Epigenetic histone methylation regulates transforming growth factor β-1 expression following bile duct ligation in rats

Background

Multiple mechanisms contribute to the liver fibrosis following cholestasis. Recent research has focused on the role of transforming growth factor β-1 (TGF-β1) in the progression of fibrosis. The aim of our study is to examine the role of epigenetic chromatin marks, such as histone H3 lysine methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-β1 gene expression in rat liver.

Methods

Time course of methylated-histone H3 and SET7/9 recruitment were determined by chromatin immunoprecipitation in livers from BDL rats on days 1, 4, 9 and 14. Levels of TGF-β1 and SET7/9 were determined by western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF-β1, serum enzymes and liver collagen content was studied in vivo.

Results

Results showed that BDL increased the expression of the TGF β-1. Increased levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased levels of repressive marks (H3K9me2 and H3K9me3) in TGF-β1 promoter accompanied the changes in expression of the TGF β-1. BDL also increased expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter. SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-β1 gene expression, serum enzymes and liver collagen content.

Conclusions

Taken together, these results show the functional role of epigenetic chromatin histone H3Kme in BDL-induced TGF-β1 expression. Pharmacologic and other therapies that reverse these modifications could have potential hepatoprotective effects for BDL-induced cirrhosis.     

miR-34a在膀胱癌中下调MTA2表达的研究

目的 研究微小核糖核酸34a（microRNA-34a,miR-34a）在膀胱癌中的表达及临床意义,确定转移相关基因2（metastasis-associated gene2,MTA2）是否为miR-34a调控的下游靶基因,探讨膀胱癌中miR-34a与MTA2的相互作用机制。方法 选取48对膀胱癌根治术后癌组织及癌旁组织,标本来源于2011年5月至2012年5月我科收治的膀胱癌患者。Real-time PCR检测miR-34a和MTA2在组织中RNA的表达情况;荧光素酶实验鉴定MTA2是否为miR-34a下游靶基因;膀胱癌细胞株T24及UMUC3中转入miR-34a后,琼脂糖凝胶电泳、免疫印迹实验检测MTA2的RNA及蛋白表达。结果 Real-time PCR检测表明,膀胱癌组织中miR-34a呈低表达,并且与肿瘤分期有关（P〈0.01）;MTA2在癌组织中表达明显上调。MiRanda、Mirwalk、Targetscan软件预测miR-34a与MTA2的mRNA有结合位点,荧光素酶实验结果表明MTA2可能是miR-34a的潜在靶基因。转染miR-34a后,分别检测MTA2的蛋白和mRNA表达情况,发现MTA2蛋白受到抑制,mRNA表达不受影响。结论 miR-34a在膀胱癌中可能通过作用于其潜在靶基因MTA2而发挥抑癌基因作用。     

Clinical Utility of Plantar Pressure Measurements as Screening in Patients With Parkinson Disease With and Without Freezing of Gait History

ObjectiveTo test the feasibility of objective assessments using the TekScan MatScan pressure mat plantar pressure measurement as a time-effective screening service for Parkinson disease (PD) with and without freezing of gait (FOG) history.DesignProspective cross-sectional study.SettingLargest medical center in southern Taiwan.InterventionsNot applicable.Main Outcome MeasuresPlantar pressure measurements including average peak pressure (PP), contact area (CA), and pressure-time integral (PTI) in static and dynamic conditions as well as clinical scores during off-medication states.ParticipantsA total of 103 patients with PD and 22 age- and sex-matched volunteers without PD (N=125).ResultsPlantar pressure assessment including PP, CA, and PTI on the total foot areas between participants with PD and controls without PD in the static conditions are similar. Patients with PD presented higher PTI on total foot areas as well as hallux, midfoot area, and medial and lateral heels during dynamic conditions than controls without PD. The PP, CA, and PTI during the static condition and CA during the dynamic condition on the hallux showed statistical significance between PD with and without FOG history. Stepwise logistic regression after controlling with age and body mass index showed only PTI on hallux (static conditions) was significantly associated with the presence of FOG. The receiver operating characteristic curve analysis in diagnostic accuracy for FOG in PTI was statistically significant (P=.002; area under the curve, 0.71).ConclusionsFOG screening using the TekScan MatScan pressure mat plantar pressure measurement could serve as a time-effective screening service at the outpatient clinic. Based on our study, PTI may be valuable in auxiliary diagnosis.     

In vivo monitoring of neural stem cells after transplantation in acute cerebral infarction with dual-modal MR imaging and optical imaging

Stem cell therapies are promising strategies for the treatment of stroke. However, their clinical translation has not been fully realized due, in part, to insufficient ability to track stem cell migration and survival longitudinally over long periods of time in vivo. In this work, we synthesized a new class of manometer-sized cationic polymersomes loaded with superparamagnetic iron oxide nanoparticles and quantum dots for in vivo dual-modal imaging of stem cells. The results demonstrated that the synthesized cationic polymersomes can act as an effective and safety carrier to transfer image labels into neural stem cells, upon which the distribution and migration of grafted stem cells could be monitored by MR imaging up to 6 weeks and by fluorescence imaging within 4 weeks in the context of ischaemic brain injury. Cationic polymersomes hold great promise in the longitudinal monitoring of transplanted stem cells by using dual-modal MRI and optical imaging.     

Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging of early acute pancreatitis

Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly dependent on serum enzyme analysis and imaging techniques that are too low in sensitivity and specificity to accurately and promptly diagnose AP. The lack of early diagnostic tools highlights the need to search for a highly effective and specific diagnostic method. In this study, we synthesized a conditionally activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a diagnostic tool for the early identification of AP. Gadolinium diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA exhibited low cytotoxicity and excellent biocompatibility when characterized in vitro and in vivo studies. L-arginine induced a gradual increase in the intensity of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to detect early AP.     

1例中间型β-地中海贫血的临床诊断和基因检测

目的通过回顾性分析1例中间型β-地中海贫血（地贫）的诊断及基因检测流程,总结中间型地贫的诊断策略。方法分析1例β-地贫合并α-地贫基因型患儿的临床表现,通过地贫基因多重PCR检测及DNA序列测定明确诊断,结合相关文献复习,探讨影响β-地贫表现型的基因因素。结果该地贫患儿基因型为B珠蛋白基因41／42突变的杂合予合并仅仅仅anti3.7基因杂合子。结论中间型地贫的诊断,需要临床表现与基因病变相一致,多重PCR结合DNA序列测定等方法可确诊罕见型基因突变。     

三种方法评估替加环素对多重耐药鲍曼不动杆菌体外药敏结果分析

目的　比较3 种药敏检测方法检测替加环素对多重耐药鲍曼不动杆菌敏感性的差异。方法　收集2018 年临床 分离耐碳青霉烯类鲍曼不动杆菌60 株,采用MIC Test Strip（MTS）法、VITEK-2 法、纸片扩散法分别检测替加环素对 耐碳青霉烯类鲍曼不动杆菌的敏感性。结果　按照FDA 标准,以MTS 法为参考,VITEK-2 法的一致率较高,纸片扩 散法的一致率较低。Vitek-2 法的MIC 值比MTS 法的MIC 值低1 ~ 2 个稀释度,利用MTS 法检测替加环素对耐碳青霉 烯鲍曼不动杆菌的耐药率达到23.3%,出现耐药株。结论　对于耐碳青霉烯类鲍曼不动杆菌,Vitek-2 法和纸片扩散法 均不适合检测替加环素的敏感性,不能作为常规方法,需用MTS 法确认。