Primate stem cells: bridge the translation from basic research to clinic application

A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates(NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges.     

Culture of newborn monkey liver epithelial progenitor cells in chemical defined serum-free medium

Studies with hepatic progenitor cells from non-human primates would allow better understanding of their human counterparts. In this study, rhesus monkey liver epithelial progenitor cells (mLEPCs) were derived from a small piece of newborn livers in chemical defined serum-free medium. Digested hepatic cells were treated in Ca²⁺-containing medium to form cell aggregates. Two types of cell aggregates were generated: elongated spindle cells and polygonal epithelial cells. Elongated spindle cells were expressed as vimentin and brachyury, and they were disappeared within 5 d in our cultures. The remaining type consisted of small polygonal epithelial cells that expressed cytokeratin 7 (CK7), CK8, CK18, nestin, CD49f, and E-cad, the markers of hepatic stem cells, but were negative for α-fetoprotein, albumin, and CK19. They can proliferate and be passaged, if on laminin or rat tail collagen gel, to initiate colonies. When cultured with dexamethasone and oncostatin M, the expression of mature hepatocyte markers, such as α-1-antitrypsin, intracytoplasmic glycogen storage, indocyanine green uptake, and lipid droplet generation, were induced in differentiated cells. If transferred onto mouse embryonic fibroblasts feeders, they gave rise to CK19-positive cholangiocytes with formation of doughnut-like structure. Thus, mLEPCs with bipotency were derived from newborn monkey liver and may serve as a preclinical model for assessment of cell therapy in humans.     

LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein

Science China Life Sciences - Large tumor suppressor 1 (LATS1) is the key kinase controlling activation of Hippo signalling pathway. Post-translational modifications of LATS1 modulate its kinase...     

蜡状芽孢杆菌S458-1对水产养殖系统中水质调节的作用

【目的】水产养殖过程中蜡状芽孢杆菌(Bacillus cereus)作为益生菌被广泛应用。本研究旨在深入了解分离于养殖水体中的一株蜡状芽孢杆菌S458-1对养殖水体以及养殖对象的影响,以期为菌株S458-1在水产养殖生产上的应用提供理论依据。【方法】根据控制变量法,各试验组鲫鱼养殖模式设置相同温度、盐度、溶氧和pH,利用分光光度法测定水体的水化学指标;利用试剂盒法测定鲫鱼的血清生理生化指标。【结果】添加菌株S458-1处理组(终浓度分别为10~6、10~7、10~8CFU/mL)与对照组(未加S458-1菌)相比:水体活性磷浓度显著性增加(P0.05);同时具有把NH_4~+-N和NO_2~–-N转化为NO_3~–-N的趋势,但无显著性差异(P0.05);养殖鲫鱼血清检测结果显示谷草转氨酶(GOT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)以及丙二醛(MDA)含量均显著降低(P0.05)。【结论】蜡状芽孢杆菌S458-1具有脱氮解磷、调节水质的作用,并可增强养殖对象的生理健康状态,可作为益生菌应用于水产养殖中,具有较高的应用价值。     

DJ‐1 inhibits autophagy activity of prostate cancer cells by repressing JNK–Bcl2–Beclin1 signaling

The regulation of DJ‐1 on AR signaling plays an important role in the pathogenesis of prostate cancer (PCa). DJ‐1 could alter autophagy and regulate Beclin1‐involved autophagy response through JNK‐dependent pathway. JNK is known to mediate autophagy through Bcl2–Beclin1 complex. Therefore, this study aimed to investigate the significance of autophagy in DJ‐1‐modulated PCa cells. The current studies showed that DJ‐1 overexpression in LNCaP decreased LC3 transformation and autophagosome formation. However, DJ‐1 knockdown exerted the opposite effect. Moreover, DJ‐1 silencing inhibited survival and promoted death in LNCaP, which was recovered by autophagy inhibition with 3‐MA. In addition, DJ‐1 overexpression inhibited the phosphorylation of JNK and Bcl2, and the dissociation of Beclin1 and Bcl2; while the effect of silencing DJ‐1 was completely opposite. More important, JNK activated by anisimycin inhibited the proliferation and promoted death of DJ‐1‐overexpressed LNCaP while increasing LC3 transformation and LC3‐puncta formation, but these results were reversed by the decrease of Beclin1 (by spautin‐1). In contrast, when DJ‐1 was silenced, the death of LNCaP, LC3 transformation, and LC3‐puncta formation were inhibited by JNK inhibitor SP600125, which promoted cell proliferation. However, Bcl2 inhibition (by ABT737) reversed all the effects of SP600125. Our results suggested that DJ‐1 in PCa cells could promote the growth of PCa through autophagy inhibition, and JNK–Bcl2–Beclin1 signaling played an important role in it. The study provided new insights into the role of DJ‐1 in the development of PCa.     

Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation

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Highlights? Cocrystal structure of KRIT1 with ICAP1 shows a bidentate interaction interface ? Cocrystal structure of ICAP1 with integrin β1 shows a PTB-peptide interaction ? KRIT1 antagonizes ICAP1-modulated integrin activation by the bidentate interaction ? KRIT1 contains a previously undescribed N-terminal Nudix domain     

低温环境下施氏鲟的人工繁殖研究

施氏鲟天然繁殖水温为16－19℃,在8－14℃水温中进行人工繁殖,获得成功,催产率85％,在低温环境（8－14℃）中催产,效应时间内水温基本稳定或升高是催产成功的关键,而温度高低与催化成功率没有明显关系。在低温环境中,催产的效应时间大幅度延长,卵母细胞游离速度十分缓慢,应多次少量注射激素,催产才能完全成功,催产激素剂量以怀卵量计算效果较佳;卵化积温非常数。神经胚期胚胎在水温低于11时畸形死亡,孵出期胚胎在水温达13℃才能正常破膜,其它时期胚胎在8．5℃水温中能正常发育。     

Genotypes of Enterocytozoon bieneusi in Livestock in China: High Prevalence and Zoonotic Potential

Despite many recent advances in genotype characterization of Enterocytozoon bieneusi worldwide and the exploration of the extent of cross-species transmission of microsporidiosis between humans and animals, the epidemiology of this neglected disease in China is poorly understood. In this study, a very high prevalence (60.3%; 94/156) of E. bieneusi infections in farmed pigs in Jilin province was detected by PCR of the ribosomal internal transcribed spacer (ITS). DNA sequence analysis of 88 E. bieneusi–positive specimens identified 12 distinct genotypes (11 known: CHN7, CS-1, CS-4, CS-6, EbpA, EbpB, EbpC, EbpD, EBITS3, G, and Henan-I; one novel: CS-9). Frequent appearance of mixed genotype infections was seen in the study animals. Weaned (74.6%; 53/71) or pre-weaned (68.8%; 22/32) pigs have infection rates significantly higher than growing pigs (35.8%; 19/53) (p<0.01). Likewise, E. bieneusi was detected in 2 of 45 sheep fecal specimens (4.4%) in Heilongjiang province, belonging to the known genotype BEB6. Genotypes EbpA, EbpC, EbpD, and Henan-I examined herein have been documented in the cases of human infections and BEB6, EbpA, EbpC, and EbpD in wastewater in central China. Infections of EbpA and EbpC in humans were also reported in other areas of the world. The other known genotypes (CHN7, CS-1, CS-4, CS-6, EBITS3, EbpB, and G) and the new genotype CS-9 were genetically clustered into a group of existing E. bieneusi genotypes with zoonotic potential. Thus, pigs could be a potential source of human E. bieneusi infections in China.     

Identification of pathogens in culture-negative infective endocarditis cases by metagenomic analysis

Background

Pathogens identification is critical for the proper diagnosis and precise treatment of infective endocarditis (IE). Although blood and valve cultures are the gold standard for IE pathogens detection, many cases are culture-negative, especially in patients who had received long-term antibiotic treatment, and precise diagnosis has therefore become a major challenge in the clinic. Metagenomic sequencing can provide both information on the pathogenic strain and the antibiotic susceptibility profile of patient samples without culturing, offering a powerful method to deal with culture-negative cases.

Methods

To assess the feasibility of a metagenomic approach to detect the causative pathogens in resected valves from IE patients, we employed both next-generation sequencing and Oxford Nanopore Technologies MinION nanopore sequencing for pathogens and antimicrobial resistance detection in seven culture-negative IE patients. Using our in-house developed bioinformatics pipeline, we analyzed the sequencing results generated from both platforms for the direct identification of pathogens from the resected valves of seven clinically culture-negative IE patients according to the modified Duke criteria.

Results

Our results showed both metagenomics methods can be applied for the causative pathogen detection in all IE samples. Moreover, we were able to simultaneously characterize respective antimicrobial resistance features.

Conclusion

Metagenomic methods for IE detection can provide clinicians with valuable information to diagnose and treat IE patients after valve replacement surgery. However, more efforts should be made to optimize protocols for sample processing, sequencing and bioinformatics analysis.

     

云南省外来有害生物入侵现状及口岸疫情截获分析

【目的】云南是外来入侵生物的重灾区,了解外来有害生物入侵现状、加强防控尤为紧迫。【方法】从入侵云南外来有害生物类别、入侵途径、造成的损失等方面对云南省外来有害生物的入侵现状进行了阐述,对云南口岸疫情进行统计分析。【结果】按进境检疫物上截获有害生物批次及疫情货物批次统计的国家主要为缅甸、老挝、泰国、越南、荷兰5个国家;按检疫方式分类统计,货检截获批次最多,旅检次之,二者之和占总截获批次的99%;按有害生物类别分类统计,昆虫截获最多,占总截获批次的70.0%至73.9%,杂草、真菌居次,细菌、线虫、病毒、螨类、其他又次之;按货物类别统计,截获有害生物批次最多为粮豆类,占总截获批次的46%。【结论】提出了相应的检疫监管对策与建议,以期为口岸检疫提供参考,降低外来有害生物的入侵风险。