the Poisson family with robust variance and 95% confidence level were used. RESULTS: A total of 217 patients were studied; 2 out of 10 had a diagnosis of gestational anemia and were compliant with treatment. Overall, 71.89% of the participants had adequate knowledge of the importance of treatment with ferrous sulfate and folic acid, and 23.96% reached an intermediate level. The relationship between the level of knowledge and adherence was close to statistical significance (p = 0.05 RPa:1.63; 95%CI: 0.99-2.71), established by adjusted analysis. Understanding the importance of antianemic treatment for the mother increased the prevalence of adherence threefold (p = 0.04; RPa: 3.17; 95%CI: 1.04-9.72). CONCLUSION: Mothers' knowledge of the importance of antianemic treatment significantly increased adherence.
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La anemia megaloblástica pertenece al subgrupo de anemias carenciales. Con el objetivo de describir el efecto del déficit de vitaminas B9 y B12 en la génesis de la anemia megaloblástica se realizó la presente investigación. La anemia megaloblástica se presenta cuando los niveles de ácido fólico (Vitamina B9) y cianocobalamina (vitamina B12) son bajos, generando así una disminución en la capacidad celular de sintetizar ácido desoxirribonucleico, lo que ocasiona alteraciones hematológicas en todas las líneas celulares de la médula ósea (eritrocitos y plaquetas), principalmente provocando la generación de hematíes de gran tamaño y con baja concentración de hemoglobina. Las vitaminas B9 y B12 participan en la síntesis normal de ácidos nucleicos, implicándose directamente en la síntesis de purinas y pirimidinas, así como la maduración celular. El déficit de estas vitaminas tiene efecto sobre el funcionamiento del sistema nervioso central.
Megaloblastic anemia belongs to the subgroup of deficiency anemias. With the objective of describing the effect of B9 and B12 vitamins deficiency on the genesis of megaloblastic anemia, this research was carried out. Megaloblastic anemia occurs when the levels of folic acid (Vitamin B9) and cyanocobalamin (vitamin B12) are low, thus generating a decrease in the cellular capacity to synthesize deoxyribonucleic acid, which causes hematological alterations in all cell lines of the marrow bone (erythrocytes and platelets), mainly causing the generation of large red blood cells with low hemoglobin concentration. Vitamins B9 and B12 participate in the normal synthesis of nucleic acids, being directly involved in the synthesis of purines and pyrimidines, as well as cell maturation. The deficiency of these vitamins has an effect on the central nervous system functioning.
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INTRODUCCIÓN Y/O ANTECEDENTES: Los defectos del tubo neural se encuentran entre las anomalías congénitas más comunes en todo el mundo, el ácido fólico (0.4-0.8 ug/día) reduce el riesgo de ocurrencia y recurrencia, por lo que se recomienda su uso concepcional y periconcepcional. El conocimiento de sus efectos protectores varía mucho en la población. OBJETIVOS: Describir el conocimiento de las puérperas sobre el uso correcto del ácido fólico y sus alcances como factor protector. MATERIAL Y MÉTODO: Se condujeron encuestas entre un grupo de mujeres puérperas del Hospital de la Mujer mediante cuestionarios estructurados para obtener información el conocimiento del uso del ácido fólico periconcepcional. RESULTADOS: Entrevistamos 87 puérperas. El conocimiento y el uso del ácido fólico entre las entrevistadas fue bajo, 51% y 48.3% respectivamente. La escolaridad en este grupo poblacional es un factor predictivo del conocimiento y uso correcto del ácido fólico. DISCUSIÓN, CONCLUSIONES Y RECOMENDACIONES: El conocimiento del ácido fólico es relativamente bajo entre las mujeres puérperas entrevistadas, su uso durante el embarazo es insuficiente y la suplementación con antes de la concepción es nula. Aún nos queda un largo camino por recorrer. Se recomienda promover el conocimiento y el uso del ácido fólico en etapa periconcepcional, así como mayor información sobre los alimentos fortificados.
INTRODUCTION AND BACKGROUND: Neural tube defects are among the most common congenital anomalies worldwide; folic acid reduces their risk of occurrence and is strongly recommended for conceptional and periconceptional use. Awareness of its protective effects varies widely among populations. OBJECTIVES: To measure the awareness of postpartum women about the correct use of folic acid and its protectants. MATERIALS AND METHODS: A survey was conducted in one group of postpartum women using structured questionnaires to obtain information on awareness and use of folic acid. RESULTS: We interviewed 87 postpartum women. Awareness and use of folic among the interviewees were low, 51% and 48.3% respectively. Schooling is a predictor of folic acid correct use and awareness. DISCUSSION, CONCLUSIONS, AND RECOMMENDATIONS: Awareness of folic acid is relatively low among pregnant Bolivian women, its use during pregnancy is insufficient and supplementation before conception is zero. We still have a long way to go. We recommend the promotion of awareness and the use of folic acid in pregnant women.
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Femenino , Embarazo , Ácido Fólico , Periodo PospartoRESUMEN
So far, liver cancer is still a highly malignant tumor with a high incidence rate in China, and it seriously affects the life and health of Chinese people. Previous studies have shown that the development of liver cancer is associated with various factors such as virus, smoking, drinking, and nonalcoholic fatty liver disease. With continuous exploration, more and more studies have pointed out that nutritional factors and living environment are associated with the development and progression of liver cancer. Folic acid is a necessary nutrient for cell growth and reproduction, and its level in human body has an impact on the growth of tumor cells and is closely associated with liver cancer. This article reviews the research advances in the association between folic acid and liver cancer in recent years, so as to provide new reference and basis for the prevention and treatment of liver cancer.
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OBJECTIVE@#To investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury.@*METHODS@#Thirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group.@*RESULTS@#At 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation ( P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation ( P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation ( P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation ( P<0.05). There was no significant difference between groups B and C at each time point after operation ( P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm 2, which was significantly more than that in group A [(298.33±153.12) cells/mm 2] ( t=6.139, P<0.001).@*CONCLUSION@#The fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.
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Ratas , Animales , Masculino , Ratas Sprague-Dawley , Poliésteres , Traumatismos de los Nervios Periféricos/cirugía , Elastómeros , Uretano , Nervio Ciático/lesiones , Carbamatos , Tejido Nervioso , Regeneración Nerviosa/fisiologíaRESUMEN
OBJECTIVE@#To explore the association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid(MMFA) and risk of preterm delivery in women with natural conception, singleton pregnancy and vaginal delivery.@*METHODS@#A retrospective cohort study was performed based on the prenatal health care system and hospital information system of Tongzhou Maternal and Child Health Hospital of Beijing and the women who had their prenatal care in the hospital from January 2015 to December 2018 were included. The information of 16 332 women who conceived naturally, had a singleton pregnancy, and delivered vaginally was collected. Compliance scores were constructed based on the time of initiation and the frequency of taking nutritional supplements. The association between maternal periconceptional micronutrient supplementation, including pure folic acid (FA) pills or MMFA and the rate of preterm delivery was evaluated using Logistic regression models.@*RESULTS@#The preterm delivery rate (gestational week < 37 weeks) of the study population was 3.8%, and the mean (standard deviation) of gestational age was (38.98±1.37) weeks. A total of 6 174 (37.8%) women took FA during the periconceptional period, 8 646 (52.9%) women took MMFA, and 1 512 (9.3%) women did not take any nutritional supplements. The association between periconceptional supplementation of FA or MMFA and risk of preterm delivery in women was not statistically significant [adjusted odds ratio (aOR)=1.01, 95%CI: 0.74-1.37]. The associations with preterm birth were not statistically significant in further analysis by the type of nutritional supplements, time of initiation, and the frequency of supplementation. In addition, the association between the compliance score of taking supplements and the rate of preterm delivery was not statistically significant, either.@*CONCLUSION@#This study did not find an association between the risk of preterm delivery and the use of FA or MMFA during the periconcep-tional period in women with natural conception, singleton pregnancy, and vaginal delivery. In the future, multicenter studies with large-scale prospective cohort or population-based randomized controlled trials are warranted to confirm the association between taking FA or MMFA during the periconceptional period and preterm delivery among women.
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Embarazo , Femenino , Niño , Recién Nacido , Humanos , Lactante , Masculino , Ácido Fólico , Nacimiento Prematuro/prevención & control , Estudios Prospectivos , Estudios Retrospectivos , Suplementos Dietéticos , MicronutrientesRESUMEN
Objective:To investigate the clinical efficacy and adverse reactions of pemetrexed disodium in the maintenance treatment of advanced lung adenocarcinoma after chemotherapy with pemetrexed disodium and platinum.Methods:The clinical data of 35 patients with stage Ⅳ lung adenocarcinoma who received chemotherapy with pemetrexed disodium and platinum and were well treated in Beijing Huairou Hospital from January 2013 to August 2020 were retrospectively analyzed. Maintenance therapy with pemetrexed disodium was initiated after the completion of combination chemotherapy until disease progression. The clinical characteristics, therapeutic effects, adverse reactions, progression-free survival, and overall survival of the 35 patients were evaluated.Results:Among the 35 patients, no patients had complete remission, 11 patients had partial remission, 22 patients had stable disease, and 2 patients had progressive disease. The objective remission rate was 31.4%, disease control rate was 94.3%, median progression-free survival was 9.53 months, median overall survival was 18.21 months, 1-year survival rate was 68.6%, 2-year survival rate was 31.4%, and 3-year survival rate was 11.4%. Gender, age, smoking, and the baseline characteristics of patients undergoing first-line pemetrexed disodium or second-line pemetrexed disodium treatment had no effects on progression-free survival (all P > 0.05). Positive gene mutation and receiving four or more chemotherapy cycles had a protective effect on progression-free survival (both P < 0.05). Chemotherapy-related adverse reactions mainly included myelosuppression, nausea, elevated transaminase, and nephrotoxicity, all of which were mild and were relieved after symptomatic treatment. Conclusion:Pemetrexed disodium is effective and safe in the maintenance treatment of advanced lung adenocarcinoma. The results of this study are scientific.
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Objective @# To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) oparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) .@*Methods @# Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot.@*Results @#FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . Conclusion TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.
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Objective @#To construct folate modified D ⁃α ⁃tocopheryl polyethylene glycol 1000 succinate ( TPGS) nanomaterials (FA⁃TPGS) , which can stably load and effectively release siRNA , and to observe the effects of nanoparticles on the cytotoxicity and spliced X ⁃box binding protein 1 ( XBP1s) of mouse leukemia cells of monocyte macrophage (RAW264. 7) .@*Methods @# Mixed FA⁃TPGS and rhodamine B (RhB) labeled XBP1 siRNA solution in a proportion of 5 ∶ 1 and obtained the nano⁃complex coated with XBP1 siRNA(FT@ XBP1) . FT@ XBP1 nanocarriers were characterized by transmission electron microscope , dynamic light scattering , ultraviolet visible spectrum analysis and/or fluorescence analysis. And the release of siRNA from FA⁃TPGS nano⁃carriers was calculated simultaneously. The cell cytotoxicity of FT@ XBP1 nanomaterials were detected by scanning electron microscopy (SEM) , CCK⁃8 and flow cytometry. And the inhibited effect of XBP1 s of RAW264. 7 cells was checked by Western blot.@*Results @#FA modified TPGS could effectively bind XBP1 siRNA. And the average particle size of FT@ XBP1 nanocarriers were(200 ± 20) nm. The relative release assays showed that acidic environments (pH 5. 0) was beneficial for siRNA to release from FT@ XBP1 . Both CCK⁃8 and apoptosis assay showed that the effects of FT@ XBP1 on the proliferation and apoptosis of RAW264. 7 cells were relatively small , and FT@ XBP1 could significantly inhibit the expression of XBP1 s protein in RAW264. 7(P < 0. 001) . @*Conclusion @# TPGS nanoparticles modified with folic acid can effectively encapsulate XBP1 siRNA and inhibit XBP1 s expression of RAW264. 7 cells with good cellular compatibility.
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AIM: To analyze the changes of serum homocysteine(Hcy), vitamin B12(VitB12)and folic acid in the serum of patients with diabetic retinopathy(DR), and to explore their significance in the occurrence and development of DR.METHODS: A case-control study was designed. A total of 95 patients with DR(DR group), 94 patients with diabetes mellitus(DM group)treated in endgcrinology department and 87 patients with age-related cataract(normal control group)from the ophthalmology department of Shenzhen People's Hospital between July 2021 and January 2022 were selected. Fasting venous blood was collected and serum was separated. The concentration of Hcy in serum was detected by enzyme linked immunosorbent assay(ELISA), and chemiluminescence immunoassay was used to detect the concentration of VitB12 and folic acid. Pearson linear correlation analysis was used to evaluate the correlation between Hcy and clinical parameters. Multivariate linear regression analysis was used to evaluate the main factors which affect Hcy level. Receiver operating characteristic(ROC)curve was designed to analyze the diagnostic value of serum Hcy, VitB12 and folic acid in DR.RESULTS: The concentration of serum Hcy in DR group was 16.52±3.54 μmol/L, which was significantly higher than that in DM group(10.86±3.47 μmol/L)and control group(6.84±1.39 μmol/L; all P&#x003C;0.05); The concentration of VitB12 in the serum of the control group was 501.79±108.95 pmol/L, which was higher than that in DM group(478.57±57.85 pmol/L)and DR group(455.88±181.49 pmol/L), but the difference was not statistically significant(P=0.054); The concentration of folic acid in serum of control group was 10.31±2.43 nmol/L, which was higher than that of DM group(9.94±1.90 nmol/L)and DR group(7.27±2.79 nmol/L), and the difference between DR group and DM group was statistically significant(P&#x003C;0.05); In DR group, Hcy expression was weakly positively correlated with triglyceride and low density lipoprotein(r=0.208, P=0.043; r=0.240, P=0.019). Multivariate linear regression showed that low density lipoprotein was an important factor which affect the expression of Hcy in DR patients. ROC curve shows that Hcy has important value in the diagnosis of DR.CONCLUSIONS: Hcy, VitB12 and folic acid are differentially expressed in DR group, DM group and normal control group. Hcy may be involved in the pathogenesis of DR, and it has important value in the diagnosis of DR. In addition, low density lipoprotein is also an important factor which affects the expression of Hcy.
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Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.
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Abstract Excessive intake of non-steroidal anti-inflammatory drugs such as, diclofenac sodium (DS) may lead to toxicity in the rats. In this work, we aimed to examine the protective impact of lentil extract (LE) and folic acid (FA) on the hematological markers, the kidney tissue oxidative stress and the renal function against diclofenac sodium (DS) in male albino rats. The rats (120-150 g) were divided into four equal groups randomly, the first group kept as the untreated control. The second group was administrated with DS (11.6 mg/kg b.wt. orally once/day). The third group was received DS+FA (11.6 mg/kg b.wt.+76.9 microgram/kg b.wt.) orally once/day. The fourth group was treated with DS+LE (11.6 mg/kg b.wt.+500 mg/kg b.wt.) orally once/day. After four weeks, the results revealed that DS produced a significant decrease in the values of red blood cells (RBCs), hemoglobin concentration (Hb), hematocrit (HCT) and white blood cells (WBCs). On the other hand, there was a significant increase in the platelets count. Also, DS induced a renal deterioration; this was evidenced by the significant increase in the serum levels of urea, creatinine, uric acid, Na, Ca, Mg as well as the nitric oxide (NO) level in the kidney tissue. Also, there were a significant reduction in the serum levels of potassium (K) and reduced glutathione (GSH) in the kidney homogenates. Moreover, the findings in the rats treated by DS+LE or DS+FA showed a potential protection on the hematological markers, oxidative stress in the kidney tissue and the renal function disturbed by DS. LE and FA could play a potent role for the prevention the adverse hematological, the kidney tissue oxidative stress and the renal dysfunction caused by DS via their anti-oxidative and bioactive phytochemicals.
Resumo A ingestão excessiva de anti-inflamatórios não esteroidais, como o diclofenaco de sódio (DS), pode causar toxicidade em ratos. Neste trabalho, objetivamos examinar o impacto protetor do extrato de lentilha (LE) e ácido fólico (AF) em marcadores hematológicos, no estresse oxidativo do tecido renal e na função renal contra o diclofenaco de sódio (DS) em ratos albinos machos. Os ratos (120-150 g) foram divididos em quatro grupos iguais aleatoriamente, sendo o primeiro grupo mantido como controle não tratado. O segundo grupo foi administrado com DS (11,6 mg / kg de peso corporal por via oral uma vez / dia). O terceiro grupo recebeu DS + FA (76,9 mg / kg de peso corporal por via oral uma vez / dia). O quarto grupo foi tratado com DS + LE (500 mg / kg de peso corporal por via oral uma vez / dia). Após quatro semanas, os resultados revelaram que o DS produziu uma diminuição significativa nos valores de glóbulos vermelhos (RBCs), concentração de hemoglobina (Hb), hematócrito (HCT) e glóbulos brancos (WBCs). Por outro lado, houve um aumento significativo na contagem de plaquetas. Além disso, o DS induziu uma deterioração renal; isso foi evidenciado pelo aumento significativo dos níveis séricos de ureia, creatinina, ácido úrico, Na, Ca, Mg e também do nível de óxido nítrico no tecido renal. Além disso, houve uma redução significativa nos níveis séricos de potássio (K) e glutationa reduzida (GSH) nos homogenatos renais. Além disso, os achados nos ratos tratados com DS + LE ou DS + FA mostraram uma proteção potencial sobre os marcadores hematológicos, estresse oxidativo no tecido renal e função renal perturbada pelo DS. LE e AF podem desempenhar um papel potente na prevenção do estresse hematológico adverso, do estresse oxidativo do tecido renal e da disfunção renal causada pelo DS por meio de seus fitoquímicos antioxidantes e bioativos.