miR24-2 accelerates progression of liver cancer cells by activating Pim1 through tri-methylation of Histone H3 on the ninth lysine

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.     

MiR‐140 modulates the inflammatory responses of Mycobacterium tuberculosis‐infected macrophages by targeting TRAF6

This study aimed to examine miR‐140 expression in clinical samples from tuberculosis (TB) patients and to explore the molecular mechanisms of miR‐140 in host‐bacterial interactions during Mycobacterium tuberculosis (M tb) infections. The miR‐140 expression and relevant mRNA expression were detected by quantitative real‐time PCR (qRT‐PCR); the protein expression levels were analysed by ELISA and western blot; M tb survival was measured by colony formation unit assay; potential interactions between miR‐140 and the 3′ untranslated region (UTR) of tumour necrosis factor receptor‐associated factor 6 (TRAF6) was confirmed by luciferase reporter assay. MiR‐140 was up‐regulated in the human peripheral blood mononuclear cells (PBMCs) from TB patients and in THP‐1 and U937 cells with M tb infection. Overexpression of miR‐140 promoted M tb survival; on the other hand, miR‐140 knockdown attenuated M tb survival. The pro‐inflammatory cytokines including interleukin 6, tumour necrosis‐α, interleukin‐1β and interferon‐γ were enhanced by M tb infection in THP‐1 and U937 cells. MiR‐140 overexpression reduced these pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection; while knockdown of miR‐140 exerted the opposite actions. TRAF6 was identified to be a downstream target of miR‐140 and was negatively modulated by miR‐140. TRAF6 overexpression increased the pro‐inflammatory cytokines levels and partially restored the suppressive effects of miR‐140 overexpression on pro‐inflammatory cytokines levels in THP‐1 and U937 cells with M tb infection. In conclusion, our results implied that miR‐140 promoted M tb survival and reduced the pro‐inflammatory cytokines levels in macrophages with M tb infection partially via modulating TRAF6 expression.     

Identification and functional characterization of CD133+GFAP+CD117+Sca1+ neural stem cells

Molecular and Cellular Biochemistry - Neural stem cells (NSCs) are responsible for maintaining the nervous system and repairing damages. Utility of NSCs could provide a novel solution to treat...     

Bibliometric analysis of Journal of Plant Ecology during 2017–2021

Issue Section: Editorial Journal of Plant Ecology (JPE) was founded in 2008. It is sponsored by the Botanical Society of China and the Institute of Botany, Chinese Academy of Sciences, and published by Oxford University Press, UK. JPE publishes diverse types of articles that fall into the broad scope of plant ecology, including plant ecophysiology, population ecology, community ecology, ecosystem ecology, landscape ecology, conservation ecology, evolutionary ecology, theoretical ecology and global change ecology.     

3A蛋白104–115位氨基酸缺失口蹄疫A型标记病毒的构建

【目的】构建一株含3A非结构蛋白104–115位氨基酸缺失的口蹄疫A型标记病毒,分析其生物学特性和发展标记疫苗的潜力。【方法】采用融合PCR技术,在当前流行毒株A/Sea-97/CHA/2014全长感染性克隆p QAHN中引入3A104–115位氨基酸的缺失,构建全长重组质粒。全长质粒经NotI线化后转染表达T7RNA聚合酶的稳定细胞系,拯救标记病毒。RT-PCR、序列分析、间接免疫荧光和Western blotting鉴定标记病毒。噬斑表型和一步生长曲线分析标记病毒的生物学特性,并用实验室开发的针对3A优势表位(AEKNPLE)的阻断ELISA方法分析其区分亲本和标记病毒感染的动物。【结果】成功拯救到一株含3A 104–115位氨基酸缺失的口蹄疫A型标记病毒,3A表位的缺失没有影响标记病毒的噬斑表型和一步生长曲线。3A单抗阻断ELISA可以明显区分标记病毒和亲本病毒感染的动物。【结论】本研究构建的3A蛋白104–115位氨基酸缺失的标记病毒可以作为发展口蹄疫鉴别诊断疫苗的候选毒株,用于我国未来口蹄疫A型的有效防控。     

Isolation and characterization of <Emphasis Type="Italic">Paenibacillus polymyxa</Emphasis> LY214, a camptothecin-producing endophytic bacterium from <Emphasis Type="Italic">Camptotheca acuminata</Emphasis>

Camptothecin (CPT) is mainly produced and extracted from Camptotheca acuminata and Nothapodytes foetida for pharmaceutical use, i.e., the starting material for chemical conversion to the clinical CPT-type drugs. As the third largest plant anticancer drug, the heavy demand on CPT from global market leads to many research efforts to identify new sources for CPT production. Herein we report the isolation and characterization of a CPT-producing endophytic bacterium Paenibacillus polymyxa LY214 from Camptotheca acuminata. A 10.7 μg l^?1 of CPT was presented in the fermentation broth of P. polymyxa LY214. Its CPT production decreased sharply when the strain of the 2nd generation of P. polymyxa LY214 was cultured and fermented. However, the CPT production remained relatively constant from 2.8 μg l^?1 of the 2nd generation to 0.8 μg l^?1 of the 8th generation of P. polymyxa LY214 under optimized fermentation conditions. A 15- to 30-fold increase of CPT yield was observed when the optimized fermentation conditions, together with the addition of putative biosynthetic precursors of CPT and adsorbent resin XAD16, were applied to ferment the strains of the 7th and 8th generation of P. polymyxa LY214. Bioinformatics analysis of the relative species of P. polymyxa LY214 indicates its potential to produce CPT, which will be helpful to decipher the mysteries of CPT biosynthesis.     

P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration

Recruitment of oligodendrocyte precursor cells (OPCs) to the lesions is the most important event for remyelination after central nervous system (CNS) injury or in demyelinating diseases. However, the underlying molecular mechanism is not fully understood. In the present study, we found high concentrations of ATP could increase the number of migrating OPCs in vitro, while after pretreatment with oxidized ATP (a P2X7 receptor antagonist), the promotive effect was attenuated. The promotive effect of 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) (a P2X7 receptor agonist) was more potent than ATP. After incubation with BzATP, the activity of Fyn, one member of the Src family of kinases, was enhanced. Moreover, the interaction between P2X7 and Fyn was identified by co-immunoprecipitation. After blocking the activity of Fyn or down-regulating the expression of Fyn, the migration of OPCs induced by BzATP was inhibited. These data indicate that P2X7 receptors/Fyn may mediate ATP-induced OPC migration under pathological conditions.

Electronic supplementary material

The online version of this article (doi:10.1007/s11302-015-9458-3) contains supplementary material, which is available to authorized users.     

Coleifolides A and B,Two New Sesterterpenoids from the Aerial Parts of Scutellaria coleifolia H.Lév.

Coleifolides A and B ( 1 and 2 ), two new sesterterpenoids with a β‐methyl‐α,β‐unsaturated‐γ‐lactone moiety, were isolated from the aerial parts of Scutellaria coleifolia H.Lév . (Lamiaceae), together with three known compounds. Their structures were elucidated by NMR and MS examinations. Coleifolides A and B were concluded to be partially racemic compounds by the HPLC analysis using a chiral column or introduction of chiral derivatizing agents. The absolute configuration of the major isomer was determined by analyses of the CD spectrum as well as NMR data of (R)‐ and (S)‐2‐NMA derivatives. Coleifolides A and B are structurally similar to manoalide derivatives, previously isolated from marine sponges, and appear to be the first examples of this type of compounds being isolated from higher plants.     

Prediction Factors of Recurrent Ischemic Events in One Year after Minor Stroke

Background

The risk of a subsequent stroke following a minor stroke is high. However, there are no effective rating scales to predict recurrent stroke following a minor one. Therefore, we assessed the risk factors associated with recurrent ischemic stroke or transient ischemic attack (TIA) within one year of minor stroke onset in order to identify possible risk factors.

Methods

Eight hundred and sixty-three non-cardioembolic ischemic stroke patients in the Chinese IntraCranial AtheroSclerosis Study that presented with minor stroke, defined as an admission National Institutes of Health stroke scale (NIHSS) score of ≤3, were consecutively enrolled in our study. Clinical information and imaging features upon admission, and any recurrent ischemic stroke or TIA within one year was recorded. Cox regression was used to identify risk factors associated with recurrent ischemic stroke or TIA within the year following stroke onset.

Results

A total of 50 patients (6.1%) experienced recurrent ischemic stroke or TIA within one year of minor stroke onset. Multivariate Cox regression model identified lower admission NIHSS score (HR, 1.75; 95% CI, 1.32 to 2.33; P<0.0001), history of coronary heart disease (HR, 2.62; 95% CI, 1.17 to 5.86; P = 0.02), severe stenosis or occlusion of large cerebral artery (HR, 4.68; 95% CI, 1.87 to 11.7; P = 0.001), and multiple acute cerebral infarcts (HR, 2.61; 95% CI, 1.01 to 6.80; P = 0.05) as independent risk factors for recurrent ischemic stroke or TIA within one year.

Conclusions

Some minor stroke patients are at higher risk for recurrent ischemic stroke or TIA. Urgent and intensified therapy may be reasonable in these patients.