Characterization of Aggregated Antibody-Silicone Oil Complexes: From Perspectives of Morphology, 3D Image,and Fcγ Receptor Activation

Pre-filled syringes (PFS) have been in widespread use as an administration device for therapeutic antibodies in recent decades. Generally, the inner barrel and syringe of PFS are coated with silicone oil (SO) for lubrication. Multiple studies have focused on the fact that the SO adsorbs denatured antibody molecules, and induces antibody aggregation. Aggregated antibodies are recognized as a potential risk for evoking immunogenic responses in patients. The characteristics of the aggregated antibody-SO complexes, including their concentration, population, shape, three-dimensional (3D) image, and Fcγ Receptors (FcγRs) activation have been obscurely acknowledged so far. In the present work, we prepared aggregated antibody-SO complexes by agitation and analyzed using multifaceted techniques such as flow imaging, confocal fluorescence microscopy, and cell-based assays for FcγRs activation. The results emphasized that the SO accelerates the increase in sub-visible particles and antibody aggregation. The confocal fluorescence microscopy analysis revealed the high-resolution 3D images of aggregated antibody-SO complexes. The FcγRs reporter cell assay clarified that the pre-mixed and agitated Ab + SO have higher FcγRs activation capability compared to the agitated Ab. Overall, this study advances the view that SO has an effect to increase the risk of agitation-induced aggregated antibody particles.     

Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors

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Hb F-Avellino [Gγ41(C7)Phe → Leu; HBG2: c.124 T > C]: A New Hemoglobin Variant Observed In A Healthy Newborn

Here we describe Hb F-Avellino [^Gγ41(C7)Phe?→?Leu; HBG2: c.124?T?>?C], a new hemoglobin (Hb) variant observed in a healthy newborn. The proband’s hemolysate was found to be mildly unstable by the isopropanol test. The occurrence of the variant was assessed by both chromatographic and electrophoretic methods. DNA sequencing analysis of the ^Gγ gene showed a T to C transition at codon 41 (TTC?>?CTC) corresponding to the Phe?→?Leu substitution. Normal functional properties have been hypothesized.     

Brief overview of selected approaches in targeting pancreatic adenocarcinoma

Introduction: Pancreatic adenocarcinoma (PDAC) has the worst prognosis of any major malignancy, with 5-year survival painfully inadequate at under 5%. Investigators have struggled to target and exploit PDAC unique biology, failing to bring meaningful results from bench to bedside. Nonetheless, in recent years, several promising targets have emerged.

Areas covered: This review will discuss novel drug approaches in development for use in PDAC. The authors examine the continued efforts to target Kirsten rat sarcoma viral oncogene homolog (KRas), which have recently been successfully abated using novel small interfering RNA (siRNA) eluting devices. The authors also discuss other targets relevant to PDAC including those downstream of mutated KRas, such as MAPK kinase and phosphatidylinositol 3-kinase.

Expert opinion: Although studies into novel biomarkers and advanced imaging have highlighted the potential new avenues toward discovering localized tumors earlier, the current therapeutic options highlight the fact that PDAC is a highly metastatic and chemoresistant cancer that often must be fought with virulent, systemic therapies. Several newer approaches, including siRNA targeting of mutated KRas and enzymatic depletion of hyaluronan with PEGylated hyaluronidase are particularly exciting given their early stage results. Further research should help in elucidating their potential impact as therapeutic options.     

Therapeutic approach by Aloe vera in experimental model of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that leads to an inflammatory demyelination, axonal damage, and progressive neurologic disability that affects ～2.5 million people worldwide. The aim of the present research was to test the therapeutic effect of Aloe vera in experimental model of MS. All experiments were conducted on C57BL/6 male mice aged 6–8 weeks. To induce the experimental autoimmune encephalomyelitis (EAE), 250 µg of the myelin oligodendrocyte glycoprotein 35–55 peptide emulsified in complete freund’s adjuvant was injected subcutaneously on day 0 over two flank areas. In addition, 200?ng of pertussis toxin in 100 µL phosphate buffered saline was injected intraperitoneally on days 0 and 2. The therapeutic protocol was carried out intragastrically using 120?mg/kg/day Aloe vera from 7 days before to 21 days after EAE induction. The mice were killed 21 days after EAE induction. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. The results indicated that treatment with Aloe vera caused a significant reduction in severity of the disease in experimental model of MS. Histological analysis showed 3?±?2 plaques in Aloe vera-treated mice compared with 5?±?1 plaques in control group. The density of mononuclear infiltration in the CNS of Aloe vera-treated mice (500?±?200) was significantly less in comparison to 700?±?185 cells in control group. Moreover, the serum level of nitric oxide in treatment group was significantly less than control animals. The level of interferon-γ in cell culture supernatant of treated mice splenocytes was lower than control group, whereas decrease in serum level of interleukin-10 in treatment group was not significant in comparison with control mice. These data indicate that Aloe vera therapy can attenuate the disease progression in experimental model of MS.     

Silver nanoparticle-embedded poly(vinyl pyrrolidone) hydrogel dressing: gamma-ray synthesis and biological evaluation

Silver nanoparticle (nAg)-embedded poly(vinyl pyrrolidone) (PVP) hydrogels, to be used as antibacterial wound dressings, were prepared by γ-irradiation at various doses: 25, 35, and 45?kGy. The formation and characteristics of the silver nanoparticles were investigated with a UV–vis spectrophotometer, transmission electron microscopy, and scanning electron microscopy with energy-dispersive X-ray. The hydrogels were characterized for physical and biological properties. Based on the antibacterial determination, the 1 and 5?mM nAg–embedded PVP hydrogels were effective, with 99.99% bactericidal activity at 12 and 6?h, respectively. The indirect cytotoxicity evaluation based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated that both the neat and the nAg-embedded PVP hydrogels were non-toxic to mouse fibroblasts (L929). The 5?mM nAg-embedded PVP hydrogels not only provided a clean, moist environment for wound healing, but also effectively prevented bacterial infection and enhanced wound recovery.     

Boehmite enhances hair follicle growth via stimulation of dermal papilla cells by upregulating β-catenin signalling

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of β-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.     

Plasma matrix metalloproteinase 7, CC-chemokine ligand 18, and periostin as markers for pulmonary sarcoidosis

BackgroundSome patients with sarcoidosis experience worsening of pulmonary lesions. However, no biomarker has been identified that reflects pulmonary disease status in sarcoidosis. We investigated the usefulness of potential markers of pulmonary fibrosis in patients with sarcoidosis.MethodsPlasma matrix metalloproteinase 7 (MMP-7), CC-chemokine ligand 18 (CCL-18), and periostin levels were evaluated in 60 patients with sarcoidosis and 30 healthy controls; bronchoalveolar lavage fluid levels were analyzed in 22 patients with sarcoidosis. To determine the usefulness of these markers, we explored potential correlations between these markers and sarcoidosis clinical characteristics.ResultsPlasma MMP-7, CCL-18, and periostin concentrations were significantly higher in patients with sarcoidosis than those in healthy controls. MMP-7 concentrations in plasma and bronchoalveolar lavage fluid were higher in patients with sarcoidosis with parenchymal infiltration than in those without lung lesions. Moreover, MMP-7 concentration was negatively correlated with pulmonary function.ConclusionAmong these novel biomarkers, MMP-7 most precisely reflected pulmonary sarcoidosis disease status and thus, might be useful for diagnosing and evaluating sarcoidosis, particularly in patients with pulmonary parenchymal lesions.     

Circulating CCL20: A potential biomarker for active vitiligo together with the number of Th1/17 cells

Background

Vitiligo is an autoimmune disease with varying pathological features. Activation of the CCL20-CCR6 axis plays an important role in chronic inflammatory diseases. However, whether CCL20-CCR6 and Th1/17 cells are indicative of active vitiligo is unclear.

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

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