对虾原肌球蛋白不同致敏途径对BALB/c小鼠致敏性的影响

随着食物过敏现象的日益普遍,其已成为工业化国家一个严重的公众健康问题。食物蛋白致敏机理的相关 研究大多借助于两大类小鼠模型,即口服致敏模型和局部或皮肤致敏模型。然而,不同模型之间的差异以及如何选 择合适的模型进行研究却鲜有人关注。鉴于此,本研究旨在通过比较对虾原肌球蛋白口服灌胃和腹腔注射两种给药 途径对BALB/c小鼠致敏性的影响,寻求最佳给药方式,以便建立有效的动物模型,并在分子及免疫水平研究其致 敏机理,从而为食物过敏原动物模型的构建提供一定的理论依据,也为研究食物过敏原致敏机制以及预防治疗食物 过敏提供重要的模型依据。结果表明,腹腔注射小鼠血清中特异性免疫球蛋白（immunoglobulin,Ig）E、组胺以及 辅助性T细胞（helper T cells,Th）2型细胞因子含量均高于口服灌胃小鼠,其致敏性更好。此外,口服灌胃小鼠血 清特异性IgG2a、干扰素-γ、调节性T细胞水平增加,表明虽有黏膜佐剂作用,但口服给药仍可能使小鼠产生口服免 疫耐受,从而降低对虾原肌球蛋白对其的致敏性。本研究表明,腹腔注射原肌球蛋白比口服灌胃更易使小鼠致敏, 其Th1/Th2平衡被打破,Th2反应占据优势,更适合用于构建食物致敏动物模型。     

Angiopoietin-like Proteins in Colorectal Cancer—A Literature Review

Colorectal cancer (CRC) is one of the most common types of malignancy, with an annual incidence of about 10% of the total number of new cases. Despite well-developed screening tests, mortality from this type of cancer remains unchanged. Therefore, it is important to search for more accurate markers that are useful in the detection of colorectal cancer (especially in its early stages), and treatment. Angiopoietin-like proteins (ANGPTLs) are a family of eight proteins with a diversity of applications, including pro- and anti-angiogenic properties. Consequently, we performed an extensive search of the literature, pertaining to our investigation, via the MEDLINE/PubMed database. Based on the available literature, we summarize that some of those proteins are characterized by increased or decreased concentrations during the course of CRC. We can also assume that some ANGPTLs can inhibit the development of CRC, while others induce its progress. Moreover, some factors are dependent on the stage or histological type of the tumor, the presence of hypoxia, or metastases. Most importantly, some ANGPTLs can be useful in anti-cancer therapy. Therefore, further studies on ANGPTLs as potential markers of CRC should be continued.     

Antitumor Effects of Orally and Intraperitoneally Administered Chitosan Oligosaccharides (COSs) on S180‐Bearing/Residual Mouse

Chitosan oligosaccharides (COSs) are hydrolysate mixture of chitin and possess various biomedical properties, such as antimicrobial, immunoenhancing, and antitumor effects. Antiproliferation activity of COS and commercially available samples was compared in the terms of A549 and HCT‐116 cells. Ten tumor cells were used to estimate cytotoxicity of COS. Although there were some researches on the antitumor effects of COS, we highlighted the in vivo antitumor activities of COS administrated orally and intraperitoneally on S180‐bearing/residual mouse. Results turned out that in vitro IC₅₀ values of COS were 48.6 ± 7.0 to 1329.9 ± 93.4 μg/mL against 10 different tumor cell lines. Then, the in vivo experiments proved that the inhibition rate was high up to 58.5%. Significant cell death and necrosis were observed in COS‐treated groups by histological analysis. COS stimulated the mRNA expression of tumor necrosis factor alpha. In summary, COS may be considered promising candidate as antitumor functional food or pharmaceutic adjuvant in oncotherapy, especially for patients after surgical resection.     

Radiation Field for Fission Neutron Enhanced Boron Neutron Capture Therapy Employing Fast Neutron Source Reactor “YAYOI”

Boron Neutron Capture Therapy (BNCT) of a localized tumor needs a sufficient thermal neutron flux at the tumor. A surgical operation including ennucleation of the main part of tumor is required for the case of thermal neutron beam from a thermal reactor because of the rapid decrease of the neutron flux in the tissue. Intermediate neutrons with little fast neutron component are only produced by a specifically designed reactor which awaits to be build.

In the present paper, a positive use of fast neutron beams in addition to BNCT is proposed for treatment of some kind of localized tumors employing a fission fast neutrons from a fast neutron source reactor “YAYOI” of University of Tokyo which is licenced as such. Dose distributions in a water phantom located at a proposed position for two collimator cases were measured and its availability was confirmed as a possible port for therapy.     

不同筛查工具对老年肿瘤患者营养筛查的比较

目的：探讨在老年肿瘤患者中合理选择营养风险筛查工具,以便及时实施营养干预,改善由于营养因素所导致的不良临床结局。方法：对130例老年肿瘤患者应用微型营养评价精法（MNA-SF）和患者主观全面评价法（PG-SGA）进行营养筛查,以白蛋白和前白蛋白为标准评定上述工具的灵敏度、特异度。结果：以白蛋白为参考标准,MNA-SF、PG-SGA的灵敏度分别为55.7%、68.3%,特异度分别为45.1%、89.7%。以前白蛋白为参考标准,MNA-SF、PG-SG的灵敏度分别为67.1%、75.2%,特异度分别为51.0%、93.1%。结论：PG-SGA考虑到多个影响营养的复杂问题,使评价结果更接近于肿瘤患者的实际营养状况。较之MNA-SF,PG-SGA更适用于老年肿瘤患者,值得推广。     

Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.     

Roles of the Unsaturated Fatty Acid Docosahexaenoic Acid in the Central Nervous System: Molecular and Cellular Insights

Fatty acids (FAs) are essential components of the central nervous system (CNS), where they exert multiple roles in health and disease. Among the FAs, docosahexaenoic acid (DHA) has been widely recognized as a key molecule for neuronal function and cell signaling. Despite its relevance, the molecular pathways underlying the beneficial effects of DHA on the cells of the CNS are still unclear. Here, we summarize and discuss the molecular mechanisms underlying the actions of DHA in neural cells with a special focus on processes of survival, morphological development, and synaptic maturation. In addition, we examine the evidence supporting a potential therapeutic role of DHA against CNS tumor diseases and tumorigenesis. The current results suggest that DHA exerts its actions on neural cells mainly through the modulation of signaling cascades involving the activation of diverse types of receptors. In addition, we found evidence connecting brain DHA and ω-3 PUFA levels with CNS diseases, such as depression, autism spectrum disorders, obesity, and neurodegenerative diseases. In the context of cancer, the existing data have shown that DHA exerts positive actions as a coadjuvant in antitumoral therapy. Although many questions in the field remain only partially resolved, we hope that future research may soon define specific pathways and receptor systems involved in the beneficial effects of DHA in cells of the CNS, opening new avenues for innovative therapeutic strategies for CNS diseases.     

pH Sensing Properties of Flexible,Bias‐Free Graphene Microelectrodes in Complex Fluids: From Phosphate Buffer Solution to Human Serum

Advances in techniques for monitoring pH in complex fluids can have a significant impact on analytical and biomedical applications. This study develops flexible graphene microelectrodes (GEs) for rapid (<5 s), very‐low‐power (femtowatt) detection of the pH of complex biofluids by measuring real‐time Faradaic charge transfer between the GE and a solution at zero electrical bias. For an idealized sample of phosphate buffer solution (PBS), the Faradaic current is varied monotonically and systematically with the pH, with a resolution of ≈0.2 pH unit. The current–pH dependence is well described by a hybrid analytical–computational model, where the electric double layer derives from an intrinsic, pH‐independent (positive) charge associated with the graphene–water interface and ionizable (negative) charged groups. For ferritin solution, the relative Faradaic current, defined as the difference between the measured current response and a baseline response due to PBS, shows a strong signal associated with ferritin disassembly and the release of ferric ions at pH ≈2.0. For samples of human serum, the Faradaic current shows a reproducible rapid (<20 s) response to pH. By combining the Faradaic current and real‐time current variation, the methodology is potentially suitable for use to detect tumor‐induced changes in extracellular pH.     

Modeling Lung Carcinoids with Zebrafish Tumor Xenograft

Lung carcinoids are neuroendocrine tumors that comprise well-differentiated typical (TCs) and atypical carcinoids (ACs). Preclinical models are indispensable for cancer drug screening since current therapies for advanced carcinoids are not curative. We aimed to develop a novel in vivo model of lung carcinoids based on the xenograft of lung TC (NCI-H835, UMC-11, and NCI-H727) and AC (NCI-H720) cell lines and patient-derived cell cultures in Tg(fli1a:EGFP)^y1 zebrafish embryos. We exploited this platform to test the anti-tumor activity of sulfatinib. The tumorigenic potential of TC and AC implanted cells was evaluated by the quantification of tumor-induced angiogenesis and tumor cell migration as early as 24 h post-injection (hpi). The characterization of tumor-induced angiogenesis was performed in vivo and in real time, coupling the tumor xenograft with selective plane illumination microscopy on implanted zebrafish embryos. TC-implanted cells displayed a higher pro-angiogenic potential compared to AC cells, which inversely showed a relevant migratory behavior within 48 hpi. Sulfatinib inhibited tumor-induced angiogenesis, without affecting tumor cell spread in both TC and AC implanted embryos. In conclusion, zebrafish embryos implanted with TC and AC cells faithfully recapitulate the tumor behavior of human lung carcinoids and appear to be a promising platform for drug screening.