Effective clearance of rituximab-resistant tumor cells by breaking the mirror-symmetry of immunoglobulin G and simultaneous binding to CD55 and CD20.

Complement-dependent cytotoxicity (CDC), which eliminates aberrant target cells through the assembly and complex formation of serum complement molecules, is one of the major effector functions of anticancer therapeutic antibodies. In this study, we discovered that breaking the symmetry of natural immunoglobulin G (IgG) antibodies significantly increased the CDC activity of anti-CD20 antibodies. In addition, the expression of CD55 (a checkpoint inhibitor in the CDC cascade) was significantly increased in a rituximab-resistant cell line generated in-house, suggesting that CD55 overexpression might be a mechanism by which cancer cells acquire rituximab resistance. Based on these findings, we developed an asymmetric bispecific antibody (SBU-CD55 × CD20) that simultaneously targets both CD55 and CD20 to effectively eliminate rituximab-resistant cancer cells. In various cancer cell lines, including rituximab-resistant lymphoma cells, the SBU-CD55 × CD20 antibody showed significantly higher CDC activity than either anti-CD20 IgG antibody alone or a combination of anti-CD20 IgG antibody and anti-CD55 IgG antibody. Furthermore, the asymmetric bispecific antibody (SBU-CD55 × CD20) exhibited significantly higher CDC activity against rituximab-resistant cancer cells compared to other bispecific antibodies with symmetric features. These results demonstrate that enhancing CDC with an asymmetric CD55-binding bispecific antibody could be a new strategy for developing therapeutics to treat patients with relapsed or refractory cancers.

Correlation Analysis of Surface and Physical Properties of Ophthalmic Lenses Containing Nanoparticles.

Since contact lenses directly contact the cornea, the surface roughness of the lens may cause various side effects. In addition, gold nanoparticles can realize a variety of colors and characteristics depending on their shape and size. In this study, the surface roughness of tinted lenses containing gold nanoparticles of various sizes was analyzed using atomic force microscopy (AFM) at aspect ratio(surface to volume ratio) ranging from 1:1 to 1:10. The characteristics of the lenses were then confirmed. As a result, tinted lenses with different colors depending on the size of the gold nanoparticles were manufactured. The surface roughness of the lens decreased with increasing size of the gold nanoparticles. However, at aspect ratio of 1:10, increase in surface roughness was observed. In addition, it was confirmed that the wettability and antibacterial properties of the lens had the same effect according to the average surface roughness value. Therefore, it was confirmed that the addition of gold nanoparticles reduced the surface roughness of the lens, which had a great effect on properties such as wettability and antimicrobial properties of the lens. The produced copolymer controls the surface roughness of the lens, and thus it is judged that it can be used as a material for various ophthalmology applications.

Development of Functional Ophthalmic Materials Using Natural Materials and Gold Nanoparticles.

Ginsenoside, known as a natural substance, is a saponin component in ginseng and has various effects, such as antibacterial, antioxidant, and anti-inflammatory effects. In addition, gold nanoparticles can realize various optical and physical properties according to particle size and shape. For polymer polymerization, ginsenoside and gold nanoparticles were used as additives and copolymerized with a basic silicone hydrogel material. As gold nanoparticles, spherical and rod-shaped particles were used, and basic physical properties, such as water content, refractive index, and wettability of the prepared ophthalmic lenses, were measured. As a result of measuring the physical properties of the resulting polymer, it was found that the contact angle decreased by about 1.6% to 83.1% as the addition ratio of ginsenoside increased. In addition, as the addition ratio of metal nanoparticles increased, the refractive index was found to increase regardless of the shape of the nanoparticles. In addition, in the case of water content, the spherical shape gradually decreased according to the addition ratio, while the rod shape gradually increased according to the addition ratio. Therefore, it was found that the addition of ginsenoside, known as a saponin-based natural substance, has excellent wettability, and gold nanoparticles with different shapes have different properties. Thus, it is judged that the resulting copolymer can be utilized as a variety of highly functional ophthalmic polymer materials with high refractive index and high wettability.

Comparative Analysis of the Nutritional Components and Antioxidant Activities of Different Brassica juncea Cultivars.

The purpose of this study was to compare the nutritional components and antioxidant activities of two different cultivars of Brassica juncea (Dolsan, Yeosu, Korea (BJD) and (Jeongseon, Gangwon, Korea (BJJ)). We investigated the proximate composition (moisture, crude ash, crude protein and crude lipid), antioxidant activities (2,2-Diphenyl-2-picrylhydrazil (DPPH) scavenging activity and ferric reducing antioxidant power (FRAP)), total phenol content, total flavonoid content and sinigrin content by high-performance liquid chromatography analysis. Our results show that the proximate compositions of BJD and BJJ were not significantly different. However, both the DPPH radical scavenging and FRAP activities of the BJJ extracts were higher than those of the BJD extracts. The total phenol contents of the BJD and BJJ extracts were 6.56 and 9.80 mg gallic acid equivalent/g, respectively. The total flavonoids content of the BJD and BJJ extracts were 20.92 and 34.81 mg rutin equivalent/g, respectively, whereas the sinigrin contents, one of the major compounds in BJD and BJJ extracts, were 16.16 mg/g and 11.73 mg/g, respectively. In this study, we confirmed that, by comparing BJJ and BJD, the sinigrin content of BJD was higher than that of BJJ, but the antioxidant activity and phenol content of BJD were superior to that of BJJ.

A novel function of Prohibitin on melanosome transport in melanocytes.

Prohibitin (PHB, also known as PHB1 or BAP32), is a highly conserved 31kDa protein that expressed in many cellular compartments, such as mitochondria, nucleus, cytosol, and plasma membrane, and plays roles in regulating the transcription of genes, apoptosis, and mitochondrial biogenesis. There is a report that Prohibitin expression is required for the stimulation of pigmentation by melanogenin. However, no studies have been published on the function of PHB in melanocytes, especially in melanosome transport. Methods: Immunofluorescence was performed to confirm the localization of PHB. siRNA transfections, Co-immunoprecipitation, western blotting and proximity ligation assay were performed to find binding state between proteins and demonstrate functions of PHB on melanosome transport. Results: PHB is located in the melanosome and perinuclear aggregation of melanosome is induced when expression of PHB is reduced with no influence on melanin contents. PHB binds directly to Rab27a and Mlph but not Myosin-Va. Rab27a and Mlph bind to specific domains of PHB. Reduced expression of PHB led to the impaired binding affinity between Rab27a and Mlph. Conclusion: PHB regulates melanosome transport by linking to Rab27a and Mlph in melanocytes. Targeting and regulating PHB not only manages pigmentation in melanocytes, but also controls hyperpigmentation in melanoma.

Smart Fluorescent Hydrogel Glucose Biosensing Microdroplets with Dual-Mode Fluorescence Quenching and Size Reduction.

Fluorescent hydrogel glucose biosensor (FHGB) microdroplets were fabricated using a microfluidic method with glass capillaries having a coaxial flow-focusing geometry with cross-linked poly(acrylic acid) (PAAc) immobilized with carbon dots (CDs), glucose oxidase (GOx), and horseradish peroxidase (HRP) after the conversion of poly(acrylamide) to PAAc. The prepared FHGB droplets showed a dual response to glucose of CD fluorescence quenching and droplet size reduction upon bienzymatic reaction with glucose; the reaction of GOx and HRP with glucose produced gluconic acid and -OH radicals, which caused CD fluorescence quenching and size reduction, respectively. These small FHGB droplets showed good sensitivity (linear range of ∼30 mM with the limit of detection of 0.052 mM), high selectivity (against the main ingredients of human blood serum), and long stability (due to dry state during storage). These FHGB droplets were tested with human blood serum, and they maintained sensing performance for a long time in the dry state. Thus, the FHGB droplets demonstrate a new method to detect glucose levels with small sample amounts by the dual-mode response. They can be further applied as implanted continuous-detection biosensor droplets because of their biocompatibility.

Deubiquitinating enzyme USP22 positively regulates c-Myc stability and tumorigenic activity in mammalian and breast cancer cells.

The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

The Highly Evolvable Antibody Fc Domain.

The Fc region of the IgG antibody recruits immune leukocytes or serum complement molecules, which in turn triggers the clearance of defective cells such as tumor cells or infected cells. In addition, the Fc region is crucial for the prolonged serum persistence of circulating IgG antibodies through an intracellular trafficking and recycling mechanism. Recently, the utility of antibody Fc has been further expanded to include a new class of antigen-binding scaffolds. This review presents the recent progress in the field of antibody Fc engineering and highlights new biomolecular, cellular, and evolutionary approaches to overcome the limitations of conventional monoclonal therapeutic antibodies by engineering the antibody Fc domain.