Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Purpose: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. Methods: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. Results: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0–21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. Conclusion These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

BACKGROUND: The skin, a vital organ protecting against microorganisms and dehydration, undergoes structural decline with aging, leading to visible issues such as wrinkles and sagging. Reduced blood vessels exacerbate vulnerability, hindering optimal cellular function and compromising skin health. Polydioxanone (PDO) biomaterials address aging concerns but produce acidic byproducts, causing inflammation. Inorganic particles and nitric oxide (NO) play crucial roles in inhibiting inflammation and promoting skin regeneration. Stem cell-derived extracellular vesicles (EVs) contribute to intercellular communication, offering the potential to enhance cell functions. The study proposes a method to enhance PDO-based medical devices by incorporating inorganic particles and immobilizing EVs, focusing on facial rejuvenation, anti-inflammatory response, collagen formation, and angiogenesis.METHOD: PDO composites with inorganic particles such as magnesium hydroxide (MH) and zinc oxide (ZO) were prepared and followed by EV immobilization. Comprehensive characterization included biocompatibility, anti-inflammation, collagen formation ability, and angiogenesis ability. RESULTS: Bulk-modified PDO composites demonstrated even dispersion of inorganic particles, pH neutralization, and enhanced biocompatibility. EVs immobilized on the composite surface exhibited spherical morphology. Inflammationrelated gene expressions decreased, emphasizing anti-inflammatory effects. Collagen-related gene and protein expressions increased, showcasing collagen formation ability. In addition, angiogenic capabilities were notably improved, indicating potential for skin rejuvenation. CONCLUSION The study successfully developed and characterized PDO composites with inorganic particles and EVs, demonstrating promising attributes for medical applications. These composites exhibit biocompatibility, anti-inflammatory properties, collagen formation ability, and angiogenic potential, suggesting their utility in skin rejuvenation and tissue engineering. Further research and clinical validation are essential.

BACKGROUND: Recent anti-cancer agents, immune checkpoint inhibitors (ICIs), have emerged as effective agents targeting the programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. While the administration of gonadotropin-releasing hormone (GnRH) analogs before cytotoxic agents is known to preserve female reproductive organ function, the potential effects of ICIs and the protective impact of GnRH analogs on female reproductive organs, especially concerning ovarian reserve and endometrial receptivity, remain unknown. In this study, we attempted to elucidate the protective or regenerative effect on the female reproductive organ of cetrorelix prior to anti-PD-L1 antibody administration.METHOD: Using a murine model, we examined the effects of Anti-PD-L1 antibody treatment on ovarian and uterine morphology, compared them with controls, and further assessed any potential protective effect of cetrorelix, a GnRH analog. Histological examinations and quantitative reverse transcription polymerase chain reaction were employed to study the morphological changes and associated gene expression patterns. RESULTS: Anti-PD-L1 treatment led to a significant depletion of primordial/primary ovarian follicles and impaired decidualization in uterine stromal cells. However, while pretreatment with cetrorelix could restore normal decidualization patterns in the uterus, it did not significantly ameliorate ovarian follicular reductions. Gene expression analysis reflected these observations, particularly with marked changes in the expression of key genes like Prl and Igfbp1, pivotal in uterine decidualization. CONCLUSION Our study underscores the potential reproductive implications of cetrorelix treatment prior to Anti-PDL1 therapy, shedding light on its short-term protective effects on the uterus. Further studies are necessary to understand long-term and clinical implications.