O-GlcNAc修饰在糖尿病心肌病中的作用及机制研究进展

<正>糖尿病是一种慢性代谢性紊乱疾病。据统计,我国2021年糖尿病患者数量已高达1.41亿[1]。糖尿病引发的心血管意外已成为患者死亡的主要原因,且死亡率明显高于非糖尿病患者[2]。糖尿病心肌病(diabetic cardiomyopathy, DCM)是一种因长期高血糖引起的心脏结构和功能异常的疾病,与多种信号通路有关。     

一种小鼠肠道纤维化模型建造的方法及评价

目的 探究一种使用酒精建造C57BL/6小鼠肠道纤维化模型的方法。方法 将6周龄C57BL/6小鼠根据不同酒精浓度分为正常对照组、50%乙醇组、三硝基苯磺酸(TNBS)/30%乙醇组、TNBS/50%乙醇组,采用灌肠液灌肠方式造模,每周灌肠1次,持续5周,第6周处死后取结直肠。整个实验期间观察小鼠生存状态、体重变化及生存率,每天进行小鼠疾病活跃指数(DAI)评价。固定包埋后,采用苏木精-伊红染色检测肠道黏膜以及腺体结构完整性;马森三色染色法检测小鼠肠道胶原沉积情况;免疫组织化学染色检测纤维化蛋白α-平滑肌肌动蛋白(α-SMA)的表达量。结果 与正常对照组比较,50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的黏膜破损、腺体丢失比例、纤维化蛋白α-SMA表达明显高于正常对照组,并且50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的DAI评分更高、胶原沉积更多,且TNBS/50%乙醇组高于TNBS/30%乙醇组,50%乙醇组与TNBS/30%乙醇组相近。结论 与正常组比较,50%乙醇组小鼠各时间点DAI评分均明显增高,整体纤维化程度与TNBS/30%乙醇组类似,单纯使用乙醇可以建造小鼠肠道的纤维化模型。     

Role of phloretin as a sensitizer to TRAIL-induced apoptosis in colon cancer

Phloretin is one of the apple polyphenols with anticancer activities. Since tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) serves important roles in inducing apoptosis, the present study examined the effect of phloretin on TRAIL-induced apoptosis in colon cancer cells. Treatment with both phloretin and TRAIL markedly suppressed the survival of cancer cells from several colon cancer cell lines compared with that of cells treated with either TRAIL or phloretin. Additionally, decreased numbers of colonies were observed following addition of phloretin and TRAIL. Furthermore, TRAIL- and phloretin-treated HT-29-Luc cells exhibited decreased luciferase activity. Increased apoptosis was observed in phloretin- and TRAIL-treated HT-29-Luc colon cancer cells, accompanying elevated levels of cleaved poly(ADP-ribose) polymerase, and caspase-3, −8 and −9. The expression levels of MCL1 apoptosis regulator BCL2 family member (Mcl-1) were decreased following addition of phloretin in colon cancer cells. In addition, overexpression of Mcl-1 in phloretin- and TRAIL-treated HT-29-Luc cells resulted in increased cell survival. Treatment of HT-29-Luc cells with a combination of cycloheximide (CHX) and phloretin led to a more prominent decrease in Mcl-1 expression compared with that in cells treated with CHX alone, while Mcl-1 expression was recovered by treatment with MG132. Binding of ubiquitin with Mcl-1 was verified using immunoprecipitation. Intraperitoneal injection of both TRAIL and phloretin into tumor xenografts was associated with a decreased tumor volume compared with that following injection with either TRAIL or phloretin. Overall, the present results suggest a synergistic effect of phloretin on TRAIL-induced apoptosis in colon cancer cells.     

不同程度近视患者行SMILE术后的有效光学区及角膜高阶像差比较

目的：比较低、中、高度近视患者行飞秒激光小切口基质透镜取出术(SMILE)后的有效光学区和角膜高阶像差。

方法：收集2019-02/2021-02在我院行SMILE手术的患者134例,均取右眼入组,按等效球镜度(SE)分为低度近视组SE>-3.00 D,中度近视组-6.00 D结果：SMILE术后1 mo,三组术后有效光学区均小于预设光学区,随着屈光度数增加,有效光学区越小(P<0.05); 术后1 mo角膜总高阶像差、球差、彗差均高于术前,除低近视度组球差术前与术后1 mo无差异(P>0.05),其余组别均有差异(P<0.05); 角膜总高阶像差、球差和彗差随着屈光度数增加而增加,三组角膜总高阶像差和球差有差异(均P<0.05),高度近视组与中度近视组、低度近视组彗差结果均有差异(P<0.05),中度近视组与低度近视组彗差结果无差异(P>0.05)。

结论：随着手术矫正的屈光度数增加,术后有效光学区减少越多,角膜高阶像差增加越明显; SMILE术后1 mo角膜高阶像差较术前增加。     

三种螺距对种植体初期稳定性影响的有限元研究

目的：利用即刻负载有限元模型,研究种植体不同螺纹螺距因素对初期稳定性的影响。方法：利用Pro／E软件、Hypermesh软件及ABAQUS有限元软件,建立四类种植体即刻负载的三维有限元模型,比较3种螺纹螺距（0．8mm、1．6mm、2．4mm）在分别垂直和水平加载时,对种植体初期稳定性的影响。结果：对不同螺纹螺距种植体来说,垂直加载和水平加载时0．8mm螺距螺纹种植体微动最小,2．4mm螺距螺纹种植体微动最大。结论：螺纹的螺距对垂直相对位移有影响,对水平相对位移影响不大。随着螺距的增加,种植体对抗垂直向载荷的抵抗力减弱。水平加载时,螺纹的螺距对颈部微动影响不明显。     

A Novel Herbal Extract Blend Product Prevents Particulate Matters-Induced Inflammation by Improving Gut Microbiota and Maintaining the Integrity of the Intestinal Barrier

Air pollutants of PM2.5 can alter the composition of gut microbiota and lead to inflammation in the lung and gastrointestinal tract. The aim of this study was to evaluate the protective effect of a novel herbal extract blend, FC, composed of Lonicera japonica extract, Momordica grosvenori extract, and broccoli seed extract, on PM2.5-induced inflammation in the respiratory and intestinal tract. A549 cells and THP-1 cells, as well as C57BL/6 mice, were stimulated with PM2.5 to establish in vitro and in vivo exposure models. The models were treated with or without FC. The expression of inflammatory cytokines and tight junction proteins were studied. Proteomic analysis was performed to elucidate mechanisms. Mouse feces were collected for gut microbiota analysis. FC was shown to modulate the upregulation of pro-inflammatory cytokines mRNA expression in A549 and THP-1 cells and downregulated tight junction proteins mRNA expression in A549 cells due to PM2.5 stimulation. In animal models, the decreased expression of the anti-inflammatory factor il-10, tight junction protein ZO-1, and the elevated expression of COX-2 induced by PM2.5 were improved by FC intervention, which may be associated with zo-1 and cox-2 signaling pathways. In addition, FC was shown to improve the gut microbiota by increasing the abundance of beneficial bacteria.     

Human Milk Metabolomics Are Related to Maternal Adiposity,Infant Growth Rate and Allergies: The Chinese Human Milk Project

The metabolomic profiles of Chinese human milk have been poorly documented. The objective of the study was to explore associations between human milk metabotypes, maternal adiposity, infant growth patterns, and risk of allergies. Two hundred mother–infant dyads from seven cities were randomly selected from the Chinese Human Milk Project (CHMP). Untargeted human milk metabolomic profiles were determined using HPLC-MS/MS. Two human milk metabotypes were identified using principal component analysis. Principal component (PC) 1 was characterized by high linoleic acid metabolites with low purine nucleosides and metabolites of glutamate and glutathione metabolism. PC 2 was characterized by high glycerophospholipids and sphingomyelins content. Higher PC1 scores were associated with slower infant growth rate and higher ambient temperature (p < 0.05). Higher PC 2 scores were related to higher maternal BMI and increased risk of infant allergies (p < 0.05). Future work is needed to understand the biologic mechanisms of these human milk metabotypes.     

Rational Design of a Skin- and Neuro-Attenuated Live Varicella Vaccine: A Review and Future Perspectives

Primary varicella-zoster virus (VZV) infection causes varicella, which remains a prominent public health concern in children. Current varicella vaccines adopt the live-attenuated Oka strain, vOka, which retains the ability to infect neurons, establish latency and reactivate, leading to vaccine-associated zoster in some vaccinees. Therefore, it is necessary to develop a safer next-generation varicella vaccine to help reduce vaccine hesitancy. This paper reviews the discovery and identification of the skin- and neuro-tropic factor, the open reading frame 7 (ORF7) of VZV, as well as the development of a skin- and neuro-attenuated live varicella vaccine comprising an ORF7-deficient mutant, v7D. This work could provide insights into the research of novel virus vaccines based on functional genomics and reverse genetics.