Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.

Purpose: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target for CLDN18.2-expressing gastric cancer (GC). We sought to examine the heterogeneity of CLDN18.2 expression between primary GC (PGC) and metastatic GC (MGC) using various scoring methods. Materials and Methods: We retrospectively analyzed data from 102 patients with pathologically confirmed paired primary and metastatic gastric or gastroesophageal junction adenocarcinomas. CLDN18.2 expression was evaluated through immunohistochemistry on formalin-fixed paraffin-embedded tissue samples. We assessed CLDN18.2 positivity using multiple scoring approaches, including the immunoreactivity score, H-score, and the percentage of tumor cells showing moderate-to-strong staining intensity. We analyzed the concordance rates between PGC and MGC and the association of CLDN18.2 positivity with clinicopathological features. Results: CLDN18.2 positivity varied from 25% to 65% depending on the scoring method, with PGC consistently showing higher expression levels than MGC. Intratumoral heterogeneity was noted in 25.5% of PGCs and 19.6% of MGCs. Intertumoral heterogeneity, manifesting as discordance in CLDN18.2 positivity between PGC and MGC, was observed in about 20% of cases, with moderate agreement across scoring methods (κ=0.47 to 0.60).In PGC, higher CLDN18.2 positivity correlated with synchronous metastasis, presence of peritoneal metastasis, poorly differentiated grade, and biopsy specimens. In MGC, positivity was associated with synchronous metastasis, presence of peritoneal metastasis, and metastatic peritoneal tissues. Conclusions CLDN18.2 expression demonstrates significant heterogeneity between PGC and MGC, with a 20% discordance rate. Comprehensive tissue sampling and reassessment of CLDN18.2 status are crucial, especially before initiating CLDN18.2-targeted therapies.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

BACKGROUND/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.