Objective To explore the association between pulmonary ventilation dysfunction in miners and exposure to heavy metals. Method Mine workers participated by providing questionnaire data and biological samples during physical exams at the Guangxi Institute of Occupational Disease Prevention. Pulmonary function was assessed, and serum heavy metal concentrations were measured by ICP-MS. Various regression models, including GLM, RCS, WQS, and BKMR, were used to analyze the link between heavy metal exposure and pulmonary dysfunction. Result 186 participants were recruited, with an average age of 45.33 (±6.90) years and 40 months median employment history. There was 119 (63.98%) male workers and 67 (36.02%) female workers, including 68 (36.56%) and 88 (47.31%) individuals reported consumed smoking and drinking. Consistent with the diagnostic standards for pulmonary function, 147 subjects exhibited normal pulmonary function, whereas 39 subjects demonstrated abnormal pulmonary function, resulting in a prevalence rate of pulmonary dysfunction of 20.97%. Logistic regression identified arsenic (As), chromium (Cr), manganese (Mn), and lead (Pb) as significant contributors to pulmonary dysfunction. RCS analysis revealed a linear relationship between Cr, Mn, and Pb levels and pulmonary dysfunction (P < 0.05). The WQS model found Cr had the highest weight (OR = 3.811). BKMR analysis showed a positive association between As, Mn, and Pb with pulmonary dysfunction, and Cr had the highest population attributable fraction. Conclusion Pulmonary dysfunction prevalence was 20.97%, with Cr, Mn, and Pb being major contributors, particularly Cr, which showed a dose-response relationship with the risk of pulmonary dysfunction.

Ion channels can selectively recognize and transport biological species via an exquisite protein conformational switch. Classically, glucose-specific ion channels strictly transport the disomer over the lisomer. Inspired by this, we report a biomimetic d-glucose-responsive ion gate. We designed and synthesized a functional receptor, a chiral biphenylboronic acid (cBBA) derivative, which was used as a responsive element in an artificial nanopore. Due to its high binding affinity for d-glucose molecules, the biomimetic ion gate exhibits a sensitive and specific gating effect in response to d-glucose stimulation, thereby modulating the ionic current rectification (ICR) behavior. Remarkably, an extremely low concentration (e.g., 10 pM) of d-glucose stimulus could generate a remarkable ionic current change. After binding of physiological concentration of d-glucose (e.g., 5 mM), the ionic current modulation drastically decreased, with the switch ratio reaching up to 1530, showing a powerful gating capacity. Particularly, other saccharide analogues or the l-glucose isomer failed to activate the ion gate. Moreover, this gating effect was pH-dependent and demonstrated reversible ON-OFF ability when altering the medium acidity. Density functional theory (DFT) calculations unraveled that the designed artificial receptor can preferentially bind d-glucose over the l-glucose enantiomer, and finite element simulations revealed the ion gating mechanism in the d-glucose sensing event. The nanopore sensor was successfully applied to the electrochemical assay of glucose in biofluids.

Objective :A high-fat/high-fructose diet (HFFD) is a leading dietary driver of the global epidemics of metabolic syndrome and type 2 diabetes. Lipopolysaccharide (LPS)-mediated metabolic endotoxemia is a core pathological link between HFFD and glucose metabolic disorders. Asprosin is a key adipokine regulating glucose homeostasis, which is dysregulated under HFFD conditions. However, the causal role and underlying mechanism of HFFD-induced LPS elevation in regulating Asprosin production and glucose metabolic dysfunction remain largely unclear. This study aimed to elucidate the regulatory axis between HFFD, LPS, Asprosin and glucose metabolism, as well as its core molecular mechanism.Methods: In vivo, metabolic endotoxemia models were established via HFFD feeding or subcutaneous LPS injection in C57BL/6J mice. Glucose metabolism and insulin sensitivity were evaluated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Serum LPS and Asprosin levels were detected by enzyme-linked immunosorbent assay (ELISA). In vitro, mouse primary preadipocytes were treated with LPS, combined with TLR4 inhibitor, mTOR inhibitor, Furin inhibitor, or TLR4 siRNA knockdown. Cell viability, Asprosin secretion, and the expression/activity of related molecules and signaling pathways were assessed by CCK-8 assay, ELISA, RT-qPCR, and Western blot.Results : HFFD feeding induced significant glucose intolerance, insulin resistance, and metabolic endotoxemia in mice, accompanied by a marked elevation in serum Asprosin levels. In vitro, LPS dose- and time-dependently stimulated Asprosin secretion from primary preadipocytes, upregulated the mRNA expression of its precursor FBN1, and increased the expression and activity of its processing protease Furin. Mechanistically, LPS treatment markedly activated the TLR4 receptor and downstream mTOR signaling pathway in preadipocytes. Inhibition of TLR4 or mTOR, as well as siRNA-mediated TLR4 knockdown, significantly reversed LPS-induced Furin activation and Asprosin overproduction.Conclusion: HFFD-induced LPS elevation promotes the synthesis and secretion of Asprosin via activating the TLR4/mTOR/Furin pathway, thereby aggravating glucose metabolic dysfunction. This study identifies a new perspective between unhealthy dietary patterns and glucose metabolic disorders, and provides a promising target for the nutritional prevention and targeted intervention of HFFD-related glucose metabolic disorders.

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). However, the impact of fructose on Hcy concentrations and whether fructose intake increases disease risk through elevated Hcy remains unclear. We hypothesized that fructose intake is related to Hcy concentrations, and Hcy acts as a mediator linking fructose with CVD and hypertension. We analyzed 2003 to 2006 NHANES data using multivariate logistic regression and restricted cubic spline (RCS) analyses to examine the relationships between fructose intake from different food sources and Hcy concentrations, and to assess whether Hcy mediates the association between fructose intake and CVD or hypertension. After adjusting for confounders, Hcy concentrations were positively associated with the intake of all beverages and foods with added sugars that contain fructose, with an odds ratio of 1.23 (95% CI: 1.01-1.48). RCS analyses showed a "J-shaped" association between Hcy concentrations and the intake of coffee/tea with added sugars, other foods (excluding coffee/tea) with added sugars, tomato catsup, and total juice. An "inverted U-shaped" association was observed with cake intake (all P < .05). Hcy mediated the associations between 4 food sources of fructose (nondiet soft drinks, coffee/tea with added sugars, high-fructose corn syrup sweetened beverages, all beverages and foods with added sugars that contain fructose) and CVD (indirect effects [IE]: 0.03%, 0.03%, 0.04%, and 0.03%) and hypertension (IE: 0.16%, 0.18%, 0.20%, and 0.14%), all P < .05. The findings suggested that various food sources of fructose are associated with Hcy concentrations, and Hcy mediates the relationship between fructose intake and CVD and hypertension.

Objectives: This study investigates the role of Nicotinamide N-methyltransferase (NNMT) in immune infiltration modulation through amino acid metabolism in gastric adenocarcinoma (STAD). Methods: Utilizing data from The Cancer Genome Atlas (TCGA) and validated with clinical samples, we analyzed NNMT expression and its prognostic implications in STAD. Differential amino acid profiles between cancerous and adjacent normal tissues were assessed, along with their associations with NNMT. Results: NNMT exhibits heightened expression in STAD cancer tissues, positively correlating with tumor immune infiltration. Additionally, twenty-eight amino acids display differential expression in gastric tissue, with their metabolic enzymes showing connections to NNMT. Conclusions: Elevated NNMT expression in STAD tissues potentially influences amino acid metabolism, thereby affecting immune infiltration dynamics and tumorigenesis in gastric adenocarcinoma.

Microglia, the resident immune cells of the central nervous system (CNS), play a dual role in neurotoxicity by releasing the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF) in response to environmental stress. Suppression of BDNF is implicated in learning and memory impairment induced by exposure to manganese (Mn) or lead (Pb) individually. Methyl CpG Binding Protein 2 (MeCp2) and its phosphorylation status are related to BDNF suppression. Protein phosphatase2A (PP2A), a member of the serine/threonine phosphatases family, dephosphorylates substrates based on the methylation state of its catalytic C subunit (PP2Ac). However, the specific impairment patterns and molecular mechanisms resulting from co-exposure to Mn and Pb remain unclear. Therefore, the purpose of this study was to explore the effects of Mn and Pb exposure, alone and in combination, on inducing neurotoxicity in the hippocampus of mice and BV2 cells, and to determine whether simultaneous exposure to both metals exacerbate their toxicity. Our findings reveal that co-exposure to Mn and Pb leads to severe learning and memory impairment in mice, which correlates with the accumulation of metals in the hippocampus and synergistic suppression of BDNF. This suppression is accompanied by up-regulation of the epigenetic repressor MeCp2 and its phosphorylation status, as well as demethylation of PP2Ac. Furthermore, inhibition of PP2Ac demethylation using ABL127, an inhibitor for its protein phosphatase methylesterase1 (PME1), or knockdown of MeCp2 via siRNA transfection in vitro effectively increases BDNF expression and mitigates BV2 cell damage induced by Mn and Pb co-exposure. We also observe abnormal activation of microglia characterized by enhanced release of the NLRP3 inflammasome, Casepase-1 and pro-inflammatory cytokines IL-1β, in the hippocampus of mice and BV2 cells. In summary, our experiments demonstrate that simultaneous exposure to Mn and Pb results in more severe hippocampus-dependent learning and memory impairment, which is attributed to epigenetic suppression of BDNF mediated by PP2A regulation.

目的:研究牛磺酸(Tau)对人外周血T淋巴细胞体外活化增殖及分化的影响及其作用机制.方法:无菌分离健康志愿者外周血淋巴细胞,建立植物凝集素(PHA)刺激T细胞体外活化增殖模型.实验设置对照组(control组)、PHA刺激组(PHA 5 μg/mL组)及Tau处理组(PHA+Tau80mmol/L组、PHA+Tau 160 mmol/L组).细胞计数试剂盒(CCK-8)法检测T淋巴细胞增殖率;瑞—吉染色法观察细胞形态及计算转化率;实时荧光定量PCR检测T细胞增殖标志物Ki67,Th1转录因子T-bet及细胞因子干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α),Th2转录因子GATA-3及白介素-4/6(IL-4/6),凋亡相关因子Fas、FasL基因表达水平;活性氧(ROS)试剂盒检测细胞内ROS水平.结果:与control组相比,PHA 5 μg/mL组T淋巴细胞转化率、增殖率、增殖标志物Ki67、Th1相关因子T-bet、IFN-γ、TNF-α、凋亡相关因子Fas基因表达及胞内ROS水平升高(P＜0.05),凋亡相关因子FasL基因,Th2相关因子GATA-3、IL-6基因表达水平降低(P＜0.05).与PHA 5 μg/mL组相比,PHA+Tau 80 mmol/L组与PHA+Tau 160 mmol/L组T淋巴细胞转化率、增殖率、Ki67基因表达及胞内ROS水平均下降(P＜0.05),Th2相关因子IL-4、IL-6基因表达水平均升高(P＜0.05),Th1相关因子IFN-y、FasL基因表达水平差异均无统计学意义(P＞0.05),PHA+Tau 80 mmol/L组Th1相关因子T-bet、TNF-α、Th2相关因子GATA-3及Fas基因表达水平差异无统计学意义(P＞0.05),PHA+Tau 160 mmol/L组Th1相关因子T-bet、TNF-α、Th2相关因子GATA-3及Fas基因表达水平升高(P＜0.05).结论:Tau可能通过下调Ki67表达和增强Fas-AICD途径抑制T细胞增殖转化,并可能通过降低胞内ROS含量,提高Th1/Th2活化水平,调节Th1/Th2平衡偏向Th1分化,发挥调节T淋巴细胞活化增殖及分化的作用.

Objective To investigate the molecular mechanism of taurine regulating the polarization of M2 macrophages by mitophagy. Methods THP-1 cells were divided into four groups: M0 group (THP-1 cells were treated by 100 nmol/L phorbol myristate ester for 48 hours to polarize into M0), M2 group (THP-1 cells were induced to polarize into M2 macrophages by 20 ng/mL interferon-4 (IL-4) for 48 hours), M2 combined with taurine groups (added with 40 or 80 mmol/L taurine on the basis of M2 macrophages). The mRNA expression of mannose receptor C type 1(MRC-1), C-C motif chemokine ligand 22(CCL22) and dendritic cell-specific ICAM-3 grabbing non-integrin (CD209) in M2 macrophages were detected by quantitative real-time PCR. Mitochondrial and lysosome probes were used to detect the number of mitochondria and lysosomes by multifunction microplate reader and confocal laser scanning microscope. The level of mitochondrial membrane potential (MMP) was detected by JC-1 MMP assay kit. The expression of mitophagy-related proteins PTEN-induced putative kinase 1 (PINK1) and microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blot analysis. Results Compared with M0 group, the expression of MRC-1, CCL22, CD209 and PINK1, the number of mitochondria and the level of MMP in M2 group were significantly increased, whereas the number of lysosomes and LC3II/LC3I ratio were decreased. Compared with M2 group, the expressions of MRC-1, CCL22 and CD209, the number of mitochondria and the level of MMP in M2 combined with taurine group dropped significantly while the number of lysosomes was found increased, and the protein expression of PINK1 and LC3II/LC3I ratio were also increased. Conclusions The polarization of M2 macrophages is regulated by taurine to prevent excessive polarization via reducing the level of MMP, improving the level of mitophagy, reducing the number of mitochondria, and inhibiting the mRNA expression of polarization markers in M2 macrophages.

目的:研究成脂诱导剂MDI对活化的人肝星状细胞的作用及其机制.方法:体外培养人肝星状细胞系LX-2细胞,实验分为4组,即空白对照组、溶剂对照组、重组人转化生长因子β1(TGF-β1)组、TGF-β1+MDI组.油红O染色法检测细胞内脂滴变化,实时荧光定量PCR(RT-qPCR)法检测肝纤维化标志物肌动蛋白α2(ACTA2)、Ⅰ型胶原蛋白α1(COL1A1)、金属蛋白酶组织抑制剂1(TIMP1)基因相对表达量.线粒体特异性荧光探针检测TGF-β1/MDI干预后LX-2细胞内线粒体数量的变化.采用western blotting法检测各组蛋白磷酸酶2A催化性C亚基(PP2Ac)蛋白表达.结果:与空白对照组和溶剂对照组比较,TGF-β1组LX-2细胞胞体增大、呈多边形且胞质增多、未见明显脂滴、线粒体数量增加,肝纤维化标志物ACTA2、COL1A1和TIMP-1 mRNA表达水平以及PP2Ac去甲基化蛋白表达水平升高(均P＜0.01).与TGF-β1组比较,TGF-β1+MDI组细胞变小、胞质内小脂滴数量增加、线粒体数量减少,ACTA2、COL1A1和TIMP-1mRNA表达水平以及PP2Ac去甲基化蛋白表达水平降低(均P＜0.05).结论:TGF-β1和MDI可能通过调控肝星状细胞的PP2Ac去甲基化水平调控人肝星状细胞活化,且与脂质生成以及线粒体数量有关.

Objective Chlorogenic acid has a various of biological effects such as anti-inflammatory and antioxidant. T cells are an important part of the immune system, and the effect of chlorogenic acid on T lymphocytes is unknown. This paper aims to study the effect of chlorogenic acid on the proliferation and immunomodulatory function of human peripheral blood T lymphocytes stimulated with phytohaemagglutinin（PHA） in vitro. Methods Human peripheral blood mononuclear cells（PBMCs） were isolated by Ficoll centrifugation, and divided into Control group, PHA group, the group co-treatment with PHA and 50 μg/mL, 100 μg/mL chlorogenic acid. CCK-8 assay was used to detect cell proliferation. The morphology of the lymphocytes was observed by Wright’s-Giemsa staining. The mRNA expression of T cell proliferation markers Ki-67, Th1 cytokines interferon-γ（IFN-γ）, tumor necrosis factor-α（TNF-α）, and transcription factor T-bet, Th2 cytokines Interleukin 4（IL-4）, Interleukin 13（IL-13）, and transcription factor GATA-3 were detected by quantitative real-time PCR. Reactive oxygen species kits were used to detect intracellular ROS levels. Results Compared with Control group, T cells significantly proliferated and transformed into lymphoblastoid cells in PHA group. Following PHA treatment, the mRNA expression levels of T cells proliferation markers Ki-67, and Th1 related factors IFN-γ, TNF-α, and T-bet were significantly increased（P＜0.05）, and Th2 related factors IL-4 and IL-13 were increased（P＞0.05）. GATA-3 mRNA was significantly decreased（P＜0.05）, and the level of intracellular ROS was significantly increased with PHA stimulation（P＜0.01）. After co-treatment with PHA and 50 μg/mL, 100 μg/mL chlorogenic acid, compared with PHA group, the proliferation and transformation of T lymphocytes and the mRNA expression of Ki-67, IFN-γ, and T-bet were significantly decreased（P＜0.05）. IL-4, IL-13, GATA-3 mRNA level significantly increased（P＜0.05）, and dose-dependently reduced intracellular ROS levels（P＜0.01）. Conclusion Chlorogenic acid inhibits the proliferation of human peripheral blood T-lymphocyte in vitro. Chlorogenic acid may exert immunomodulatory functions by downregulating ROS levels and inhibiting Th1 factor expression to promote Th2 differentiation.

Impaired glucose regulation is one of the most important risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which have become a major public health issue worldwide. Dysregulation of carbohydrate metabolism in liver has been shown to play a critical role in the development of glucose intolerance but the molecular mechanism has not yet been fully understood. In this study, we investigated the role of hepatic LCMT1 in the regulation of glucose homeostasis using a liver-specific LCMT1 knockout mouse model. The hepatocyte-specific deletion of LCMT1 significantly upregulated the hepatic glycogen synthesis and glycogen accumulation in liver. We found that the liver-specific knockout of LCMT1 improved high fat diet-induced glucose intolerance and insulin resistance. Consistently, the high fat diet-induced downregulation of glucokinase (GCK) and other important glycogen synthesis genes were reversed in LCMT1 knockout liver. In addition, the expression of GCK was significantly upregulated in MIHA cells treated with siRNA targeting LCMT1 and improved glycogen synthesis. In this study, we provided evidences to support the role of hepatic LCMT1 in the development of glucose intolerance induced by high fat diet and demonstrated that inhibiting LCMT1 could be a novel therapeutic strategy for the treatment of glucose metabolism disorders.

《食品理化检验》是四年制卫生检验与检疫专业的核心课程之一,开展《食品理化检验》课程思政建设对于培养新时代卫生检验与检疫人才具有重要意义.文章首先阐述了该门课程思政教育开展中的难点,并从利用实验课时开展思政教学、基于学科专业知识恰当融入思政元素、建立多元化的课程思政评价方式等三方面深入探讨解决方案,为《食品理化检验》课程思政的建设提供思路和借鉴.

Non-alcoholic fatty liver disease (NAFLD) is a progressive disorder of liver metabolism and has become the most common chronic liver disease worldwide. Benzo[a]pyrene (BaP) is recognized as a potent carcinogen, but the effect of low-dose BaP on the development of NAFLD has not been well-studied, and its molecular mechanism is still unknown. In this study, we demonstrated that low-dose BaP induced hepatic steatosis in a mouse model with a notable increase in hepatic lipid content. Interestingly, mRNA expression of genes related to fatty acids uptake or synthesis was not significantly altered after BaP exposure. Instead, we found that low-dose BaP promoted lipid deposition in primary mouse hepatocytes by inhibiting autophagy, which was regulated through Leucine carboxyl methyltransferase-1 (LCMT1) mediated Protein Phosphatases 2A subunit C (PP2Ac) methylation. The role of LCMT1 in BaP-induced steatosis was further validated in a liver-specific lcmt1 knockout (L-LCMT1 KO) mouse model. In this study, we provided evidence to support a novel mechanism by which BaP induces the development of hepatic steatosis through PP2Ac mediated autophagy inhibition. These findings provided new insight into the pathogenesis of NAFLD induced by environmental exposure to low-dose BaP.

目的:研究4-辛基衣康酸(4OI)对M2型巨噬细胞(Mφ)极化的干预作用,初步探讨糖酵解及脂肪酸氧化在其中的作用机制.方法:将Mφ分为M0组(100nmol/L佛波酯刺激48h诱导为M0型)、M2组[M0组基础上用20ng/mL白细胞介素4(IL-4)刺激48 h诱导为M2型]、M2+4OI-L组(M2组基础上用100 μmol/L4OI处理12 h)、M2+4OI-H组(M2组基础上用200 μmol/L 4OI处理12 h).实时荧光定量PCR检测M2型Mφ极化相关标志物白细胞介素10(IL-10)、甘露糖受体(MRC-1)、细胞趋化因子(CCL-22)、DC特异性细胞间黏附分子3结合非整合素(CD209)、细胞因子信号抑制物(SOCS1)、过氧化物酶体增殖物激活受体γ(PPAR-γ)、脂肪酸氧化限速酶碱棕榈酰基转移酶-1α(CPT-1α)的mRNA表达水平;微量法酶活性试剂盒检测糖酵解限速酶己糖激酶(HK)和丙酮酸激酶(PK)活性,刃天青法检测细胞内呼吸链代谢酶活性.结果:M0极化为M2时,与M0组比较,伪足伸出细胞和梭形细胞占比和M2型极化相关标志物 CCL-22、IL-10、MRC-1、CD209、SOCS1和PPA4R-γmRNA表达水平上升(P＜0.01);HK和PK活性升高(P＜0.05);CPT-1αmRNA水平和线粒体呼吸链代谢酶活性升高(P＜0.01).4OI干预后,与M2组比较,伪足伸出细胞和梭形细胞占比和M2型极化相关标志物CCL-22、IL-10、MRC-1、CD209、SOCS1和PPAR-γmRNA表达水平下降(P＜0.05);HK和PK活性降低(P＜0.05);CPT-1αmRNA水平进一步升高(P＜0.01);线粒体呼吸链代谢酶活性无明显变化.结论:4OI可能通过抑制M2型Mφ糖酵解降低M2型Mφ极化相关标志物的表达,通过进一步促进脂肪酸氧化水平,维持M2细胞内线粒体呼吸链代谢酶活性和细胞氧化磷酸化稳定.

目的 建立肝特异性LCMT1基因敲除小鼠模型.方法 运用CRISPR/Cas9技术构建肝特异性LCMT1-KO小鼠.通过RT-PCR、实时定量PCR、Western Blot和HE染色等方法鉴定及比较野生和敲除小鼠的差异;观察和分析两组小鼠的一般情况、繁殖能力和子代存活率.结果 成功鉴定子代的基因型;LCMT1-KO小鼠肝LCMT1 mRNA和蛋白质水平显著低于对照组小鼠;两组小鼠的饮食、饮水、体重、繁殖能力、子代存活率、肝外观和HE染色无明显差异;LCMT1-KO小鼠心脏、大脑和肾组织中LCMT1表达与对照组相比没有显著变化;LCMT1-KO小鼠sgRNA未发生脱靶.结论 成功构建肝特异性LCMT1基因敲除小鼠,为研究LCMT1基因在疾病中的调控作用提供实验手段.

BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most malignant type of cancers. Leuci carboxyl methyltransferase 1 (LCMT1) is a protein methyltransferase that plays an improtant regulatory role in both normal and cancer cells. The aim of this study is to evaluate the expression pattern and clinical significance of LCMT1 in HCC.METHODS:The expression pattern and clinical relevance of LCMT1 were determined using the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) program, and our datasets. Gain-of-function and loss-of-function studies were employed to investigate the cellular functions of LCMT1 in vitro and in vivo. Quantitative real-time polymerase chain reaction (RT-PCR) analysis, western blotting, enzymatic assay, and high-performance liquid chromatography were applied to reveal the underlying molecular functions of LCMT1.RESULTS:LCMT1 was upregulated in human HCC tissues, which correlated with a "poor" prognosis. The siRNA-mediated knockdown of LCMT1 inhibited glycolysis, promoted mitochondrial dysfunction, and increased intracellular pyruvate levels by upregulating the expression of alani-neglyoxylate and serine-pyruvate aminotransferase (AGXT). The overexpression of LCMT1 showed the opposite results. Silencing LCMT1 inhibited the proliferation of HCC cells in vitro and reduced the growth of tumor xenografts in mice. Mechanistically, the effect of LCMT1 on the proliferation of HCC cells was partially dependent on PP2A.CONCLUSIONS:Our data revealed a novel role of LCMT1 in the proliferation of HCC cells. In addition, we provided novel insights into the effects of glycolysis-related pathways on the LCMT1regulated progression of HCC, suggesting LCMT1 as a novel therapeutic target for HCC therapy.

目的:探讨果糖饮水对小鼠代谢和学习记忆影响的性别差异及产生差异的可能机制.方法:选取6～8周龄C57BL/6N雌、雄小鼠适应性饲养1周,按性别随机分为4组,每组6只,分别为雄性对照组、雄性果糖组、雌性对照组和雌性果糖组,其中对照组小鼠给予标准饲料加普通饮用水,果糖组给予标准饲料加30％果糖饮用水,每周记录小鼠体重.持续喂养11周后用Morris水迷宫实验测试小鼠空间记忆能力.喂养12周处死小鼠,取动物血清、肝脏和内脏脂肪;检测血清天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;肝组织行苏木精—伊红(HE)染色、油红O染色,观察肝脏组织病理学变化;RT-qPCR检测肝脏ChREBP、SREBP-1c、ACC1、CPT-1、FGF21基因表达.结果:喂养12周后,雌性果糖组体重、肝重及内脏脂肪重量显著高于雌性对照组(P＜0.05),而雄鼠体重、肝重及内脏脂肪重量不受果糖影响;与对照组比较,雌、雄果糖组空腹血糖均升高(P＜0.05),雌性果糖组较雄性果糖组增加更为显著;与相应对照组相比,雌、雄果糖组血清AST、ALT水平未发生改变(P＞0.05),雌性果糖组血清TC、HDL-C、LDL-C水平显著升高(P＜0.05),雄性果糖组血清TG、LDL-C水平显著升高(P＜0.01);肝组织病理结果显示,与相应对照组相比,雌性果糖组小鼠的肝脏出现了明显的脂质沉积、炎症细胞浸润等改变;水迷宫结果显示,与相应对照组相比,雌性果糖组在第4天和第5天的逃避潜伏期显著延长(P＜0.05),第6天穿越平台次数及在目标象限停留时间显著减少(P＜0.05);雄性果糖组未发生显著变化(P＞0.05);与相应对照组相比,小鼠的平均泳速没有显著变化(P＞0.05);脂肪生成基因ChREBP、SREBP-1c、ACC1表达在雌、雄小鼠中没有变化(P＞0.05);脂肪酸氧化关键基因CPT-1仅在雌鼠中表达降低(P＜0.01);影响食欲的因子FGF21在雄鼠中表达增加(P＜0.01).结论:30％果糖饮水对C57BL/6N小鼠代谢及学习记忆的影响存在着性别差异,果糖饮水更易诱导雌性小鼠出现糖脂代谢紊乱及学习记忆能力降低,造成这种性别差异的原因可能是雌、雄小鼠对果糖的偏好不同.

金属在自然界中普遍存在,地壳自然运动和人类工业活动使金属在环境中的浓度越来越高.重金属的半衰期长,在环境中存在的时间久,人们就有可能从被污染的食物、水和空气中摄入重金属.中国一般人群全血中铅的含量为34.9 μg/L,镉为0.49 μg/L[1].重金属可在人体内蓄积,长时间低浓度重金属暴露会对人体各个器官系统产生危害.发育中的神经系统对重金属毒性非常敏感,环境中的铅暴露会使儿童出现心理发育异常、智商下降和注意多动障碍等健康效应[2].一项病例对照研究显示铅可对皮肤产生损害,血铅高者正常部位的皮肤弹性下降,皮肤角化过度[3].有些重金属会引起人体代谢功能异常,镉暴露会直接引起肾小血管和肾小管损伤,导致肾功能障碍[4].锰是人体生长发育的必需金属元素,但是孕期过量锰暴露会损害胎儿的神经系统导致子代运动功能失调[5].然而,现实中重金属的来源复杂、暴露途径多样、分子组成相似,与机体必需微量元素特别是金属元素的摄取有竞争抑制作用,还会和体内的蛋白质结合,本文对重金属复合暴露的健康效应作综述.

目的 探索亮氨酸羧基甲基转移酶1(LCMT1)高表达对锰诱导神经细胞损伤的拮抗作用.方法 利用脂质体将LCMT1-PCDNA 3.0和PCDNA 3.0质粒分别转染小鼠神经母细胞瘤细胞(N2a细胞),通过G418筛选稳定高表达LCMT1的LCMT1-N2a细胞和PCDNA-N2a细胞,Western blot检测显示LCMT1蛋白过表达情况.将LCMT1-N2a细胞和PCDNA-N2a细胞分别暴露于空白培养基(对照组)和不同浓度氯化锰(250、500、1000、2000μmol/L)12 h后以刃天青法检测细胞活性.随后,用流式细胞仪检测染锰(0、500、1000μmol/L)12 h后细胞的凋亡率.结果 LCMT1蛋白在LCMT1-PCDNA 3.0细胞中的表达高于对照组且差异具有统计学意义(P<0.05);转染后细胞的形态与转染前无明显变化.锰暴露可使PCDNA-N2a细胞活性下降且有剂量-反应关系,相同浓度锰暴露下LCMT1-N2a细胞存活率高于PCDNA3.0 N2a(P<0.05).PCDNA3.0 N2a细胞的凋亡率随着染锰浓度增加而升高且存在剂量-反应关系;在相同的染锰剂量下,LCMT1-PCDNA3.0 N2a细胞的凋亡率低于PCDNA3.0 N2a细胞(P<0.05).结论 LCMT1高表达可以拮抗锰致N2a细胞细胞活性的下降和细胞凋亡.

目的 探索苯并(a)芘(BaP)对人肝癌细胞株Hep G2细胞脂质含量及脂代谢的影响.方法 0、0.01、1nmol/LBaP作用Hep G2细胞,采用刃天青检测细胞活性,油红O染色、甘油三脂试剂盒检测细胞内甘油三脂含量,实时荧光定量PCR检测脂代谢相关调节因子的mRNA表达.结果 经BaP处理后,Hep G2细胞活性不变,细胞内脂质增加,LXR-α、FANS、MPC1、MPC2、CD36的mRNA表达增加,DAGT1、MPT的mRNA表达下降(P＜0.05),FABP1的mRNA表达没有明显改变.结论 BaP影响Hep G2细胞脂质代谢,促进细胞脂质沉积.