Design,synthesis and SAR studies of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine as aminopeptidase N/CD13 inhibitors

Aminopeptidase N (APN), belonged to metalloproteinase, is an essential peptidase involved in the process of tumor invasion and metastasis. A series of tripeptide analogs with the scaffold 3-phenylpropane-1,2-diamine were designed, synthesized and evaluated for their ability to inhibit APN. Preliminary activity evaluation showed that most of target compounds possessed potent inhibitory activities against APN. With in this series, compound A6 and B6 exhibited good potency with the IC₅₀ values of 8.8 ± 1.3 μM and 8.6 ± 1.1 μM, respectively.     

Changes in fatty acids and sterols during batch growth of <Emphasis Type="Italic">Pavlova viridis</Emphasis> in photobioreactor

Changes in the composition of fatty acids and sterols of Pavlova viridis cultured in an air-lift photobioreactor were studied using gas chromatography-mass spectrometry (GC-MS). The results show that radical changes in fatty acid and sterol contents and compositions occurred during growth phase transitions: the total lipid increased along with the culture age, from 166.4 mg g⁻¹ (late exponential phase) to 232.7 mg g⁻¹ (linear phase), and increased further to be 235.1 mg g⁻¹ in the stationary phase. Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA), decreased along with the culture time, PUFAs, and EPA contents maximized in the late exponential phase to become 46.2 mg g⁻¹ and 22.1 mg g⁻¹ respectively; there was no significant change in docosahexaenoic acid (DHA) content during the whole growth phase, although it reached the peak in the linear phase with 3.5 mg g⁻¹. As for the sterols, two unique sterols with two hydroxyl groups, termed pavlovols, were observed. 4α,24-Dimethylcholestan-3β,4β-diol, one of the pavlovols, increased almost 2-fold from the late exponential phase (2.5 mg g⁻¹) to the stationary phase (4.3 mg g⁻¹). On the contrary, the contents of stigmasterol and sitosterol decreased with culture age, with the maximum content of 2.4 mg g⁻¹ and 3.1 mg g⁻¹, both obtained in the late exponential phase, respectively. The results indicate that growth phase control could be used as a methodology to optimize the total lipid, EPA, PUFA, and sterol contents with the potential for both aquaculture feeds and nutraceutical applications, especially for further research into unique pavlovols.     

Expressions of Raldh3 and Raldh4 during zebrafish early development

Retinoic acid (RA) plays crucial roles in vertebrate embryogenesis. Four retinal dehydrogenases (Raldhs) that are responsible for RA synthesis have been characterized in mammals. However, only Raldh2 ortholog is identified in zebrafish. Here, we report the identification of raldh3 and raldh4 genes in zebrafish. The predicted proteins encoded by zebrafish raldh3 and raldh4 exhibit 70.0% and 73.5% amino acid identities with mouse Raldh3 and Raldh4, respectively. RT-PCR analyses reveal that both raldh3 and raldh4 mRNAs are present in early development. However, whole mount in situ hybridization shows that raldh3 mRNA is first expressed in the developing eye region of zebrafish embryos at 10-somite stage. At 24 hpf (hours post fertilization), raldh3 mRNA is expressed in the ventral retina of eye. At 36 hpf, the mRNA is also expressed in otic vesicle in addition to ventral retina, and it maintains its expression pattern till 2 dpf (days post fertilization). At 3 dpf, raldh3 mRNA becomes very weak in ventral retina but is present in otic vesicle at a high level. At 5 dpf and 7 dpf, raldh3 is no longer expressed in eyes but is expressed in otic vesicles at a very low level. raldh4 mRNA is initially detected in developing liver and intestine regions at 2 dpf embryos. Its expression level becomes very high in these two regions of embryos from 3 dpf to 5 dpf. Analysis on the sections of 5 dpf embryos reveals that raldh4 is expressed in the epithelium of intestine. At 7 dpf, raldh4 mRNA is only weakly expressed in the epithelium of intestinal bulb.     

Visualizing Dynamics of Cell Signaling In Vivo with a Phase Separation-Based Kinase Reporter

1. Download high-res image (259KB)
2. Download full-size image

     

A Novel CXCR4 antagonist enhances angiogenesis via modifying the ischaemic tissue environment

Endothelial progenitor cells (EPCs) play a capital role in angiogenesis via directly participating in neo‐vessel formation and secreting pro‐angiogenic factors. Stromal cell‐derived factor 1 (SDF‐1) and its receptor CXCR4 play a critical role in the retention and quiescence of EPCs within its niche in the bone marrow. Disturbing the interaction between SDF‐1 and CXCR4 is an effective strategy for EPC mobilization. We developed a novel CXCR4 antagonist P2G, a mutant protein of SDF‐1β with high antagonistic activity against CXCR4 and high potency in enhancing ischaemic angiogenesis and blood perfusion. However, its direct effects on ischaemic tissue remain largely unknown. In this study, P2G was found to possess a robust capability to promote EPC infiltration and incorporation in neo‐vessels, enhance the expression and function of pro‐angiogenic factors, such as SDF‐1, vascular endothelial growth factor and matrix metalloprotein‐9, and activate cell signals involved in angiogenesis, such as proliferating cell nuclear antigen, protein kinase B (Akt), extracellular regulated protein kinases and mammalian target of rapamycin, in ischaemic tissue. Moreover, P2G can attenuate fibrotic remodelling to facilitate the recovery of ischaemic tissue. The capability of P2G in direct augmenting ischaemic environment for angiogenesis suggests that it is a potential candidate for the therapy of ischaemia diseases.     

Effects of phosphatidyl serine on immune response in the shrimp Litopenaeus vannamei

Phosphatidyl serine plays an important role in animal innate immunity. Given its important functions, numerous investigations have been carried out on its immunological function in many animals. However, studies of phosphatidyl serine in the white shrimp Litopenaeus vannamei, an economically important animal, are rare. In this paper, we demonstrated influences of injecting phosphatidyl serine (PS) on immune response including some parameters from pro-phenol oxidase activating system (pro-PO system) and hemocyanin-derived phenol oxidase activity (Hd-PO) along with antibacterial and bacteriolytic activities in the white shrimp Litopenaeus vannamei with different PS concentrations (5, 10 and 20 μg mL^?1). The results showed that PS could affect immune response of L. vannamei significantly (P<0.05), including total hemocyte counts (THC), PO activity from hemocyte, phenol oxidase (PO) activity from plasma, hemocyanin concentration, Hd-PO activity as well as antibacterial and bacteriolytic activities in the plasma. Among the lines, 20 μg mL^?1 PS had the strongest effect on the above parameters, whereas 5 μg mL^?1 had the least effect. The experimental results indicated that PS was able to activate exocytosis of pro-PO and formation of Hd-PO in white shrimp after injection, further regulating the immune process reflected by variation of antibacterial and bacteriolytic activities in a certain way.