Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a 5-year survival low of 2% in advanced cases. Despite being a fatal disease, there is a lack of a good predictor of prognosis which can aid in the management of patients. The tumor microenvironment of PDAC, including immune cells, plays a vital role in the progression and invasiveness of PDAC. Cluster of differentiation 47 (CD47) which has a “don’t eat me signal” to macrophages through receptor signal regulatory protein alpha, prevents immune cell surveillance of cancer cells. This contributes to the immune escape and invasiveness of cancer. Methods: We obtained pancreatic cancer tissue microarray samples from 98 patients treated in Hanyang University Hospital. The diagnosis was proven by a tissue biopsy obtained after surgical resection. Immunohistochemical staining was done using CD47 antibody. Data was analyzed using R software ver. 4.3.3. Results: In a study of 98 patients with PDAC, CD47 expression (54.1%) was significantly correlated with advanced disease stage. Positive CD47 expression was associated with lower overall survival (P = 0.028) and disease-free survival (P = 0.005) in all patients. In advanced-stage patients, CD47 remained a predictor of lower overall survival (P = 0.012) and diseasefree survival (P = 0.023). Multivariate analysis identified positive CD47 expression as an independent factor affecting overall survival (P = 0.048). These results emphasize CD47’s prognostic relevance in PDAC, particularly in advanced stages. Conclusion Positive CD47 expression in PDAC indicates an advanced stage of the disease and independently predicts poor outcomes. This highlights CD47’s role as a crucial prognostic marker in advanced PDAC stages.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Purpose: One of the novel cell sources of cell-based liver regenerative medicine is human chemically-derived hepatic progenitors (hCdHs). We previously established this cell by direct hepatocyte reprogramming with a combination of small molecules (hepatocyte growth factor, A83-01, CHIR99021). However, there have been several issues concerning the cell’s stability and maintenance, namely the occurrences of epithelial-mesenchymal transition (EMT) that develop fibrotic phenotypes, resulting in the loss of hepatic progenitor characteristics. These hepatic progenitor attributes are thought to be regulated by SOX9, a transcription factor essential for hepatic progenitor cells and cholangiocytes. Methods: To suppress the fibrotic phenotype and improve our long-term hCdHs culture technology, we utilized the epigenetic modulating drugs DNA methyltransferase inhibitor (5-azacytidine) and histone deacetylase inhibitor (sodium butyrate) that have been reported to suppress and revert hepatic fibrosis. To confirm the essential role of SOX9 to our cell, we used clustered regularly interspaced short palindromic repeats-interference (CRISPRi) to repress the SOX9 expression. Results: The treatment of only 5-azacytidine significantly reduces the fibrosis/mesenchymal marker and EMT-related transcription factor expression level in the early passages. Interestingly, this treatment also increased the hepatic progenitor markers expression, even during the reprogramming phase. Then, we confirmed the essential role of SOX9 by repressing the SOX9 expression with CRISPRi which resulted in the downregulation of several essential hepatic progenitor cell markers. Conclusion These results highlight the capacity of 5-azacytidine to inhibit EMT-driven hepatic fibrosis and the significance of SOX9 on hepatic progenitor cell stemness properties.