Macrophages exhibit dynamic functional phenotype shifts under diverse influences, releasing either anti-inflammatory or pro-inflammatory cytokines and playing a pivotal role in ulcerative colitis (UC) pathogenesis. In recent years, the role of enteric glial cells (EGCs) in maintaining intestinal homeostasis has been increasingly recognized. In this study, we investigated whether the alleviation of UC by curcumin is associated with the regulation of EGCs-macrophage interactions, thereby affecting macrophage polarization and its specific mechanisms. Through animal experiments and flow cytometry, we evaluated the efficacy of curcumin in alleviating UC and its impact on macrophages. Furthermore, GDNF intervention confirmed its pivotal role in curcumin's ability to alleviate UC. Finally, molecular docking, cell experiments, laser confocal microscopy, and transmission electron microscopy were employed to elucidate the molecular mechanism. It was found that curcumin can alleviate UC by promoting macrophages' polarization into anti-inflammatory subtypes, increasing the level of glial cell neurotrophic factor (GDNF) in UC mice, and GDNF treatment can alleviate DSS-induced colon injury. Importantly, we demonstrated that GDNF regulates macrophages' polarization by interacting with CK2 to affect the morphological characteristics of macrophage nucleus. The results of this study further enrich the existing pathways for curcumin to alleviate UC and provide new ideas for the prevention and treatment of UC.

The damage to the mechanical barrier of the intestinal mucosa is the initiating factor and the core link of the progression of ulcerative colitis (UC). Protecting the mechanical barrier of the intestinal mucosa is of great significance for improving the health status of UC patients. ZO-1 is a key scaffold protein of the mechanical barrier of the intestinal mucosa, and its fusion with the membrane of the intestinal epithelium is a necessary condition to maintain the integrity of the mechanical barrier of the intestinal mucosa. Enteric glial cells (EGCs) play an important role in the maintenance of intestinal homeostasis and have become a new target for regulating intestinal health in recent years. In this study, we found that glycyrol (GC), a representative coumarin compound isolated from Licorice (Glycyrrhiza uralensis Fisch, used for medicine and food), can alleviate UC by promoting the production of neurotrophic factor GDNF in mice EGCs. Specifically, we demonstrated that GC promotes the production of GDNF, then activates its receptor RET, promotes ZO-1 fusion with cell membranes, and protects the intestinal mucosal mechanical barrier. The results of this study can provide new ideas for the prevention and treatment of UC.

Aging impairs cognitive function, whereas nutritional intervention can delay aging and age-related diseases. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, the effects of LYC on memory and behavioral deficits induced by D-galactose (D-gal) treatment and the relative contribution of LYC-derived gut microbiota in these process were investigated. Results demonstrated that LYC showed effective protection on D-gal induced cognitive deficit and neuronal damage. Moreover, LYC treatment has beneficial effects on gut barrier damage, microbiota dysbiosis and levels of SCFAs in D-gal-induced subacute aging mice. Next, fecal microbiota transplantation (FMT) experiment was performed and increased SCFAs were observed in mice received stools from D-gal+LYC group when compared with D-gal-FMT group. Thus, we added SCFAs treatment served as a control group in order to evaluated whether the alterations of gut-brain axis could be attributed to LYC-reshaped gut microbiota and SCFAs. Results showed that recipient mice received SCFAs and stools from D-gal+LYC group have similar beneficial effects in improving gut and brain function, demonstrated as: improved intestinal health via elevating antioxidant enzymes contents, increasing the expressions of tight junctions proteins and protecting gut barrier, enhanced mice working memory capacity via alleviating hippocampal neurons impairment, improving synaptic function and enhancing mitochondrial function in the intestinal pseudo-aseptic mice. In conclusion, our results demonstrated that LYC-derived microbiome played a pivotal role in the regulation of cognitive functions during aging and enhanced SCFAs formation might be an important signaling molecule connecting gut microbiome and brain.

Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes’ support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases.

The incidence of neurodegenerative diseases is severely increasing with ageing. Lycopene (LYC), a carotenoid pigment, has been reported to have antioxidant, anti-inflammatory and neuroprotective properties. In the present study, we aimed to investigate the ameliorative effect of LYC on D-galactose (D-gal) induced cognitive defects and the underlying mechanisms. Forty-five female CD-1 mice (2 months old) were separated into three groups to be fed with either a normal diet or a LYC diet (0.03%, w/w, mixed into normal diet). Meanwhile, the mice were treated by intraperitoneal injection of normal saline or D-gal 150 mg/kg/day for 8 weeks. The behavioral test results indicated that LYC alleviated D-gal induced cognitive impairments. LYC ameliorated brain ageing by decreasing the number of SA-β-gal- stained neurons, downregulating the protein expression of the cellular senescence associated genes P19/P21/P53, increasing the activities of the antioxidant enzymes GSH and SOD, downregulating the level of ROS, inhibiting the activation of MAPKs signaling and downregulating the levels of the inflammatory cytokines IL-1β and TNFɑ in mouse brains. LYC ameliorated synaptic dysfunction by increasing the expression of the neurotrophic factor BDNF and synaptic proteins. Moreover, LYC attenuated D-gal-induced mitochondrial morphological damage, and promoted the expression of mitochondrial functional proteins. LYC also promoted insulin signal transduction in mouse brains through the regulation of IRS-1/AKT/GSK3β signaling.

Maintaining the integrity and stability of the gut tract is essential for the health of the body. Autophagy is a promising target for balancing gut homeostasis, and numerous studies have focused on regulating autophagy to improve gut health. In this study, we found that glycyrol (GC), a representative coumarin compound isolated from Glycyrrhiza uralensis Fisch (used for medicine and food), can attenuate colon injury by activating autophagy. Specifically, we demonstrated that GC can act on ubiquitin-specific protease 8 (USP8), inhibit the interaction between SQSTM1/p62 and USP8, promote the ubiquitination of p62, and activate autophagy. Collectively, the findings of the present study suggest that GC is a novel and promising colon protector and deserves further investigation.

目的:对围放疗期的食管癌病人实施营养教育路径，探讨对其营养状况、营养知识-态度-行为、营养治疗依从性、膳食摄入水平的影响。方法:选取山西省某三级甲等医院肿瘤中心于2021年6月-8月接受放疗的30例病人作为对照组，进行常规营养宣教。2021年10月-12月接受放疗的30例病人作为试验组，采用三大模块构成的营养护理路径进行管理，比较两组病人营养状况、营养知识-态度-行为、营养治疗依从性和膳食摄入水平。结果:试验组放疗中、放疗后、出院后4周营养评分均优于对照组（P<0.05）；放疗后试验组的营养知识-态度-行为、口服营养补充剂治疗依从性、依从意愿及依从信心得分均优于对照组（P<0.05）；在放疗过程中，随着放疗的进行，两组病人简明膳食自评工具（SDSAT）评分均呈进行性下降，在放疗后达最低点，但试验组优于对照组，在出院后4周两组病人的能量摄入均得到不同程度的增加。结论:路径式健康教育应用于食管癌放疗病人营养管理中，可有效提高病人的遵医行为，改善营养状况。

目的:比较研究中国、日本和德国公共卫生硕士(master of public health,MPH)教育的培养模式,提出改革我国MPH培养模式的可行性建议与策略.方法:运用文献研究法、案例分析法、比较研究法.结论:国内MPH教育培养模式的主要不足有生源有限、专业学位特色不鲜明、就业去向单一等,准确借鉴日本和德国MPH教育先进经验有助于改进国内MPH培养模式.

目的 探究维生素D(vitamin D,VD)缺乏经Hippo-YAP信号通路抑制胎盘的发育,进而导致胎儿宫内生长受限的发生机制.方法 按照体质量将4w龄SD雌性大鼠随机分为VD缺乏组(vitamin D deficiency,VDD)与对照组(CTRL),VDD组采用VD缺乏饲料喂养,CTRL组采用标准饲料喂养,喂养8周后雌雄合笼.结果 妊娠13d(GD13)与 GD18 时,VDD 组孕鼠的血清 25(OH)D 浓度分别为(2.82±0.18)ng/ml 和(14.67±7.92)ng/ml,对照组孕鼠的血清25(OH)D浓度分别为(36.58±10.58)ng/ml和(19.92±6.91)ng/ml,组间比较在GD13时有差异(P＜0.0001).GD13 时,VDD 组孕鼠的胚胎着床数(12.83±1.17)显著低于 CTRL 组的(15.83±1.47)(P＜0.01);GD18 时,VDD组孕鼠胚胎着床数(12.83±2.23),显著低于CTRL组的(15.67±1.03)(P＜0.05),VDD 组孕鼠的胎儿流产率也明显上升.GD18时,VDD组孕鼠的胎盘重量平均为(2.93±0.42)g,显著低于CTRL组的(6.38±0.48)g(P＜0.0001);VDD组孕鼠的胎盘海绵体滋养层细胞面积为(11.63±0.03)％,显著小于CTRL组的(22.63±0.01)％(P＜0.05);VDD组的活胎数,孕鼠孕期增重显著降低(P＜0.01或P＜0.0001),吸收胎数显著增加(P＜0.05).GD13时,与CTRL组相比,VDD组孕鼠胎盘组织中YAP1蛋白表达水平显著降低(P＜0.01),P-YAP蛋白表达水平显著增高(P＜0.001).结论 母体VD缺乏是导致妊娠后胚胎发育迟缓的重要原因,其机制可能涉及Hippo-YAP信号通路的激活,在孕前及孕期合理补充VD对胎儿健康具有重要意义.

ObjectiveTo investigate the effect of iron on serum 25-hydroxyvitamin D3 (25-(OH)D3), 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and the expression of vitamin D receptor (VDR) in rat kidney. Methods With 7 days′ adaptive feeding, thirty newly weaned male Sprague-Dawley (SD) rats were randomly divided into a control group (n = 6) and a model group (n = 24) according to body weight. The rats in the control group were fed with normal diet and those in the model group were fed with iron deficiency diet for 6 weeks. After successful modeling, the rats in model group were randomly divided into four group (6 rats in each group) with iron deficiency, and low, moderate and high iron according to hemoglobin (Hb) content. The rats in the control group and the iron deficiency group were given normal saline, and the rats in the low, moderate and high iron groups were given iron dextran at dosages of 11, 33 and 99 mg/kg by gastric gavage, respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate. Blood samples of the rats were collected from the abdominal aorta for serum isolation and kidney tissue specimens were collected and stored at – 80 ℃ for later detections. Serum 25-(OH)D3 and 1,25-(OH)2D3 were detected with enzyme-linked immunosorbent assay (ELISA) kit method. Renal tissue iron content of the rats was measured with biochemical kit method. Protein expression of vitamin D receptor (VDR) in the rats′ kidney was determined with Western blot and immunohistochemistry method. Results The model rats′ Hb was significantly lower than that of the control rats (P < 0.05); the Hb of the rats in low, moderate and high iron groups were significantly increased compared to that of the rats in the iron deficiency group (all P < 0.05). Significantly decreased serum 25-(OH)D3/1,25-(OH)2D3 and VDR in kidney were detected in the rats of iron deficiency group contrasting to those of the rats in control group (P < 0.05 for all). In the rats of low, moderate and high iron groups, serum 25-(OH)D3 and 1,25-(OH)2D3 increased significantly (P < 0.05 for all) and with the increases of serum 25-(OH)D3 and 1,25-(OH)2D3, the VDR in kidney was gradually up-regulated in comparison with those in the rats of iron deficiency group. ConclusionIn rats, iron content affects the activation of VD3 and the expression of VDR protein in kidney.

Lycopene (LYC) has been regarded as a nutraceutical that has powerful antioxidant and hepatoprotective bioactivities. In the present study, we aimed to investigate the beneficial effects of LYC on hepatic insulin signal transduction under oxidative stress conditions and the possible involvement of FGF21 and mitochondria pathways. Two-month-old CD-1 mice were treated by intraperitoneal injection of D-galactose (D-gal) 150 mg/kg/day for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC increased the expression of FGF21, alleviated mitochondrial dysfunction and improved hepatic insulin signal transduction in D-gal-treated mice. Furthermore, knockdown of FGF21 by small interfering RNA notably suppressed mitochondrial function and blunted LYC-stimulated insulin signal transduction in H2O2-treated HepG2 cells. Moreover, suppressed mitochondrial function via oligomycin also inhibited insulin signal transduction, indicating that LYC supplementation ameliorated oxidative stress-induced hepatic dysfunction of insulin signal transduction by up-regulating FGF21 and enhancing mitochondrial function.

Lycopene (LYC) possesses bioactivity to improve the pathogenesis of several chronic diseases via antioxidant-associated mechanisms. The purpose of this study was to investigate whether LYC could attenuate D-galactose (D-gal)-induced mitochondrial dysfunction and insulin signaling impairment in mouse kidneys and livers. Two-month-old CD-1 mice were treated by intraperitoneal injection of 150 mg kg-1 day-1D-gal for 8 weeks and received 0.03% LYC (w/w, mixed into diet). The results showed that LYC ameliorated oxidative stress triggered by D-gal by enhancing the Nrf2 antioxidant defense pathway and increasing the expression of the antioxidant response genes HO-1 and NQO1 in mouse kidneys and livers. LYC inhibited the MAPK and NFκB pathways and attenuated renal and hepatic inflammatory responses. Moreover, LYC upregulated the expression of genes related to mitochondrial biosynthesis and oxidative phosphorylation and improved insulin signal transduction through the IRS-1/AKT/GSK3β pathway in mouse kidneys and livers.

目的:了解全日制公共卫生硕士(master of public health,MPH)对教学现状的评价及原因.方法:采用问卷对某医学院校2017-2019级全日制MPH教学现状及影响因素进行普查.结果:全日制MPH教学状况有待提升.培养目标不突出、实践教学较少、教学手段和方式运用不当是主要原因.结论:应从调整课程设置、增加实践教学及合理运用教学方法提升MPH教学质量.

目的 探究番茄红素是否可以抑制脂多糖(lipopolysaccharide,LPS)诱导的3T3-L1前脂肪细胞炎症反应、氧化应激以及胰岛素信号转导紊乱,明确线粒体在其中的介导机制.方法 利用LPS诱导3T3-L1前脂肪细胞发生炎症反应,并通过番茄红素进行干预,之后采用H2DCFDA染色、JC-1染色以及Western blots分析番茄红素对LPS诱导的细胞炎症、活性氧(reactive oxygen species,ROS)积累、胰岛素信号紊乱以及线粒体损伤的改善作用;之后利用寡霉素预先孵育细胞,以抑制线粒体功能,分析线粒体是否可介导番茄红素改善细胞胰岛素信号.结果 与LPS组相比,番茄红素可以显著抑制MAPKs信号通路的激活、下调促炎因子COX-2表达,改善细胞炎症反应;可上调抗氧化酶HO-1及NQO-1表达,抑制LPS诱导的ROS积累;番茄红素还促进了IRS-1 Tyr612位点磷酸化及其下游靶基因AKT、GSK3β 磷酸化,改善了细胞胰岛素信号转导;且通过增强线粒体膜电势以及促进线粒体呼吸链复合物I-III表达,改善了线粒体功能;用寡霉素预先孵育细胞,发现番茄红素对IRS-1/AKT/GSK3β 胰岛素信号通路的调节作用减弱.结论 本研究结果表明番茄红素对线粒体功能的增强可能在其改善细胞胰岛素信号过程中起到一定作用.

目的 探讨维生素D(vitamin D,VD)与铁联合对脂多糖(lipopolysaccharide,LPS)所致的结肠炎性细胞的影响及作用机制.方法 将SW480细胞随机分为对照组(control),模型组(model,1μg/ml LPS),25(OH)D3干预组[1 p g/ml LPS+500 ng/ml 25(OH)D3],铁干预组[1 μ g/ml LPS+1 mmol/L 柠檬酸铁铵(ferric ammonium citrate,FAC)],联合干预组[1μg/ml LPS+500 ng/ml25(OH)D3+1 mmol/L FAC],干预24h后收集细胞,免疫荧光检测各组细胞活性氧(reactive oxygen species,ROS)水平;酶联免疫吸附试剂 盒(enzyme linked immunosorbent assay,ELISA)检测细胞IL-6、TNF-α、1,25(OH)2D3水平;western blots法检测各组细胞p38、p-p38、CYP27B1和CYP24A1蛋白表达水平.结果 与对照组相比,模型组的ROS、IL-6和TNF-α 水平明显增加(P＜0.05),p38蛋白磷酸化水平也明显增加(P＜0.05),CYP27B1蛋白表达水平增加,CYP24A1表达降低,25(OH)D3+FAC联合干预组的1,25(OH)2D3水平增加(P＜0.05);与模型组比较,25(OH)D3+FAC联合干预组的ROS、IL-6和TNF-α 水平明显降低(P＜0.05),p38蛋白磷酸化水平与CYP27B1蛋白表达明显降低(P＜0.05),CYP24A1表达增加.结论 维生素D与铁联合能够有效降低LPS所致的结肠炎性细胞的炎症水平,该过程可能是由p38丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路介导的.

目的 新冠肺炎疫情暴露了我国公共卫生体系中长期以来积累的短板,其中最难以忽视的是优秀公共卫生人才的短缺,而作为培养高素质人才的公共卫生硕士(master of public health,MPH)传统教育已不能满足社会的需求,文章旨在为深化我国MP H教育改革提出参考性建议.方法 采用案例比较的方法选取中英美三国中六所具有典型代表的高校进行研究.结果 围绕其培养目标、招生生源、培养方式、课程设置、实践基地、毕业考核等方面进行中外对比和深入剖析,发现我国MP H培养过程中存在一些不足.结论 应针对我国MP H培养体系中的诸多问题开展深入讨论并进行相应的改革.

目的 探讨铁和维生素D(VD)对孕期SD大鼠的贫血是否存在交互作用.方法 24只雌性SD大鼠适应性喂养7d后,按体质量随机分为正常组(+Fe+VD:Fe=181.6 mg/kg,VD3=2250 IU/kg,)、缺维生素D组(+Fe-VD:Fe=181.6 mg/kg,VD3=0 IU/kg,)、缺铁组(-Fe+VD:Fe=24.2 mg/kg,VD3=2250 IU/kg,)、缺铁缺维生素D组(-Fe-VD:Fe=24.2 mg/kg,VD3=0 IU/kg)4组,每组6只.8w后,雌雄鼠1:1合笼.孕鼠GD18d时,用2％戊巴比妥钠溶液进行腹腔注射麻醉,腹主动脉取血.结果 血清铁(serum iron,SI)和血清铁蛋白(serum ferritin,SF)在+Fe+VD、+Fe-VD、-Fe+VD、-Fe-VD组依次降低;血清可溶性转铁蛋白受体水平(serum soluble transferrin receptor,sTfR)在各组依次升高;与+Fe+VD组相比,-Fe-VD组的血清25-(OH)D3水平较低(P<0.01);与+Fe+VD组相比,其他各组血红蛋白(hemoglobin,Hb)、红细胞数目(number of red blood cells,RBC)、红细胞压积(hematocrit,HCT)、平均红细胞体积(mean red blood cell volume,MCV)、平均红细胞血红蛋白含量(average red blood cell hemoglobin content,MCH)等的水平均较低(P<0.05);与+Fe+VD组相比,其他各组的红细胞分布宽度变异系数(coefficient of variation of red blood cell distribution width,RDW)水平均较高(P<0.001).铁和维生素D3交互作用在Hb、RBC、HCT、RDW、MCV、MCH、MCHC水平差异均有统计学意义(P<0.05).结论 在妊娠期贫血发展进程中,铁与维生素D3可能存在交互作用.

Introduction: Maternal vitamin D deficiency (VDD) is associated with intrauterine growth restriction (IUGR), but the exact mechanism remains unclear. Here we explored the mechanism through which VDD induced IUGR.Methods: Female SD rats were fed a control normal diet (VD > 800 IU/Kg) or VDD diet (VD: 0 IU/Kg) for 8 weeks. Then, females were mated with 12-week-old male SD rats, and fetal and placental tissue were collected on the gestational day 13 (GD13) or 18 (GD18) to analyze the effects of VDD on pregnancy outcome and embryonic development. In vitro, the VDR gene of HTR-8/SVneo cells was knocked down to establish VDD model. Then, HTR-8/SVneo cells were treated with the MST1/2 inhibitor XMU-MP-1 or 0.1 mu M/L calcitriol for 24 h (h). The mechanism of Hippo-YAP signaling pathway in VDD-induced placental dysplasia was further investigated by western blot, invasion assay, wound healing assay and Hoechst/PI staining. Results: The IUGR of the pregnant rats in the VDD group was significant, the placental structure and function were damaged, and there was an obvious inflammatory response, accompanied by a significant increase in the level of the transcription co-activator YAP phosphorylation. In vitro, VDD significantly inhibited the migratory and invasive abilities of HTR-8/SVneo cells, accompanied by decreased EMT capacity and increased apoptosis. When intervening with XMU-MP-1 in advance, we found that the effects of VDD were neutralized by Hippo-YAP signaling blocker.Discussion: Maternal VDD causes placental dysplasia and IUGR, and these abnormal changes may be associated with the activation of Hippo-YAP signaling pathway.

Objective:To systematically evaluate the relationship between gestational vitamin D deficiency and spontaneous abortion.Methods:Databases including PubMed, Web of Science, Ebsco, Cochrane, Embase, CNKI, Wanfang database, China Biomedical Literature Service System, etc. were searched for cohort studies and case-control studies on the correlation between gestational vitamin D deficiency/insufficiency and abortion outcomes, respectively from the establishment of individual database to December 2021. Two investigators independently performed literature screening, data extraction and risk of bias assessment for included studies. Meta-analysis was conducted with RevMan 5.4.1 and Stata 15.1.Results:Eventually, 12 cohort studies and 5 case-control studies were included. A total of 19,308 pregnant women were enrolled, among whom 1 405 abortions were observed. 8 studies were published in Chinese and 9 in English. 10 studies were from China and 1 study each was from Iran, Egypt, Sweden, United States, Denmark, Turkey and Australia. The standards for vitamin D deficiency and the diagnostic criteria for miscarriage were basically the same across studies. After adjusting for confounding factors such as age and race, the meta-analysis showed that gestational vitamin D deficiency/insufficiency would increase the risk of miscarriage. A subgroup analysis of women with miscarriage in early pregnancy showed results consistent with that in overall population. No significant publication bias were identified via meta-analysis.Conclusion:Gestational vitamin D deficiency and insufficiency are related to the occurrence of spontaneous abortion and can increase the risk of early spontaneous abortion.