Extracellular vesicles in bone and tooth: A state-of-art paradigm in skeletal regeneration

Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment.     

急性髓系白血病mRNA与非编码RNA差异表达谱及CeRNA调控网络分析

利用GEO数据库(gene expression omnibus database)通过生物信息学分析方法探讨急性髓系白血病(acute myelogenous leukemia,AML)的发病机制。检索GEO数据库中AML相关芯片数据集GSE142698、GSE142699和GSE96535。利用GEO2R分析得到差异mRNAs、miRNAs以及差异lncRNAs。利用在线生物信息学分析工具DAVID对差异mRNAs进行GO富集分析和KEGG通路分析。利用miRWalk数据库预测AML相关miRNAs的靶向mRNAs,利用Spongescan数据库预测AML相关miRNAs的靶向lncRNAs,构建lncRNA-miRNA-mRNA竞争性内源RNA （competing endogenous RNA,ceRNA）调控网络。共筛选出29个显著差异mRNAs、70个显著差异miRNAs和20 005个显著差异lncRNAs。GO富集分析和KEGG通路分析显示,差异表达基因主要涉及蛋白磷酸化、细胞分裂、细胞增殖的负调控、基因表达的正向调节、周期蛋白依赖的丝氨酸/苏氨酸激酶活性的调节等生物过程以及细胞周期、细胞衰老、癌症通路、PI3K-Akt通路等信号通路。将miRWalk数据库预测的靶向mRNAs与差异mRNAs取交集,Spongescan数据库预测的靶向lncRNAs与差异lncRNAs取交集,分别确定了25个mRNAs、6个lncRNAs参与AML相关ceRNA调控网络的构建。结果表明,lncRNAs可能作为关键的ceRNA,通过调控miRNA和相关靶基因参与AML的发生与发展,研究结果为AML诊断和治疗的分子生物学研究提供了新的依据。     

炎症介质在内毒素引起大鼠肠系膜血管床降钙素基因相关肽释放中的作用

本研究在离体大鼠肠系膜血管床灌流模型上,采用特异放免法测定灌流液中的降钙素基因相关肽（ＣＧＲＰ）,观察几种常见炎症介质在内毒素引起ＣＧＲＰ释放中的作用。结果显示：前列腺素合成酶抑制剂地塞米松、布洛芬与消炎痛,缓激肽受体Ｂ２拮抗剂ＨＯＥ１４０,血小板激活因子拮抗剂ＷＥＢ２０８６,组胺Ｈ１受体拮抗剂苯海拉明以及和组胺Ｈ２受体拮抗剂西咪替丁,均能明显抑剂制内毒素引起的ＣＧＲＰ释放,５羟色胺受体拮抗剂ＩＣＳ２０５９３０却无明显作用。从而提示：内毒素引起ＣＧＲＰ释放是通过炎症介质前列腺素、缓激肽、血小板激活因子和组胺介导的,阻断或减少炎症介质的产生可望减轻内毒素血症时ＣＧＲＰ的过量释放。     

大熊猫臼齿釉质的超微结构和氨基酸组成

大熊猫臼齿釉质的超微结构特征主要是施氏明暗带的宽度一般由8—15条釉柱组成;釉柱的横切面一般呈六角形或四角形,由里向外,釉柱的直径逐渐增大。在靠近釉牙本质界处,釉柱数量逐渐减少,有时甚至完全缺失,形成无釉柱结构的釉质。大熊猫臼齿釉质的氨基酸组成主要以甘氨酸,丙氨酸,谷氨酸,天冬氨酸和亮氨酸的含量为最高,而蛋氨酸,胱氨酸和酪氨酸的含量为最低。另外,还含有少量的羟脯氨酸。这种组成模式一般与人类和其它哺乳动物牙齿釉质的氨基酸组成相类似。     

不同林龄和密度对马尾松人工林凋落叶养分变化的影响

该文选择广西南宁市横县镇龙林场的4种林龄(幼龄林、中龄林、成熟林和过熟林)和4种密度(低密度林、中低密度林、中高密度林和高密度林)马尾松人工林共8种林分作为研究对象,分析了未破碎和破碎两个不同降解阶段的凋落叶C、N、P含量及其生态化学计量学特征。结果表明:(1)不同林龄中,凋落叶初始C、N含量在过熟林和成熟林中较高,P含量没有显著变化,且C∶N比值和C∶P比值从幼龄林到成熟林逐渐升高,说明较高林龄马尾松对N和P重吸收较低,而较低林龄马尾松对N和P重吸收较强,需要较大。(2)不同密度林中,随着林木密度的增加,凋落叶初始C含量逐渐升高,N含量无显著变化,P含量降低;高密度林凋落叶的初始C∶P比值和N∶P比值较高,说明高种植密度下马尾松可能对N和P养分的需求较大,P重吸收较强。(3)不同林龄和不同密度马尾松林的破碎凋落叶C含量、C∶N比值、C∶P比值和N∶P比值比未破碎凋落叶的低,N和P含量较高,说明凋落物在降解过程中出现N和P养分的富集现象。(4)中林龄和较高种植密度的马尾松破碎凋落叶与未破碎凋落物的C含量差值最大,C∶N比值和C∶P比值较低,说明这两种林分的凋落叶C的降解速率可能较大。上述结果说明,中龄林和中高、高密度林的马尾松可能对N和P养分的需求较大,重吸收效率较高,且凋落叶C的潜在分解速率较高,可能利于有机碳较快进入土壤中。     

Krüppel-Like Factor 6 Rendered Rat Schwann Cell More Sensitive to Apoptosis via Upregulating FAS Expression

Krüppel-like factor 6 (KLF6) is a tumor suppressor gene and play a role in the regulation of cell proliferation and apoptosis. After the peripheral nerve injury (PNI), the microenvironment created by surrounding Schwann cells (SCs) is a critical determinant of its regenerative potential. In this study, we examined the effects of KLF6 on SCs responses during PNI. Both KLF6 mRNA and protein expression levels were upregulated in the injured sciatic nerve, and immunofluorescence results showed that many KLF6-positive cells simultaneously expressed the SC markers S-100 and p75NTR. The apoptosis inducers TNFα and cisplatin upregulated KLF6 expression in primary cultured SCs and the SC line RSC96. Although KLF6 overexpression exacerbated cisplatin- and TNFα-induced apoptosis, expression levels of the apoptosis regulators Bcl2 and Bax were not significantly affected in either KLF6-overexpressing or KLF6-depleted RSC96 cells. Realtime PCR arrays and qRT-PCR demonstrated that KLF6 overexpression upregulated four pro-apoptotic genes, FAS, TNF, TNFSF12, and PYCARD, and inhibited expression of the anti-apoptotic IL10 gene expression. Further analysis revealed that FAS protein expression was positively correlated with KLF6 expression in SCs. These data suggest that KLF6 upregulation may render SCs more vulnerable to apoptosis after injury via upregulating FAS expression.     

Analyzing the action of evolutionarily conserved modules on HMW-GS 1Ax1 promoter activity

Key message

The specific and high-level expression of 1Ax1 is determined by different promoter regions. HMW-GS synthesis occurs in aleurone layer cells. Heterologous proteins can be stored in protein bodies.

Abstract

High-molecular-weight glutenin subunit (HMW-GS) is highly expressed in the endosperm of wheat and relative species, where their expression level and allelic variation affect the bread-making quality and nutrient quality of flour. However, the mechanism regulating HMW-GS expression remains elusive. In this study, we analyzed the distribution of cis-acting elements in the 2659-bp promoter region of the HMW-GS gene 1Ax1, which can be divided into five element-enriched regions. Fragments derived from progressive 5′ deletions were used to drive GUS gene expression in transgenic wheat, which was confirmed in aleurone layer cells, inner starchy endosperm cells, starchy endosperm transfer cells, and aleurone transfer cells by histochemical staining. The promoter region ranging from ??297 to ??1 was responsible for tissue-specific expression, while fragments from ??1724 to ??618 and from ??618 to ??297 were responsible for high-level expression. Under the control of the 1Ax1 promoter, heterologous protein could be stored in the form of protein bodies in inner starchy endosperm cells, even without a special location signal. Our findings not only deepen our understanding of glutenin expression regulation, trafficking, and accumulation but also provide a strategy for the utilization of wheat endosperm as a bioreactor for the production of nutrients and metabolic products.

     

Influence of Celery on the Remediation of PAHs-contaminated Farm Soil

Polycyclic aromatic hydrocarbons (PAHs) contamination has been considered as one of the major environmental concerns for farmland soil all over the world including China. Due to small per capita land area, to find crops or vegetable, which could not only degrade the PAHs contaminants but also would not concentrate PAHs, was particularly important. Celery was selected as the phytoremediator in this experiment, and the soil enzyme activity, PAHs-degrading microorganisms, and the speciation of PAHs in soil were studied. The results showed that celery could significantly enhance the remediation of PAHs compared with the controlled experiment after 90 days (p< 0.01), and the removal efficiency were 31.29%, 30.79%, and 50.21% in the soil, non-rhizosphere soil, and rhizosphere soil, respectively. The soil enzyme activity and PAHs-degrading microorganisms significantly increased in rhizosphere soil compared with non-rhizosphere soil (p< 0.05), and the bioaccessibility of PAHs in soil could have been enhanced in the presence of celery root exudates. Those would help the bioremediation of PAHs by soil microorganisms. Meanwhile, the concentration of PAHs in the edible portion of celery was only 17.13 ± 1.24 μg/kg, and the bioconcentration factors in the aboveground part of celery were only 0.025. This study provides a potential in-site farmland soil phytoremediation technology that could have practical utility.     

Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

Isoniazid (INH) is one of the most commonly used antituberculosis drugs, but its clinical applications have been limited by severe hepatic toxicity. Quercetin (Que), a natural flavonoid, has been proved to have many medicinal properties. This study aimed to clarify the possible protective effects of Que against INH‐induced hepatotoxicity using HepG2 cells. Our results indicated that Que significantly increased cell viability, superoxide dismutase, and GSH levels, while decreased alanine aminotransferase/aspartate aminotransferase levels. Besides, Que significantly abrogated INH‐induced cell apoptosis by upregulating the expression levels of Bcl‐2 and decreasing the levels of Bax, cleaved caspase‐3, and cleaved caspase‐9. Furthermore, Que obviously reversed the inhibition of INH on Sirtuin 1 (SIRT1) expression and extracellular signal‐regulated kinase (ERK) phosphorylation. Next, the SIRT1 inhibitor EX527 blocked the enhancement of Que upon ERK phosphorylation. Notably, EX527 partially abolished the beneficial effects of Que. In brief, our results provided the first evidence that Que protected against INH‐induced HepG2 cells by regulating the SIRT1/ERK pathway.