SBI Pharmaceuticals (Japan)

Non-Fungible Tokens (NFTs) have gained attention as a technology for guaranteeing ownership of digital content, leading to rapid market expansion. However, NFTs are limited in that they guarantee ownership only for a single, explicitly designated digital asset. For instance, if an image associated with an NFT undergoes modifications such as resolution reduction or trimming, it falls outside the scope of the NFT’s guarantee. In this study, we propose a new NFT scheme capable of guaranteeing ownership for multiple digital assets that fall within a defined visual similarity threshold. The core of this method lies in replacing conventional cryptographic hash functions with Image Hash functions, allowing the scope of ownership to cover a "range" of similar content rather than a single exact match. This enables highly similar content to be automatically included within the NFT’s scope of guarantee without explicit designation. To verify the feasibility of this scheme, we implemented and evaluated a prototype using four types of Image Hash functions against common image transformations, such as resolution reduction and trimming, on the Polygon blockchain. The results indicate that both Average Hash (aHash) and Perceptual Hash (pHash) are suitable functions, and that the NFT verification process can be performed efficiently. This method provides a novel mechanism to dynamically extend the scope of NFT ownership, paving the way for new potential applications for NFTs.

This study explores the different growth paths of newly graduated employees who entered the workforce for the first time, comparing those who developed quickly with those who progressed more slowly. Over 9 months, 89 participants—new employees with no prior full-time work experience—completed monthly reports with 25 questions designed to track their workplace learning and development. Among them, 47 employees reached Level 2 (Elementary Apprenticeship: carrying out routine tasks with limited independence), while 42 advanced to Level 3 (Intermediate Apprenticeship: managing tasks more independently and taking initiative with some support). The results show that faster growth is supported by three main factors: building basic business skills, receiving effective support from supervisors, and staying engaged through challenge and enjoyment. These findings highlight how skill development, workplace support, and motivation work together to shape the early career growth of first-time employees.

Porcine liver decomposition product (PLDP) is a functional food that enhances delayed memory recall and frontal lobe function in humans and exerts antidepressant and anxiolytic effects. In the present study, the previously unexplored anti-inflammatory effects of PLDP were investigated both in vitro and in vivo. The effects of PLDP on interleukin (IL)-1β production were examined in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and on their transition to an M1 or M2 phenotype. The effects of PLDP administered 30 min before the initiation of a formalin-induced inflammation-related behavior were also evaluated. Furthermore, the effects of PLDP on LPS-induced inflammation related to cytokine production and behavior in vivo were examined. PLDP was orally administered for five consecutive days and 24 h after LPS administration the mice were evaluated in an open field test and plasma cytokine production was measured. PLDP and its lipid fraction, PLDP extracted lipids (PEL) suppressed LPS-induced IL-1β production. Flow cytometry revealed that PEL shifted Raw 264.7 cells to the M2 phenotype. Moreover, PEL reduced phase 2 inflammation-related behavior in formalin-induced inflammation. In the LPS-induced inflammation model, PLDP improved the LPS-attenuated locomotor activity and exploratory behavior and reduced the increased plasma interferon-γ levels. These results suggest that PLDP exerts anti-inflammatory effects and shifts macrophages to the M2 phenotype. Furthermore, our results indicate that the lipid components in PLDP, especially phospholipids, could exert considerable central neuroprotective effects.

Abstract Introduction: Clinical use of the cytidine-analogue antiviral, cidofovir (CDV), is limited by nephrotoxicity. The lipid-conjugated CDV, brincidofovir (BCV), is characterized by a lack of nephrotoxicity, as well as superior activity compared to CDV. The objectives of this study were to examine the preclinical efficacy of BCV against glioblastoma (GBM), a malignant tumor with an extremely poor prognosis, and to identify biomarkers predicting the efficacy of BCV against GBM. Methods: BCV cytotoxicity was tested in vitro in 11 human GBM cell lines, using the CellTiter-Glo® (CTG) assay. Those cell lines were then analyzed by whole-transcriptome sequencing, and differential gene expression analysis between BCV-sensitive and non-BCV sensitive cell lines was performed using DESeq2 software. To examine the influence of O6-methylguanine-DNA methyltransferase (MGMT) expression on BCV sensitivity, monoclonal MGMT-overexpressing cell lines were established using lentiviral vector-based gene transfer in U87MG cells. MGMT gene and protein expression were confirmed using qPCR and western blot, respectively, and the BCV IC50 values were compared among these cell lines using the CTG assay. Finally, the in vivo anti-tumor efficacy of BCV was evaluated in nude mice that were orthotopically implanted with firefly luciferase-transfected U87MG cells. Mice were i.p. administered vehicle or BCV (10, 20, or 40 mg/kg) twice weekly, and bioluminescence imaging (BLI) was performed twice weekly after i.p. D-Luciferin injection to evaluate intracerebral tumor growth. Survival was evaluated using the Kaplan-Meyer method. Results: The CTG assay revealed a median BCV IC50 value of 2.2 μM. Sub-micromolar BCV IC50 values were obtained in KALS-1, T98G, and LN-18 cells. In these highly sensitive cell lines, differential gene expression analysis identified glypican 6 (GPC6) as the gene showing the most significantly decreased expression, and neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 (NYAP2) as the gene with the most significantly increased expression. Compared to the parent MGMT-negative U87MG cells, two MGMT-overexpressing cell lines exhibited BCV IC50 values that were lower by 16.3-fold and 2.5-fold. In vivo experiments demonstrated that BCV significantly decreased intracranial tumor growth, determined as BLI, in a dose-dependent manner during the treatment period compared with the vehicle group. With the exception of weight loss in the BCV 40 mg/kg group, no apparent systemic toxicity was observed in the other BCV dose groups. Compared with the vehicle group, the BCV 20 mg/kg group exhibited significantly increased survival. Conclusion: BCV exerted antitumor effects on GBM in vitro and in vivo, regardless of MGMT status, and improved survival in vivo. Low GPC6 expression and high NYAP2 expression could serve as clinical pharmacologically significant biomarkers that predict high sensitivity to BCV. Citation Format: Kyounghee Seo, Tomoko Ozawa, David R. Raleigh, Shoji Nagatani, Masatoshi Hazama. Preclinical efficacy assessment of brincidofovir against glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3043.

Germline mutations of CIDEB, a lipid droplets (LDs)-associated protein, confer protection against various liver diseases in humans. It remains to be determined whether liver-specific inhibition of CIDEB will bring clinical benefits. We aim to establish pharmacological proof of concept by testing GalNAc-conjugated Cideb surrogate siRNAs in respective animal models of obesity and MASH and to develop siRNA drug candidates for clinical investigations. Surrogate siRNAs targeting mouse Cideb were designed and evaluated via a panel of assays. Concurrently, humanized CIDEB knock-in mice were generated as a research tool to facilitate human therapeutic siRNA discovery. In vivo administration of the surrogate siRNAs was conducted in the diet-induced obesity (DIO) model and CDAA-HFD model of MASH. In the DIO model, Cideb knockdown led to significant reductions of serum total cholesterol (TC) and triglyceride (TG) levels, a significant decrease in hepatic macro-steatosis and notable weight loss. In the CDAA-HFD model, Cideb siRNA treatment significantly reduced liver TC and TG levels. Furthermore, remarkable reductions of hepatic steatosis and the composite NAS score were observed with a concomitant amelioration of liver fibrosis. Transcriptome analyses revealed that integrin pathways may contribute to the major pharmacological activities upon Cideb inactivation beyond lipid metabolism. CIDEB exhibits significant potential as a therapeutic target for the treatment of MASH. Liver-targeting siRNA candidates are under development for therapeutic hypothesis testing in humans.

For therapeutic approaches for upper tract urothelial carcinomas, the absorption and reduced scattering coefficients of these tissues are essential parameters to quantitatively evaluate the distribution of light treatment effects. The and spectra of the human ureter, fatty tissue, ureteral and renal pelvic carcinomas, and porcine ureter and fatty tissue are measured over 400 to 700nm to evaluate projected light penetration depths . The optical properties were determined with a double integrating sphere optical system and inverse Monte Carlo methods. was calculated and compared between normal and cancerous human tissues as well as between normal human and porcine tissues. and spectra of each tissue were determined. The of the normal human ureter was less than those of the ureteral and renal pelvic carcinomas, whereas that of the porcine ureter was similar to that of the human ureter over 400 to 600nm and times smaller above 600nm. Optical properties of human and porcine upper urinary tracts provide insights into light distributions and the validity of ex vivo porcine models in preclinical evaluations of laser treatments.

The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the "DOSAGE AND ADMINISTRATION," "ADVERSE REACTIONS," and "PHARMACOKINETICS" sections was 3, 16, and 62, respectively. Furthermore, in the "ADVERSE REACTIONS" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the "PHARMACOKINETICS" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.

The discovery of novel therapeutic antimicrobials has become an urgent issue in response to the global crisis of the spread of multi-drug-resistant bacteria. In this report, we propose an efficient screening method for antimicrobial agents with therapeutic potential from soil bacteria. With this method, colonies of the soil bacteria were formed first on agar plates containing only an extract of soil, followed by an overlay of soft agar containing the pathogens, an antibiotic target. Then, we selected the colonies that formed the inhibitory zones on soft agar and evaluated the therapeutic efficacy of their culture supernatants using a silkworm bacterial infection model. Using Staphylococcus aureus as an indicator strain to obtain bacteria that produce therapeutically effective antimicrobials, we succeeded in reducing the screening size by 20-fold compared to the conventional method. An analysis of 86 antibiotics producers identified in this study indicated that the majority belonged to Streptomyces sp. and Lysobacter sp., well-known producers of secondary metabolites. Besides, the presence of eight genera and 37 species among the identified species indicated the diversity of antibiotic producers. Based on the finding of our study, we propose this method as an efficient way to discover novel antimicrobial agents that are therapeutically effective.

Photodynamic therapy (PDT) is a clinically approved, minimally invasive treatment for malignant tumors. Protoporphyrin IX (PpIX), derived from 5-aminolevulinic acid (5-ALA) as the prodrug, is one of the photosensitizers used in PDT. Recently, we reported a significant difference in response to 5-ALA-mediated PDT treatment in two canine primary lung adenocarcinoma cell lines (sensitive to PDT: HDC cells, resistant to PDT: LuBi cells). This study aimed to examine the difference in cytotoxicity of 5-ALA-mediated PDT in these cells. Although intracellular PpIX levels before irradiation were similar between HDC and LuBi cells, the percentage of ROS-positive cells and apoptotic cells in LuBi cells treated with 5-ALA-mediated PDT was significantly lower than that in HDC cells treated with 5-ALA-mediated PDT. A high dosage of the NO donor, DETA NONOate, significantly increased the cytotoxicity of 5-ALA-mediated PDT against LuBi cells. These results suggest that the sensitivity of 5-ALA-mediated PDT might be correlated with NO.