Immuno‐modification of enhancing stem cells targeting for myocardial repair

Despite the controversy in mechanism, rodent and clinical studies have demonstrated beneficial effects of stem/progenitor cell therapy after myocardial infarction (MI). In a rat ischaemic reperfusion MI model, we investigated the effects of immunomodification of CD 34⁺ cells on heart function and myocardial conduction. Bispecific antibody (BiAb), consisting of an anti‐myosin light chain antibody and anti‐CD45 antibody, injected intravenously was used to direct human CD34⁺ cells to injured myocardium. Results were compared to echocardiography guided intramyocardial (IM) injection of CD34⁺ cells and PBS injected intravenously. Treatment was administered 2 days post MI. Echocardiography was performed at 5 weeks and 3 months which demonstrated LV dilatation prevention and fractional shortening improvement in both the BiAb and IM injection approaches, with BiAb achieving better results. Histological analyses demonstrated a decrease in infarct size and increase in arteriogenesis in both BiAb and IM injection. Electrophysiological properties were studied 5 weeks after treatments by optical mapping. Conduction velocity (CV), action potential duration (APD) and rise time were significantly altered in the MI area. The BiAb treated group demonstrated a more normalized activation pattern of conduction and normalization of CV at shorter pacing cycle lengths. The ventricular tachycardia inducibility was lowest in the BiAb treatment group. Intravenous administration of BiAb offers an effective means of stem cell delivery for myocardial repair post‐acute MI. Such non‐invasive approach was shown to offer a distinct advantage to more invasive direct IM delivery.     

COMIT: identification of noncoding motifs under selection in coding sequences

Coding nucleotide sequences contain myriad functions independent of their encoded protein sequences. We present the COMIT algorithm to detect functional noncoding motifs in coding regions using sequence conservation, explicitly separating nucleotide from amino acid effects. COMIT concurs with diverse experimental datasets, including splicing enhancers, silencers, replication motifs, and microRNA targets, and predicts many novel functional motifs. Intriguingly, COMIT scores are well-correlated to scores uncalibrated for amino acids, suggesting that nucleotide motifs often override peptide-level constraints.     

植物病毒基因沉默抑制子研究进展

RNAi普遍存在于真核生物中,是植物应对外来病毒入侵的一种防御机制。但是植物病毒能通过产生不同的抑制子蛋白来抑制寄主基因沉默的发生。病毒抑制子通过干扰基因沉默的起始、siRNA的积累或干扰系统性基因沉默等方式抑制寄主的基因沉默。有的病毒抑制子蛋白还能促进病毒的积累和胞间移动,加强侵染组织的病毒病症状表现。主要阐述了RNAi的机制、病毒抑制PTGS的作用方式、几种常见的沉默抑制子以及抑制子与病毒侵染的关系。     

棉株根系伤流中的细胞分裂素类物质

棉株根系伤流有明显昼夜节奏,白天多,夜晚较少。白天中又以上午9～12时的伤流量为最高。伤流中CTK量及其浓度也以白天为高。在切除地上部4天以后,从蕾期和铃期棉株已不再能收集到伤流液,但盛花期棉株在切除地上部6天以后,仍产生了相当多的伤流,其中仍含有丰富的CTK类物质。盛花期棉株根系伤流量及其中CTK水平高于铃期棉株,提示铃期棉株根系活力已开始趋向衰老。根据Sephadex LH-20柱层析及高效液相层析鉴定出棉株根系伤流中的CTK类物质有Z,ZR,和IPA。     

β‐catenin regulates IRF3‐mediated innate immune signalling in colorectal cancer

Objective

β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.

Materials and Methods

Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.

Results

We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.

Conclusion

Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.

     

Up-Regulation of Cdc37 Contributes to Schwann Cell Proliferation and Migration After Sciatic Nerve Crush

Cell division cycle protein 37 (Cdc37), a molecular chaperone takes part in a series of cellular processes including cell signal transduction, cell cycle progression, cell proliferation, cell motility, oncogenesis and malignant progression. It can not only recruit immature protein kinases to HSP90 but also work alone. Cdc37 was reported to be associated with neurogenesis, neurite outgrowth, axon guidance and myelination. However, the roles of Cdc37 on Schwann cells (SC) after peripheral nerve injury (PNI) remain unknown. In this study, we found that the expression of Cdc37 increased and reached the peak at 1 week after sciatic nerve crush (SNC), which was consistent with that of proliferation cell nuclear antigen. Immunofluorescence verified that Cdc37 co-localized with SC in vivo and in vitro. Intriguingly, Cdc37 protein level was potentiated in the model of TNF-α-induced SC proliferation. Moreover, we found that Cdc37 silencing impaired proliferation of SC in vitro. Moreover, Cdc37 suppression attenuated kinase signaling pathways of Raf–ERK and PI3K/AKT which are crucial cell signaling for SC proliferation. Finally, we found that Cdc37 silencing inhibited SC migration in vitro. In conclusion, we demonstrated that the way Cdc37 contributed to SC proliferation is likely via activating kinase signaling pathways of Raf–ERK and PI3K/AKT, and CDC37 was also involved in SC migration after SNC.     

Genetic background affects pathogenicity island function and pathogen emergence in Streptomyces

With few exceptions, thaxtomin A (ThxA), a nitrated diketopiperazine, is the pathogenicity determinant for plant‐pathogenic Streptomyces species. In Streptomyces scabiei (syn. S. scabies), the ThxA biosynthetic cluster is located within a 177‐kb mobile pathogenicity island (PAI), called the toxicogenic region (TR). In S. turgidiscabies, the ThxA biosynthetic cluster is located within a 674‐kb pathogenicity island (PAIst). The emergence of new plant pathogens occurs in this genus, but not frequently. This raises the question of whether the mobilization of these pathogenicity regions, through mating, is widespread and whether TR and PAIst can confer plant pathogenicity. We showed that ThxA biosynthetic clusters on TR and PAIst were transferred into strains from five non‐pathogenic Streptomyces species through mating with S. scabiei and S. turgidiscabies. However, not all of the transconjugants produced ThxA and exhibited the virulence phenotype, indicating that the genetic background of the recipient strains affects the functionality of the ThxA biosynthetic cluster and therefore would be expected to affect the emergence of novel pathogenic Streptomyces species. Thxs have been patented as natural herbicides, but have yet to be commercialized. Our results also demonstrated the potential of the heterologous production of ThxA as a natural and biodegradable herbicide in non‐pathogenic Streptomyces species.