A pentapeptide enabled AL3810 liposome-based glioma-targeted therapy with immune opsonic effect attenuated

AL3810,a molecular dual inhibitor of the vascular endothelial growth factor receptor(VEGFR)and fibroblast growth factor receptor(FGFR),has earned the permission of phase II clinical trial for tumor treatment by China FDA.As a reversible ATP-competitive inhibitor,AL3810 targets ATP-binding site on intracellular region of VEGFR and FGFR,whereas,AL3810 lacking interplay with extracellular region of receptors rendered deficient bloodebrain tumor barrier(BBTB)recognition,poor brain penetration and unsatisfactory anti-glioma efficacy.Integrin avb3 overexpressed on capillary endothelial cells of BBTB as well as glioma cells illuminated ligand-modified liposomes for pinpoint spatial delivery into glioma.The widely accepted peptide c(RGDyK)-modified liposome loading AL3810 of multiple dosing caused hypothermia,activated anti-c(RGDyK)-liposome IgG and IgM antibody and pertinent complements C3 b and C5 b-9,and experienced complement-dependent opsonization.We newly proposed a pentapeptide mn with superb avb3-binding affinity and tailored AL3810-loaded mn-modified liposome that afforded impervious blood circulation,targeting ability,and glioma therapeutic expertise as vastly alleviated immune opsonization on the underpinning of the finite antibodies and complements assembly.Stemming from attenuated immunogenicity,peptide mn strengthened liposome functions as a promising nanocarrier platform for molecular targeting agents.

Assessment of physical stress during the perioperative period of endoscopic submucosal dissection

The advantage of endoscopic submucosal dissection(ESD)is that it is less invasive than surgery.ESD is one of the best treatments for older patients as surgery in this age group of patients is difficult.However,it is unclear how much lower the physical stress of ESD is compared with that of surgery.Thus,objective methods are required to assess physical stress in patients who have undergone ESD.The current review of ESD aimed to summarize the recent advancements in the assessment of physical stress during the perioperative period,focusing on changes in energy metabolism and serum opsonic activity(SOA).Based on metabolic changes,resting energy expenditure(REE)was measured using an indirect calorimeter.The stress factor calculated from the REE and the basal energy expenditure computed using the Harris-Benedict equation can be used to assess physical stress.SOA was assessed using the chemiluminescence method,wherein the use of chemiluminescent probes(i.e.,lucigenin and luminol)allowed quantification of reactive oxygen species generated by neutrophils.Using an auto luminescence analyzer,the results were evaluated based on the maximum light emission and area under the emission curve.These quantifiable results revealed the minimal invasiveness of ESD.

Repeated inoculations of Mycobacterium bovis Bacille Calmette-Guérin (BCG) are needed to induce a strong humoral immune response against antigens expressed by the bacteria

The cellular immune response elicited by Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been carefully investigated, but the humoral immune response has been partially neglected. BALB/c mice were immunized with BCG strain used to immunize humans. Anti-BCG antibodies, as assayed by ELISA, began to appear in the sera after the third week of immunization and plateaued three weeks after the 8th immunization. The total immunoglobulins (Igs) were purified by caprylic acid method from pooled serum collected after the 8th immunization. Anti-BCG antigen antibodies were detected in the total Igs preparation as well as in IgG, IgM, IgA, IgG1, IgG2a, and IgG2b, but not in the IgG3. Distinct BCG proteins were recognized the IgGs in Western blot analysis. Opsonization of BCG bacilli by the purified Igs potentiated internalization of the bacteria by murine Raw 264.7 macrophages. The intracellular BCG elimination coincided with the induction of NO production, which was more pronounced in cells infected with opsonized BCG compared to those infected with the non-opsonized bacteria. Coincidently, the production of NO was also higher in macrophages infected with opsonized BCG (maximal NO production at 48 h of incubation). The obtained results demonstrate that repeated inoculations of BCG effectively activate the humoral immune response, justifying the use of BCG as a live recombinant vaccine vector to insert genes encoding virulence factors controlled by antibodies.