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.

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.

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.

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.

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.

Background: This study aimed to determine whether a shorter high-dose rifampicin regimen is non-inferior to the standard 6-month tuberculosis regimen. Methods: This multicenter, randomized, open-label, non-inferiority trial enrolled participants with respiratory specimen positivity by Xpert MTB/RIF assay or Mycobacterium tuberculosis culture without rifampicin-resistance. Participants were randomized at 1:1 to the investigational or control group. The investigational group received high-dose rifampicin (30 mg/kg/day), isoniazid, and pyrazinamide until culture conversion, followed by high-dose rifampicin and isoniazid for 12 weeks. The control group received the standard 6-month regimen. The primary outcome was the rate of unfavorable outcomes at 18 months post-randomization. The non-inferiority margin was set at <6% difference in unfavorable outcomes rates. The study is registered with ClinicalTrials.gov (NCT04485156) Results: Between 4 November 2020 and 3 January 2022, 76 participants were enrolled. Of these, 58 were included in the modified intention-to-treat analysis. Unfavorable outcomes occurred in 10 (31.3%) of 32 in the control group and 10 (38.5%) of 26 in the investigational group. The difference was 7.2% (95% confidence interval, ∞ to 31.9%), failing to prove non-inferiority. Serious adverse events and grade 3 or higher adverse events did not differ between the groups. Conclusion The shorter high-dose rifampicin regimen failed to demonstrate non-inferiority but had an acceptable safety profile.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.