In light of the burgeoning successes of cancer immunotherapy, glioblastoma (GBM) remains refractory due to an immunosuppressive microenvironment originating from its molecular heterogeneity. Thus, identifying promising therapeutic targets for treating GBM and discovering methodologies to effectively regulate them is still a tremendous challenge. Here we describe photodynamic protein tyrosine phosphatase 1B (PTP1B) proteolysis mediated by a proteolysis-targeting chimera (PROTAC) nanoassembly. The PTP1B-targeting PROTAC is conjugated with a photosensitizer via a cathepsin B (Cat B)-cleavable peptide, which spontaneously forms nanoassemblies due to intermolecular π-π stacking interactions. In GBM models, PROTAC nanoassemblies significantly accumulate in the tumor region across the disrupted blood-brain barrier (BBB), triggering a burst release of the photosensitizer and active PROTAC by Cat B-mediated enzymatic cleavage. Upon laser irradiation, photodynamic therapy (PDT) synergizes with PROTAC-mediated PTP1B proteolysis to induce potent immunogenic cell death (ICD) in tumor cells. Subsequently, persistent PTP1B degradation by nanoassemblies in Cat B-overexpressed intratumoral T cells downregulates exhaustion markers, reinvigorating their functionality. These sequential processes of photodynamic PTP1B proteolysis ultimately augment T cell-mediated antitumor immunity as well as protective immunity, completely eradicating the primary GBM and preventing its recurrence. Overall, our findings underscore the therapeutic potential of combining PDT with PROTAC activity for GBM immunotherapy.

PURPOSE: The purpose of this study was to compare the surface characteristics and healing patterns after implantation of implants treated with SLA and those treated with both SLA and femtosecond laser. MATERIALS AND METHODS: A total of 10 male New Zealand white rabbits were used to compare recovery levels between implants treated with SLA (SLA group) and those treated with both SLA and femtosecond laser (SF group). The implants’ surface characteristics were determined through topographic evaluation, element analysis, surface roughness, and wettability evaluation. In total, 4 implants were placed in each rabbit (2 in each tibia), with 20 implants per treatment group. Using the implant stability quotient (ISQ), marginal bone volume, and histological analysis (bone-to-implant contact (BIC), bone volume/tissue volume (BV/TV)), and post implantation outcomes were assessed. Outcome data were analyzed using independent t-tests, Mann-Whitney U tests, Wilcoxon signed-rank tests, and one-way ANOVA (α = 0.05). RESULTS: No significant differences were noted between SLA and SF groups in terms of ISQ, marginal bone volume, BIC, and BV/TV (P > .05). However, significant differences in ISQ were observed within each group over time (P < .05). Furthermore, significant differences were noted in the marginal bone volume of the SF group (P < .05) and the BV/TV of the SLA group between weeks 4 and 6 (P < .05). CONCLUSION Surface treatment via SLA and femtosecond laser is feasible compared with SLA treatment alone in terms of ISQ, marginal bone volume, BIC, and BV/TV. However, further clinical research is warranted.

PURPOSE: The purpose of this clinical study was to evaluate the extent of intraoral occlusal adjustment required for zirconia crowns designed with a dynamic jaw motion tracking method compared to a conventional approach. MATERIALS AND METHODS: Fifteen patients needing zirconia crown restorations in the anterior or posterior regions participated in this study. Following tooth preparation, dynamic jaw motion tracking records were gathered using a tracking device. These records were imported into computer-aided design software and aligned with scanned upper and lower jaw data to design each crown's occlusal surface. Two crowns were fabricated for each patient: one using motion tracking data and another without it. Crowns were scanned pre- and post-adjustment following standard protocols. The scanned data were analyzed with 3D inspection software to calculate occlusal adjustments in the segmented occlusal area as root mean square values, with a paired t-test used for statistical analysis (α = 0.05). RESULTS: Crowns designed with motion tracking data required significantly less intraoral occlusal adjustment than those designed conventionally (P = .028). CONCLUSION Dynamic jaw motion tracking in crown design reduces the extent of intraoral occlusal adjustment, potentially enhancing clinical efficiency.

As research on the unique effects of space environment, especially microgravity and cosmic radiation, on the cardiovascular system is being conducted, research on the development of cardiovascular therapeutics using the space environment is attracting attention. This review comprehensively analyzes the current status and prospects of cardiovascular therapeutics development research utilizing space environment.Microgravity environment has been shown to have a positive effect on the proliferation and differentiation of cardiac progenitor cells and induced pluripotent stem cell-derived cardio myocytes. Cardiac tissue culture and organoid technology have enabled more effective drug screening and disease modeling than on the ground, and changes in gene expression such as Aquaporin-4 have been found to play an important role in cardiac function. Cosmic radiation can cause myocardial remodeling, fibrosis, and vascular endothelial dysfunction, and the underlying mechanisms of these effects include increased oxidative stress, promotion of inflammatory responses, deoxyribo nucleic acid damage, and cell death. Currently, the development of drugs that can prevent or treat cardiovascular damage caused by the space environment is in the early stages, and future research is expected to focus on developing personalized treatments and exploring the potential applications of space medicine research results to terrestrial medicine.

Background/Aims: Adiponectin, a hormone primarily produced by adipocytes, typically shows an inverse relationship with body mass index (BMI). However, some studies have reported a positive correlation between the two. Thus, this study aimed to examine the relationship between adiponectin level and BMI in diabetic patients, focusing on the impact of past obesity on current adiponectin levels. Methods: We conducted an observational study analyzing data from 323 diabetic patients at Kyungpook National University Hospital. Based on past and current BMIs, participants were categorized into never-obese (nn, n = 106), previously obese (on, n = 43), and persistently obese (oo, n = 73) groups based on a BMI threshold of 25 kg/m2. Adiponectin level and BMI were key variables. Kaplan–Meier analysis assessed their impact on all-cause mortality up to August 2023, with survival differences based on adiponectin quartiles and follow-up starting from patient enrollment (2010–2015). Results: The analysis revealed a significant inverse correlation between adiponectin level and past maximum BMI. The on group exhibited approximately 10% lower adiponectin levels compared to the nn group. This association remained significant after adjusting for current BMI, age, and sex, highlighting the lasting influence of previous obesity on adiponectin levels. Furthermore, survival analysis indicated that patients in the lowest adiponectin quartile had reduced survival, with a statistically significant trend (p = 0.062). Conclusions Findings of this study suggest that lower adiponectin levels, potentially reflecting past obesity, are associated with decreased survival in diabetic patients, underscoring a critical role of adiponectin in long-term health outcomes.

Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

Background and Objectives: Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively. Results: Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs. Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

PURPOSE: The purpose of this study was to compare the surface characteristics and healing patterns after implantation of implants treated with SLA and those treated with both SLA and femtosecond laser. MATERIALS AND METHODS: A total of 10 male New Zealand white rabbits were used to compare recovery levels between implants treated with SLA (SLA group) and those treated with both SLA and femtosecond laser (SF group). The implants’ surface characteristics were determined through topographic evaluation, element analysis, surface roughness, and wettability evaluation. In total, 4 implants were placed in each rabbit (2 in each tibia), with 20 implants per treatment group. Using the implant stability quotient (ISQ), marginal bone volume, and histological analysis (bone-to-implant contact (BIC), bone volume/tissue volume (BV/TV)), and post implantation outcomes were assessed. Outcome data were analyzed using independent t-tests, Mann-Whitney U tests, Wilcoxon signed-rank tests, and one-way ANOVA (α = 0.05). RESULTS: No significant differences were noted between SLA and SF groups in terms of ISQ, marginal bone volume, BIC, and BV/TV (P > .05). However, significant differences in ISQ were observed within each group over time (P < .05). Furthermore, significant differences were noted in the marginal bone volume of the SF group (P < .05) and the BV/TV of the SLA group between weeks 4 and 6 (P < .05). CONCLUSION Surface treatment via SLA and femtosecond laser is feasible compared with SLA treatment alone in terms of ISQ, marginal bone volume, BIC, and BV/TV. However, further clinical research is warranted.