Objective To investigate the associations between metabolic obesity phenotypes and the risk of developing sarcopenia among middle-aged and older Chinese adults,and further examine the potential moderating roles of age and sex in the associations. Methods On the basis of the data from the China Health and Retirement Longitudinal Study conducted in 2011-2012,a total of 7 421 participants aged 45 years and older were enrolled in this study.Sarcopenia was diagnosed according to the 2019 criteria established by the Asian Working Group for Sarcopenia.According to the body mass index and overall metabolic status,the participants were classified into four metabolic obesity phenotypes:metabolically healthy normal weight,metabolically healthy overweight/obesity,metabolically unhealthy normal weight,and metabolically unhealthy overweight/obesity (MUOO).A multivariate logistic regression model was adopted to assess the association between each metabolic phenotype and the risk of sarcopenia.Stratified analyses were performed by sex and age groups,accompanied by heterogeneity testing.Additionally,Bayesian statistical methods were utilized to verify the reliability and robustness of the findings,particularly within the older age subgroup. Results The analysis revealed a significant moderating effect of age on the association between MUOO and sarcopenia risk.Specifically,among individuals younger than 60 years old,those with MUOO exhibited a significantly elevated risk of sarcopenia (OR=1.56,95%CI=1.03-2.37).This association was further supported by Bayesian analysis,which confirmed the consistency and robustness of the observed trend in the older age group.Stratified analyses by both sex and age uncovered notable heterogeneity:MUOO was identified as a significant risk factor for sarcopenia among men under 60 years old (OR=2.01),whereas it was associated with a significantly lower risk of sarcopenia among women aged 75 years and older (OR=0.13). Conclusions The association between MUOO and sarcopenia risk is markedly influenced by both age and sex.Middle-aged men with MUOO show increased susceptibility to sarcopenia,while MUOO may exert a potential protective effect among older women.These findings underscore the importance of incorporating metabolic status,age,and sex into the design of sarcopenia prevention and management strategies,advocating for personalized precision interventions.
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BackgroundAlzheimer’s disease (AD) is an age-related neurodegenerative disorder with no effective interventions for curing or modifying its progression. However, emerging research suggests that vitamin A in the diet may play a role in both the prevention and treatment of AD, although the exact mechanisms are not fully understood.ObjectivesThis study aims to investigate the dietary vitamin A modifies the gut microbiota and intestinal tissue transcriptome, impacting intestinal permeability and the release of inflammatory factors, thereby influencing Aβ pathology shedding light on its potential as a dietary intervention for AD prevention and treatment.MethodsThe APP/PS1-AD mouse model was employed and divided into three dietary groups: vitamin A-deficient (VAD), normal vitamin A (VAN), and vitamin A-supplemented (VAS) for a 12-week study. Neurobehavioral functions were assessed using the Morris Water Maze Test (MWM). Enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of Diamine Oxidase (DAO), D-lactate, IL-6, IL-1β, and TNF-a cytokines. Serum vitamin A levels were analyzed via LC-MS/MS analysis. Immunohistochemical analysis and morphometry were performed to evaluate the deposition of Aβ in brain tissue. The gut microbiota of APP/PS1 mice was analyzed using 16S rRNA sequencing analysis. Additionally, transcriptomic analysis was conducted on intestinal tissue from APP/PS1 mice.ResultsNo significant changes in food intake and body weight were observed among the groups. However, the VAD and VAS groups showed reduced food intake compared to the VAN group at various time points. In terms of cognitive function, the VAN group performed better in the Morris Water Maze Test, indicating superior learning and memory abilities. The VAD and VAS groups exhibited impaired performance, with the VAS group performing relatively better than the VAD group. Serum vitamin A concentrations differed significantly among the groups, with the VAS group having the highest concentration. Aβ levels were significantly higher in the VAD group compared to both the VAN and VAS groups. Microbial analysis revealed that the VAS and VAN groups had higher microbial diversity than the VAD group, with specific taxa characterizing each group. The VAN group was characterized by taxa such as Actinohacteriota and Desulfovibrionaceae, while the VAD group was characterized by Parabacteroides and Tannerellaceae. The VAS group showed similarities with both VAN and VAD groups, with taxa like Desulfobacterota and Desulfovibrionaceae being present. The VAD vs. VAS, VAD vs. VAN, and VAS vs. VAN comparisons identified 571, 313, and 243 differentially expressed genes, respectively, which associated with cellular and metabolic processes, and pathway analysis revealed enrichment in pathways related to chemical carcinogenesis, drug metabolism, glutathione metabolism, and immune-related processes. The VAD group exhibited higher levels of D-lactate, diamine oxidase, and inflammatory cytokines (TNF-a, IL-1β, IL-6) compared to the VAN and VAS groups.ConclusionDietary vitamin A supplementation modulates the gut microbiota, intestinal permeability, inflammatory factors, and Aβ protein formation, offering insights into the pathogenesis of AD and potential therapeutic avenues for further exploration. This research highlights the intricate interplay between diet, gut microbiota, and neurodegenerative processes, emphasizing the importance of dietary interventions in managing AD-related pathologies.
Background Cognitive decline poses one of the greatest global challenges for health and social care, particularly in China, where the burden on the older adult population is most pronounced. Despite the rapid expansion of internet access, there is still limited understanding of the long-term cognitive impacts of internet use among middle-aged and older adults. Objective This study aims to explore the association between internet use and age-related cognitive decline among middle-aged and older Chinese adults. To gain a more comprehensive understanding of the effects of internet use, we also focused on assessing the impact of both the frequency of internet use and the types of internet devices on cognition. Moreover, we assessed the mediating role of internet use on cognitive function for characteristics significantly linked to cognition in stratified analysis. Methods We analyzed data based on 12,770 dementia-free participants aged ≥45 years from the China Health and Retirement Longitudinal Study. We used a fixed effects model to assess the relationship between internet use and cognitive decline and further validated it using multiple linear regression analysis, generalized estimating equations, propensity score matching, inverse probability of treatment weighting, and overlap weighting. We further examined the varying effects of internet device type and frequency on cognitive function using fixed effects models and Spearman rank correlations. The Karlson-Holm-Breen method was used to estimate the mediating role of internet use in the urban-rural cognitive gap. Results Participants using the internet (n=1005) were younger, more likely to be male, more educated, married, retired and living in an urban area and had higher cognitive assessment scores than nonusers (n=11,765). After adjusting for demographic and health-related risk factors, there was a positive correlation between internet use and cognitive function (β=0.551, 95% CI 0.391-0.710). Over the follow-up period, persistent internet users had a markedly lower 5-year incidence of neurodegenerative diseases, at 2.2% (15/671), compared with nonusers, at 5.3% (379/7099; P<.001). The negative impact of aging (>50 years) on cognitive function was consistently less pronounced among internet users than among nonusers. Furthermore, increased frequency of internet use was associated with greater cognitive benefits for middle-aged and older adults (rs=0.378, P<.001). Among digital devices used for internet access, cell phones (β=0.398, 95% CI 0.283-0.495) seemed to have a higher level of cognitive protection than computers (β=0.147, 95% CI 0.091-0.204). The urban-rural disparity in cognitive function was partially attributed to the disparity in internet use (34.2% of the total effect, P<.001). Conclusions This study revealed that the use of internet by individuals aged 45 years and older is associated with a reduced risk of cognitive decline. Internet use has the potential to be a viable, cost-effective, nonpharmacological intervention for cognitive decline among middle-aged and older adults.
EDITORIAL article Front. Nutr., 20 November 2023Sec. Nutrition and Microbes Volume 10 - 2023 | https://doi.org/10.3389/fnut.2023.1328660
Background and aims: Malnutrition is widely present and influences the prognosis of elderly inpatients, so it is helpful to be able to identify it with a convenient method. However, in the widely accepted criteria for malnutrition, the Global Leadership Initiative on Malnutrition (GLIM), a lot of metrics can be used to define the phenotypic and etiological criteria. To identify muscle mass reduction, anthropometric parameters such as calf circumference (CC) and hand grip strength (HGS) are preferable to other expensive methods in many situations because they are easy and inexpensive to measure, but their applicability needs to be verified in specific clinical scenarios. This study aims to verify the value of CC- and HGS-identified muscle loss in diagnosing malnutrition and predicting in-hospital complications (IHC) and prolonged length of hospital stay (PLOS) in elderly inpatients using machine learning methods. Methods: A sample of 7122 elderly inpatients who were enrolled in a previous multicenter cohort study in China were screened for eligibility for the current study and were then retrospectively diagnosed for malnutrition using 33 GLIM criteria that differ in their combinations of phenotypic and etiological criteria, in which CC or CC+HGS were used to identify muscle mass reduction. The diagnostic consistency with the subjective global assessment (SGA) criteria at admission was evaluated according to Kappa coefficients. The association and the predictive value of the GLIM-defined malnutrition with 30-day IHC and PLOS were evaluated with logistic regression and randomized forest models. Results: In total, 2526 inpatients (average age 74.63 ± 7.12 years) were enrolled in the current study. The prevalence of malnutrition identified by the 33 criteria combinations ranged from 3.3% to 27.2%. The main IHCs was infectious complications (2.5%). The Kappa coefficients ranged from 0.130 to 0.866. Logistic regression revealed that malnutrition was identified by 31 GLIM criteria combinations that were significantly associated with 30-day IHC, and 22 were significantly associated with PLOS. Random forest prediction revealed that GLIM 15 (unconscious weight loss + muscle mass reduction, combined with disease burden/inflammation) performs best in predicting IHC; GLIM 30 (unconscious weight loss + muscle mass reduction + BMI reduction, combined with disease burden/inflammation) performs best in predicting PLOS. Importantly, CC alone performs better than CC+HGS in the criteria combinations for predicting adverse clinical outcomes. Conclusion: Muscle mass reduction defined by a reduced CC performs well in the GLIM criteria combinations for diagnosing malnutrition and predicting IHC and PLOS in elderly Asian inpatients. The applicability of other anthropometric parameters in these applications needs to be further explored.
目的 了解8~9月龄婴儿智能发育测验阳性检出现状及其影响因素,为及早干预提供科学依据.方法 对1127例2020年3月至2021年7月在北京通州区潞河医院常规体检的8~9月龄婴儿进行丹佛发育筛查测验(DDST),并通过单因素分析和多元回归分析婴儿性别、身长别体重、血红蛋白水平、胎龄、出生体重、母亲年龄、孕母健康状况等暴露因素与DDST阳性之间的关系.结果 调查对象的总DDST阳性率为7.1%.其中低出生体重儿DDST阳性检出率(35.1%)高于正常体重儿(6.2%);早产儿DDST阳性率(28.3%)高于足月儿(5.9%),差异均有统计学意义(P<0.01).多因素Logistic回归分析发现低出生体重儿DDST阳性的风险高于正常体重儿,OR值=3.634(95%CI:1.687~7.831)倍;早产儿高于足月儿,OR=4.013(95%CI:1.646-9.783).结论 早产与低出生体重是婴儿DDST阳性的危险因素,应加强对该地区孕产妇的健康管理,减少早产儿和低出生体重儿的发生几率并加强产后管理,预防婴儿智能发育迟缓的发生.
OBJECTIVE:Analyze the relationship between dietary nutrients and body mass index of children and adolescents aged 7-17 in China. METHODS:The data comes from the "China Health and Nutrition Survey", and 5562 children and adolescents aged 7-17 who participated in at least one round(2000, 2006, 2011 and 2015) of the survey and had complete dietary and physical measurement survey data were selected as the research objects. A three-level(community-individual-observation level) linear random intercept mixed effect model of body mass index was constructed to analyze the influence of dietary nutrient intake of children and adolescents of different genders in urban and rural areas on their body mass index(BMI).24 hours for 3 consecutive days and family weight accounting were used to evaluate the dietary nutrient intake. RESULTS:BMI of urban children and adolescents is higher than that of rural children and adolescents. The BMI of children and adolescents aged 12-17 is higher than that of children and adolescents aged 7-11. BMI of boys was higher than that of girls, but the difference was statistically significant only in 2011 and 2015. After controlling for confounding factors such as individual level(survey year, age, physical activity and family per capita income) and community level(community urbanization index), the three-level model showed that the BMI of rural boys increased with the increase of cholesterol intake(P<0.01). BMI of urban girls increased with the increase of vitamin B_1 intake(P<0.05) and iron intake(P<0.01). BMI of rural girls increased with the increase of vitamin E intake(P<0.001) and sodium intake(P<0.05). CONCLUSION:There are some differences in dietary nutrients that affect the BMI level of 7-17 years old children and adolescents between urban and rural areas.
BACKGROUND:Malnutrition is prevalent in elderly inpatients and is associated with various adverse outcomes during their hospital stay, but the diagnosis of malnutrition still lacks widely applicable criteria. This study aimed to investigate the association of malnutrition diagnosed with the SGA, ESPEN 2015, and GLIM criteria, respectively, with in-hospital complications in elderly patients.METHOD:Hospitalized patients over 65 years old who had been assessed with the SGA guideline for malnutrition at admission were retrospectively recruited from a large observational cohort study conducted in 34 level-A tertiary hospitals in 18 cities in China from June to September 2014. Malnutrition was then retrospectively diagnosed using the GLIM and ESPEN 2015 criteria, respectively, for comparison with the results of the SGA scale. The risk factors for malnutrition were analyzed using logistic regression, and the value of the three diagnostic criteria in predicting the in-hospital complications was subsequently explored using multivariate regression and the random forest machine learning algorithm.RESULTS:A total of 2526 subjects who met the inclusion and exclusion criteria of the study were selected from the 7122 patients in the dataset, with an average age of 74.63 ± 7.12 years, 59.2% male, and 94.2% married. According to the GLIM, SGA, and ESPEN 2015 criteria, the detection rates of malnutrition were 37.8% (956 subjects), 32.8% (829 subjects), and 17.0% (429 subjects), respectively. The diagnostic consistency between the GLIM and the SGA criteria is better than that between the ESPEN 2015 and the SGA criteria (Kappa statistics, 0.890 vs. 0.590). Logistic regression showed that the risk of developing complications in the GLIM-defined malnutrition patients is 2.414 times higher than that of normal patients, higher than those of the ESPEN 2015 and SGA criteria (1.786 and 1.745 times, respectively). The random forest classifications show that the GLIM criteria have a higher ability to predict complications in these elderly patients than the SGA and ESPEN 2015 criteria with a mean decrease in accuracy of 12.929, 10.251, and 5.819, respectively, and a mean decrease in Gini of 2.055, 1.817, and 1.614, respectively.CONCLUSION:The prevalence of malnutrition diagnosed with the GLIM criteria is higher than that of the SGA and the ESPEN 2015 criteria. The GLIM criteria are better than the SGA and the ESPEN 2015 criteria for predicting in-hospital complications in elderly patients.
目的 研究甘薯提取物(sweet potato extract,SPE)对结直肠癌(colorectal cancer,CRC)荷瘤鼠肝脏中多种免疫细胞因子表达水平的影响.方法 20只雄性Balb/c裸鼠分为2组(对照组、SPE组,每组10只).对照组正常饮食、饮水;SPE组经饮水摄入甘薯提取物(平均摄入量2 g/d);2组均在第5周第1 d腹腔接种人结直肠癌LoVo细胞,第8周末处死所有动物,通过抗体芯片技术检测肝组织中多种免疫细胞因子的表达水平.结果 SPE干预使肝组织中c-c基序趋化配体(c-c motif chemokine ligand,CCL)11(P<0.05)、c-x-c基序趋化配体(c-x-c motif chemokine ligand,CXCL)11(P<0.01)、白细胞介素(interleukin,IL)-10(P<0.05)、IL-12(P<0.05)、IL-22(P<0.01)、IL-23(P<0.05)、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-3、MMP-9(P<0.01)、双调蛋白和血管生成素样3蛋白表达水平显著降低,巨噬细胞集落刺激因子(macrophage-colony stimulating factor,M-CSF)(P<0.01)和血管生成素样2蛋白(P<0.05)水平升高,粒细胞-巨噬细胞集落刺激因子(granulocyte macrophage-colony stimulating factor,GM-CSF)、?干扰素(interferon?,INF?)、CCL2、CCL3、CCL20、IL-17A、血管生成素样1蛋白无显著改变.结论 经口摄入SPE可降低CRC荷瘤鼠肝组织整体炎症反应,调节血管生成及组织重塑因子,有助于恢复肝功能的动态平衡.
BackgroundAccumulating evidence indicates that sporamin, the main storage protein in the sweet potato (Ipomoea batatas), can suppress the development of colorectal cancer (CRC), but the changes in the gut microbiome after sporamin intervention and its relationships with the pathogenesis of CRC have not been investigated.MethodsTwelve male athymic BALB/c nude mice were randomly divided into four groups, CG1, CG2, TCG, and TTG. Mice in TCG and TTG were intraperitoneally transplanted with the LoVo cancer cells before the interventions started. CG2 and TTG were intragastrically infused with sporamin (0.5 g/kg BW/ day) for four weeks while CG1 and TCG were infused with the same volume of water during the experiment. Fecal samples were collected after the interventions and then examined for the changes in the microbiota using the 16S ribosomal RNA (rRNA) sequencing technology. The functional capabilities of the gut microbiota were predicted with the PICRUSt pipeline. Transcriptomic profiling of the tumor tissues was carried out for tumor-bearing mice with the RNA-sequencing (RNA-seq) technology and the resultant differentially expressed genes (DEGs) were then analyzed in terms of gene ontology (GO), protein-protein interaction (PPI), transcription factors (TF) prediction, and biological pathway annotations. ResultsSporamin significantly reduced the tumor burden of tumor-bearing mice and brought beneficial changes to the gut microbiome in both kinds of mice. It significantly increased the proportions of Barnesiella and Lactobacillus but reduced that of Bacteroides in tumor-bearing mice. The phenylalanine metabolism pathway, the glyoxylate, dicarboxylate metabolism, the bacterial secretion system, the glycan biosynthesis and metabolism, and the biosynthesis of stilbenoid, diarylheptanoid, and gingerol were favorably modulated by sporamin intervention. Sporamin mainly modulate the expression of the genes involved in the protein processing in the endoplasmic reticulum, the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, and the mineral absorption pathway. ConclusionSporamin could favorably alter the gut microbiome and its metabolome, improving the gut microenvironment and the viability of the gut microbiota and increasing the detoxification and bioactive substance production activities in the large intestine, by which the host’s metabolome may be altered and in turn exerts a suppressing effect on the protein synthesis and growth of tumor tissues.
目的 研究维生素A缺乏(vitamin A deficiency,VAD)对阿尔茨海默症(Alzheimer's disease,AD)模型APP/PS1小鼠认知功能和补体系统的影响,探索补体因子影响APP/PS1小鼠认知功能的作用机制.方法 将20只雄性APP/PS 1小鼠随机分为维生素A缺乏组(VAD)和维生素A正常组(vitamin A normal,VAN),进行45周的特殊饲料干预.45周后,进行新物体识别实验和Y迷宫实验以检测小鼠的认知功能,采用免疫组化和Western Blot检测小鼠皮质中的补体系统起始因子C1q的蛋白表达情况,采用实时荧光定量聚合酶链式反应(real-time quantitative polymerase chain reaction,RT-qPCR)检测小鼠海马中C1q以及其他补体因子的mRNA表达情况.结果 新物体识别实验和Y迷宫实验的结果显示,维生素A缺乏使APP/PS1小鼠认知功能障碍加重.免疫组化和Western Blot的结果显示,与VAN组相比,VAD干预45周后皮质中的C1q的蛋白表达量显著升高(P<0.05).RT-qPCR结果显示,VAD干预45周后,海马中C1q和C1r的mRNA表达显著上调(P<0.05),C4、C4BP和C5的mRNA表达显著下调(P<0.05),而C1s、C2、C3和C5aR1的mRNA表达无明显变化.结论 长期缺乏维生素A会加重AD模型APP/PS1小鼠的认知功能障碍并影响大脑中的补体系统,且补体因子可能参与VAD影响认知功能的作用机制.
Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer's disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL/6J amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-β peptides (Aβ40 and Aβ42) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and γ-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of Lactobacillus and significantly different α- and β-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism.
目的 比较老年肌少症性肥胖不同诊断方法的检出率,并分析诊断标准间的一致性.方法 回顾分析2014年12月至2017年7月北京医院营养科696例老年人临床资料,根据"2019亚洲肌少症诊断和治疗共识",将696例老年人分为肌肉减少症组(63例)和非肌肉减少症组(633例).分别采用世界卫生组织(World Health Organization,WHO)法,60%体脂率法和体重指数(body mass index,BMI)法的肥胖诊断标准,对比三种方法对老年肌少症性肥胖检出率和诊断一致性.结果 肌肉减少症组BMI、握力、骨骼肌质量及血液白蛋白、甘油三酯和血红蛋白水平低于非肌肉减少症组(P<0.05),而年龄、体脂百分率、合并冠心病率高于非肌肉减少症组(P<0.05).WHO法、60%体脂率法和BMI法对老年肌少症性肥胖症的检出率分别为7.90%、6.75%、0.86%,其中60%体脂率法与WHO法诊断一致性较好(Kappa=0.853,P<0.01);BMI法与WHO法诊断一致性较差(Kappa=0.059,P<0.01),BMI法的检出率明显低于另两种方法(P<0.01).结论 WHO法对老年肌少症性肥胖的检出率最高;60%体脂率法与WHO法的诊断一致性较好;BMI法检出率最低,不能有效检出老年肌少症性肥胖者.
目的 系统评价口服益生菌对结直肠癌患者术后感染的影响.方法 计算机检索PubMed、The Cochrane Library、EMbase、CNKI、WanFang Data和VIP数据库,搜集有关益生菌干预结直肠癌患者术后感染的随机对照试验(randomized controlled trials,RCTs),检索时限均为建库至2020年3月.由2名研究者独立筛选文献、提取资料并进行质量评价,采用RevMan 5.3软件与Stata 14.0软件进行Meta分析.结果 共纳入13个RCTs(1122例患者),Meta分析结果显示:益生菌干预的试验组术后感染的总发生率低于对照组(OR=0.32,95%CI:0.24~0.44).同时,试验组手术部位感染(OR=0.42,95%CI:0.27~0.66)、尿路感染(OR=0.30,95%CI:0.16~0.59)和肺部感染(OR=0.38,95%CI:0.23~0.66)的发生率也低于对照组,但腹腔脓肿(OR=0.55,95%CI:0.20~1.51)差异无统计学意义(P>0.05).2组研究对象在吻合口瘘(OR=0.41,95%CI:0.19~0.87)和住院时间(WMD=-1.44,95%CI:-2.18~-0.71)差异也具有统计学意义.亚组分析结果提示2种及2种以上益生菌的联合效果可能高于单一益生菌干预的效果.结论 结直肠癌患者口服益生菌可降低术后感染的发生率,改善患者预后.
Sporamin, a proteinase inhibitor isolated from the sweet potato (Ipomoea batatas), has shown promising anticancer effect against colorectal cancer (CRC) in vitro and in vivo but its mechanisms of action are poorly understood. In the present study, high throughput RNA sequencing (RNA-seq) technology was applied to explore the transcriptomic changes induced by sporamin in the presence of thapsigargin (TG), a non-12-O-tetradecanolphorbol-13-acetate type cancer promoter, in the LoVo human CRC cells. Cellular total RNA was extracted from the cells after they were treated with vehicle (CTL), 1 μM of thapsigargin (TG), or 1 μM of TG plus 30 μM of sporamin (TGSP) for 24 h. The migratory capacity of the cells was determined by wound healing assay. The gene expression profiles of the cells were determined by RNA-seq on an Illumina platform. GO enrichment analysis, KEGG pathway analysis, protein-protein interaction (PPI) network construction, and transcription factors (TF) prediction were all performed based on the differentially expressed genes (DEGs) across groups with a series of bioinformatics tools. Finally, the effect and potential molecular targets of the sporamin at the transcriptome level were evaluated. Sporamin significantly inhibited the migration of cells induced by TG. Among the 17915 genes detected in RNA-seq, 46 DEGs were attributable to the effect of sporamin. RT-PCR experiment validated that the expression of RGPD2, SULT1A3, and BIVM-ERCC5 were up-regulated while NYP4R, FOXN1, PAK6, and CEACAM20 were down-regulated. Sporamin enhanced the mineral absorption pathway, worm longevity regulating pathway, and pyrimidine metabolism pathway. Two TFs (SMIM11A and ATOH8) were down-regulated by sporamin. HMOX1 (up-regulated) and NME1-NME2 (down-regulated) were the main nodes in a PPI network consisting of 16 DEGs that were modulated by sporamin in the presence of TG. Sporamin could favorably alter the gene expression profile of CRC cells, up-regulating the genes that contribute to the homeostasis of intracellular metal ions and the activities of essential enzymes and DNA damage repairment. More studies are warranted to verify its effect on specific genes and delineate the mechanism of action implicated in the process.
目的 探索甘薯提取物对结直肠癌荷瘤裸鼠粪便中钙卫蛋白(calprotectin,CP)、乳铁蛋白(lactoferrin,LTF)、二胺氧化酶(diamine oxidase,DAO)及氨基酸含量的影响,分析其可能的作用机理.方法 将12只雄性裸鼠随机分为4组:空白对照组(CG1)、甘薯提取物组(CG2)、移植瘤模型组(TCG)、移植瘤模型+甘薯提取物组(TTG).每组3只小鼠,分别干预1个月,在第23、30 d收集粪便检测CP、LTF、DAO和氨基酸含量.结果 实验第23 d TCG组CP、LTF和DAO含量即均显著高于CG1组(P<0.05),TTG组LTF和DAO含量比TCG组显著降低(P<0.05);到第30 d时,TTG组CP和LTF含量显著低于TCG组(P<0.05),但DAO显著升高(P<0.05).此外,CG2组动物粪便中16种氨基酸含量比CG1组均升高(P<0.05);TTG组除缬氨酸、蛋氨酸、异亮氨酸、酪氨酸和组氨酸外其余氨基酸含量比TCG组均升高(P<0.05).结论 经口摄入甘薯提取物有助于改善荷瘤鼠体内的氨基酸代谢失衡状况,显著降低肠道炎症介质CP和LTF的水平,并提高DAO含量,有助于保护肠粘膜的完整性和抑制肿瘤.
目的 建立气相色谱-串联质谱法同时检测代用茶中16种农药残留的分析方法 .方法代用茶样品中的农残经乙腈提取后,用25 mgN-丙基乙二胺(primary secondary amine,PSA)、150 mg MgSO4净化,引入分析保护剂补偿基质效应,用气相色谱-串联质谱法测定其中16种农药残留.结果 16种农药成分在0.005~0.400μg/mL范围内有良好线性关系,相关系数均大于0.98;检出限均在0.003~0.007 mg/kg之间,定量限在0.011~0.022 mg/kg之间;在3个添加水平下(0.04、0.10和0.40 mg/kg)的平均回收率为80.2%~104%,相对标准偏差(n=6)为3.4%~12.4%.结论 本方法样品处理简单快速,灵敏度和选择性高,重复性好,适用于代用茶中多种农药残留的同时检测.
BACKGROUND Colorectal cancer (CRC) is the third most common malignancy of the digestive tract and the fifth leading cause of cancer-related mortality in China. Sporamin, a Kunitz-type trypsin inhibitor isolated from sweet potato, is a potential anti-cancer agent with activities against a number of malignant tumor cells in vitro. The liver secretes a myriad of endocrine factors that may facilitate the growth and transformation of tumors in the development of CRC. AIM To investigate the effects of sporamin on liver morphology and biomarkers of xenografted CRC in the liver of athymic BALB/c mice. METHODS Twenty-seven male BALB/c nude mice were randomly divided into control, vehicle, and sporamin groups. Mice in the latter two groups were intraperitoneally xenografted with LoVo colorectal carcinoma cells and intragastrically infused with saline or sporamin (0.5 g/kg body weight/d), respectively, for 3 wk. Hematoxylin and eosin (HE) staining of the sections was performed to observe morphological changes in hepatic tissue and real-time fluorescent quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to measure the expression of β-catenin and vascular endothelial growth factor (VEGF) in the liver. RESULTS Sporamin significantly reduced the number and weight of tumor nodules formed in the abdominal cavity. Compared with the vehicle group, the mean tumor weight (± SD) in the sporamin group was significantly reduced (0.44 ± 0.10 g vs 0.26 ± 0.15 g) and the total number of tumors decreased from 93 to 55. HE staining showed that enlargement of the nucleus and synthesis of proteins within hepatocytes, as well as infiltration of inflammatory cells into the liver, were attenuated by sporamin. Immunohistochemical staining and ELISA showed that the concentrations of β-catenin and VEGF in the liver were significantly reduced by sporamin. Compared with the vehicle group, the expression of β-catenin measured in integrated optical density units per area was reduced in the sporamin group (47.29 ± 9.10 vs 26.14 ± 1.72; P = 0.003). Expression of VEGF was also reduced after sporamin intervention from 20.78 ± 2.06 in the vehicle group to 15.80 ± 1.09 in the sporamin group (P = 0.021). Compared with the vehicle group, the concentration of β-catenin decreased from 134.42 ± 22.04 pg/mL to 109.07 ± 9.65 pg/mL after sporamin intervention (P = 0.00002). qPCR indicated that compared to the vehicle group, relative mRNA expression of β-catenin and VEGF in the liver of mice in the sporamin-treated group was significantly reduced to 71% ± 1% (P = 0.000001) and 23% ± 7% (P = 0.00002), respectively, of the vehicle group levels. CONCLUSION Sporamin down-regulates the expression and secretion of β-catenin and VEGF in the liver, which subsequently inhibits the transcription of downstream genes involved in cancer progression and angiogenesis.