APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway

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Specific cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting

Background

Cancer stem cells (CSCs) are highly proliferative and tumorigenic, which contributes to chemotherapy resistance and tumor occurrence. CSCs specific therapy may achieve excellent therapeutic effects, especially to the drug-resistant tumors.

Results

In this study, we developed a kind of targeting nanoparticle system based on cationic albumin functionalized with hyaluronic acid (HA) to target the CD44 overexpressed CSCs. All-trans-retinoic acid (ATRA) was encapsulated in the nanoparticles with ultrahigh encapsulation efficiency (EE%) of 93% and loading content of 8.37%. TEM analysis showed the nanoparticles were spherical, uniform-sized and surrounded by a coating layer consists of HA. Four weeks of continuously measurements of size, PDI and EE% revealed the high stability of nanoparticles. Thanks to HA conjugation on the surface, the resultant nanoparticles (HA-eNPs) demonstrated high affinity and specific binding to CD44-enriched B16F10 cells. In vivo imaging revealed that HA-eNPs can targeted accumulate in tumor-bearing lung of mouse. The cytotoxicity tests illustrated that ATRA-laden HA-eNPs possessed better killing ability to B16F10 cells than free drug or normal nanoparticles in the same dose, indicating its good targeting property. Moreover, HA-eNPs/ATRA treatment decreased side population of B16F10 cells significantly in vitro. Finally, tumor growth was significantly inhibited by HA-eNPs/ATRA in lung metastasis tumor mice.

Conclusions

These results demonstrate that the HA functionalized albumin nanoparticles is an efficient system for targeted delivery of antitumor drugs to eliminate the CSCs.

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Transient growth‐enhancing effects of elevated maternal thyroid hormones at no apparent oxidative cost during early postnatal period

Maternal thyroid hormones (THs) have been proven crucial for embryonic development in humans, but their influence within the natural variation on wild animals remains unknown. So far the only two studies that experimentally investigated the potential fitness consequences of maternal THs in birds found inconsistent results. More studies are thus required to assess the general effects of maternal THs and their influences on more behavioral and physiological parameters. In this study, we experimentally elevated yolk TH content in a wild migratory passerine species, the collared flycatcher Ficedula albicollis, to investigate the effects on hatching success, nestling growth and oxidative stress. We found that TH‐injected eggs had a higher hatching success, and the nestlings hatched from TH‐injected eggs were heavier and larger than control nestlings, but only during the early postnatal period. These differences vanished by fledging. Nestlings from TH‐injected eggs exhibited lower activity of the glutathione‐s‐transferase, a major antioxidant enzyme, than control nestlings at day 12, a few days before fledging, but they did not differ in oxidative damage and overall intracellular oxidative state. These results suggest that the early growth‐enhancing effects incurred no observable oxidative stress. We hypothesize that such a transient growth‐enhancing effect might be adaptive in advancing the development and maturation of the offspring so they are well‐prepared in time for the upcoming migration. Further studies investigating whether such advancing effects can influence long‐term fitness, will be more than valuable.     

A bursal pentapeptide (BPP-I), a novel bursal-derived peptide, exhibits antiproliferation of tumor cell and immunomodulator activity

The bursa of Fabricius (BF) is the central humoral immune organ unique to birds. Here, we isolated a novel bursal pentapeptide I (BPP-I), LGPGP, from BF. BPP-I could play inhibition effect on MCF-7 but not on CEF or Vero cell proliferation in vitro, and enhance antitumor factor p53 protein expression. Also, BPP-I stimulated antibody production in a dose-dependent manner in hybridoma cell. Furthermore, BPP-I could induce various immune responses in mice immunization experiments, including increase antibody production and cytokines IL-4 and IFN-γ level, and induce T-cell immunophenotyping. These results suggest that BPP-I is a potential immunomodulator of antitumor and immunity. The study could provide some novel insights on the probable candidate reagent for the antitumor and immune improvement.     

Heat shock proteins: A dual carrier-adjuvant for an anti-drug vaccine against heroin

Heroin is a highly abused opioid that has reached epidemic status within the United States. Yet, existing therapies to treat addiction are inadequate and frequently result into rates of high recidivism. Vaccination against heroin offers a promising alternative therapeutic option but requires further development to enhance the vaccine’s performance. Hsp70 is a conserved protein with known immunomodulatory properties and is considered an excellent immunodominant antigen. Within an antidrug vaccine context, we envisioned Hsp70 as a potential dual carrier-adjuvant, wherein immunogenicity would be increased by co-localization of adjuvant and antigenic drug hapten. Recombinant Mycobacterium tuberculosis Hsp70 was appended with heroin haptens and the resulting immunoconjugate granted anti-heroin antibody production and blunted heroin-induced antinociception. Moreover, Hsp70 as a carrier protein surpassed our benchmark Her-KLH cocktail through antibody-mediated blockade of 6-acetylmorphine, the main mediator of heroin’s psychoactivity. The work presents a new avenue for exploration in the use of hapten-Hsp70 conjugates to elicit anti-drug immune responses.     

闽江口鱼类功能多样性

根据2016年春季(5月)、夏季(8月)、秋季(11月)和冬季(2月)在闽江口海域进行底拖网作业的渔业资源调查样品,应用鱼类形态功能特征点数据分析了福建闽江口海域的鱼类功能多样性现状及时空变异.结果表明: 功能多样性与物种丰度具有相同的变化趋势,各站位鱼类物种丰度分别为:春季(17.8±5.1);夏季(22.4±5.6);秋季(17.7±6.3);冬季(12.1±2.3).鱼类集群功能多样性指数夏季最高,为(33.94±28.70),冬季最低(9.93±8.83),春季为(11.30±7.55),秋季为(19.05±19.32).群落内功能种呈现显著的季节演替,春季为太的黄鲫(占比为26%),夏季为六指马鲅(26%),秋季为龙头鱼,占比高达69%,显著高于其他物种的总和,冬季为棘头梅童鱼(38%).鱼类功能的季节性变动主要受其生活史及与其他物种之间的种间关系影响.     

昆明西山滇青冈林内滇青冈种子库动态的研究

通过对昆明西山滇青冈林内滇青冈种子库的跟踪取样调查和种子埋藏试验,对滇青冈种子库的动态进行了研究。昆虫在种子成熟前侵入种子,经种子雨进入种子库时已有71.8%的种子失去萌发能力。种子雨输入种子库的绝大部分种子停留在表面种子库,其中48.55%的种子被虫害,25.36%被某些非生物或生物搬运,17.39%的腐烂,8.7%的被动物当场取食,没有种子萌发,影响种子库动态的各种因子的作用大小在时间上是变化。被搬运的种子中,有4.9%的由表面种子库转移到埋藏种子库。土层是滇青冈种子的安全生境,土壤种子库的存在时间超过250天。埋入土壤的试验种子一直处于静止状态,到6月雨季后有80%种子萌发,20%的腐烂。萌发种子数是当年产种子的0.26%。滇青冈林内的滇青冈种子库是季节性的,种子库对种群个体的补充作用是有限的。     

Gene regulatory network inference by point-based Gaussian approximation filters incorporating the prior information

Abstract

The extended Kalman filter (EKF) has been applied to inferring gene regulatory networks. However, it is well known that the EKF becomes less accurate when the system exhibits high nonlinearity. In addition, certain prior information about the gene regulatory network exists in practice, and no systematic approach has been developed to incorporate such prior information into the Kalman-type filter for inferring the structure of the gene regulatory network. In this paper, an inference framework based on point-based Gaussian approximation filters that can exploit the prior information is developed to solve the gene regulatory network inference problem. Different point-based Gaussian approximation filters, including the unscented Kalman filter (UKF), the third-degree cubature Kalman filter (CKF₃), and the fifth-degree cubature Kalman filter (CKF₅) are employed. Several types of network prior information, including the existing network structure information, sparsity assumption, and the range constraint of parameters, are considered, and the corresponding filters incorporating the prior information are developed. Experiments on a synthetic network of eight genes and the yeast protein synthesis network of five genes are carried out to demonstrate the performance of the proposed framework. The results show that the proposed methods provide more accurate inference results than existing methods, such as the EKF and the traditional UKF.

     

Design and synthesis of novel D-ring fused steroidal heterocycles

Using dehydroepiandrosterone as the starting material, we have synthesized a series of steroid analogs possessing a D-ring fused with heterocycles which are pyridine, imidazo [2,1-b]thiazoles or substituted thiazole imines. All the final structures are first reported and identified by NMR and MS spectroscopys, the yields of these products are moderate to good and the reaction conditions are mild. The cytotoxicity of the synthesized compounds against EC-109(human esophageal carcinoma), EC-9706(human esophageal carcinoma), MGC-803(human gastric carcinoma) were investigated.