Molecular and magnetic resonance imaging: The value of immunoliposomes

Molecular imaging has the potential to transform the field of diagnostic imaging through enabling far more detailed investigation and characterisation of disease processes than is currently possible. Magnetic resonance imaging (MRI) is capable of three-dimensional non-invasive imaging of opaque tissues at near cellular resolution. Among the imaging techniques available today, MRI has, perhaps, the greatest potential to exploit the possibilities that molecular imaging presents. Nanoparticles are the focus of intense research, due to a wide variety of potential applications in the biomedical, optical, and electronic fields. In this article we examine the progress made in the development of nanoparticles as targeted contrast agents for molecular magnetic resonance imaging. In particular, we will examine the potential of antibody-targeted liposomes (immunoliposomes) as vehicles for delivering MRI contrast agents to cellular biomarkers, thus enabling visualisation of structures and processes at the molecular level. We will address some of the challenges that must be faced by researchers in this field before the progress made in the laboratory can be translated into improved clinical diagnostics and therapeutics.     

Safety assessment of Cry1Ab/Ac fusion protein

Cry1ab/ac gene was fused by both the cry1ab gene (GenBank Accession No. X54939) and the cry1ac gene (GenBank Accession No. Y09787), which was widely used in genetically modified (GM) rice, cotton, maize and so on. In order to support the safety assessment of GM food or feed products containing Cry1Ab/Ac protein, sufficient quantities of Cry1Ab/Ac protein were produced in Escherichia coli for in vitro evaluation and animal studies. The Cry1Ab/Ac protein does not possess the characteristics associated with food toxins or allergens, i.e., it has no sequence homology with any known allergens or toxins, and no N-glycosylation sites, can be rapidly degraded in gastric and intestinal fluids, and is devoid of adverse effects in mice by gavage at a high dose level of 5 g (Cry1Ab/Ac protein)/kg body weight. In conclusion, there is a reasonable certainty of no harm resulting from the inclusion of the Cry1Ab/Ac protein in human food or animal feed.     

Syntheses, antiproliferative activity and theoretical characterization of acitretin-type retinoids with changes in the lipophilic part

Acitretin analogs, incorporating changes in the lipophilic part, were efficiently synthesized from commercially available aromatic aldehydes or methyl ketones using the Wittig or Horner-Wadsworth-Emmons reaction. Their antiproliferative activity was evaluated against human breast MCF-7 epithelial cells. Analogs 3, 4, 8 and 11 exhibited strong, dose-dependent, antiproliferative activity on the tested cell line. Analog 3, incorporating three methoxy groups in the aromatic ring, exhibited the strongest inhibitory effect at 10 μM. High-level all electron conventional ab initio and density functional theory quantum chemical calculations were performed to obtain the molecular structure, electron charge distribution and polarization properties of all compounds of interest in this work. The most active analogs were planar and were characterized by larger dipole moments than the other synthesized molecules. Another factor of importance to the analysis of the activity of these molecules is the dipole polarizability.     

Syk mediates BCR- and CD40-signaling integration during B cell activation

CD40 is essential for optimal B cell activation. It has been shown that CD40 stimulation can augment BCR-induced B cell responses, but the molecular mechanism(s) by which CD40 regulates BCR signaling is poorly understood. In this report, we attempted to characterize the signaling synergy between BCR- and CD40-mediated pathways during B cell activation. We found that spleen tyrosine kinase (Syk) is involved in CD40 signaling, and is synergistically activated in B cells in response to BCR/CD40 costimulation. CD40 stimulation alone also activates B cell linker (BLNK), Bruton tyrosine kinase (Btk), and Vav-2 downstream of Syk, and significantly enhances BCR-induced formation of complex consisting of, Vav-2, Btk, BLNK, and phospholipase C-gamma2 (PLC-γ2) leading to activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase, Akt, and NF-κB required for optimal B cell activation. Therefore, our data suggest that CD40 can strengthen BCR-signaling pathway and quantitatively modify BCR signaling during B cell activation.     

呼吸系统感染性疾病快速诊断技术的应用

目的为临床提供快速准确的呼吸道常见感染性疾病病因诊断依据，以便尽快诊断、正确治疗、预防传播，协助临床排除SARS(严重急性呼吸综合征)及禽流感诊断。方法用酶免疫方法对呼吸道感染病人鼻咽喉分泌物、血清及尿液标本进行检测，得到A群链球菌抗原、流感病毒A型和B型抗原、呼吸道合胞病毒抗原、肺炎支原体抗体IgM、嗜肺军团菌I型抗原的定性结果。每项试验操作简单并可在30min内完成。结果一年半时间共检测来自879位病人的1152份标本，阳性结果共124个，总感染率为14．1％。A群链球菌抗原检测标本446份，阳性率为11．9％；流感病毒A型和B型抗原266份，阳性率为11．7％；呼吸道合胞病毒抗原116份，阳性率为21．6%；肺炎支原体抗体227份，阳性率为5．3％、嗜肺军团菌1型抗原97份，阳性率为3．1％。SARS流行期间这五种病原体的感染率为20．2％，阳性结果中未发现一例SARS病人。SARS流行前一年多的时间里所检测病原体感染率仅为12．0%。结论采用酶免疫法检测呼吸道病原体，结果快速可靠，为临床提供了早期诊断和正确治疗的依据，可以尽早有效地排除SARS诊断，并减少抗生素滥用现象。     

Susceptibilities of the Invasive Fall Armyworm (Spodoptera frugiperda) to the Insecticidal Proteins of Bt maize in China

To control the fall armyworm (FAW), Spodoptera frugiperda (Smith), a serious threat to maize production in China, the Chinese government has issued biosafety certificates for transgenic insect-resistant maize expressing Bt (Bacillus thuringiensis) toxins including Bt-Cry1Ab maize (crop event DBN9936), Bt-Vip3Aa maize (event DBN9501), Bt-(Cry1Ab+Vip3Aa) maize with superimposed traits (event DBN9936 × DBN9501) and Bt-(Cry1Ab+Vip3Aa) maize with superimposed traits (event Bt11 × MIR162), but the susceptibility baselines of geographically distinct FAW populations to these events, which form the basis for managing resistance development in the pest to these events, are not clear. We used the diet-incorporated bioassays method to detect the susceptibilities of the seven FAW populations collected from Yunnan, Henan and Hubei provinces in China in 2021 to the insecticidal proteins of the four Bt maize events. The result showed that the susceptibilities of different geographical populations to Bt insecticidal proteins were significantly different. In the seven populations, the range in median lethal concentrations (LC₅₀) of Cry1Ab expressed in DBN9936 was 0.87–2.63 μg/g, 0.14–0.30 μg/g for Vip3Aa expressed in DBN9501, 0.78–1.86 μg/g for Cry1Ab+Vip3Aa expressed in DBN9936 × DBN9501, and 0.36–1.42 μg/g for CryAb+Vip3Aa expressed in Bt11 × MIR162. The growth inhibition responses also showed that the susceptibilities varied with the different median growth inhibitory concentration (GIC₅₀) ranges (0.38–1.22, 0.08–0.28, 0.28–0.87, and 0.24–0.78 μg/g, respectively). The variations in the ranges of the susceptibility baselines of the geographical populations of fall armyworm in China to the insecticidal proteins expressed in the four events provide a scientific basis for monitoring FAW population resistance to Bt maize and managing the populations using different Bt maize events.     

Identification of CD123+ myeloid dendritic cells as an early-stage immature subset with strong tumoristatic potential

CD123 has been identified as a specific surface marker for plasmacytoid dendritic cells (PDCs). However, CD123 has recently been shown to be expressed on freshly isolated or in vitro generated myeloid dendritic cells (MDCs). In this article, we investigated whether the expression of CD123 on monocyte-derived MDCs was related to their function, especially to tumor-inhibiting potential. MDCs were induced from cord blood CD14(+) monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days, and then CD123(+) cells were isolated by positive immunomagnetic cell selection. We observed that CD123(+) cells lost monocyte CD14 expression, acquired immature myeloid dendritic cell phenotype and morphology. They exerted more significant endocytosis and less antigen-presenting function than CD123(-)MDCs which are often referred to as typical MDCs. Meanwhile, CD123(+) MDCs exhibited more significant tumor-inhibiting activity toward hematological tumor cell lines of U937 and Jurkat even at a low effector:target ratio. CD123(+) MDCs expressed higher level of cytoplasmic TNF-alpha-related apoptosis-inducing ligand (TRAIL), but no detectable surface TRAIL and very little soluble TRAIL. Pretreatment with recombinant human TRAIL receptor 2:Fc fusion protein significantly reduced the tumor-inhibiting effect of CD123(+) MDCs, but not of CD123(-) MDCs. Overall, our data demonstrated that CD123(+) MDCs were an early-stage immature DC subset, with a significant tumor-inhibiting activity partially via involvement of enhanced cytoplasmic TRAIL.     

含有RGD序列多肽构效关系的研究

目的：探讨含RGD多肽的构效关系。方法：采用分子力学和量子化学方法对某些含RGD序列多肽的化学结构进行分子模拟和量化计算。结果：优化了各化合物的空间结构，得到了优势构象和优势构象的能量，研究了分子的电荷分布，前线轨道能量等。结论：借助于理论计算可解释含RGD（Arg-Gly-Asp)序列多肽的构效关系，确定了多肽与受体结合时的活性位点，对其活性差异给予较好的分析，可望为合成具有更高活性的含RGD序列多肽提供理论指导。     

Steady-state versus chemotherapy-based hematopoietic cell mobilization after anti-CD38-based induction therapy in newly diagnosed multiple myeloma

Background

The incorporation of anti-CD38 monoclonal antibodies (mAb) in induction regimens of newly diagnosed transplant-eligible multiple myeloma (MM) patients has been established as a new standard. However, the optimal strategy of stem cell mobilization in this context is not yet clear.

Study Design and Methods

From May 2020 till September 2022, we retrospectively reviewed patients receiving anti-CD38 mAb-based induction therapy followed by stem cell mobilization either in a steady-state protocol (SSM) using 10 μg/kg granulocyte colony-stimulating factor (G-CSF) for 5 days or in a chemotherapy-based protocol (CM) using 1–4 g/m² cyclophosphamide and G-CSF.

Results

Overall, 85 patients (median age 61 years) were included in the analysis. In total, 90 mobilization attempts were performed, 42 with SSM and 48 with CM. There was no significant difference in the median concentration of CD34+ cells in peripheral blood (PB) prior to apheresis between SSM and CM (61/μL vs. 55.4/μL; p = .60). Cumulative CD34+ yields did not differ between the groups with median of 6.68 and 6.75 × 10⁶/kg body weight, respectively (p = .35). The target yield (≥4 × 10⁶ CD34+ cells/kg body weight) was reached in 88% (CM) and 86% (SSM), with a high proportion even after a single apheresis session (76% vs. 75%). Plerixafor was found to be more frequently used in SSM (52%) than in CM (23%; p < .01). A total of 83 patients underwent autologous transplantation and all were engrafted.

Conclusions

Stem cell collection in patients undergoing anti-CD38-based induction therapy is feasible with either CM or SSM, although SSM more frequently requires plerixafor.